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  1. 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.

  2. 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/).

  3. Hussein N, Weng SF, Kai J, Kleijnen J, Qureshi N
    Cochrane Database Syst Rev, 2018 03 14;3:CD010849.
    PMID: 29537064 DOI: 10.1002/14651858.CD010849.pub3
    BACKGROUND: Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. 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 genetic counselling 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 improve reproductive outcomes in women and their partners who are 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. 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 the registers: 20 June 2017.Date of latest search of all other sources: 16 November 2017.

    SELECTION CRITERIA: Any randomised or quasi-randomised controlled trials (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 25 papers, describing 16 unique trials which were potentially eligible for inclusion in the review. However, after assessment, no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found.

    MAIN RESULTS: No randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were included. One ongoing trial has been identified which may potentially eligible for inclusion once completed.

    AUTHORS' CONCLUSIONS: As no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease were found for inclusion in this review, the research evidence for current policy recommendations is limited to non-randomised studies.Information from well-designed, adequately powered, randomised trials is desirable in order to make more robust recommendations for practice. However, such trials must also consider the legal, ethical, and cultural barriers to implementation of preconception genetic risk assessment.

  4. Dixit R, Nettem S, Madan SS, Soe HHK, Abas AB, Vance LD, et al.
    Cochrane Database Syst Rev, 2018 Mar 16;3(3):CD011130.
    PMID: 29546732 DOI: 10.1002/14651858.CD011130.pub3
    BACKGROUND: Sickle cell disease (SCD) is a group of disorders that affects haemoglobin, which causes distorted sickle- or crescent-shaped red blood cells. It is characterized by anaemia, increased susceptibility to infections and episodes of pain. The disease is acquired by inheriting abnormal genes from both parents, the combination giving rise to different forms of the disease. Due to increased erythropoiesis in people with SCD, it is hypothesized that they are at an increased risk for folate deficiency. For this reason, children and adults with SCD, particularly those with sickle cell anaemia, commonly take 1 mg of folic acid orally every day on the premise that this will replace depleted folate stores and reduce the symptoms of anaemia. It is thus important to evaluate the role of folate supplementation in treating SCD.

    OBJECTIVES: To analyse the efficacy and possible adverse effects of folate supplementation (folate occurring naturally in foods, provided as fortified foods or additional supplements such as tablets) in people with SCD.

    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. We also conducted additional searches in both electronic databases and clinical trial registries.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 17 November 2017.

    SELECTION CRITERIA: Randomised, placebo-controlled trials of folate supplementation for SCD.

    DATA COLLECTION AND ANALYSIS: Four review authors assessed We used the standard Cochrane-defined methodological procedures.Four review authors independently assessed the eligibility and risk of bias of the included trials and extracted and analysed the data included in the review. The quality of the evidence was assessed using GRADE.

    MAIN RESULTS: One trial, undertaken in 1983, was eligible for inclusion in the review. This was a double-blind placebo-controlled quasi-randomised triaI of supplementation of folic acid in people with SCD. A total of 117 children with homozygous sickle cell (SS) disease aged six months to four years of age participated over a one-year period (analysis was restricted to 115 children).Serum folate measures, obtained after trial entry at six and 12 months, were available in 80 of 115 (70%) participants. There were significant differences between the folic acid and placebo groups with regards to serum folate values above 18 µg/L and values below 5 µg/L (low-quality evidence). In the folic acid group, values above 18 µg/L were observed in 33 of 41 (81%) compared to six of 39 (15%) participants in the placebo (calcium lactate) group. Additionally, there were no participants in the folic acid group with serum folate levels below 5 µg/L, whereas in the placebo group, 15 of 39 (39%) participants had levels below this threshold. Haematological indices were measured in 100 of 115 (87%) participants at baseline and at one year. After adjusting for sex and age group, the investigators reported no significant differences between the trial groups with regards to total haemoglobin concentrations, either at baseline or at one year (low-quality evidence). It is important to note that none of the raw data for the outcomes listed above were available for analysis.The proportions of participants who experienced certain clinical events were analysed in all 115 participants, for which raw data were available. There were no statistically significant differences noted; however, the trial was not powered to investigate differences between the folic acid and placebo groups with regards to: minor infections, risk ratio (RR) 0.99 (95% confidence interval (CI) 0.85 to 1.15) (low-quality evidence); major infections, RR 0.89 (95% CI 0.47 to 1.66) (low-quality evidence); dactylitis, RR 0.67 (95% CI 0.35 to 1.27) (low-quality evidence); acute splenic sequestration, RR 1.07 (95% CI 0.44 to 2.57) (low-quality evidence); or episodes of pain, RR 1.16 (95% CI 0.70 to 1.92) (low-quality evidence). However, the investigators reported a higher proportion of repeat dactylitis episodes in the placebo group, with two or more attacks occurring in 10 of 56 participants compared to two of 59 in the folic acid group (P < 0.05).Growth, determined by height-for-age and weight-for-age, as well as height and growth velocity, was measured in 103 of the 115 participants (90%), for which raw data were not available. The investigators reported no significant differences in growth between the two groups.The trial had a high risk of bias with regards to random sequence generation and incomplete outcome data. There was an unclear risk of bias in relation to allocation concealment, outcome assessment, and selective reporting. Finally, There was a low risk of bias with regards to blinding of participants and personnel. Overall the quality of the evidence in the review was low.There were no trials identified for other eligible comparisons, namely: folate supplementation (fortified foods and physical supplementation with tablets) versus placebo; folate supplementation (naturally occurring in diet) versus placebo; folate supplementation (fortified foods and physical supplementation with tablets) versus folate supplementation (naturally occurring in diet).

    AUTHORS' CONCLUSIONS: One doubIe-blind, placebo-controlled triaI on folic acid supplementation in children with SCD was included in the review. Overall, the trial presented mixed evidence on the review's outcomes. No trials in adults were identified. With the limited evidence provided, we conclude that, while it is possible that folic acid supplementation may increase serum folate levels, the effect of supplementation on anaemia and any symptoms of anaemia remains unclear.If further trials were conducted, these may add evidence regarding the efficacy of folate supplementation. Future trials should assess clinical outcomes such as folate concentration, haemoglobin concentration, adverse effects and benefits of the intervention, especially with regards to SCD-related morbidity. Such trials should include people with SCD of all ages and both sexes, in any setting. To investigate the effects of folate supplementation, trials should recruit more participants and be of longer duration, with long-term follow-up, than the trial currently included in this review. However, we do not envisage further trials of this intervention will be conducted, and hence the review will no longer be regularly updated.

