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  1. Eachempati P, Kumbargere Nagraj S, Kiran Kumar Krishanappa S, George RP, Soe HHK, Karanth L
    Cochrane Database Syst Rev, 2019 11 13;2019(11).
    PMID: 31721146 DOI: 10.1002/14651858.CD011116.pub3
    BACKGROUND: The gag reflex is an involuntary defence mechanism to protect the pharynx and throat from foreign objects. Gagging is a common problem encountered during dental treatment, making therapeutic procedures distressing and often difficult or even impossible to perform. Various interventions can be used to control the gag reflex: anti-nausea medicines, sedatives, local and general anaesthetics, herbal remedies, behavioural therapies, acupressure, acupuncture, laser, and prosthetic devices. This is an update of the Cochrane Review first published in 2015.

    OBJECTIVES: To assess the effects of pharmacological and non-pharmacological interventions for the management of gagging in people undergoing dental treatment.

    SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the Cochrane Oral Health's Trials Register (to 18 March 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 2) in the Cochrane Library (searched 18 March 2019), MEDLINE Ovid (1946 to 18 March 2019), Embase Ovid (1980 to 18 March 2019), CINAHL EBSCO (1937 to 18 March 2019), AMED Ovid (1985 to 18 March 2019), and the proceedings of the International Association for Dental Research (IADR) online (2001 to 18 March 2019). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. We also conducted forwards citation searching on the included studies via Google Scholar. No restrictions were placed on the language or date of publication when searching the electronic databases.

    SELECTION CRITERIA: We included randomised controlled trials (RCTs), involving people who were given a pharmacological or non-pharmacological intervention to manage gagging that interfered with dental treatment. We excluded quasi-RCTs. We excluded trials with participants who had central or peripheral nervous system disorders, who had oral lesions or were on systemic medications that might affect the gag sensation, or had undergone surgery which might alter anatomy permanently.

    DATA COLLECTION AND ANALYSIS: We independently selected trials, extracted data, and assessed risk of bias. We followed Cochrane's statistical guidelines. We assessed the overall certainty of the evidence using GRADE.

    MAIN RESULTS: We included four trials at unclear risk of bias with 328 participants (263 adults and 65 children who were four years or older), in which one trial compared acupuncture and acupressure (with thumb, device and sea band) at P6 (point located three-finger breadths below the wrist on the inner forearm in between the two tendons) to sham acupuncture and acupressure with and without sedation. One trial compared acupuncture at P6 point to sham acupuncture. These trials reported both completion of dental procedure and reduction in gagging (assessor and patient reported) as their outcomes. One cross-over and one split-mouth trial studied the effect of laser at P6 point compared to control. One trial reported reduction in gagging and another reported presence or absence of gagging during dental procedure. Acupuncture at P6 showed uncertain evidence regarding the successful completion of dental procedure (RR 1.78, 95% CI 1.05 to 3.01; two trials, 59 participants; very low-certainty evidence) and uncertain evidence regarding the reduction in gagging (RR 2.57, 95% CI 1.12 to 5.89; one trial, 26 participants; very low-certainty evidence) in comparison to sham acupuncture. Acupuncture at P6 with sedation did not show any difference when compared to sham acupuncture with sedation (RR 1.08, 95% CI 0.91 to 1.28; one trial, 34 participants; very low-certainty evidence). Acupressure using thumb pressure with or without sedation showed no clear difference in completing dental procedure (RR 0.96, 95% CI 0.84 to 1.10; one trial, 39 participants; very low-certainty evidence; and RR 0.85, 95% CI 0.50 to 1.46; one trial, 30 participants; very low-certainty evidence; respectively), or reduction in gagging (RR 1.06, 95% CI 0.92 to 1.23; one trial, 39 participants; very low-certainty evidence; and RR 0.92, 95% CI 0.60 to 1.41; one trial, 30 participants; very low-certainty evidence; respectively) when compared to sham acupressure with or without sedation. Acupressure at P6 with device showed uncertain evidence regarding the successful completion of dental procedure (RR 2.63, 95% CI 1.33 to 5.18; one trial, 34 participants; very low-certainty evidence) and uncertain evidence regarding the reduction in gagging (RR 3.94, 95% CI 1.63 to 9.53; one trial, 34 participants; very low-certainty evidence) when compared to sham acupressure. However, device combined with sedation showed no difference for either outcome (RR 1.16, 95% CI 0.90 to 1.48; one trial, 27 participants; very low-certainty evidence; and RR 1.26, 95% CI 0.93 to 1.69; one trial, 27 participants; very low-certainty evidence; respectively). Acupressure using a sea band with or without sedation showed no clear difference in completing dental procedure (RR 0.88, 95% CI 0.67 to 1.17; one trial, 21 participants; very low-certainty evidence; and RR 1.80, 95% CI 0.63 to 5.16; one trial, 19 participants; very low-certainty evidence; respectively), or reduction in gagging (RR 0.88, 95% CI 0.67 to 1.17; one trial, 21 participants; very low-certainty evidence; and RR 2.70, 95% CI 0.72 to 10.14; one trial, 19 participants; very low-certainty evidence; respectively) when compared to sham acupressure with or without sedation. Laser at P6 showed a difference in absence of gagging (odds ratio (OR) 86.33, 95% CI 29.41 to 253.45; one trial, 40 participants; very low-certainty evidence) and reduction in gagging (MD 1.80, 95% CI 1.53 to 2.07; one trial, 25 participants; very low-certainty evidence) during dental procedure when compared to dummy laser application. No noteworthy adverse effects were reported. For acupuncture at P6, the trial authors were unsure whether the reported adverse effects were due to participant anxiety or due to the intervention. None of the trials on acupressure or laser reported on this outcome. We did not find trials evaluating any other interventions used to manage gagging in people undergoing dental treatment.

    AUTHORS' CONCLUSIONS: We found very low-certainty evidence from four trials that was insufficient to conclude if there is any benefit of acupuncture, acupressure or laser at P6 point in reducing gagging and allowing successful completion of dental procedures. We did not find any evidence on any other interventions for managing the gag reflex during dental treatment. More well-designed and well-reported trials evaluating different interventions are needed.

  2. Myint KT, Sahoo S, Thein AW, Moe S, Ni H
    PMID: 26451693 DOI: 10.1002/14651858.CD010790.pub2
    BACKGROUND: Sickle cell disease includes a group of inherited haemoglobinopathies affecting multiple organs including the eyes. Some people with the disease develop ocular manifestations due to vaso-occlusion. Vision-threatening complications of sickle cell disease are mainly due to proliferative sickle retinopathy which is characterized by proliferation of new blood vessels. Laser photocoagulation is widely applicable in proliferative retinopathies such as proliferative sickle retinopathy and proliferative diabetic retinopathy. It is important to evaluate the efficacy and safety of laser photocoagulation in the treatment of proliferative sickle retinopathy to prevent sight-threatening complications.

    OBJECTIVES: To evaluate the effectiveness of various techniques of laser photocoagulation therapy in sickle cell disease-related retinopathy.

    SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 21 September 2015.We also searched the following resources (24 March 2015): Latin American and Carribean Health Science Literature Database (LILACS); WHO International Clinical Trials Registry Platforms (ICTRP); and ClinicalTrials.gov.

    SELECTION CRITERIA: Randomised controlled trials comparing laser photocoagulation to no treatment in children and adults.

    DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, the risk of bias of the included trials and extracted and analysed data. We contacted the trial authors for additional information.

    MAIN RESULTS: Two trials (341 eyes of 238 children and adults) were included comparing efficacy and safety of laser photocoagulation to no therapy in people with proliferative sickle retinopathy. There were 121 males and 117 females with an age range from 13 to 67 years. The laser photocoagulation technique used was different in the two trials; one single-centre trial employed sectoral scatter laser photocoagulation using an argon laser; and the second, two-centre trial, employed feeder vessel coagulation using argon laser in one centre and xenon arc in the second centre. The follow-up period ranged from a mean of 21 to 32 months in one trial and 42 to 47 months in the second. Both trials were at risk of selection bias (random sequence generation) because of the randomisation method employed for participants with bilateral disease. One study was considered to be at risk of reporting bias.Using sectoral scatter laser photocoagulation, one trial (174 eyes) reported that complete regression of proliferative sickle retinopathy was seen in 30.2% in the laser group and 22.4% in the control group (no difference between groups). The same trial reported the development of new proliferative sickle retinopathy in 34.3% of laser-treated eyes and in 41.3% of eyes given no treatment; again, there was no difference between treatment groups. The second trial, using feeder vessel coagulation, did not present full data for either treatment group for these outcomes.There was evidence from both trials (341 eyes) that laser photocoagulation using scatter laser or feeder vessel coagulation may prevent the loss of vision in eyes with proliferative sickle retinopathy (at median follow up of 21 to 47 months). Data from both trials indicated that laser treatment prevented the occurrence of vitreous haemorrhage with both argon and xenon laser; with the protective effect being greater with feeder vessel laser treatment compared to scatter photocoagulation.Regarding adverse effects, the incidence of retinal tear was minimal, with only one event reported. Combined data from both trials were available for 341 eyes; there was no difference between the laser and control arms for retinal detachment. In relation to choroidal neovascularization, treatment with xenon arc was found to be associated with a significantly higher risk, but visual loss related to this complication is uncommon with long-term follow up of three years or more.Data regarding quality of life and other adverse effects were not reported in the included trials.

    AUTHORS' CONCLUSIONS: Our conclusions are based on the data from two trials conducted over 20 years ago. In the absence of further evidence, laser treatment for sickle cell disease-related retinopathy should be considered as a one of therapeutic options for preventing visual loss and vitreous haemorrhage. However, it does not appear to have a significant different effect on other clinical outcomes such as regression of proliferative sickle retinopathy and development of new ones. No evidence is available assessing efficacy in relation to patient-important outcomes (such as quality of life or the loss of a driving licence). There is limited evidence on safety, overall, scatter argon laser photocoagulation is superior in terms of adverse effects, although feeder vessel coagulation has a better effect in preventing vitreous haemorrhage. Further research is needed to examine the safety of laser treatment compared to other interventions such as intravitreal injection of anti-vascular endothelial growth factors. In addition, patient-important outcomes as well as cost-effectiveness should be addressed.

