OBJECTIVES: To assess the benefits and safety of growth hormone therapy in people with thalassaemia.
SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of latest search: 14 November 2019. We also searched the reference lists of relevant articles, reviews and clinical trial registries. Date of latest search: 06 January 2020.
SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing the use of growth hormone therapy to placebo or standard care in people with thalassaemia of any type or severity.
DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion. Data extraction and assessment of risk of bias were also conducted independently by two authors. The certainty of the evidence was assessed using GRADE criteria.
MAIN RESULTS: We included one parallel trial conducted in Turkey. The trial recruited 20 children with homozygous beta thalassaemia who had short stature; 10 children received growth hormone therapy administered subcutaneously on a daily basis at a dose of 0.7 IU/kg per week and 10 children received standard care. The overall risk of bias in this trial was low except for the selection criteria and attrition bias which were unclear. The certainty of the evidence for all major outcomes was moderate, the main concern was imprecision of the estimates due to the small sample size leading to wide confidence intervals. Final height (cm) (the review's pre-specified primary outcome) and change in height were not assessed in the included trial. The trial reported no clear difference between groups in height standard deviation (SD) score after one year, mean difference (MD) -0.09 (95% confidence interval (CI) -0.33 to 0.15 (moderate-certainty evidence). However, modest improvements appeared to be observed in the following key outcomes in children receiving growth hormone therapy compared to control (moderate-certainty evidence): change between baseline and final visit in height SD score, MD 0.26 (95% CI 0.13 to 0.39); height velocity, MD 2.28 cm/year (95% CI 1.76 to 2.80); height velocity SD score, MD 3.31 (95% CI 2.43 to 4.19); and change in height velocity SD score between baseline and final visit, MD 3.41 (95% CI 2.45 to 4.37). No adverse effects of treatment were reported in either group; however, while there was no clear difference between groups in the oral glucose tolerance test at one year, fasting blood glucose was significantly higher in the growth hormone therapy group compared to control, although both results were still within the normal range, MD 6.67 mg/dL (95% CI 2.66 to 10.68). There were no data beyond the one-year trial period.
AUTHORS' CONCLUSIONS: A small single trial contributed evidence of moderate certainty that the use of growth hormone for a year may improve height velocity of children with thalassaemia although height SD score in the treatment group was similar to the control group. There are no randomised controlled trials in adults or trials that address the use of growth hormone therapy over a longer period and assess its effect on final height and quality of life. The optimal dosage of growth hormone and the ideal time to start this therapy remain uncertain. Large well-designed randomised controlled trials over a longer period with sufficient duration of follow up are needed.
METHODS: We compared two methods of OSCE feedback delivered to fourth year medical students in Malaysia: (i) Face to face (FTF) immediate feedback (semester one) (ii) Individualised enhanced written (EW) feedback containing detailed scores in each domain, examiners' free text comments and the marking rubric (semester two). Both methods were evaluated by students and staff examiners, and students' responses were compared against their OSCE performance.
RESULTS: Of the 116 students who sat for both formative OSCEs, 82.8% (n=96) and 86.2% (n=100) responded to the first and second survey respectively. Most students were comfortable to receive feedback (91.3% in FTF, 96% in EW) with EW feedback associated with higher comfort levels (p=0.022). Distress affected a small number with no differences between either method (13.5% in FTF, 10% in EW, p=0.316). Most students perceived both types of feedback improved their performance (89.6% in FTF, 95% in EW); this perception was significantly stronger for EW feedback (p=0.008). Students who preferred EW feedback had lower OSCE scores compared to those preferring FTF feedback (mean scores ± SD: 43.8 ± 5.3 in EW, 47.2 ± 6.5 in FTF, p=0.049). Students ranked the "marking rubric" to be the most valuable aspect of the EW feedback. Tutors felt both methods of feedback were equally beneficial. Few examiners felt they needed training (21.4% in FTF, 15% in EW) but students perceived this need for tutors' training differently (53.1% in FTF, 46% in EW) CONCLUSION: Whilst both methods of OSCE feedback were highly valued, students preferred to receive EW feedback and felt it was more beneficial. Learning cultures of Malaysian students may have influenced this view. Information provided in EW feedback should be tailored accordingly to provide meaningful feedback in OSCE exams.