  5. Wahabi HA, Fayed AA, Esmaeil SA, Bahkali KH
    Cochrane Database Syst Rev, 2018 08 06;8:CD005943.
    PMID: 30081430 DOI: 10.1002/14651858.CD005943.pub5
    BACKGROUND: Miscarriage is a common complication encountered during pregnancy. It is defined as spontaneous pregnancy loss before 20 weeks' gestation. Progesterone's physiological role is to prepare the uterus for the implantation of the embryo, enhance uterine quiescence and suppress uterine contractions, hence, it may play a role in preventing rejection of the embryo. Inadequate secretion of progesterone in early pregnancy has been linked to the aetiology of miscarriage and progesterone supplementation has been used as a treatment for threatened miscarriage to prevent spontaneous pregnancy loss. This update of the Cochrane Review first published in 2007, and previously updated in 2011, investigates the evidence base for this practice.

    OBJECTIVES: To determine the efficacy and the safety of progestogens in the treatment of threatened miscarriage.

    SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (8 August 2017) and reference lists of retrieved trials.

    SELECTION CRITERIA: Randomised, quasi-randomised or cluster-randomised controlled trials, that compared progestogen with placebo, no treatment or any other treatment for the treatment of threatened miscarriage in women carrying singleton pregnancy.

    DATA COLLECTION AND ANALYSIS: At least two review authors assessed the trials for inclusion in the review, assessed trial quality and extracted the data and graded the body of evidence.

    MAIN RESULTS: We included seven trials (involving 696 participants) in this update of the review. The included trials were conducted in different countries, covering the full spectrum of the World Bank's economic classification, which enhances the applicability of evidence drawn from this review. Two trials were conducted in Germany and Italy which are high-income countries, while four trials were conducted in upper-middle income countries; two in Iran, one in Malaysia and the fourth in Turkey, and the seventh trial was conducted in Jordan, which is a lower-middle income country. In six trials all the participants met the inclusion criteria and in the seventh study, we included in the meta-analysis only the subgroup of participants who met the inclusion criteria. We assessed the body of evidence for the main outcomes using the GRADE tool and the quality of the evidence ranged from very low to moderate. Downgrading of evidence was based on the high risk of bias in six of the seven included trials and a small number of events and wide confidence intervals for some outcomes.Treatment of miscarriage with progestogens compared to placebo or no treatment probably reduces the risk of miscarriage; (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.47 to 0.87; 7 trials; 696 women; moderate-quality evidence). Treatment with oral progestogen compared to no treatment also probably reduces the miscarriage rate (RR 0.57, 95% CI 0.38 to 0.85; 3 trials; 408 women; moderate-quality evidence). However treatment with vaginal progesterone compared to placebo, probably has little or no effect in reducing the miscarriage rate (RR 0.75, 95% CI 0.47 to 1.21; 4 trials; 288 women; moderate-quality evidence). The subgroup interaction test indicated no difference according to route of administration between the oral and vaginal subgroups of progesterone.Treatment of preterm birth with the use of progestogens compared to placebo or no treatment may have little or no effect in reducing the rate of preterm birth (RR 0.86, 95% CI 0.52 to 1.44; 5 trials; 588 women; low-quality evidence).We are uncertain if treatment of threatened miscarriage with progestogens compared to placebo or no treatment has any effect on the rate of congenital abnormalities because the quality of the evidence is very low (RR 0.70, 95% CI 0.10 to 4.82; 2 trials; 337 infants; very-low quality evidence).

    AUTHORS' CONCLUSIONS: The results of this Cochrane Review suggest that progestogens are probably effective in the treatment of threatened miscarriage but may have little or no effect in the rate of preterm birth. The evidence on congenital abnormalities is uncertain, because the quality of the evidence for this outcome was based on only two small trials with very few events and was found to be of very low quality.

  6. Kiran Kumar Krishanappa S, Eachempati P, Kumbargere Nagraj S, Shetty NY, Moe S, Aggarwal H, et al.
    Cochrane Database Syst Rev, 2018 08 16;8:CD011784.
    PMID: 30113083 DOI: 10.1002/14651858.CD011784.pub3
    BACKGROUND: An oro-antral communication is an unnatural opening between the oral cavity and maxillary sinus. When it fails to close spontaneously, it remains patent and is epithelialized to develop into an oro-antral fistula. Various surgical and non-surgical techniques have been used for treating the condition. Surgical procedures include flaps, grafts and other techniques like re-implantation of third molars. Non-surgical techniques include allogenic materials and xenografts. This is an update of a review first published in May 2016.

    OBJECTIVES: To assess the effectiveness and safety of various interventions for the treatment of oro-antral communications and fistulae due to dental procedures.

    SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 23 May 2018), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2018, Issue 4), MEDLINE Ovid (1946 to 23 May 2018), and Embase Ovid (1980 to 23 May 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. No restrictions were placed on the language or date of publication when searching the electronic databases. We also searched the reference lists of included and excluded trials for any randomised controlled trials (RCTs).

    SELECTION CRITERIA: We included RCTs evaluating any intervention for treating oro-antral communications or oro-antral fistulae due to dental procedures. We excluded quasi-RCTs and cross-over trials. We excluded studies on participants who had oro-antral communications, fistulae or both related to Caldwell-Luc procedure or surgical excision of tumours.

    DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials. Two review authors assessed trial risk of bias and extracted data independently. We estimated risk ratios (RR) for dichotomous data, with 95% confidence intervals (CI). We assessed the overall quality of the evidence using the GRADE approach.

    MAIN RESULTS: We included only one study in this review, which compared two surgical interventions: pedicled buccal fat pad flap and buccal flap for the treatment of oro-antral communications. The study involved 20 participants. The risk of bias was unclear. The relevant outcome reported in this trial was successful (complete) closure of oro-antral communication.The quality of the evidence for the primary outcome was very low. The study did not find evidence of a difference between interventions for the successful (complete) closure of an oro-antral communication (RR 1.00, 95% Cl 0.83 to 1.20) one month after the surgery. All oro-antral communications in both groups were successfully closed so there were no adverse effects due to treatment failure.We did not find trials evaluating any other intervention for treating oro-antral communications or fistulae due to dental procedures.

    AUTHORS' CONCLUSIONS: We found very low quality evidence from a single small study that compared pedicled buccal fat pad and buccal flap. The evidence was insufficient to judge whether there is a difference in the effectiveness of these interventions as all oro-antral communications in the study were successfully closed by one month after surgery. Large, well-conducted RCTs investigating different interventions for the treatment of oro-antral communications and fistulae caused by dental procedures are needed to inform clinical practice.

  7. 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.

  8. El Sayed I, Liu Q, Wee I, Hine P
    Cochrane Database Syst Rev, 2018 09 24;9:CD002150.
    PMID: 30246875 DOI: 10.1002/14651858.CD002150.pub2
    BACKGROUND: Scrub typhus, an important cause of acute fever in Asia, is caused by Orientia tsutsugamushi, an obligate intracellular bacterium. Antibiotics currently used to treat scrub typhus include tetracyclines, chloramphenicol, macrolides, and rifampicin.