  3. Ngim CF, Lai NM, Hong JY, Tan SL, Ramadas A, Muthukumarasamy P, et al.
    Cochrane Database Syst Rev, 2017 09 18;9:CD012284.
    PMID: 28921500 DOI: 10.1002/14651858.CD012284.pub2
    BACKGROUND: Thalassaemia is a recessively-inherited blood disorder that leads to anaemia of varying severity. In those affected by the more severe forms, regular blood transfusions are required which may lead to iron overload. Accumulated iron from blood transfusions may be deposited in vital organs including the heart, liver and endocrine organs such as the pituitary glands which can affect growth hormone production. Growth hormone deficiency is one of the factors that can lead to short stature, a common complication in people with thalassaemia. Growth hormone replacement therapy has been used in children with thalassaemia who have short stature and growth hormone deficiency.

    OBJECTIVES: To assess the benefits and safety of growth hormone therapy in people with thalassaemia.

    SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles, reviews and clinical trial registries. Our database and trial registry searches are current to 10 August 2017 and 08 August 2017, respectively.

    SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing the use of growth hormone therapy to placebo or standard care in people with thalassaemia of any type or severity.

    DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion. Data extraction and assessment of risk of bias were also conducted independently by two authors. The quality of the evidence was assessed using GRADE criteria.

    MAIN RESULTS: One parallel trial conducted in Turkey was included. The trial recruited 20 children with homozygous beta thalassaemia who had short stature; 10 children received growth hormone therapy administered subcutaneously on a daily basis at a dose of 0.7 IU/kg per week and 10 children received standard care. The overall risk of bias in this trial was low except for the selection criteria and attrition bias which were unclear. The quality of the evidence for all major outcomes was moderate, the main concern was imprecision of the estimates due to the small sample size leading to wide confidence intervals. Final height (cm) (the review's pre-specified primary outcome) and change in height were not assessed in the included trial. The trial reported no clear difference between groups in height standard deviation (SD) score after one year, mean difference (MD) -0.09 (95% confidence interval (CI) -0.33 to 0.15 (moderate quality evidence). However, modest improvements appeared to be observed in the following key outcomes in children receiving growth hormone therapy compared to control (moderate quality evidence): change between baseline and final visit in height SD score, MD 0.26 (95% CI 0.13 to 0.39); height velocity, MD 2.28 cm/year (95% CI 1.76 to 2.80); height velocity SD score, MD 3.31 (95% CI 2.43 to 4.19); and change in height velocity SD score between baseline and final visit, MD 3.41 (95% CI 2.45 to 4.37). No adverse effects of treatment were reported in either group; however, while there was no clear difference between groups in the oral glucose tolerance test at one year, fasting blood glucose was significantly higher in the growth hormone therapy group compared to control, although both results were still within the normal range, MD 6.67 mg/dL (95% CI 2.66 to 10.68). There were no data beyond the one-year trial period.

    AUTHORS' CONCLUSIONS: A small single trial contributed evidence of moderate quality that the use of growth hormone for a year may improve height velocity of children with thalassaemia although height SD score in the treatment group was similar to the control group. There are no randomised controlled trials in adults or trials that address the use of growth hormone therapy over a longer period and assess its effect on final height and quality of life. The optimal dosage of growth hormone and the ideal time to start this therapy remain uncertain. Large well-designed randomised controlled trials over a longer period with sufficient duration of follow up are needed.

  4. Kumbargere Nagraj S, George RP, Shetty N, Levenson D, Ferraiolo DM, Shrestha A
    Cochrane Database Syst Rev, 2017 12 20;12:CD010470.
    PMID: 29260510 DOI: 10.1002/14651858.CD010470.pub3
    BACKGROUND: The sense of taste is very much essential to the overall health of an individual. It is a necessary component to enjoy one's food, which in turn provides nutrition to an individual. Any disturbance in taste perception can hamper quality of life in such patients by influencing their appetite, body weight and psychological well-being. Taste disorders have been treated using different modalities of treatment and there is no consensus for the best intervention. Hence this Cochrane Review was undertaken. This is an update of the Cochrane Review first published in November 2014.

    OBJECTIVES: To assess the effects of interventions for the management of patients with taste disturbances.

    SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 4 July 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017 Issue 6) in the Cochrane Library (searched 4 July 2017); MEDLINE Ovid (1946 to 4 July 2017); Embase Ovid (1980 to 4 July 2017); CINAHL EBSCO (1937 to 4 July 2017); and AMED Ovid (1985 to 4 July 2017). The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for trials. Abstracts from scientific meetings and conferences were searched on 25 September 2017. No restrictions were placed on the language or date of publication when searching the electronic databases.

    SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing any pharmacological agent with a control intervention or any non-pharmacological agent with a control intervention. We also included cross-over trials in the review.

    DATA COLLECTION AND ANALYSIS: Two pairs of review authors independently, and in duplicate, assessed the quality of trials and extracted data. Wherever possible, we contacted trial authors for additional information. We collected adverse events information from the trials.

    MAIN RESULTS: We included 10 trials (581 participants), nine of which we were able to include in the quantitative analyses (566 participants). We assessed three trials (30%) as having a low risk of bias, four trials (40%) at high risk of bias and three trials (30%) as having an unclear risk of bias. We only included studies on taste disorders in this review that were either idiopathic, or resulting from zinc deficiency or chronic renal failure.Of these, nine trials with 544 people compared zinc supplements to placebo for patients with taste disorders. The participants in two trials were children and adolescents with respective mean ages of 10 and 11.2 years and the other seven trials had adult participants. Out of these nine, two trials assessed the patient-reported outcome for improvement in taste acuity using zinc supplements (risk ratio (RR) 1.40, 95% confidence interval (CI) 0.94 to 2.09; 119 participants, very low-quality evidence). We meta-analysed for taste acuity improvement using objective outcome (continuous data) in idiopathic and zinc-deficient taste disorder patients (standardised mean difference (SMD) 0.44, 95% CI 0.23 to 0.65; 366 participants, three trials, very low-quality evidence). We also analysed one cross-over trial separately using the first half of the results for taste detection (mean difference (MD) 2.50, 95% CI 0.93 to 4.07; 14 participants, very low-quality evidence), and taste recognition (MD 3.00, 95% CI 0.66 to 5.34; 14 participants, very low-quality evidence). We meta-analysed taste acuity improvement using objective outcome (dichotomous data) in idiopathic and zinc-deficient taste disorder patients (RR 1.42, 95% 1.09 to 1.84; 292 participants, two trials, very low-quality evidence). Out of the nine trials using zinc supplementation, four reported adverse events like eczema, nausea, abdominal pain, diarrhoea, constipation, decrease in blood iron, increase in blood alkaline phosphatase, and minor increase in blood triglycerides.One trial tested taste discrimination using acupuncture (MD 2.80, 95% CI -1.18 to 6.78; 37 participants, very low-quality evidence). No adverse events were reported in the acupuncture trial.None of the included trials could be included in the meta-analysis for health-related quality of life in taste disorder patients.

    AUTHORS' CONCLUSIONS: We found very low-quality evidence that was insufficient to conclude on the role of zinc supplements to improve taste acuity reported by patients and very low-quality evidence that zinc supplements improve taste acuity in patients with zinc deficiency/idiopathic taste disorders. We did not find any evidence to conclude the role of zinc supplements for improving taste discrimination, or any evidence addressing health-related quality of life due to taste disorders.We found very low-quality evidence that is not sufficient to conclude on the role of acupuncture for improving taste discrimination in cases of idiopathic dysgeusia (distortion of taste) and hypogeusia (reduced ability to taste). We were unable to draw any conclusions regarding the superiority of zinc supplements or acupuncture as none of the trials compared these interventions.

  5. Arora A, Khattri S, Ismail NM, Kumbargere Nagraj S, Prashanti E
    Cochrane Database Syst Rev, 2017 12 21;12:CD012595.
    PMID: 29267989 DOI: 10.1002/14651858.CD012595.pub2
    BACKGROUND: School dental screening refers to visual inspection of children's oral cavity in a school setting followed by making parents aware of their child's current oral health status and treatment needs. Screening at school intends to identify children at an earlier stage than symptomatic disease presentation, hence prompting preventive and therapeutic oral health care for the children. This review evaluates the effectiveness of school dental screening in improving oral health status.

    OBJECTIVES: To assess the effectiveness of school dental screening programmes on overall oral health status and use of dental services.

    SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 15 March 2017), the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Register of Studies, to 15 March 2017), MEDLINE Ovid (1946 to 15 March 2017), and Embase Ovid (15 September 2016 to 15 March 2017). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on language or publication status when searching the electronic databases; however, the search of Embase was restricted to the last six months due to the Cochrane Centralised Search Project to identify all clinical trials and add them to CENTRAL.

    SELECTION CRITERIA: We included randomised controlled trials (RCTs) (cluster or parallel) that evaluated school dental screening compared with no intervention or with one type of screening compared with another.

    DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.

    MAIN RESULTS: We included six trials (four were cluster-RCTs) with 19,498 children who were 4 to 15 years of age. Four trials were conducted in the UK and two were based in India. We assessed two trials to be at low risk of bias, one trial to be at high risk of bias and three trials to be at unclear risk of bias.None of the six trials reported the proportion of children with untreated caries or other oral diseases.Four trials evaluated traditional screening versus no screening. We performed a meta-analysis for the outcome 'dental attendance' and found an inconclusive result with high heterogeneity. The heterogeneity was found it to be, in part, due to study design (three cluster-RCTs and one individual-level RCT). Due to the inconsistency, we downgraded the evidence to 'very low certainty' and are unable to draw conclusions about this comparison.Two cluster-RCTs (both four-arm trials) evaluated criteria-based screening versus no screening and showed a pooled effect estimate of RR 1.07 (95% CI 0.99 to 1.16), suggesting a possible benefit for screening (low-certainty evidence). There was no evidence of a difference when criteria-based screening was compared to traditional screening (RR 1.01, 95% CI 0.94 to 1.08) (very low-certainty evidence).In one trial, a specific (personalised) referral letter was compared to a non-specific one. Results favoured the specific referral letter with an effect estimate of RR 1.39 (95% CI 1.09 to 1.77) for attendance at general dentist services and effect estimate of RR 1.90 (95% CI 1.18 to 3.06) for attendance at specialist orthodontist services (low-certainty evidence).One trial compared screening supplemented with motivation to screening alone. Dental attendance was more likely after screening supplemented with motivation, with an effect estimate of RR 3.08 (95% CI 2.57 to 3.71) (low-certainty evidence).None of the trials had long-term follow-up to ascertain the lasting effects of school dental screening.None of the trials reported cost-effectiveness and adverse events.