METHODS: This retrospective chart review involved dengue patients with dengue non-structural protein 1 (NS1) antigen positivity admitted to a tertiary hospital in Malaysia from January to July 2015. A comparison was made between older people (aged ≥60 y) and others.
RESULTS: Among 406 dengue patients, 43 (10.6%) were older people. Older dengue patients were less likely to present with persistent vomiting (adjusted OR [AOR] 0.247, 95% CI 0.093 to 0.656, p=0.005), while restlessness and confusion were more common at presentation (AOR 3.356, 95% CI 1.024 to 11.003, p=0.046). Older patients had significantly lower albumin upon admission (38 vs 40 g/L, p=0.036) and during hospital stay (35 vs 37 g/L, p=0.015). Compared with younger patients, older patients were more likely to have experienced nadir platelet counts of <50×109/L (AOR 2.897, 95% CI to 1.176 to 7.137, p=0.021). They were also more likely to require an extended hospital stay (AOR 3.547, 95% CI 1.575 to 7.986, p=0.002).
CONCLUSIONS: Diagnosis of dengue in older people may be challenging because of atypical presentations. Increased vigilance is necessary as there is an increased tendency to develop severe thrombocytopenia, hypoalbuminemia and prolonged hospitalisation in older people.
OBJECTIVES: We evaluated the association between TSB and kernicterus spectrum disorder (KSD).
METHODS: We searched PubMed, EMBASE, and CENTRAL till July 2021. Two authors independently selected relevant cohort studies, extracted data (CHARMS checklist), assessed risk of bias (RoB) (QUIPS tool), and rated certainty-of-evidence (Grades of Recommendation, Assessment, Development, and Evaluation). We pooled adjusted odds ratio (aOR) (random-effect) via generic inverse variance methods.
RESULTS: From 2,826 records retrieved, we included 37 studies (n = 648,979). Fifteen studies had low, 16 moderate, and 6 high RoB, with majority having concerns on confounder adjustment and statistical analysis. Twenty-two studies contributed meta-analysis data, and 15 were summarized narratively. TSB appears associated with KSD in infants with certain risk factors (aOR 1.10, 95% CI: 1.07-1.13; 5 studies [n = 4,484]). However, TSB (aOR 1.10, 95% CI: 0.98-1.23; 1 study [n = 34,533]) or hyperbilirubinemia (aOR 1.00, 95% CI: 0.51-1.95; 2 studies [n = 56,578]) have no clear association with kernicterus or neurological diagnosis in overall neonatal population (moderate-certainty-evidence). One study shows that infants with hyperbilirubinemia appear likelier to develop attention-deficit disorder (aOR 1.90, 95% CI: 1.10-3.28) and autistic spectrum disorder (aOR 1.60, 95% CI: 1.03-2.49, n = 56,019) (low-certainty-evidence). Certain clinical factors appear associated with KSD, although very few studies contributed to the analyses.
CONCLUSIONS: Despite the importance of this question, there is insufficient high-quality evidence on the independent prognostic value of TSB for adverse neurodevelopmental outcomes in most neonatal populations. Future studies should incorporate all known risk factors alongside TSB in a multivariable analysis to improve certainty-of-evidence.
OBJECTIVES: To assess the benefits and safety of growth hormone therapy in people with thalassaemia.
SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles, reviews and clinical trial registries. Our database and trial registry searches are current to 10 August 2017 and 08 August 2017, respectively.
SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing the use of growth hormone therapy to placebo or standard care in people with thalassaemia of any type or severity.
DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion. Data extraction and assessment of risk of bias were also conducted independently by two authors. The quality of the evidence was assessed using GRADE criteria.