    OBJECTIVES: To assess and compare the effects of different antibiotic regimens for treatment of scrub typhus.

    SEARCH METHODS: We searched the following databases up to 8 January 2018: the Cochrane Infectious Diseases Group specialized trials register; CENTRAL, in the Cochrane Library (2018, Issue 1); MEDLINE; Embase; LILACS; and the metaRegister of Controlled Trials (mRCT). We checked references and contacted study authors for additional data. We applied no language or date restrictions.

    SELECTION CRITERIA: Randomized controlled trials (RCTs) or quasi-RCTs comparing antibiotic regimens in people with the diagnosis of scrub typhus based on clinical symptoms and compatible laboratory tests (excluding the Weil-Felix test).

    DATA COLLECTION AND ANALYSIS: For this update, two review authors re-extracted all data and assessed the certainty of evidence. We meta-analysed data to calculate risk ratios (RRs) for dichotomous outcomes when appropriate, and elsewhere tabulated data to facilitate narrative analysis.

    MAIN RESULTS: We included six RCTs and one quasi-RCT with 548 participants; they took place in the Asia-Pacific region: Korea (three trials), Malaysia (one trial), and Thailand (three trials). Only one trial included children younger than 15 years (N = 57). We judged five trials to be at high risk of performance and detection bias owing to inadequate blinding. Trials were heterogenous in terms of dosing of interventions and outcome measures. Across trials, treatment failure rates were low.Two trials compared doxycycline to tetracycline. For treatment failure, the difference between doxycycline and tetracycline is uncertain (very low-certainty evidence). Doxycycline compared to tetracycline may make little or no difference in resolution of fever within 48 hours (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.90 to 1.44, 55 participants; one trial; low-certainty evidence) and in time to defervescence (116 participants; one trial; low-certainty evidence). We were unable to extract data for other outcomes.Three trials compared doxycycline versus macrolides. For most outcomes, including treatment failure, resolution of fever within 48 hours, time to defervescence, and serious adverse events, we are uncertain whether study results show a difference between doxycycline and macrolides (very low-certainty evidence). Macrolides compared to doxycycline may make little or no difference in the proportion of patients with resolution of fever within five days (RR 1.05, 95% CI 0.99 to 1.10; 185 participants; two trials; low-certainty evidence). Another trial compared azithromycin versus doxycycline or chloramphenicol in children, but we were not able to disaggregate date for the doxycycline/chloramphenicol group.One trial compared doxycycline versus rifampicin. For all outcomes, we are uncertain whether study results show a difference between doxycycline and rifampicin (very low-certainty evidence). Of note, this trial deviated from the protocol after three out of eight patients who had received doxycycline and rifampicin combination therapy experienced treatment failure.Across trials, mild gastrointestinal side effects appeared to be more common with doxycycline than with comparator drugs.

    AUTHORS' CONCLUSIONS: Tetracycline, doxycycline, azithromycin, and rifampicin are effective treatment options for scrub typhus and have resulted in few treatment failures. Chloramphenicol also remains a treatment option, but we could not include this among direct comparisons in this review.Most available evidence is of low or very low certainty. For specific outcomes, some low-certainty evidence suggests there may be little or no difference between tetracycline, doxycycline, and azithromycin as treatment options. Given very low-certainty evidence for rifampicin and the risk of inducing resistance in undiagnosed tuberculosis, clinicians should not regard this as a first-line treatment option. Clinicians could consider rifampicin as a second-line treatment option after exclusion of active tuberculosis.Further research should consist of additional adequately powered trials of doxycycline versus azithromycin or other macrolides, trials of other candidate antibiotics including rifampicin, and trials of treatments for severe scrub typhus. Researchers should standardize diagnostic techniques and reporting of clinical outcomes to allow robust comparisons.

  9. Hoe VC, Urquhart DM, Kelsall HL, Zamri EN, Sim MR
    Cochrane Database Syst Rev, 2018 10 23;10:CD008570.
    PMID: 30350850 DOI: 10.1002/14651858.CD008570.pub3
    BACKGROUND: Work-related upper limb and neck musculoskeletal disorders (MSDs) are one of the most common occupational disorders worldwide. Studies have shown that the percentage of office workers that suffer from MSDs ranges from 20 to 60 per cent. The direct and indirect costs of work-related upper limb MSDs have been reported to be high in Europe, Australia, and the United States. Although ergonomic interventions are likely to reduce the risk of office workers developing work-related upper limb and neck MSDs, the evidence is unclear. This is an update of a Cochrane Review which was last published in 2012.

    OBJECTIVES: To assess the effects of physical, cognitive and organisational ergonomic interventions, or combinations of those interventions for the prevention of work-related upper limb and neck MSDs among office workers.

    SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CINAHL, Web of Science (Science Citation Index), SPORTDiscus, Embase, the US Centers for Disease Control and Prevention, the National Institute for Occupational Safety and Health database, and the World Health Organization's International Clinical Trials Registry Platform, to 10 October 2018.

    SELECTION CRITERIA: We included randomised controlled trials (RCTs) of ergonomic interventions for preventing work-related upper limb or neck MSDs (or both) among office workers. We only included studies where the baseline prevalence of MSDs of the upper limb or neck, or both, was less than 25%.

    DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias. We included studies with relevant data that we judged to be sufficiently homogeneous regarding the interventions and outcomes in the meta-analysis. We assessed the overall quality of the evidence for each comparison using the GRADE approach.