    AUTHORS' CONCLUSIONS: The trials included in this review evaluated short-term effects of screening, assessing follow-up periods of three to eight months. We found very low certainty evidence that was insufficient to allow us to draw conclusions about whether there is a role for traditional school dental screening in improving dental attendance. For criteria-based screening, we found low-certainty evidence that it may improve dental attendance when compared to no screening. However, when compared to traditional screening there was no evidence of a difference in dental attendance (very low-certainty evidence).We found low-certainty evidence to conclude that personalised or specific referral letters improve dental attendance when compared to non-specific counterparts. We also found low-certainty evidence that screening supplemented with motivation (oral health education and offer of free treatment) improves dental attendance in comparison to screening alone.We did not find any trials addressing cost-effectiveness and adverse effects of school dental screening.

  6. Sasongko TH, Nagalla S
    Cochrane Database Syst Rev, 2021 Dec 21;12(12):CD009191.
    PMID: 34932828 DOI: 10.1002/14651858.CD009191.pub4
    BACKGROUND: Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of long-standing anemia and disturbed circulation through the renal medullary capillaries. Due to the improvement in life expectancy of people with sickle cell disease, there has been a corresponding significant increase in the incidence of renal complications. Microalbuminuria and proteinuria are noted to be a strong predictor of subsequent renal failure. There is extensive experience and evidence with angiotensin-converting enzyme (ACE) inhibitors over many years in a variety of clinical situations for patients who do not have sickle cell disease, but their effect in people with this disease is unknown. It is common practice to administer ACE inhibitors for sickle nephropathy due to their renoprotective properties; however, little is known about their effectiveness and safety in this setting. This is an update of a Cochrane Review first published in 2013 and 2015.

    OBJECTIVES: To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects.

    SEARCH METHODS: The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of the most recent search: 18 October 2021. We also searched clinical trial registries. Date of the most recent search: 22 August 2021.

    SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen.

    DATA COLLECTION AND ANALYSIS: Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments.

    MAIN RESULTS: Seven studies were identified through the searches. Six studies were excluded. The included study randomized 22 participants (7 males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. Overall, the certainty of the evidence provided in this review was very low, since most risk of bias domains were judged to have either an unclear or a high risk of bias. Because of this, we are uncertain whether captopril makes any difference, in total urinary albumin excretion (at six months) as compared to the placebo group, although it yielded a mean difference of -49.00 (95% confidence interval (CI) -124.10 to 26.10) or in the absolute change score, although it yielded a mean difference of -63.00 (95% CI -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean (standard deviation) of 45 (23) mg/day and the placebo group was noted to increase by 18 (45) mg/day. Serum creatinine and potassium levels were reported constant throughout the study (very low-certainty evidence). The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure (very low-certainty evidence).

    AUTHORS' CONCLUSIONS: Overall, we judged the certainty of the evidence to be very low. The included study selectively reported its results, was not powered to detect a group difference, should it exist, and otherwise did not offer enough information to allow us to judge the bias inherent in the study. Indirectness (in relation to the limited age and type of population included) and imprecision (wide confidence intervals around the effect estimate) were observed. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study. Overall, we judged the certainty of this evidence to be very low.

  7. Ho JJ, Adnan AS, Kueh YC, Ambak NJ, Van Rostenberghe H, Jummaat F
    Cochrane Database Syst Rev, 2019 Jul 12;7(7):CD009692.
    PMID: 31425606 DOI: 10.1002/14651858.CD009692.pub2
    BACKGROUND: Oedema is a common clinical symptom in people with nephrotic syndrome and human albumin has been widely used in the treatment of oedema by increasing vascular volume and this inducing diuresis. It may be used with or without diuretics such as furosemide. However, the quantitative contribution of human albumin in treating oedema is not fully understood. If human albumin were found to be effective and safe in the treatment of oedema, it could help clinicians to develop therapeutic strategies to improve the management of diuretic resistance associated with nephrotic syndrome.

    OBJECTIVES: This review aimed to examine the benefits and harms of human albumin infusion for treating oedema associated with nephrotic syndrome.

    SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 23 June 2019 through contact with the Information Specialists using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

    SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs evaluating the effect of human albumin infusion compared with placebo or no intervention, human albumin with diuretics compared with diuretic alone, human albumin compared with diuretics and other treatments, clinical outcomes, death, quality of life, kidney function and adverse effects in people with nephrotic syndrome. We excluded cross-over studies but data for the first period was to be included if available.

    DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration were used. Two authors independently assessed eligibility, risk of bias, study quality and extracted data. We calculated mean difference (MD) for continuous data with 95% confidence intervals (CI). We assessed the certainty of the evidence using GRADE.

    MAIN RESULTS: One study met our inclusion criteria (26 children with minimal change nephrotic syndrome) and 11 were excluded (nine cross-over studies, one where albumin was not used for nephrotic syndrome and one where authors did not state whether the children had oedema). Risk of bias for the included study was unclear for selection bias, high for performance and detection bias, low for attrition bias, and high for selective reporting. The included study compared albumin plus furosemide with an equal volume of dextrose. Of our prespecified outcomes, the authors reported clinical improvement as weight change, serum sodium and adverse outcomes (blood pressure). The authors reported a greater weight loss in the albumin treated group initially but no difference overall at 10 days. However, the data in the text and the figures were inconsistent so we could not confirm the authors statements (very low certainty evidence). It is uncertain whether albumin infusion improves serum sodium when compared with an equal volume of dextrose (MD 2.00 mEq/L, 95% CI -0.09 to 4.09), systolic blood pressure (MD 2.00 mmHg, 95% CI -3.52 to 7.52) or diastolic blood pressure (MD 2.00 mmHg, 95%CI -4.29 to 8.29). Death, quality of life, and kidney function were not reported.

    AUTHORS' CONCLUSIONS: We identified only one small study that was relevant to our review, therefore we are unable to draw any conclusions regarding the use of human albumin with or without diuretics in nephrotic syndrome. More RCTs are needed.

  8. Jaafar SH, Ho JJ, Lee KS
    Cochrane Database Syst Rev, 2016 Aug 26;2016(8):CD006641.
    PMID: 27562563 DOI: 10.1002/14651858.CD006641.pub3
    BACKGROUND: Mother-infant proximity and interactions after birth and during the early postpartum period are important for breast-milk production and breastfeeding success. Rooming-in and separate care are both traditional practices. Rooming-in involves keeping the mother and the baby together in the same room after birth for the duration of hospitalisation, whereas separate care is keeping the baby in the hospital nursery and the baby is either brought to the mother for breastfeeding or she walks to the nursery.

    OBJECTIVES: To assess the effect of mother-infant rooming-in versus separation on the duration of breastfeeding (exclusive and total duration of breastfeeding).

    SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 May 2016) and reference lists of retrieved studies.

    SELECTION CRITERIA: Randomised or quasi-randomised controlled trials (RCTs) investigating the effect of mother-infant rooming-in versus separate care after hospital birth or at home on the duration of breastfeeding, proportion of breastfeeding at six months and adverse neonatal and maternal outcomes.

    DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion and assessed trial quality. Two review authors extracted data. Data were checked for accuracy. We assessed the quality of the evidence using the GRADE approach.

    MAIN RESULTS: We included one trial (involving 176 women) in this review. This trial included four groups with a factorial design. The factorial design took into account two factors, i.e. infant location in relation to the mother and the type of infant apparel. We combined three of the groups as the intervention (rooming-in) group and the fourth group acted as the control (separate care) and we analysed the results as a single pair-wise comparison. Primary outcomesThe primary outcome, duration of any breastfeeding, was reported by authors as median values because the distribution was found to be skewed. They reported the overall median duration of any breastfeeding to be four months, with no difference found between groups. Duration of exclusive breastfeeding and the proportion of infants being exclusively breastfed at six months of age was not reported in the trial. There was no difference found between the two groups in the proportion of infants receiving any breastfeeding at six months of age (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.51 to 1.39; one trial; 137 women; low-quality evidence). Secondary outcomesThe mean frequency of breastfeeds per day on day four postpartum for the rooming-in group was 8.3 (standard deviation (SD) 2.2), slightly higher than the separate care group, i.e. seven times per day. However, between-group comparison of this outcome was not appropriate since every infant in the separate care group was breastfed at a fixed schedule of seven times per day (SD = 0) resulting in no estimable comparison. The rate of exclusive breastfeeding on day four postpartum before discharge from hospital was significantly higher in the rooming-in group 86% (99 of 115) compared with separate care group, 45% (17 of 38), (RR 1.92; 95% CI 1.34 to 2.76; one trial, 153 women; low-quality evidence). None of our other pre-specified secondary outcomes were reported.

    AUTHORS' CONCLUSIONS: We found little evidence to support or refute the practice of rooming-in versus mother-infant separation. Further well-designed RCTs to investigate full mother-infant rooming-in versus partial rooming-in or separate care including all important outcomes are needed.