MAIN RESULTS: One parallel trial conducted in Turkey was included. The trial recruited 20 children with homozygous beta thalassaemia who had short stature; 10 children received growth hormone therapy administered subcutaneously on a daily basis at a dose of 0.7 IU/kg per week and 10 children received standard care. The overall risk of bias in this trial was low except for the selection criteria and attrition bias which were unclear. The quality of the evidence for all major outcomes was moderate, the main concern was imprecision of the estimates due to the small sample size leading to wide confidence intervals. Final height (cm) (the review's pre-specified primary outcome) and change in height were not assessed in the included trial. The trial reported no clear difference between groups in height standard deviation (SD) score after one year, mean difference (MD) -0.09 (95% confidence interval (CI) -0.33 to 0.15 (moderate quality evidence). However, modest improvements appeared to be observed in the following key outcomes in children receiving growth hormone therapy compared to control (moderate quality evidence): change between baseline and final visit in height SD score, MD 0.26 (95% CI 0.13 to 0.39); height velocity, MD 2.28 cm/year (95% CI 1.76 to 2.80); height velocity SD score, MD 3.31 (95% CI 2.43 to 4.19); and change in height velocity SD score between baseline and final visit, MD 3.41 (95% CI 2.45 to 4.37). No adverse effects of treatment were reported in either group; however, while there was no clear difference between groups in the oral glucose tolerance test at one year, fasting blood glucose was significantly higher in the growth hormone therapy group compared to control, although both results were still within the normal range, MD 6.67 mg/dL (95% CI 2.66 to 10.68). There were no data beyond the one-year trial period.
AUTHORS' CONCLUSIONS: A small single trial contributed evidence of moderate quality that the use of growth hormone for a year may improve height velocity of children with thalassaemia although height SD score in the treatment group was similar to the control group. There are no randomised controlled trials in adults or trials that address the use of growth hormone therapy over a longer period and assess its effect on final height and quality of life. The optimal dosage of growth hormone and the ideal time to start this therapy remain uncertain. Large well-designed randomised controlled trials over a longer period with sufficient duration of follow up are needed.
OBJECTIVES: To assess the risks and benefits of fluid supplementation compared to standard fluid management in term and preterm newborn infants with unconjugated hyperbilirubinaemia who require phototherapy.
SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5), MEDLINE via PubMed (1966 to 7 June 2017), Embase (1980 to 7 June 2017), and CINAHL (1982 to 7 June 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA: We included randomised controlled trials that compared fluid supplementation against no fluid supplementation, or one form of fluid supplementation against another.
DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group using the Covidence platform. Two review authors independently assessed the eligibility and risk of bias of the retrieved records. We expressed our results using mean difference (MD), risk difference (RD), and risk ratio (RR) with 95% confidence intervals (CIs).
MAIN RESULTS: Out of 1449 articles screened, seven studies were included. Three articles were awaiting classification, among them, two completed trials identified from the trial registry appeared to be unpublished so far.There were two major comparisons: IV fluid supplementation versus no fluid supplementation (six studies) and IV fluid supplementation versus oral fluid supplementation (one study). A total of 494 term, healthy newborn infants with unconjugated hyperbilirubinaemia were evaluated. All studies were at high risk of bias for blinding of care personnel, five studies had unclear risk of bias for blinding of outcome assessors, and most studies had unclear risk of bias in allocation concealment. There was low- to moderate-quality evidence for all major outcomes.In the comparison between IV fluid supplementation and no supplementation, no infant in either group developed bilirubin encephalopathy in the one study that reported this outcome. Serum bilirubin was lower at four hours postintervention for infants who received IV fluid supplementation (MD -34.00 μmol/L (-1.99 mg/dL), 95% CI -52.29 (3.06) to -15.71 (0.92); participants = 67, study = 1) (low quality of evidence, downgraded one level for indirectness and one level for suspected publication bias). Beyond eight hours postintervention, serum bilirubin