    MAIN RESULTS: We included 15 RCTs (2165 workers). We judged one study to have a low risk of bias and the remaining 14 studies to have a high risk of bias due to small numbers of participants and the potential for selection bias.Physical ergonomic interventionsThere is inconsistent evidence for arm supports and alternative computer mouse designs. There is moderate-quality evidence that an arm support with an alternative computer mouse (two studies) reduced the incidence of neck or shoulder MSDs (risk ratio (RR) 0.52; 95% confidence interval (CI) 0.27 to 0.99), but not the incidence of right upper limb MSDs (RR 0.73; 95% CI 0.32 to 1.66); and low-quality evidence that this intervention reduced neck or shoulder discomfort (standardised mean difference (SMD) -0.41; 95% CI -0.69 to -0.12) and right upper limb discomfort (SMD -0.34; 95% CI -0.63 to -0.06).There is moderate-quality evidence that the incidence of neck or shoulder and right upper limb disorders were not considerably reduced when comparing an alternative computer mouse and a conventional mouse (two studies; neck or shoulder: RR 0.62; 95% CI 0.19 to 2.00; right upper limb: RR 0.91; 95% CI 0.48 to 1.72), and also when comparing an arm support with a conventional mouse and a conventional mouse alone (two studies) (neck or shoulder: RR 0.91; 95% CI 0.12 to 6.98; right upper limb: RR 1.07; 95% CI 0.58 to 1.96).Workstation adjustment (one study) and sit-stand desks (one study) did not have an effect on upper limb pain or discomfort, compared to no intervention.Organisational ergonomic interventionsThere is very low-quality evidence that supplementary breaks (two studies) reduce discomfort of the neck (MD -0.25; 95% CI -0.40 to -0.11), right shoulder or upper arm (MD -0.33; 95% CI -0.46 to -0.19), and right forearm or wrist or hand (MD -0.18; 95% CI -0.29 to -0.08) among data entry workers.Training in ergonomic interventionsThere is low to very low-quality evidence in five studies that participatory and active training interventions may or may not prevent work-related MSDs of the upper limb or neck or both.Multifaceted ergonomic interventionsFor multifaceted interventions there is one study (very low-quality evidence) that showed no effect on any of the six upper limb pain outcomes measured in that study.

    AUTHORS' CONCLUSIONS: We found inconsistent evidence that the use of an arm support or an alternative mouse may or may not reduce the incidence of neck or shoulder MSDs. For other physical ergonomic interventions there is no evidence of an effect. For organisational interventions, in the form of supplementary breaks, there is very low-quality evidence of an effect on upper limb discomfort. For training and multifaceted interventions there is no evidence of an effect on upper limb pain or discomfort. Further high-quality studies are needed to determine the effectiveness of these interventions among office workers.

  10. Ni H, Moe S, Soe Z, Myint KT, Viswanathan KN
    Cochrane Database Syst Rev, 2018 Dec 11;12:CD011594.
    PMID: 30536566 DOI: 10.1002/14651858.CD011594.pub2
    BACKGROUND: Several dual bronchodilator combinations of long-acting beta2-agonist (LABA) and long-acting muscarinic antagonist (LAMA) have been approved for treatment of stable chronic obstructive pulmonary disease (COPD). The current GOLD (Global Initiative for Chronic Obstructive Lung Disease) recommendations suggest the use of LABA/LAMA combinations in people with group B COPD with persistent symptoms, group C COPD with further exacerbations on LAMA therapy alone and group D COPD with or without inhaled corticosteroids (ICS). Fixed-dose combination (FDC) of aclidinium/formoterol is one of the approved LABA/LAMA therapies for people with stable COPD.

    OBJECTIVES: To assess the efficacy and safety of combined aclidinium bromide and long-acting beta2-agonists in stable COPD.

    SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov, World Health Organization (WHO) trials portal, United States Food and Drug Administration (FDA) and manufacturers' websites as well as the reference list of published trials up to 12 October 2018.

    SELECTION CRITERIA: Parallel-group randomised controlled trials (RCTs) assessing combined aclidinium bromide and LABAs in people with stable COPD.

    DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane for data collection and analysis. The primary outcomes were exacerbations requiring a short course of an oral steroid or antibiotic, or both; quality of life measured by a validated scale and non-fatal serious adverse events (SAEs). Where the outcome or study details were not reported, we contacted the study investigators or pharmaceutical company trial co-ordinators (or both) for missing data.

    MAIN RESULTS: We identified RCTs comparing aclidinium/formoterol FDC versus aclidinium, formoterol or placebo only. We included seven multicentre trials of four to 52 weeks' duration conducted in outpatient settings. There were 5921 participants, whose mean age ranged from 60.7 to 64.7 years, mostly men with a mean smoking pack-years of 46.4 to 61.3 of which 43.9% to 63.4% were current smokers. They had a moderate-to-severe degree of COPD with a mean postbronchodilator forced expiratory volume in one second (FEV1) between 50.5% and 61% of predicted normal and the baseline mean FEV1 of 1.23 L to 1.43 L. We assessed performance and detection biases as low for all studies whereas selection, attrition and reporting biases were either low or unclear.FDC versus aclidiniumThere was no evidence of a difference between FDC and aclidinium for exacerbations requiring steroids or antibiotics, or both (OR 0.95, 95% CI 0.71 to 1.27; 2 trials, 2156 participants; moderate-certainty evidence); quality of life measured by St George's Respiratory Questionnaire (SGRQ) total score (MD -0.92, 95% CI -2.15 to 0.30); participants with significant improvement in SGRQ score (OR 1.17, 95% CI 0.97 to 1.41; 2 trials, 2002 participants; moderate-certainty evidence); non-fatal SAE (OR 1.19, 95% CI 0.79 to 1.80; 3 trials, 2473 participants; moderate-certainty evidence); hospital admissions due to severe exacerbations (OR 0.62, 95% CI 0.29 to 1.29; 2 trials, 2156 participants; moderate-certainty evidence) or adverse events (OR 0.95, 95% CI 0.76 to 1.18; 3 trials, 2473 participants; moderate-certainty evidence). Compared with aclidinium, FDC improved symptoms (Transitional Dyspnoea Index (TDI) focal score: MD 0.37, 95% CI 0.07 to 0.68; 2 trials, 2013 participants) with a higher chance of achieving a minimal clinically important difference (MCID) of at least one unit improvement (OR 1.34, 95% CI 1.11 to 1.62; high-certainty evidence); the number needed to treat for an additional beneficial outcome (NNTB) being 14 (95% CI 9 to 39).FDC versus formoterolWhen compared to formoterol, combination therapy reduced exacerbations requiring steroids or antibiotics, or both (OR 0.78, 95% CI 0.62 to 0.99; 3 trials, 2694 participants; high-certainty evidence); may decrease SGRQ total score (MD -1.88, 95% CI -3.10 to -0.65; 2 trials, 2002 participants; low-certainty evidence; MCID for SGRQ is 4 units); increased TDI focal score (MD 0.42, 95% CI 0.11 to 0.72; 2 trials, 2010 participants) with more participants attaining an MCID (OR 1.30, 95% CI 1.07 to 1.56; high-certainty evidence) and an NNTB of 16 (95% CI 10 to 60). FDC lowered the risk of adverse events compared to formoterol (OR 0.78, 95% CI 0.65 to 0.93; 5 trials, 3140 participants; high-certainty evidence; NNTB 22). However, there was no difference between FDC and formoterol for hospital admissions, all-cause mortality and non-fatal SAEs.FDC versus placeboCompared with placebo, FDC demonstrated no evidence of a difference in exacerbations requiring steroids or antibiotics, or both (OR 0.82, 95% CI 0.60 to 1.12; 2 trials, 1960 participants; moderate-certainty evidence) or hospital admissions due to severe exacerbations (OR 0.55, 95% CI 0.25 to 1.18; 2 trials, 1960 participants; moderate-certainty evidence), although estimates were uncertain. Quality of life measure by SGRQ total score was significantly better with FDC compared to placebo (MD -2.91, 95% CI -4.33 to -1.50; 2 trials, 1823 participants) resulting in a corresponding increase in SGRQ responders who achieved at least four units decrease in SGRQ total score (OR 1.72, 95% CI 1.39 to 2.13; high-certainty evidence) with an NNTB of 7 (95% CI 5 to 12). FDC also improved symptoms measured by TDI focal score (MD 1.32, 95% CI 0.96 to 1.69; 2 studies, 1832 participants) with more participants attaining at least one unit improvement in TDI focal score (OR 2.51, 95% CI 2.02 to 3.11; high-certainty evidence; NNTB 4). There were no differences in non-fatal SAEs, adverse events and all-cause mortality between FDC and placebo.Combination therapy significantly improved trough FEV1 compared to aclidinium, formoterol or placebo.