  9. Ibrahim NR, Van Rostenberghe H, Ho JJ, Nasir A
    Cochrane Database Syst Rev, 2021 Aug 19;8(8):CD012322.
    PMID: 34415568 DOI: 10.1002/14651858.CD012322.pub2
    BACKGROUND: There is presently no certainty about the ideal feeding intervals for preterm infants. Shorter feeding intervals of, for example, two hours, have the theoretical advantage of allowing smaller volumes of milk. This may have the potential to reduce the incidence and severity of gastro-oesophageal reflux. Longer feeding intervals have the theoretical advantage of allowing more gastric emptying between two feeds. This potentially provides periods of rest (and thus less hyperaemia) for an immature digestive tract.

    OBJECTIVES: To determine the safety of shorter feeding intervals (two hours or shorter) versus longer feeding intervals (three hours or more) and to compare the effects in terms of days taken to regain birth weight and to achieve full feeding.

    SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to run comprehensive searches in CENTRAL (2020, Issue 6) and Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions, and CINAHL on 25 June 2020. We searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.

    SELECTION CRITERIA: We included RCTs and quasi-RCTs comparing short (e.g. one or two hours) versus long (e.g. three or four hours) feeding intervals in preterm infants of any birth weight, all or most of whom were less than 32 weeks' gestation. Infants could be of any postnatal age at trial entry, but eligible infants should not have received feeds before study entry, with the exception of minimal enteral feeding. We included studies of nasogastric or orogastric bolus feeding, breast milk or formula, in which the feeding interval is the intervention.

    DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. Our primary outcomes were days taken to achieve full enteral feeding and days to regain birth weight. Our other outcomes were duration of hospital stay, episodes of necrotising enterocolitis (NEC) and growth during hospital stay (weight, length and head circumference).

    MAIN RESULTS: We included four RCTs, involving 417 infants in the review. One study involving 350 infants is awaiting classification. All studies compared two-hourly versus three-hourly feeding interval. The risk of bias of the included studies was generally low, but all studies had high risk of performance bias due to lack of blinding of the intervention. Three studies were included in meta-analysis for the number of days taken to achieve full enteral feeding (351 participants). The mean days to achieve full feeds was between eight and 11 days. There was little or no difference in days taken to achieve full enteral feeding between two-hourly and three-hourly feeding, but this finding was of low certainty (mean difference (MD) ‒0.62, 95% confidence interval (CI) ‒1.60 to 0.36). There was low-certainty evidence that the days taken to regain birth weight may be slightly longer in infants receiving two-hourly feeding than in those receiving three-hourly feeding (MD 1.15, 95% CI 0.11 to 2.20; 3 studies, 350 participants). We are uncertain whether shorter feeding intervals have any effect on any of our secondary outcomes including the duration of hospital stay (MD ‒3.36, 95% CI ‒9.18 to 2.46; 2 studies, 207 participants; very low-certainty evidence) and the risk of NEC (typical risk ratio 1.07, 95% CI 0.54 to 2.11; 4 studies, 417 participants; low-certainty evidence). No study reported growth during hospital stay.

    AUTHORS' CONCLUSIONS: The low-certainty evidence we found in this review suggests that there may be no clinically important differences between two- and three-hourly feeding intervals. There is insufficient information about potential feeding complications and in particular NEC. No studies have looked at the effect of other feeding intervals and there is no long-term data on neurodevelopment or growth.

  10. Hussein N, Henneman L, Kai J, Qureshi N
    Cochrane Database Syst Rev, 2021 Oct 11;10(10):CD010849.
    PMID: 34634131 DOI: 10.1002/14651858.CD010849.pub4
    BACKGROUND: Globally, about 6% of children are born with a serious birth defect of genetic or partially genetic origin. Carrier screening or testing is one way to identify couples at increased risk of having a child with an autosomal recessive condition. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in high-risk populations of specific ancestral backgrounds. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if testing is only offered in an antenatal setting. This is an update of a previously published review.

    OBJECTIVES: To assess the effectiveness of systematic preconception genetic risk assessment to enable autonomous reproductive choice and to improve reproductive outcomes  in women and their partners who are both identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care.

    SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. Date of latest search of the registers: 04 August 2021. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials. Date of latest search of all these sources: 25 June 2021.  SELECTION CRITERIA: Any randomised controlled trials (RCTs) or quasi-RCTs (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease when compared to usual care.

    DATA COLLECTION AND ANALYSIS: We identified 37 papers, describing 22 unique trials which were potentially eligible for inclusion in the review. However, after assessment, we found no RCTs of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

    MAIN RESULTS: No RCTs of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease are included. A trial identified earlier has published its results and has subsequently been listed as excluded in this review.

    AUTHORS' CONCLUSIONS: As there are no RCTs of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease included in either the earlier or current versions of this review, we recommend considering potential non-RCTs studies (for example prospective cohorts or before-and-after studies) for future reviews. While RCTs are desirable to inform evidence-based practice and robust recommendations, the ethical, legal and social implications associated with using this trial design to evaluate the implementation of preconception genetic risk assessment involving carrier testing and reproductive autonomy must also be considered.  In addition, rather than focusing on single gene-by-gene carrier testing for specific autosomal-recessive conditions as the intervention being evaluated, preconception expanded genetic screening should also be included in future searches as this has received much attention in recent years as a more pragmatic strategy. The research evidence for current international policy recommendations is limited to non-randomised studies.

  11. Parsons C, Lim WY, Loy C, McGuinness B, Passmore P, Ward SA, et al.
    Cochrane Database Syst Rev, 2021 Feb 03;2(2):CD009081.
    PMID: 35608903 DOI: 10.1002/14651858.CD009081.pub2
    BACKGROUND: Dementia is a progressive syndrome characterised by deterioration in memory, thinking and behaviour, and by impaired ability to perform daily activities. Two classes of drug - cholinesterase inhibitors (donepezil, galantamine and rivastigmine) and memantine - are widely licensed for dementia due to Alzheimer's disease, and rivastigmine is also licensed for Parkinson's disease dementia. These drugs are prescribed to alleviate symptoms and delay disease progression in these and sometimes in other forms of dementia. There are uncertainties about the benefits and adverse effects of these drugs in the long term and in severe dementia, about effects of withdrawal, and about the most appropriate time to discontinue treatment.

    OBJECTIVES: To evaluate the effects of withdrawal or continuation of cholinesterase inhibitors or memantine, or both, in people with dementia on: cognitive, neuropsychiatric and functional outcomes, rates of institutionalisation, adverse events, dropout from trials, mortality, quality of life and carer-related outcomes.

    SEARCH METHODS: We searched the Cochrane Dementia and Cognitive Improvement Group's Specialised Register up to 17 October 2020 using terms appropriate for the retrieval of studies of cholinesterase inhibitors or memantine. The Specialised Register contains records of clinical trials identified from monthly searches of a number of major healthcare databases, numerous trial registries and grey literature sources.

    SELECTION CRITERIA: We included all randomised, controlled clinical trials (RCTs) which compared withdrawal of cholinesterase inhibitors or memantine, or both, with continuation of the same drug or drugs.

    DATA COLLECTION AND ANALYSIS: Two review authors independently assessed citations and full-text articles for inclusion, extracted data from included trials and assessed risk of bias using the Cochrane risk of bias tool. Where trials were sufficiently similar, we pooled data for outcomes in the short term (up to 2 months after randomisation), medium term (3-11 months) and long term (12 months or more). We assessed the overall certainty of the evidence for each outcome using GRADE methods.

    MAIN RESULTS: We included six trials investigating cholinesterase inhibitor withdrawal, and one trial investigating withdrawal of either donepezil or memantine. No trials assessed withdrawal of memantine only. Drugs were withdrawn abruptly in five trials and stepwise in two trials. All participants had dementia due to Alzheimer's disease, with severities ranging from mild to very severe, and were taking cholinesterase inhibitors without known adverse effects at baseline. The included trials randomised 759 participants to treatment groups relevant to this review. Study duration ranged from 6 weeks to 12 months. There were too few included studies to allow planned subgroup analyses. We considered some studies to be at unclear or high risk of selection, performance, detection, attrition or reporting bias. Compared to continuing cholinesterase inhibitors, discontinuing treatment may be associated with worse cognitive function in the short term (standardised mean difference (SMD) -0.42, 95% confidence interval (CI) -0.64 to -0.21; 4 studies; low certainty), but the effect in the medium term is very uncertain (SMD -0.40, 95% CI -0.87 to 0.07; 3 studies; very low certainty). In a sensitivity analysis omitting data from a study which only included participants who had shown a relatively poor prior response to donepezil, inconsistency was reduced and we found that cognitive function may be worse in the discontinuation group in the medium term (SMD -0.62; 95% CI -0.94 to -0.31). Data from one longer-term study suggest that discontinuing a cholinesterase inhibitor is probably associated with worse cognitive function at 12 months (mean difference (MD) -2.09 Standardised Mini-Mental State Examination (SMMSE) points, 95% CI -3.43 to -0.75; moderate certainty). Discontinuation may make little or no difference to functional status in the short term (SMD -0.25, 95% CI -0.54 to 0.04; 2 studies; low certainty), and its effect in the medium term is uncertain (SMD -0.38, 95% CI -0.74 to -0.01; 2 studies; very low certainty). After 12 months, discontinuing a cholinesterase inhibitor probably results in greater functional impairment than continuing treatment (MD -3.38 Bristol Activities of Daily Living Scale (BADLS) points, 95% CI -6.67 to -0.10; one study; moderate certainty). Discontinuation may be associated with a worsening of neuropsychiatric symptoms over the short term and medium term, although we cannot exclude a minimal effect (SMD - 0.48, 95% CI -0.82 to -0.13; 2 studies; low certainty; and SMD -0.27, 95% CI -0.47 to -0.08; 3 studies; low certainty, respectively). Data from one study suggest that discontinuing a cholinesterase inhibitor may result in little to no change in neuropsychiatric status at 12 months (MD -0.87 Neuropsychiatric Inventory (NPI) points; 95% CI -8.42 to 6.68; moderate certainty). We found no clear evidence of an effect of discontinuation on dropout due to lack of medication efficacy or deterioration in overall medical condition (odds ratio (OR) 1.53, 95% CI 0.84 to 2.76; 4 studies; low certainty), on number of adverse events (OR 0.85, 95% CI 0.57 to 1.27; 4 studies; low certainty) or serious adverse events (OR 0.80, 95% CI 0.46 to 1.39; 4 studies; low certainty), and on mortality (OR 0.75, 95% CI 0.36 to 1.55; 5 studies; low certainty). Institutionalisation was reported in one trial, but it was not possible to extract data for the groups relevant to this review.