was similar between the two groups. Duration of phototherapy was significantly shorter for fluid-supplemented infants, but the estimate was affected by heterogeneity which was not clearly explained (MD -10.70 hours, 95% CI -15.55 to -5.85; participants = 218; studies = 3; I² = 67%). Fluid-supplemented infants were less likely to require exchange transfusion (RR 0.39, 95% CI 0.21 to 0.71; RD -0.01, 95% CI -0.04 to 0.02; participants = 462; studies = 6; I² = 72%) (low quality of evidence, downgraded one level due to inconsistency, and another level due to suspected publication bias), and the estimate was similarly affected by unexplained heterogeneity. The frequencies of breastfeeding were similar between the fluid-supplemented and non-supplemented infants in days one to three based on one study (estimate on day three: MD 0.90 feeds, 95% CI -0.40 to 2.20; participants = 60) (moderate quality of evidence, downgraded one level for imprecision).One study contributed to all outcome data in the comparison of IV versus oral fluid supplementation. In this comparison, no infant in either group developed abnormal neurological signs. Serum bilirubin, as well as the rate of change of serum bilirubin, were similar between the two groups at four hours after phototherapy (serum bilirubin: MD 11.00 μmol/L (0.64 mg/dL), 95% CI -21.58 (-1.26) to 43.58 (2.55); rate of change of serum bilirubin: MD 0.80 μmol/L/hour (0.05 mg/dL/hour), 95% CI -2.55 (-0.15) to 4.15 (0.24); participants = 54 in both outcomes) (moderate quality of evidence for both outcomes, downgraded one level for indirectness). The number of infants who required exchange transfusion was similar between the two groups (RR 1.60, 95% CI 0.60 to 4.27; RD 0.11, 95% CI -0.12 to 0.34; participants = 54). No infant in either group developed adverse effects including vomiting or abdominal distension.
AUTHORS' CONCLUSIONS: There is no evidence that IV fluid supplementation affects important clinical outcomes such as bilirubin encephalopathy, kernicterus, or cerebral palsy in healthy, term newborn infants with unconjugated hyperbilirubinaemia requiring phototherapy. In this review, no infant developed these bilirubin-associated clinical complications. Low- to moderate-quality evidence shows that there are differences in total serum bilirubin levels between fluid-supplemented and control groups at some time points but not at others, the clinical significance of which is uncertain. There is no evidence of a difference between the effectiveness of IV and oral fluid supplementations in reducing serum bilirubin. Similarly, no infant developed adverse events or complications from fluid supplementation such as vomiting or abdominal distension. This suggests a need for future research to focus on different population groups with possibly higher baseline risks of bilirubin-related neurological complications, such as preterm or low birthweight infants, infants with haemolytic hyperbilirubinaemia, as well as infants with dehydration for comparison of different fluid supplementation regimen.
METHODS: We searched PubMed, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL Plus for articles published from their date of inception to June 2021. RCTs investigating the efficacy or safety of VNS on post-stroke recovery were included. The outcomes were upper limb sensorimotor function, health-related quality of life, level of independence, cardiovascular effects, and adverse events. The risk of bias was assessed using the Cochrane risk-of-bias tool, while the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. Review Manager 5.4 was used to conduct the meta-analysis.
RESULTS: Seven RCTs (n = 236 subjects) met the eligibility criteria. Upper limb sensorimotor function, assessed by the Fugl-Meyer Assessment for Upper Extremity (FMA-UE), improved at day 1 (n = 4 RCTs; standardized mean difference [SMD] 1.01; 95% confidence interval [CI]: 0.35-1.66) and day 90 post-intervention (n = 3 RCTs; SMD 0.64; 95% CI: 0.31-0.98; moderate certainty of evidence) but not at day 30 follow-up (n = 2 RCTs; SMD 1.54; 95% CI: -0.39 to 3.46). Clinically significant upper limb sensorimotor function recovery, as defined by ≥6 points increase in FMA-UE, was significantly higher at day 1 (n = 2 RCTs; risk ratio [RR] 2.01; 95% CI: 1.02-3.94) and day 90 post-intervention (n = 2 RCTs; RR 2.14; 95% CI: 1.32-3.45; moderate certainty of the evidence). The between-group effect sizes for upper limb sensorimotor function recovery was medium to large (Hedges' g 0.535-2.659). While the level of independence improved with VNS, its impact on health-related quality of life remains unclear as this was only studied in two trials with mixed results. Generally, adverse events reported were mild and self-limiting.