    AUTHORS' CONCLUSIONS: FDC improved dyspnoea and lung function compared to aclidinium, formoterol or placebo, and this translated into an increase in the number of responders on combination treatment. Quality of life was better with combination compared to formoterol or placebo. There was no evidence of a difference between FDC and monotherapy or placebo for exacerbations, hospital admissions, mortality, non-fatal SAEs or adverse events. Studies reported a lower risk of moderate exacerbations and adverse events with FDC compared to formoterol; however, larger studies would yield a more precise estimate for these outcomes.

  11. Eachempati P, Kumbargere Nagraj S, Kiran Kumar Krishanappa S, Gupta P, Yaylali IE
    Cochrane Database Syst Rev, 2018 12 18;12:CD006202.
    PMID: 30562408 DOI: 10.1002/14651858.CD006202.pub2
    BACKGROUND: With the increased demand for whiter teeth, home-based bleaching products, either dentist-prescribed or over-the-counter products have been exponentially increasing in the past few decades. This is an update of a Cochrane Review first published in 2006.

    OBJECTIVES: To evaluate the effects of home-based tooth whitening products with chemical bleaching action, dispensed by a dentist or over-the-counter.

    SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 12 June 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library (searched 12 June 2018), MEDLINE Ovid (1946 to 12 June 2018), and Embase Ovid (1980 to 12 June 2018). The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (12 June 2018) and the World Health Organization International Clinical Trials Registry Platform (12 June 2018) were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.

    SELECTION CRITERIA: We included in our review randomised controlled trials (RCTs) which involved adults who were 18 years and above, and compared dentist-dispensed or over-the-counter tooth whitening (bleaching) products with placebo or other comparable products.Quasi-randomised trials, combination of in-office and home-based treatments, and home-based products having physical removal of stains were excluded.

    DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials. Two pairs of review authors independently extracted data and assessed risk of bias. We estimated risk ratios (RRs) for dichotomous data, and mean differences (MDs) or standardised mean difference (SMD) for continuous data, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach.

    MAIN RESULTS: We included 71 trials in the review with 26 studies (1398 participants) comparing a bleaching agent to placebo and 51 studies (2382 participants) comparing a bleaching agent to another bleaching agent. Two studies were at low overall risk of bias; two at high overall risk of bias; and the remaining 67 at unclear overall risk of bias.The bleaching agents (carbamide peroxide (CP) gel in tray, hydrogen peroxide (HP) gel in tray, HP strips, CP paint-on gel, HP paint-on gel, sodium hexametaphosphate (SHMP) chewing gum, sodium tripolyphosphate (STPP) chewing gum, and HP mouthwash) at different concentrations with varying application times whitened teeth compared to placebo over a short time period (from 2 weeks to 6 months), however the certainty of the evidence is low to very low.In trials comparing one bleaching agent to another, concentrations, application method and application times, and duration of use varied widely. Most of the comparisons were reported in single trials with small sample sizes and event rates and certainty of the evidence was assessed as low to very low. Therefore the evidence currently available is insufficient to draw reliable conclusions regarding the superiority of home-based bleaching compositions or any particular method of application or concentration or application time or duration of use.Tooth sensitivity and oral irritation were the most common side effects which were more prevalent with higher concentrations of active agents though the effects were mild and transient. Tooth whitening did not have any effect on oral health-related quality of life.

    AUTHORS' CONCLUSIONS: We found low to very low-certainty evidence over short time periods to support the effectiveness of home-based chemically-induced bleaching methods compared to placebo for all the outcomes tested.We were unable to draw any conclusions regarding the superiority of home-based bleaching compositions or any particular method of application or concentration or application time or duration of use, as the overall evidence generated was of very low certainty. Well-planned RCTs need to be conducted by standardising methods of application, concentrations, application times, and duration of treatment.

  12. Karanth L, Barua A, Kanagasabai S, Nair NS
    Cochrane Database Syst Rev, 2019 02 13;2:CD009824.
    PMID: 30758840 DOI: 10.1002/14651858.CD009824.pub4
    BACKGROUND: Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate (DDAVP) is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of DDAVP in these groups of pregnant women should be evaluated.This is an update of a Cochrane Review first published in 2013 and updated in 2015.

    OBJECTIVES: To evaluate the efficacy and safety of DDAVP in preventing and treating acute bleeding in pregnant women with bleeding disorders.

    SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched several clinical trial registries and grey literature (27 August 2017).Date of most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register: 01 October 2018.

    SELECTION CRITERIA: Randomised and quasi-randomised controlled trials investigating the efficacy of DDAVP versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible.

    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: No randomised controlled trials were identified investigating the relative effectiveness of DDAVP for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high-quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with DDAVP.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high-quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using DDAVP in this population are needed.Given that there are unlikely to be any trials published in this area, this review will no longer be regularly updated.

  13. 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.

  14. Arora A, Khattri S, Ismail NM, Kumbargere Nagraj S, Eachempati P
    Cochrane Database Syst Rev, 2019 08 08;8:CD012595.
    PMID: 31425627 DOI: 10.1002/14651858.CD012595.pub3
    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. It is an update of the original review, which was first published in December 2017.

    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 4 March 2019), the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Register of Studies, to 4 March 2019), MEDLINE Ovid (1946 to 4 March 2019), and Embase Ovid (15 September 2016 to 4 March 2019). 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 seven trials (five were cluster-RCTs) with 20,192 children who were 4 to 15 years of age. Trials assessed follow-up periods of three to eight months. Four trials were conducted in the UK, two were based in India and one in the USA. We assessed two trials to be at low risk of bias, two trials to be at high risk of bias and three trials to be at unclear risk of bias.None of the trials had long-term follow-up to ascertain the lasting effects of school dental screening.None of the trials reported the proportion of children with untreated caries or other oral diseases, cost effectiveness or adverse events.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 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).Only one trial reported the proportion of children with treated dental caries. This trial evaluated a post screening referral letter based on the common-sense model of self-regulation (a theoretical framework that explains how people understand and respond to threats to their health), with or without a dental information guide, compared to a standard referral letter. The findings were inconclusive. Due to high risk of bias, indirectness and imprecision, we assessed the evidence as very low certainty.