    AUTHORS' CONCLUSIONS: This review suggests that discontinuing cholinesterase inhibitors may result in worse cognitive, neuropsychiatric and functional status than continuing treatment, although this is supported by limited evidence, almost all of low or very low certainty. As all participants had dementia due to Alzheimer's disease, our findings are not transferable to other dementia types. We were unable to determine whether the effects of discontinuing cholinesterase inhibitors differed with baseline dementia severity. There is currently no evidence to guide decisions about discontinuing memantine. There is a need for further well-designed RCTs, across a range of dementia severities and settings. We are aware of two ongoing registered trials. In making decisions about discontinuing these drugs, clinicians should exercise caution, considering the evidence from existing trials along with other factors important to patients and their carers.

  12. Swe KM, Abas AB, Bhardwaj A, Barua A, Nair NS
    Cochrane Database Syst Rev, 2013 Jun 28;2013(6):CD009415.
    PMID: 23807756 DOI: 10.1002/14651858.CD009415.pub2
    BACKGROUND: Haemoglobinopathies, inherited disorders of haemoglobin synthesis (thalassaemia) or structure (sickle cell disease), are responsible for significant morbidity and mortality throughout the world. The WHO estimates that, globally, 5% of adults are carriers of a haemoglobin condition, 2.9% are carriers of thalassaemia and 2.3% are carriers of sickle cell disease. Carriers are found worldwide as a result of migration of various ethnic groups to different regions of the world. Zinc is an easily available supplement and intervention programs have been carried out to prevent deficiency in people with thalassaemia or sickle cell anaemia. It is important to evaluate the role of zinc supplementation in the treatment of thalassaemia and sickle cell anaemia to reduce deaths due to complications.

    OBJECTIVES: To assess the effect of zinc supplementation in the treatment of thalassaemia and sickle cell disease.

    SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 01 February 2013.

    SELECTION CRITERIA: Randomised, placebo-controlled trials of zinc supplements for treating thalassaemia or sickle cell disease administered at least once a week for at least a month.

    DATA COLLECTION AND ANALYSIS: Two review authors assessed the eligibility and risk of bias of the included trials, extracted and analysed data and wrote the review. We summarised results using risk ratios or rate ratios for dichotomous data and mean differences for continuous data. We combined trial results where appropriate.

    MAIN RESULTS: We identified nine trials for inclusion with all nine contributing outcome data. Two trials reported on people with thalassaemia (n = 152) and seven on sickle cell anaemia (n = 307).In people with thalassaemia, in one trial, the serum zinc level value showed no difference between the zinc supplemented group and the control group, mean difference 47.40 (95% confidence interval -12.95 to 107.99). Regarding anthropometry, in one trial, height velocity was significantly increased in patients who received zinc supplementation for one to seven years duration, mean difference 3.37 (95% confidence interval 2.36 to 4.38) (total number of participants = 26). In one trial, however, there was no difference in body mass index between treatment groups.Zinc acetate supplementation for three months (in one trial) and one year (in two trials) (total number of participants = 71) was noted to increase the serum zinc level significantly in patients with sickle cell anaemia, mean difference 14.90 (95% confidence interval 6.94 to 22.86) and 20.25 (95% confidence interval 11.73 to 28.77) respectively. There was no significant difference in haemoglobin level between intervention and control groups, at either three months (one trial) or one year (one trial), mean difference 0.06 (95% confidence interval -0.84 to 0.96) and mean difference -0.07 (95% confidence interval -1.40 to 1.26) respectively. Regarding anthropometry, one trial showed no significant changes in body mass index or weight after one year of zinc acetate supplementation. In patients with sickle cell disease, the total number of sickle cell crises at one year were significantly decreased in the zinc sulphate supplemented group as compared to controls, mean difference -2.83 (95% confidence interval -3.51 to -2.15) (total participants 130), but not in zinc acetate group, mean difference 1.54 (95% confidence interval -2.01 to 5.09) (total participants 22). In one trial at three months and another at one year, the total number of clinical infections were significantly decreased in the zinc supplemented group as compared to controls, mean difference 0.05 (95% confidence interval 0.01 - 0.43) (total number of participants = 36), and mean difference -7.64 (95% confidence interval -10.89 to -4.39) (total number of participants = 21) respectively.

    AUTHORS' CONCLUSIONS: According to the results, there is no evidence from randomised controlled trials to indicate any benefit of zinc supplementation with regards to serum zinc level in patients with thalassaemia. However, height velocity was noted to increase among those who received this intervention.There is mixed evidence on the benefit of using zinc supplementation in people with sickle cell disease. For instance, there is evidence that zinc supplementation for one year increased the serum zinc levels in patients with sickle cell disease. However, though serum zinc level was raised in patients receiving zinc supplementation, haemoglobin level and anthropometry measurements were not significantly different between groups. Evidence of benefit is seen with the reduction in the number of sickle cell crises among sickle cell patients who received one year of zinc sulphate supplementation and with the reduction in the total number of clinical infections among sickle cell patients who received zinc supplementation for both three months and for one year.The conclusion is based on the data from a small group of trials,which were generally of good quality, with a low risk of bias. The authors recommend that more trials on zinc supplementation in thalassaemia and sickle cell disease be conducted given that the literature has shown the benefits of zinc in these types of diseases.

  13. Moncrieff G, Gyte GM, Dahlen HG, Thomson G, Singata-Madliki M, Clegg A, et al.
    Cochrane Database Syst Rev, 2022 Mar 04;3(3):CD010088.
    PMID: 35244935 DOI: 10.1002/14651858.CD010088.pub3
    BACKGROUND: Routine vaginal examinations are undertaken at regular time intervals during labour to assess whether labour is progressing as expected. Unusually slow progress can be due to underlying problems, described as labour dystocia, or can be a normal variation of progress. Evidence suggests that if mother and baby are well, length of labour alone should not be used to decide whether labour is progressing normally. Other methods to assess labour progress include intrapartum ultrasound and monitoring external physical and behavioural cues. Vaginal examinations can be distressing for women, and overdiagnosis of dystocia can result in iatrogenic morbidity due to unnecessary intervention. It is important to establish whether routine vaginal examinations are effective, both as an accurate measure of physiological labour progress and to distinguish true labour dystocia, or whether other methods for assessing labour progress are more effective. This Cochrane Review is an update of a review first published in 2013.

    OBJECTIVES: To compare the effectiveness, acceptability, and consequences of routine vaginal examinations compared with other methods, or different timings, to assess labour progress at term.

    SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth Trials Register (which includes trials from CENTRAL, MEDLINE, Embase, CINAHL, and conference proceedings) and ClinicalTrials.gov (28 February 2021). We also searched the reference lists of retrieved studies.

    SELECTION CRITERIA: We included randomised controlled trials (RCTs) of vaginal examinations compared with other methods of assessing labour progress and studies assessing different timings of vaginal examinations. Quasi-RCTs and cluster-RCTs were eligible for inclusion. We excluded cross-over trials and conference abstracts.

    DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all studies identified by the search for inclusion in the review. Four review authors independently extracted data. Two review authors assessed risk of bias and certainty of the evidence using GRADE.

    MAIN RESULTS: We included four studies that randomised a total of 755 women, with data analysed for 744 women and their babies. Interventions used to assess labour progress were routine vaginal examinations, routine ultrasound assessments, routine rectal examinations, routine vaginal examinations at different frequencies, and vaginal examinations as indicated. We were unable to conduct meta-analysis as there was only one study for each comparison.  All studies were at high risk of performance bias due to difficulties with blinding. We assessed two studies as high risk of bias and two as low or unclear risk of bias for other domains. The overall certainty of the evidence assessed using GRADE was low or very low.  Routine vaginal examinations versus routine ultrasound to assess labour progress (one study, 83 women and babies) Study in Turkey involving multiparous women with spontaneous onset of labour. Routine vaginal examinations may result in a slight increase in pain compared to routine ultrasound (mean difference -1.29, 95% confidence interval (CI) -2.10 to -0.48; one study, 83 women, low certainty evidence) (pain measured using a visual analogue scale (VAS) in reverse: zero indicating 'worst pain', 10 indicating no pain). The study did not assess our other primary outcomes: positive birth experience; augmentation of labour; spontaneous vaginal birth; chorioamnionitis; neonatal infection; admission to neonatal intensive care unit (NICU). Routine vaginal examinations versus routine rectal examinations to assess labour progress (one study, 307 women and babies) Study in Ireland involving women in labour at term. We assessed the certainty of the evidence as very low. Compared with routine rectal examinations, routine vaginal examinations may have little or no effect on: augmentation of labour (risk ratio (RR) 1.03, 95% CI 0.63 to 1.68; one study, 307 women); and spontaneous vaginal birth (RR 0.98, 95% CI 0.90 to 1.06; one study, 307 women). We found insufficient data to fully assess: neonatal infections (RR 0.33, 95% CI 0.01 to 8.07; one study, 307 babies); and admission to NICU (RR 1.32, 95% CI 0.47 to 3.73; one study, 307 babies). The study did not assess our other primary outcomes: positive birth experience; chorioamnionitis; maternal pain. Routine four-hourly vaginal examinations versus routine two-hourly examinations (one study, 150 women and babies) UK study involving primiparous women in labour at term. We assessed the certainty of the evidence as very low. Compared with routine two-hourly vaginal examinations, routine four-hourly vaginal examinations may have little or no effect, with data compatible with both benefit and harm, on: augmentation of labour (RR 0.97, 95% CI 0.60 to 1.57; one study, 109 women); and spontaneous vaginal birth (RR 1.02, 95% CI 0.83 to 1.26; one study, 150 women). The study did not assess our other primary outcomes: positive birth experience; chorioamnionitis; neonatal infection; admission to NICU; maternal pain. Routine vaginal examinations versus vaginal examinations as indicated (one study, 204 women and babies)  Study in Malaysia involving primiparous women being induced at term. We assessed the certainty of the evidence as low. Compared with vaginal examinations as indicated, routine four-hourly vaginal examinations may result in more women having their labour augmented (RR 2.55, 95% CI 1.03 to 6.31; one study, 204 women). There may be little or no effect on: • spontaneous vaginal birth (RR 1.08, 95% CI 0.73 to 1.59; one study, 204 women); • chorioamnionitis (RR 3.06, 95% CI 0.13 to 74.21; one study, 204 women); • neonatal infection (RR 4.08, 95% CI 0.46 to 35.87; one study, 204 babies); • admission to NICU (RR 2.04, 95% CI 0.63 to 6.56; one study, 204 babies). The study did not assess our other primary outcomes of positive birth experience or maternal pain.