CONCLUSION: VNS may be an effective and safe adjunct to standard rehabilitation for post-stroke recovery; however, its clinical significance and long-term efficacy and safety remain unclear.
METHODS: This is a single-center retrospective observational study in a Malaysian tertiary referral center. Children with intussusception admitted between year 2012 and 2016 were included and medical records reviewed. Factors associated with success or failure of USGHR were identified using multivariable logistic regression.
RESULTS: Of the 172 cases included, 151 cases (87.8%) underwent USGHR, of whom 129 cases were successfully reduced (success rate of 85.4%). One perforation (0.7%) was reported. Age more than 3years old (aOR=7.16; 95% CI=1.07-47.94; p=0.042), anemia (aOR=10.12; 95% CI=1.12-91.35; p=0.039), thrombocytosis (aOR=11.21; 95% CI=2.06-64.33; p=0.005) and ultrasound findings of free fluid (aOR=9.39; 95% CI=1.62-54.38; p=0.012) and left-sided intussusception (aOR=8.18;95% CI=1.22-54.90, p=0.031) were independently associated with USGHR irreducibility. Symptom duration, blood in stool, vomiting and other clinical presentations, however, showed no association.
CONCLUSIONS: USGHR with water is effective in the non-operative management of pediatric intussusception. Prolonged symptom duration need not necessarily preclude USGHR. The findings of anemia and thrombocytosis as independent predictors of USGHR irreducibility deserve further study.
TYPE OF STUDY: Treatment study LEVEL OF EVIDENCE: III.
METHODS: This retrospective study involved consecutive hospitalized patients with non-structural protein 1 (NS1) antigen positivity during an outbreak (Jan to April 2014). Multiplex RT-PCR was performed directly on NS1 positive serum samples to detect and determine the DENV serotypes. All PCR-positive serum samples were inoculated onto C6/36 cells. Multiplex PCR was repeated on the supernatant of the first blind passage of the serum-infected cells. Random samples of supernatant from the first passage of C6/36 infected cells were subjected to whole genome sequencing. Clinical and laboratory variables were compared between patients with and without DENV co-infections.
RESULTS: Of the 290 NS1 positive serum samples, 280 were PCR positive for DENV. Medical notes of 262 patients were available for analysis. All 4 DENV serotypes were identified. Of the 262 patients, forty patients (15.3 %) had DENV co-infections: DENV-1/DENV-2(85 %), DENV-1/DENV-3 (12.5 %) and DENV-2/DENV-3 (2.5 %). Another 222 patients (84.7 %) were infected with single DENV serotype (mono-infection), with DENV- 1 (76.6 %) and DENV- 2 (19.8 %) predominating. Secondary dengue infections occurred in 31.3 % patients. Whole genome sequences of random samples representing DENV-1 and DENV-2 showed heterogeneity amongst the DENVs. Multivariate analysis revealed that pleural effusion and the presence of warning signs were significantly higher in the co-infected group, both in the overall and subgroup analysis. Diarrhoea was negatively associated with co-infection. Additionally, DENV-2 co-infected patients had higher frequency of patients with severe thrombocytopenia (platelet count < 50,000/mm(3)), whereas DENV-2 mono-infections presented more commonly with myalgia. Elevated creatinine levels were more frequent amongst the co-infected patients in univariate analysis. Haemoconcentration and haemorrhagic manifestations were not higher amongst the co-infected patients. Serotypes associated with severe dengue were: DENV-1 (n = 9), DENV-2 (n = 1), DENV-3 (n = 1) in mono-infected patients and DENV-1/DENV-2 (n = 5) and DENV-1/DENV-3 (n = 1) amongst the co-infected patients.
CONCLUSION: DENV co-infections are not uncommon in a hyperendemic region and co-infected patients are skewed towards more severe clinical manifestations compared to mono-infected patients.