    AUTHORS' CONCLUSIONS: The trials included in this review evaluated short-term effects of screening. We found very low-certainty evidence that is 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 is 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 may 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) may improve dental attendance in comparison to screening alone. For children requiring treatment, we found very-low certainty evidence that was inconclusive regarding whether or not a referral letter based on the 'common-sense model of self-regulation' was better than a standard referral letter.We did not find any trials addressing possible adverse effects of school dental screening or evaluating its effectiveness for improving oral health.

  15. Than NN, Soe HHK, Palaniappan SK, Abas AB, De Franceschi L
    Cochrane Database Syst Rev, 2019 09 09;9:CD011358.
    PMID: 31498421 DOI: 10.1002/14651858.CD011358.pub3
    BACKGROUND: Sickle cell disease is an autosomal recessive inherited haemoglobinopathy which causes painful vaso-occlusive crises due to sickle red blood cell dehydration. Vaso-occlusive crises are common painful events responsible for a variety of clinical complications; overall mortality is increased and life expectancy decreased compared to the general population. Experimental studies suggest that intravenous magnesium has proven to be well-tolerated in individuals hospitalised for the immediate relief of acute (sudden onset) painful crisis and has the potential to decrease the length of hospital stay. Some in vitro studies and open studies of long-term oral magnesium showed promising effect on pain relief but failed to show its efficacy. The studies show that oral magnesium therapy may prevent sickle red blood cell dehydration and prevent recurrent painful episodes. There is a need to access evidence for the impact of oral and intravenous magnesium effect on frequency of pain, length of hospital stay and quality of life. This is an updated version of the review.

    OBJECTIVES: To evaluate the effects of short-term intravenous magnesium on the length of hospital stay and quality of life in children and adults with sickle cell disease. To determine the effects of long-term oral magnesium therapy on the frequency of painful crises and the quality of life in children and adults with sickle cell disease.

    SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 03 February 2019.Date of last search of other resources (clinical trials registries): 04 April 2019.

    SELECTION CRITERIA: We searched for published and unpublished randomized controlled studies of oral or intravenous magnesium compared to placebo or no magnesium.

    DATA COLLECTION AND ANALYSIS: Authors independently assessed the study quality and extracted the data using standard Cochrane methodologies.

    MAIN RESULTS: We included five randomized placebo-controlled studies with a total of 386 participants (aged three to 53 years). Of these, two shorter parallel studies (n = 306) compared intravenous magnesium sulphate to placebo (normal saline) for admission to hospital due to a vaso-occlusive crisis, for which we were able to analyse data. The quality of evidence was moderate for studies in this comparison, mainly due to limitations due to risk of bias and imprecision. Two of the three longer-term studies comparing oral magnesium pidolate to placebo had a cross-over design. The third was a parallel factorial study which compared hydroxyurea and oral magnesium to each other and to placebo over a longer period of time; we only present the comparison of oral magnesium to placebo from this study. The quality of evidence was very low with uncertainty of the estimation.The eight-hourly dose levels in the two studies of intravenous magnesium were different; one used 100 mg/kg while the second used 40 mg/kg. Only one of these studies (n = 104) reported the mean daily pain score while hospitalised (a non-significant difference between groups, moderate quality evidence). The second study (n = 202) reported a number of child- and parent-reported quality of life scores. None of the scores showed any difference between treatment groups (low quality evidence). Data from one study (n = 106) showed no difference in length of stay in hospital between groups (low quality evidence). Both studies reported on adverse events, but not defined by severity as we had planned. One study showed significantly more participants receiving intravenous magnesium experienced warmth at infusion site compared to placebo; there were no differences between groups for other adverse events (low quality evidence).Three studies (n = 80) compared oral magnesium pidolate to placebo. None of them reported data which we were able to analyse. One study (n = 24) reported on the number of painful days and stated there was no difference between two groups (low quality evidence). None of the studies reported on quality of life or length of hospital stay. Two studies (n = 68) reported there were no differences in levels of magnesium in either plasma or red blood cells (moderate quality evidence). Two studies (n = 56) reported adverse events. One reported episodes of mild diarrhoea and headache, all of which resolved without stopping treatment. The second study reported adverse events as gastrointestinal disorders, headache or migraine, upper respiratory infections and rash; which were all evenly distributed across treatment groups (moderate quality evidence).

    AUTHORS' CONCLUSIONS: Moderate to low quality evidence showed neither intravenous magnesium and oral magnesium therapy has an effect on reducing painful crisis, length of hospital stay and changing quality of life in treating sickle cell disease. Therefore, no definitive conclusions can be made regarding its clinical benefit. Further randomized controlled studies, perhaps multicentre, are necessary to establish whether intravenous and oral magnesium therapies have any effect on improving the health of people with sickle cell disease.

  16. Yeo KT, Kong JY, Sasi A, Tan K, Lai NM, Schindler T
    Cochrane Database Syst Rev, 2019 10 28;2019(10).
    PMID: 31684689 DOI: 10.1002/14651858.CD012888.pub2
    BACKGROUND: Feeding practices around the time of packed red blood cell transfusion have been implicated in the subsequent development of necrotising enterocolitis (NEC) in preterm infants. Specifically, it has been suggested that withholding feeds around the time of transfusion may reduce the risk of subsequent NEC. It is important to determine if withholding feeds around transfusion reduces the risk of subsequent NEC and associated mortality.

    OBJECTIVES: • To assess the benefits and risks of stopping compared to continuing feed management before, during, and after blood transfusion in preterm infants • To assess the effects of stopping versus continuing feeds in the following subgroups of infants: infants of different gestations; infants with symptomatic and asymptomatic anaemia; infants who received different feeding schedules, types of feed, and methods of feed delivery; infants who were transfused with different blood products, at different blood volumes, via different routes of delivery; and those who received blood transfusion with and without co-interventions such as use of diuretics • To determine the effectiveness and safety of stopping feeds around the time of a blood transfusion in reducing the risk of subsequent necrotising enterocolitis (NEC) in preterm infants SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 11), in the Cochrane Library; MEDLINE (1966 to 14 November 2018); Embase (1980 to 14 November 2018); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 14 November 2018). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials (RCTs), cluster-RCTs, and quasi-RCTs.

    SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared stopping feeds versus continuing feeds around the time of blood transfusion in preterm infants.

    DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trial quality, and extracted data from the included studies.

    MAIN RESULTS: The search revealed seven studies that assessed effects of stopping feeds during blood transfusion. However, only one RCT involving 22 preterm infants was eligible for inclusion in the review. This RCT had low risk of selection bias but high risk of performance bias, as care personnel were not blinded to the study allocation. The primary objective of this trial was to investigate changes in mesenteric blood flow, and no cases of NEC were reported in any of the infants included in the trial. We were unable to draw any conclusions from this single study. The overall GRADE rating for quality of evidence was very low.

    AUTHORS' CONCLUSIONS: Randomised controlled trial evidence is insufficient to show whether stopping feeds has an effect on the incidence of subsequent NEC or death. Large, adequately powered RCTs are needed to address this issue.

  17. 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.

  18. Lai NM, Chang SMW, Ng SS, Tan SL, Chaiyakunapruk N, Stanaway F
    Cochrane Database Syst Rev, 2019 11 25;2019(11).
    PMID: 31763689 DOI: 10.1002/14651858.CD013243.pub2
    BACKGROUND: Dementia is a chronic condition which progressively affects memory and other cognitive functions, social behaviour, and ability to carry out daily activities. To date, no treatment is clearly effective in preventing progression of the disease, and most treatments are symptomatic, often aiming to improve people's psychological symptoms or behaviours which are challenging for carers. A range of new therapeutic strategies has been evaluated in research, and the use of trained animals in therapy sessions, termed animal-assisted therapy (AAT), is receiving increasing attention.

    OBJECTIVES: To evaluate the efficacy and safety of animal-assisted therapy for people with dementia.

    SEARCH METHODS: We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group's Specialised Register on 5 September 2019. ALOIS contains records of clinical trials identified from monthly searches of major healthcare databases, trial registries, and grey literature sources. We also searched MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCOhost), ISI Web of Science, ClinicalTrials.gov, and the WHO's trial registry portal.

    SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster-randomised trials, and randomised cross-over trials that compared AAT versus no AAT, AAT using live animals versus alternatives such as robots or toys, or AAT versus any other active intervention.

    DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of Cochrane Dementia. Two review authors independently assessed the eligibility and risk of bias of the retrieved records. We expressed our results using mean difference (MD), standardised mean difference (SMD), and risk ratio (RR) with their 95% confidence intervals (CIs) where appropriate.

    MAIN RESULTS: We included nine RCTs from 10 reports. All nine studies were conducted in Europe and the US. Six studies were parallel-group, individually randomised RCTs; one was a randomised cross-over trial; and two were cluster-RCTs that were possibly related where randomisation took place at the level of the day care and nursing home. We identified two ongoing trials from trial registries. There were three comparisons: AAT versus no AAT (standard care or various non-animal-related activities), AAT using live animals versus robotic animals, and AAT using live animals versus the use of a soft animal toy. The studies evaluated 305 participants with dementia. One study used horses and the remainder used dogs as the therapy animal. The duration of the intervention ranged from six weeks to six months, and the therapy sessions lasted between 10 and 90 minutes each, with a frequency ranging from one session every two weeks to two sessions per week. There was a wide variety of instruments used to measure the outcomes. All studies were at high risk of performance bias and unclear risk of selection bias. Our certainty about the results for all major outcomes was very low to moderate. Comparing AAT versus no AAT, participants who received AAT may be slightly less depressed after the intervention (MD -2.87, 95% CI -5.24 to -0.50; 2 studies, 83 participants; low-certainty evidence), but they did not appear to have improved quality of life (MD 0.45, 95% CI -1.28 to 2.18; 3 studies, 164 participants; moderate-certainty evidence). There were no clear differences in all other major outcomes, including social functioning (MD -0.40, 95% CI -3.41 to 2.61; 1 study, 58 participants; low-certainty evidence), problematic behaviour (SMD -0.34, 95% CI -0.98 to 0.30; 3 studies, 142 participants; very-low-certainty evidence), agitation (SMD -0.39, 95% CI -0.89 to 0.10; 3 studies, 143 participants; very-low-certainty evidence), activities of daily living (MD 4.65, 95% CI -16.05 to 25.35; 1 study, 37 participants; low-certainty evidence), and self-care ability (MD 2.20, 95% CI -1.23 to 5.63; 1 study, 58 participants; low-certainty evidence). There were no data on adverse events. Comparing AAT using live animals versus robotic animals, one study (68 participants) found mixed effects on social function, with longer duration of physical contact but shorter duration of talking in participants who received AAT using live animals versus robotic animals (median: 93 seconds with live versus 28 seconds with robotic for physical contact; 164 seconds with live versus 206 seconds with robotic for talk directed at a person; 263 seconds with live versus 307 seconds with robotic for talk in total). Another study showed no clear differences between groups in behaviour measured using the Neuropsychiatric Inventory (MD -6.96, 95% CI -14.58 to 0.66; 78 participants; low-certainty evidence) or quality of life (MD -2.42, 95% CI -5.71 to 0.87; 78 participants; low-certainty evidence). There were no data on the other outcomes. Comparing AAT using live animals versus a soft toy cat, one study (64 participants) evaluated only social functioning, in the form of duration of contact and talking. The data were expressed as median and interquartile ranges. Duration of contact was slightly longer in participants in the AAT group and duration of talking slightly longer in those exposed to the toy cat. This was low-certainty evidence.

    AUTHORS' CONCLUSIONS: We found low-certainty evidence that AAT may slightly reduce depressive symptoms in people with dementia. We found no clear evidence that AAT affects other outcomes in this population, with our certainty in the evidence ranging from very-low to moderate depending on the outcome. We found no evidence on safety or effects on the animals. Therefore, clear conclusions cannot yet be drawn about the overall benefits and risks of AAT in people with dementia. Further well-conducted RCTs are needed to improve the certainty of the evidence. In view of the difficulty in achieving blinding of participants and personnel in such trials, future RCTs should work on blinding outcome assessors, document allocation methods clearly, and include major patient-important outcomes such as affect, emotional and social functioning, quality of life, adverse events, and outcomes for animals.

  19. Kumbargere Nagraj S, Eachempati P, Uma E, Singh VP, Ismail NM, Varghese E
    Cochrane Database Syst Rev, 2019 Dec 11;12(12):CD012213.
    PMID: 31825092 DOI: 10.1002/14651858.CD012213.pub2
    BACKGROUND: Halitosis or bad breath is a symptom in which a noticeably unpleasant breath odour is present due to an underlying oral or systemic disease. 50% to 60% of the world population has experienced this problem which can lead to social stigma and loss of self-confidence. Multiple interventions have been tried to control halitosis ranging from mouthwashes and toothpastes to lasers. This new Cochrane Review incorporates Cochrane Reviews previously published on tongue scraping and mouthrinses for halitosis.