    AUTHORS' CONCLUSIONS: Based on these findings, we cannot be certain which method is most effective or acceptable for assessing labour progress. Further large-scale RCT trials are required. These should include essential clinical and experiential outcomes. This may be facilitated through the development of a tool to measure positive birth experiences. Data from qualitative studies are also needed to fully assess whether methods to evaluate labour progress meet women's needs for a safe and positive labour and birth, and if not, to develop an approach that does.

  14. Abdul Wahid SF, Ismail NA, Wan Jamaludin WF, Muhamad NA, Abdul Hamid MKA, Harunarashid H, et al.
    Cochrane Database Syst Rev, 2018 Aug 29;8(8):CD010747.
    PMID: 30155883 DOI: 10.1002/14651858.CD010747.pub2
    BACKGROUND: Revascularisation is the gold standard therapy for patients with critical limb ischaemia (CLI). In over 30% of patients who are not suitable for or have failed previous revascularisation therapy (the 'no-option' CLI patients), limb amputation is eventually unavoidable. Preliminary studies have reported encouraging outcomes with autologous cell-based therapy for the treatment of CLI in these 'no-option' patients. However, studies comparing the angiogenic potency and clinical effects of autologous cells derived from different sources have yielded limited data. Data regarding cell doses and routes of administration are also limited.

    OBJECTIVES: To compare the efficacy and safety of autologous cells derived from different sources, prepared using different protocols, administered at different doses, and delivered via different routes for the treatment of 'no-option' CLI patients.

    SEARCH METHODS: The Cochrane Vascular Information Specialist (CIS) searched the Cochrane Vascular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), and trials registries (16 May 2018). Review authors searched PubMed until February 2017.

    SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving 'no-option' CLI patients comparing a particular source or regimen of autologous cell-based therapy against another source or regimen of autologous cell-based therapy.

    DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the eligibility and methodological quality of the trials. We extracted outcome data from each trial and pooled them for meta-analysis. We calculated effect estimates using a risk ratio (RR) with 95% confidence interval (CI), or a mean difference (MD) with 95% CI.

    MAIN RESULTS: We included seven RCTs with a total of 359 participants. These studies compared bone marrow-mononuclear cells (BM-MNCs) versus mobilised peripheral blood stem cells (mPBSCs), BM-MNCs versus bone marrow-mesenchymal stem cells (BM-MSCs), high cell dose versus low cell dose, and intramuscular (IM) versus intra-arterial (IA) routes of cell implantation. We identified no other comparisons in these studies. We considered most studies to be at low risk of bias in random sequence generation, incomplete outcome data, and selective outcome reporting; at high risk of bias in blinding of patients and personnel; and at unclear risk of bias in allocation concealment and blinding of outcome assessors. The quality of evidence was most often low to very low, with risk of bias, imprecision, and indirectness of outcomes the major downgrading factors.Three RCTs (100 participants) reported a total of nine deaths during the study follow-up period. These studies did not report deaths according to treatment group.Results show no clear difference in amputation rates between IM and IA routes (RR 0.80, 95% CI 0.54 to 1.18; three RCTs, 95 participants; low-quality evidence). Single-study data show no clear difference in amputation rates between BM-MNC- and mPBSC-treated groups (RR 1.54, 95% CI 0.45 to 5.24; 150 participants; low-quality evidence) and between high and low cell dose (RR 3.21, 95% CI 0.87 to 11.90; 16 participants; very low-quality evidence). The study comparing BM-MNCs versus BM-MSCs reported no amputations.Single-study data with low-quality evidence show similar numbers of participants with healing ulcers between BM-MNCs and mPBSCs (RR 0.89, 95% CI 0.44 to 1.83; 49 participants) and between IM and IA routes (RR 1.13, 95% CI 0.73 to 1.76; 41 participants). In contrast, more participants appeared to have healing ulcers in the BM-MSC group than in the BM-MNC group (RR 2.00, 95% CI 1.02 to 3.92; one RCT, 22 participants; moderate-quality evidence). Researchers comparing high versus low cell doses did not report ulcer healing.Single-study data show similar numbers of participants with reduction in rest pain between BM-MNCs and mPBSCs (RR 0.99, 95% CI 0.93 to 1.06; 104 participants; moderate-quality evidence) and between IM and IA routes (RR 1.22, 95% CI 0.91 to 1.64; 32 participants; low-quality evidence). One study reported no clear difference in rest pain scores between BM-MNC and BM-MSC (MD 0.00, 95% CI -0.61 to 0.61; 37 participants; moderate-quality evidence). Trials comparing high versus low cell doses did not report rest pain.Single-study data show no clear difference in the number of participants with increased ankle-brachial index (ABI; increase of > 0.1 from pretreatment), between BM-MNCs and mPBSCs (RR 1.00, 95% CI 0.71 to 1.40; 104 participants; moderate-quality evidence), and between IM and IA routes (RR 0.93, 95% CI 0.43 to 2.00; 35 participants; very low-quality evidence). In contrast, ABI scores appeared higher in BM-MSC versus BM-MNC groups (MD 0.05, 95% CI 0.01 to 0.09; one RCT, 37 participants; low-quality evidence). ABI was not reported in the high versus low cell dose comparison.Similar numbers of participants had improved transcutaneous oxygen tension (TcO₂) with IM versus IA routes (RR 1.22, 95% CI 0.86 to 1.72; two RCTs, 62 participants; very low-quality evidence). Single-study data with low-quality evidence show a higher TcO₂ reading in BM-MSC versus BM-MNC groups (MD 8.00, 95% CI 3.46 to 12.54; 37 participants) and in mPBSC- versus BM-MNC-treated groups (MD 1.70, 95% CI 0.41 to 2.99; 150 participants). TcO₂ was not reported in the high versus low cell dose comparison.Study authors reported no significant short-term adverse effects attributed to autologous cell implantation.

    AUTHORS' CONCLUSIONS: Mostly low- and very low-quality evidence suggests no clear differences between different stem cell sources and different treatment regimens of autologous cell implantation for outcomes such as all-cause mortality, amputation rate, ulcer healing, and rest pain for 'no-option' CLI patients. Pooled analyses did not show a clear difference in clinical outcomes whether cells were administered via IM or IA routes. High-quality evidence is lacking; therefore the efficacy and long-term safety of autologous cells derived from different sources, prepared using different protocols, administered at different doses, and delivered via different routes for the treatment of 'no-option' CLI patients, remain to be confirmed.Future RCTs with larger numbers of participants are needed to determine the efficacy of cell-based therapy for CLI patients, along with the optimal cell source, phenotype, dose, and route of implantation. Longer follow-up is needed to confirm the durability of angiogenic potential and the long-term safety of cell-based therapy.

  15. Karanth L, Abas AB
    Cochrane Database Syst Rev, 2021 Dec 09;12(12):CD011059.
    PMID: 34881425 DOI: 10.1002/14651858.CD011059.pub4
    BACKGROUND: Bleeding disorders are uncommon but may pose significant bleeding complications during pregnancy, labour and following delivery for both the woman and the foetus. While many bleeding disorders in women tend to improve in pregnancy, thus decreasing the haemorrhagic risk to the mother at the time of delivery, some do not correct or return quite quickly to their pre-pregnancy levels in the postpartum period. Therefore, specific measures to prevent maternal bleeding and foetal complications during childbirth, are required. The safest method of delivery to reduce morbidity and mortality in these women is controversial. This is an update of a previously published review.

    OBJECTIVES: To assess the optimal mode of delivery in women with, or carriers of, bleeding disorders.

    SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the Cochrane Pregnancy and Childbirth Group's Trials Register as well as trials registries and the reference lists of relevant articles and reviews. Date of last search of the Group's Trials Registers: 21 June 2021.

    SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled clinical trials investigating the optimal mode of delivery in women with, or carriers of, any type of bleeding disorder during pregnancy were eligible for the review.

    DATA COLLECTION AND ANALYSIS: No trials matching the selection criteria were eligible for inclusion.

    MAIN RESULTS: No trials matching the selection criteria were eligible for inclusion.

    AUTHORS' CONCLUSIONS: The review did not identify any randomised controlled trials investigating the safest mode of delivery and associated maternal and foetal complications during delivery in women with, or carriers of, a bleeding disorder. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials, case studies) to decide upon the optimal mode of delivery to ensure the safety of both mother and foetus. Given the ethical considerations, the rarity of the disorders and the low incidence of both maternal and foetal complications, future randomised controlled trials to find the optimal mode of delivery in this population are unlikely to be carried out. Other high quality controlled studies (such as risk allocation designs, sequential design, and parallel cohort design) are needed to investigate the risks and benefits of natural vaginal and caesarean section in this population or extrapolation from other clinical conditions that incur a haemorrhagic risk to the baby, such as platelet alloimmunisation.

  16. Qureshi N, Da Silva MLR, Abdul-Hamid H, Weng SF, Kai J, Leonardi-Bee J
    Cochrane Database Syst Rev, 2021 Oct 07;10(10):CD012985.
    PMID: 34617591 DOI: 10.1002/14651858.CD012985.pub2
    BACKGROUND: Familial hypercholesterolaemia is a common inherited condition that is associated with premature cardiovascular disease. The increased cardiovascular morbidity and mortality, resulting from high levels of cholesterol since birth, can be prevented by starting lipid-lowering therapy. However, the majority of patients in the UK and worldwide remain undiagnosed. Established diagnostic criteria in current clinical practice are the Simon-Broome and Dutch Lipid Clinical network criteria and patients are classified as having probable, possible or definite familial hypercholesterolaemia.

    OBJECTIVES: To assess the effectiveness of healthcare interventions strategies to systematically improve identification of familial hypercholesterolaemia in primary care and other community settings compared to usual care (incidental approaches to identify familial hypercholesterolaemia in primary care and other community settings).

    SEARCH METHODS: We searched the Cochrane Inborn Errors of Metabolism Trials Register. Date of last search: 13 September 2021. We also searched databases (Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, PubMed, Embase, CINAHL, Web of Science, and SCOPUS) as well as handsearching relevant conference proceedings, reference lists of included articles, and the grey literature. Date of last searches: 05 March 2020.  SELECTION CRITERIA: As per the Effective Practice and Organisation of Care (EPOC) Group guidelines, we planned to include randomised controlled trials (RCTs), cluster-RCTs and non-randomised studies of interventions (NRSI). Eligible NRSI were non-randomised controlled trials, prospective cohort studies, controlled before-and-after studies, and interrupted-time-series studies. We planned to selected studies with healthcare interventions strategies that aimed to systematically identify people with possible or definite clinical familial hypercholesterolaemia, in primary care and other community settings. These strategies would be compared with usual care or no intervention. We considered participants of any age from the general population who access primary care and other community settings.

    DATA COLLECTION AND ANALYSIS: Two authors planned to independently select studies according to the inclusion criteria, to extract data and assess for risk of bias and the certainty of the evidence (according to the GRADE criteria). We contacted corresponding study authors in order to obtain further information for all the studies considered in the review.

    MAIN RESULTS: No eligible RCTs or NRSIs were identified for inclusion, however, we excluded 28 studies.

    AUTHORS' CONCLUSIONS: Currently, there are no RCTs or controlled NRSI evidence to determine the most appropriate healthcare strategy to systematically identify possible or definite clinical familial hypercholesterolaemia in primary care or other community settings. Uncontrolled before-and-after studies were identified, but were not eligible for inclusion. Further studies assessing healthcare strategies of systematic identification of familial hypercholesterolaemia need to be conducted with diagnosis confirmed by genetic testing or validated through clinical phenotype (or both).

  17. Ni H, Soe Z, Moe S
    Cochrane Database Syst Rev, 2014 Sep 19;2014(9):CD010509.
    PMID: 25234126 DOI: 10.1002/14651858.CD010509.pub2
    BACKGROUND: Bronchodilators are the mainstay for symptom relief in the management of stable chronic obstructive pulmonary disease (COPD). Aclidinium bromide is a new long-acting muscarinic antagonist (LAMA) that differs from tiotropium by its higher selectivity for M3 muscarinic receptors with a faster onset of action. However, the duration of action of aclidinium is shorter than for tiotropium. It has been approved as maintenance therapy for stable, moderate to severe COPD, but its efficacy and safety in the management of COPD is uncertain compared to other bronchodilators.

    OBJECTIVES: To assess the efficacy and safety of aclidinium bromide in stable COPD.

    SEARCH METHODS: We identified randomised controlled trials (RCT) from the Cochrane Airways Group Specialised Register of trials (CAGR), as well as www.clinicaltrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), US Food and Drug Administration (FDA) website and Almirall Clinical Trials Registry and Results. We contacted Forest Laboratories for any unpublished trials and checked the reference lists of identified articles for additional information. The last search was performed on 7 April 2014 for CAGR and 11 April 2014 for other sources.

    SELECTION CRITERIA: Parallel-group RCTs of aclidinium bromide compared with placebo, long-acting beta2-agonists (LABA) or LAMA in adults with stable COPD.

    DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed the risk of bias, and extracted data. We sought missing data from the trial authors as well as manufacturers of aclidinium. We used odds ratios (OR) for dichotomous data and mean difference (MD) for continuous data, and reported both with their 95% confidence intervals (CI). We used standard methodological procedures expected by The Cochrane Collaboration. We applied the GRADE approach to summarise results and to assess the overall quality of evidence.

    MAIN RESULTS: This review included 12 multicentre RCTs randomly assigning 9547 participants with stable COPD. All the studies were industry-sponsored and had similar inclusion criteria with relatively good methodological quality. All but one study included in the meta-analysis were double-blind and scored low risk of bias. The study duration ranged from four weeks to 52 weeks. Participants were more often males, mainly Caucasians, mean age ranging from 61.7 to 65.6 years, and with a smoking history of 10 or more pack years. They had moderate to severe symptoms at randomisation; the mean post-bronchodilator forced expiratory volume in one second (FEV1) was between 46% and 57.6% of the predicted normal value, and the mean St George's Respiratory Questionnaire score (SGRQ) ranged from 45.1 to 50.4 when reported.There was no difference between aclidinium and placebo in all-cause mortality (low quality) and number of patients with exacerbations requiring a short course of oral steroids or antibiotics, or both (moderate quality). Aclidinium improved quality of life by lowering the SGRQ total score with a mean difference of -2.34 (95% CI -3.18 to -1.51; I(2) = 48%, 7 trials, 4442 participants) when compared to placebo. More patients on aclidinium achieved a clinically meaningful improvement of at least four units decrease in SGRQ total score (OR 1.49; 95% CI 1.31 to 1.70; I(2) = 34%; number needed to treat (NNT) = 10, 95% CI 8 to 15, high quality evidence) over 12 to 52 weeks than on placebo. Aclidinium also resulted in a significantly greater improvement in pre-dose FEV1 than placebo with a mean difference of 0.09 L (95% CI 0.08 to 0.10; I(2) = 39%, 9 trials, 4963 participants). No trials assessed functional capacity. Aclidinium reduced the number of patients with exacerbations requiring hospitalisation by 4 to 20 fewer per 1000 over 4 to 52 weeks (OR 0.64; 95% CI 0.46 to 0.88; I(2) = 0%, 10 trials, 5624 people; NNT = 77, 95% CI 51 to 233, high quality evidence) compared to placebo. There was no difference in non-fatal serious adverse events (moderate quality evidence) between aclidinium and placebo.Compared to tiotropium, aclidinium did not demonstrate significant differences for exacerbations requiring oral steroids or antibiotics, or both, exacerbation-related hospitalisations and non-fatal serious adverse events (very low quality evidence). Inadequate data prevented the comparison of aclidinium to formoterol or other LABAs.

    AUTHORS' CONCLUSIONS: Aclidinium is associated with improved quality of life and reduced hospitalisations due to severe exacerbations in patients with moderate to severe stable COPD compared to placebo. Overall, aclidinium did not significantly reduce mortality, serious adverse events or exacerbations requiring oral steroids or antibiotics, or both.Currently, the available data are insufficient and of very low quality in comparisons of the efficacy of aclidinium versus tiotropium. The efficacy of aclidinium versus LABAs cannot be assessed due to inaccurate data. Thus additional trials are recommended to assess the efficacy and safety of aclidinium compared to other LAMAs or LABAs.

  18. Kumbargere Nagraj S, Prashanti E, Aggarwal H, Lingappa A, Muthu MS, Kiran Kumar Krishanappa S, et al.
    Cochrane Database Syst Rev, 2018 Mar 04;3(3):CD011930.
    PMID: 29502332 DOI: 10.1002/14651858.CD011930.pub3
    BACKGROUND: Post-extraction bleeding (PEB) is a recognised, frequently encountered complication in dental practice, which is defined as bleeding that continues beyond 8 to 12 hours after dental extraction. The incidence of post-extraction bleeding varies from 0% to 26%. If post-extraction bleeding is not managed, complications can range from soft tissue haematomas to severe blood loss. Local causes of bleeding include soft tissue and bone bleeding. Systemic causes include platelet problems, coagulation disorders or excessive fibrinolysis, and inherited or acquired problems (medication induced). There is a wide array of techniques suggested for the treatment of post-extraction bleeding, which include interventions aimed at both local and systemic causes. This is an update of a review published in June 2016.

    OBJECTIVES: To assess the effects of interventions for treating different types of post-extraction bleeding.

    SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 24 January 2018), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2017, Issue 12), MEDLINE Ovid (1946 to 24 January 2018), Embase Ovid (1 May 2015 to 24 January 2018) and CINAHL EBSCO (1937 to 24 January 2018). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. We searched the reference lists of relevant systematic reviews.

    SELECTION CRITERIA: We considered randomised controlled trials (RCTs) that evaluated any intervention for treating PEB, with male or female participants of any age, regardless of type of teeth (anterior or posterior, mandibular or maxillary). Trials could compare one type of intervention with another, with placebo, or with no treatment.

    DATA COLLECTION AND ANALYSIS: Three pairs of review authors independently screened search records. We obtained full papers for potentially relevant trials. If data had been extracted, we would have followed the methods described in the Cochrane Handbook for Systematic Reviews of Interventions for the statistical analysis.

    MAIN RESULTS: We did not find any randomised controlled trial suitable for inclusion in this review.

    AUTHORS' CONCLUSIONS: We were unable to identify any reports of randomised controlled trials that evaluated the effects of different interventions for the treatment of post-extraction bleeding. In view of the lack of reliable evidence on this topic, clinicians must use their clinical experience to determine the most appropriate means of treating this condition, depending on patient-related factors. There is a need for well designed and appropriately conducted clinical trials on this topic, which conform to the CONSORT statement (www.consort-statement.org/).

  19. Poirot E, Skarbinski J, Sinclair D, Kachur SP, Slutsker L, Hwang J
    Cochrane Database Syst Rev, 2013 Dec 09;2013(12):CD008846.
    PMID: 24318836 DOI: 10.1002/14651858.CD008846.pub2
    BACKGROUND: Mass drug administration (MDA), defined as the empiric administration of a therapeutic antimalarial regimen to an entire population at the same time, has been a historic component of many malaria control and elimination programmes, but is not currently recommended. With renewed interest in MDA and its role in malaria elimination, this review aims to summarize the findings from existing research studies and program experiences of MDA strategies for reducing malaria burden and transmission.