    OBJECTIVES: The objectives of this review were to assess the effects of various interventions used to control halitosis due to oral diseases only. We excluded studies including patients with halitosis secondary to systemic disease and halitosis-masking interventions.

    SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 8 April 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 3) in the Cochrane Library (searched 8 April 2019), MEDLINE Ovid (1946 to 8 April 2019), and Embase Ovid (1980 to 8 April 2019). We also searched LILACS BIREME (1982 to 19 April 2019), the National Database of Indian Medical Journals (1985 to 19 April 2019), OpenGrey (1992 to 19 April 2019), and CINAHL EBSCO (1937 to 19 April 2019). The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (8 April 2019), the World Health Organization International Clinical Trials Registry Platform (8 April 2019), the ISRCTN Registry (19 April 2019), the Clinical Trials Registry - India (19 April 2019), were searched for ongoing trials. We also searched the cross-references of included studies and systematic reviews published on the topic. No restrictions were placed on the language or date of publication when searching the electronic databases.

    SELECTION CRITERIA: We included randomised controlled trials (RCTs) which involved adults over the age of 16, and any intervention for managing halitosis compared to another or placebo, or no intervention. The active interventions or controls were administered over a minimum of one week and with no upper time limit. We excluded quasi-randomised trials, trials comparing the results for less than one week follow-up, and studies including advanced periodontitis.

    DATA COLLECTION AND ANALYSIS: Two pairs of review authors independently selected trials, extracted data, and assessed risk of bias. We estimated mean differences (MDs) for continuous data, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach.

    MAIN RESULTS: We included 44 trials in the review with 1809 participants comparing an intervention with a placebo or a control. The age of participants ranged from 17 to 77 years. Most of the trials reported on short-term follow-up (ranging from one week to four weeks). Only one trial reported long-term follow-up (three months). Three studies were at low overall risk of bias, 16 at high overall risk of bias, and the remaining 25 at unclear overall risk of bias. We compared different types of interventions which were categorised as mechanical debridement, chewing gums, systemic deodorising agents, topical agents, toothpastes, mouthrinse/mouthwash, tablets, and combination methods. Mechanical debridement: for mechanical tongue cleaning versus no tongue cleaning, the evidence was very uncertain for the outcome dentist-reported organoleptic test (OLT) scores (MD -0.20, 95% CI -0.34 to -0.07; 2 trials, 46 participants; very low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Chewing gums: for 0.6% eucalyptus chewing gum versus placebo chewing gum, the evidence was very uncertain for the outcome dentist-reported OLT scores (MD -0.10, 95% CI -0.31 to 0.11; 1 trial, 65 participants; very low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Systemic deodorising agents: for 1000 mg champignon versus placebo, the evidence was very uncertain for the outcome patient-reported visual analogue scale (VAS) scores (MD -1.07, 95% CI -14.51 to 12.37; 1 trial, 40 participants; very low-certainty evidence). No data were reported for dentist-reported OLT score or adverse events. Topical agents: for hinokitiol gel versus placebo gel, the evidence was very uncertain for the outcome dentist-reported OLT scores (MD -0.27, 95% CI -1.26 to 0.72; 1 trial, 18 participants; very low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Toothpastes: for 0.3% triclosan toothpaste versus control toothpaste, the evidence was very uncertain for the outcome dentist-reported OLT scores (MD -3.48, 95% CI -3.77 to -3.19; 1 trial, 81 participants; very low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Mouthrinse/mouthwash: for mouthwash containing chlorhexidine and zinc acetate versus placebo mouthwash, the evidence was very uncertain for the outcome dentist-reported OLT scores (MD -0.20, 95% CI -0.58 to 0.18; 1 trial, 44 participants; very low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Tablets: no data were reported on key outcomes for this comparison. Combination methods: for brushing plus cetylpyridium mouthwash versus brushing, the evidence was uncertain for the outcome dentist-reported OLT scores (MD -0.48, 95% CI -0.72 to -0.24; 1 trial, 70 participants; low-certainty evidence). No data were reported for patient-reported OLT score or adverse events.

    AUTHORS' CONCLUSIONS: We found low- to very low-certainty evidence to support the effectiveness of interventions for managing halitosis compared to placebo or control for the OLT and patient-reported outcomes tested. We were unable to draw any conclusions regarding the superiority of any intervention or concentration. Well-planned RCTs need to be conducted by standardising the interventions and concentrations.

  20. Mulimani P, Ballas SK, Abas AB, Karanth L
    Cochrane Database Syst Rev, 2019 Dec 16;12(12):CD011633.
    PMID: 31841224 DOI: 10.1002/14651858.CD011633.pub3
    BACKGROUND: Sickle cell disease is the most common single gene disorder and the commonest haemoglobinopathy found with high prevalence in many populations across the world. Management of dental complications in people with sickle cell disease requires special consideration for three main reasons. Firstly, dental and oral tissues are affected by the blood disorder resulting in several oro-facial abnormalities. Secondly, living with a haemoglobinopathy and coping with its associated serious consequences may result in individuals neglecting their oral health care. Finally, the treatment of these oral complications must be adapted to the systemic condition and special needs of these individuals, in order not to exacerbate or deteriorate their general health. Guidelines for the treatment of dental complications in this population who require special care are unclear and even unavailable in many aspects. Hence this review was undertaken to provide a basis for clinical care by investigating and analysing the existing evidence in the literature for the treatment of dental complications in people with sickle cell disease. This is an update of a previously published review.

    OBJECTIVES: To assess methods of treating dental complications in people with sickle cell disease.

    SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Review Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 01 August 2019. Additionally, we searched nine online databases (PubMed, Google Scholar, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Literature in the Health Sciences in Latin America and the Caribbean database, African Index Medicus, Index Medicus for South East Asia Region, Index Medicus for the Eastern Mediterranean Region, Indexing of Indian Medical Journals). We also searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organizations, pharmaceutical companies and researchers working in this field. Date of last search: 07 November 2019.

    SELECTION CRITERIA: We searched for published or unpublished randomised controlled studies of treatments for dental complications in people with sickle cell disease.

    DATA COLLECTION AND ANALYSIS: Two review authors intended to independently extract data and assess the risk of bias of the included studies using standard Cochrane methodologies; however, no studies were identified for inclusion in the review.

    MAIN RESULTS: No randomised controlled studies were identified.

    AUTHORS' CONCLUSIONS: This Cochrane Review did not identify any randomised controlled studies assessing interventions for the treatment of dental complications in people with sickle cell disease. There is an important need for randomised controlled studies in this area, so as to identify the most effective and safe method for treating dental complications in people with sickle cell disease.

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