    OBJECTIVES: To assess the impact of antimalarial MDA on population asexual parasitaemia prevalence, parasitaemia incidence, gametocytaemia prevalence, anaemia prevalence, mortality and MDA-associated adverse events.

    SEARCH METHODS: We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE+, EMBASE, to February 2013. We also searched CABS Abstracts, LILACS, reference lists, and recent conference proceedings.

    SELECTION CRITERIA: Cluster-randomized trials and non-randomized controlled studies comparing therapeutic MDA versus placebo or no MDA, and uncontrolled before-and-after studies comparing post-MDA to baseline data were selected. Studies administering intermittent preventive treatment (IPT) to sub-populations (for example, pregnant women, children or infants) were excluded.

    DATA COLLECTION AND ANALYSIS: Two authors independently reviewed studies for inclusion, extracted data and assessed risk of bias. Studies were stratified by study design and then subgrouped by endemicity, by co-administration of 8-aminoquinoline plus schizonticide drugs and by plasmodium species. The quality of evidence was assessed using the GRADE approach.

    MAIN RESULTS: Two cluster-randomized trials, eight non-randomized controlled studies and 22 uncontrolled before-and-after studies are included in this review. Twenty-two studies (29 comparisons) compared MDA to placebo or no intervention of which two comparisons were conducted in areas of low endemicity (≤5%), 12 in areas of moderate endemicity (6-39%) and 15 in areas of high endemicity (≥ 40%). Ten studies evaluated MDA plus other vector control measures. The studies used a wide variety of MDA regimens incorporating different drugs, dosages, timings and numbers of MDA rounds. Many of the studies are now more than 30 years old. Areas of low endemicity (≤5%)Within the first month post-MDA, a single uncontrolled before-and-after study conducted in 1955 on a small Taiwanese island reported a much lower prevalence of parasitaemia following a single course of chloroquine compared to baseline (1 study, very low quality evidence). This lower parasite prevalence was still present after more than 12 months (one study, very low quality evidence). In addition, one cluster-randomized trial evaluating MDA in a low endemic setting reported zero episodes of parasitaemia at baseline, and throughout five months of follow-up in both the control and intervention arms (one study, very low quality evidence). Areas of moderate endemicity (6-39%)Within the first month post-MDA, the prevalence of parasitaemia was much lower in three non-randomized controlled studies from Kenya and India in the 1950s (RR 0.03, 95% CI 0.01 to 0.08, three studies, moderate quality evidence), and in three uncontrolled before-and-after studies conducted between 1954 and 1961 (RR 0.29, 95% CI 0.17 to 0.48, three studies,low quality evidence).The longest follow-up in these settings was four to six months. At this time point, the prevalence of parasitaemia remained substantially lower than controls in the two non-randomized controlled studies (RR 0.18, 95% CI 0.10 to 0.33, two studies, low quality evidence). In contrast, the two uncontrolled before-and-after studies found mixed results: one found no difference and one found a substantially higher prevalence compared to baseline (not pooled, two studies, very low quality evidence). Areas of high endemicity (≥40%)Within the first month post-MDA, the single cluster-randomized trial from the Gambia in 1999 found no significant difference in parasite prevalence (one study, low quality evidence). However, prevalence was much lower during the MDA programmes in three non-randomized controlled studies conducted in the 1960s and 1970s (RR 0.17, 95% CI 0.11 to 0.27, three studies, moderate quality evidence), and within one month of MDA in four uncontrolled before-and-after studies (RR 0.37, 95% CI 0.28 to 0.49, four studies,low quality evidence).Four trials reported changes in prevalence beyond three months. In the Gambia, the single cluster-randomized trial found no difference at five months (one trial, moderate quality evidence). The three uncontrolled before-and-after studies had mixed findings with large studies from Palestine and Cambodia showing sustained reductions at four months and 12 months, respectively, and a small study from Malaysia showing no difference after four to six months of follow-up (three studies,low quality evidence). 8-aminoquinolines We found no studies directly comparing MDA regimens that included 8-aminoquinolines with regimens that did not. In a crude subgroup analysis with a limited number of studies, we were unable to detect any evidence of additional benefit of primaquine in moderate- and high-transmission settings. Plasmodium species In studies that reported species-specific outcomes, the same interventions resulted in a larger impact on Plasmodium falciparum compared to P. vivax.

    AUTHORS' CONCLUSIONS: MDA appears to reduce substantially the initial risk of malaria parasitaemia. However, few studies showed sustained impact beyond six months post-MDA, and those that did were conducted on small islands or in highland settings.To assess whether there is an impact of MDA on malaria transmission in the longer term requires more quasi experimental studies with the intention of elimination, especially in low- and moderate-transmission settings. These studies need to address any long-term outcomes, any potential barriers for community uptake, and contribution to the development of drug resistance.

  20. Marjoribanks J, Farquhar C, Roberts H, Lethaby A, Lee J
    Cochrane Database Syst Rev, 2017 Jan 17;1(1):CD004143.
    PMID: 28093732 DOI: 10.1002/14651858.CD004143.pub5
    BACKGROUND: Hormone therapy (HT) is widely provided for control of menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005. OBJECTIVES: To assess effects of long-term HT (at least 1 year's duration) on mortality, cardiovascular outcomes, cancer, gallbladder disease, fracture and cognition in perimenopausal and postmenopausal women during and after cessation of treatment. SEARCH METHODS: We searched the following databases to September 2016: Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and PsycINFO. We searched the registers of ongoing trials and reference lists provided in previous studies and systematic reviews. SELECTION CRITERIA: We included randomised double-blinded studies of HT versus placebo, taken for at least 1 year by perimenopausal or postmenopausal women. HT included oestrogens, with or without progestogens, via the oral, transdermal, subcutaneous or intranasal route. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the quality of the evidence by using GRADE methods. MAIN RESULTS: We included 22 studies involving 43,637 women. We derived nearly 70% of the data from two well-conducted studies (HERS 1998; WHI 1998). Most participants were postmenopausal American women with at least some degree of comorbidity, and mean participant age in most studies was over 60 years. None of the studies focused on perimenopausal women.In relatively healthy postmenopausal women (i.e. generally fit, without overt disease), combined continuous HT increased the risk of a coronary event (after 1 year's use: from 2 per 1000 to between 3 and 7 per 1000), venous thromboembolism (after 1 year's use: from 2 per 1000 to between 4 and 11 per 1000), stroke (after 3 years' use: from 6 per 1000 to between 6 and 12 per 1000), breast cancer (after 5.6 years' use: from 19 per 1000 to between 20 and 30 per 1000), gallbladder disease (after 5.6 years' use: from 27 per 1000 to between 38 and 60 per 1000) and death from lung cancer (after 5.6 years' use plus 2.4 years' additional follow-up: from 5 per 1000 to between 6 and 13 per 1000).Oestrogen-only HT increased the risk of venous thromboembolism (after 1 to 2 years' use: from 2 per 1000 to 2 to 10 per 1000; after 7 years' use: from 16 per 1000 to 16 to 28 per 1000), stroke (after 7 years' use: from 24 per 1000 to between 25 and 40 per 1000) and gallbladder disease (after 7 years' use: from 27 per 1000 to between 38 and 60 per 1000) but reduced the risk of breast cancer (after 7 years' use: from 25 per 1000 to between 15 and 25 per 1000) and clinical fracture (after 7 years' use: from 141 per 1000 to between 92 and 113 per 1000) and did not increase the risk of coronary events at any follow-up time.Women over 65 years of age who were relatively healthy and taking continuous combined HT showed an increase in the incidence of dementia (after 4 years' use: from 9 per 1000 to 11 to 30 per 1000). Among women with cardiovascular disease, use of combined continuous HT significantly increased the risk of venous thromboembolism (at 1 year's use: from 3 per 1000 to between 3 and 29 per 1000). Women taking HT had a significantly decreased incidence of fracture with long-term use.Risk of fracture was the only outcome for which strong evidence showed clinical benefit derived from HT (after 5.6 years' use of combined HT: from 111 per 1000 to between 79 and 96 per 1000; after 7.1 years' use of oestrogen-only HT: from 141 per 1000 to between 92 and 113 per 1000). Researchers found no strong evidence that HT has a clinically meaningful impact on the incidence of colorectal cancer.One trial analysed subgroups of 2839 relatively healthy women 50 to 59 years of age who were taking combined continuous HT and 1637 who were taking oestrogen-only HT versus similar-sized placebo groups. The only significantly increased risk reported was for venous thromboembolism in women taking combined continuous HT: Their absolute risk remained low, at less than 1/500. However, other differences in risk cannot be excluded, as this study was not designed to have the power to detect differences between groups of women within 10 years of menopause.For most studies, risk of bias was low in most domains. The overall quality of evidence for the main comparisons was moderate. The main limitation in the quality of evidence was that only about 30% of women were 50 to 59 years old at baseline, which is the age at which women are most likely to consider HT for vasomotor symptoms. AUTHORS' CONCLUSIONS: Women with intolerable menopausal symptoms may wish to weigh the benefits of symptom relief against the small absolute risk of harm arising from short-term use of low-dose HT, provided they do not have specific contraindications. HT may be unsuitable for some women, including those at increased risk of cardiovascular disease, increased risk of thromboembolic disease (such as those with obesity or a history of venous thrombosis) or increased risk of some types of cancer (such as breast cancer, in women with a uterus). The risk of endometrial cancer among women with a uterus taking oestrogen-only HT is well documented.HT is not indicated for primary or secondary prevention of cardiovascular disease or dementia, nor for prevention of deterioration of cognitive function in postmenopausal women. Although HT is considered effective for the prevention of postmenopausal osteoporosis, it is generally recommended as an option only for women at significant risk for whom non-oestrogen therapies are unsuitable. Data are insufficient for assessment of the risk of long-term HT use in perimenopausal women and in postmenopausal women younger than 50 years of age.
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