Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials

BackgroundDrug-induced orthostatic hypotension (OH) is common, and its resulting cerebral hypoperfusion is linked to adverse outcomes including falls, strokes, cognitive impairment, and increased mortality. The extent to which specific medications are associated with OH remains unclear.Methods and findingsWe conducted a systematic review and meta-analysis to evaluate the extent to which specific drug groups are associated with OH. EMBASE, MEDLINE, and Web of Science databases were searched from inception through 23 November 2020. Placebo-controlled randomised controlled trials (RCTs) on any drug reporting on OH as an adverse effect in adults (≥18 years) were eligible. Three authors extracted data on the drug, OH, dose, participant characteristics, and study setting. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to appraise evidence. Summary odds ratios (ORs) were estimated for OH using fixed effects Mantel–Haenszel statistics. We conducted subgroup analysis on validity of OH measurement, drug dose, risk of bias, age, and comorbidity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to summarise the certainty of evidence. Of 36,940 citations, 69 eligible RCTs were included in the meta-analysis comprising 27,079 participants. Compared with placebo, beta-blockers and tricyclic antidepressants were associated with increased odds of OH (OR 7.76 [95% CI 2.51, 24.03]; OR 6.30 [95% CI 2.86, 13.91]). Alpha-blockers, antipsychotics, and SGLT-2 inhibitors were associated with up to 2-fold increased odds of OH, compared to placebo. There was no statistically significant difference in odds of OH with vasodilators (CCBs, ACE inhibitors/ARBs, SSRIs), compared to placebo. Limitations of this study are as follows: data limited to placebo-controlled studies, (excluding head-to-head trials), many RCTs excluded older participants; therefore results may be amplified in older patients in the clinical setting. The study protocol is publicly available on PROSPERO (CRD42020168697).ConclusionsMedications prescribed for common conditions (including depression, diabetes, and lower urinary tract symptoms) were associated with significantly increased odds of OH. Drugs causing sympathetic inhibition were associated with significantly increased odds of OH, while most vasodilators were associated with small nonsignificant differences in odds of OH, compared to placebo. Drugs targeting multiple parts of the orthostatic blood pressure (BP) reflex pathway (e.g. sympathetic inhibition, vasodilation, cardio-inhibitory effects) may carry cumulative risk, suggesting that individuals with polypharmacy could benefit from postural BP monitoring.

Cini Bhanu and colleagues evaluate the extent to which different drug groups are associated with orthostatic hypertension in this systematic review and meta-analysis.     

Zinc supplementation in children with cholera in Bangladesh: randomised controlled trial

Objective To investigate the impact of zinc supplementation in children with cholera.Design Double blind, randomised, placebo controlled trial.Setting Dhaka Hospital, Bangladesh.Participants 179 children aged 3-14 years with watery diarrhoea and stool dark field examination positive for Vibrio cholerae and confirmed by stool culture.Intervention Children were randomised to receive 30 mg elemental zinc per day (n=90) or placebo (n=89) until recovery. All children received erythromycin suspension orally in a dose of 12.5 mg/kg every six hours for three days.Main outcome measures Duration of diarrhoea and stool output.Results 82 children in each group completed the study. More patients in the zinc group than in the control group recovered by two days (49% v 32%, P=0.032) and by three days (81% v 68%, P=0.03). Zinc supplemented patients had 12% shorter duration of diarrhoea than control patients (64.1 v 72.8 h, P=0.028) and 11% less stool output (1.6 v 1.8 kg/day, P=0.039).Conclusion Zinc supplementation significantly reduced the duration of diarrhoea and stool output in children with cholera. Children with cholera should be supplemented with zinc to reduce its duration and severity.Trial registration Clinical trials {"type":"clinical-trial","attrs":{"text":"NCT00226616","term_id":"NCT00226616"}}NCT00226616.     

Methods of hysterectomy: systematic review and meta-analysis of randomised controlled trials

Objective To evaluate the most appropriate surgical method of hysterectomy (abdominal, vaginal, or laparoscopic) for women with benign disease.Design Systematic review and meta-analysis.Data sources Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials, Medline, Embase, and Biological Abstracts.Selection of studies Only randomised controlled trials were selected; participants had to have benign gynaecological disease; interventions had to comprise at least one hysterectomy method compared with another; and trials had to report primary outcomes (time taken to return to normal activities, intraoperative visceral injury, and major long term complications) or secondary outcomes (operating time, other immediate complications of surgery, short term complications, and duration of hospital stay).Results 27 trials (total of 3643 participants) were included. Return to normal activities was quicker after vaginal than after abdominal hysterectomy (weighted mean difference 9.5 (95% confidence interval 6.4 to 12.6) days) and after laparoscopic than after abdominal hysterectomy (difference 13.6 (11.8 to 15.4) days), but was not significantly different for laparoscopic versus vaginal hysterectomy (difference -1.1 (-4.2 to 2.1) days). There were more urinary tract injuries with laparoscopic than with abdominal hysterectomy (odds ratio 2.61 (95% confidence interval 1.22 to 5.60)), but no other intraoperative visceral injuries showed a significant difference between surgical approaches. Data were notably absent for many important long term patient outcome measures, where the analyses were underpowered to detect important differences, or they were simply not reported in trials.Conclusions Significantly speedier return to normal activities and other improved secondary outcomes (shorter duration of hospital stay and fewer unspecified infections or febrile episodes) suggest that vaginal hysterectomy is preferable to abdominal hysterectomy where possible. Where vaginal hysterectomy is not possible, laparoscopic hysterectomy is preferable to abdominal hysterectomy, although it brings a higher chance of bladder or ureter injury.     

Zinc supplementation during pregnancy: a double blind randomised controlled trial.

OBJECTIVE--To see whether zinc supplementation during pregnancy improves maternal and fetal outcome. DESIGN--Prospective study started at booking and continued till discharge of mother and baby from the maternity hospital. Mothers were randomly assigned to receive zinc supplementation or placebo in a double blind trial. SETTING--Mothers booking at one hospital. PATIENTS--Women booking before 20 weeks of gestation who agreed to take part in the study. 494 Mothers were followed up till the end of pregnancy. There was no difference between the groups given zinc and placebo in their social or medical backgrounds. INTERVENTIONS--Mothers in the active treatment group received one capsule of 20 mg elemental zinc daily and those in the placebo treated group a capsule identical in appearance and taste with the active capsule but which contained inert substances. MAIN OUTCOME MEASURE--Various adverse outcomes were tested, including maternal bleeding, hypertension, complications of labour and delivery, gestational age, Apgar scores, and neonatal abnormalities. The main outcome measure was birth weight. RESULTS--There were no differences whatsoever between mothers given a zinc supplement and those given a placebo. CONCLUSION--Zinc supplementation in pregnancy in the United Kingdom does not seem to offer any benefits to the mother or her fetus.     

Blood pressure control by home monitoring: meta-analysis of randomised trials

Objective To determine the effect of home blood pressure monitoring on blood pressure levels and proportion of people with essential hypertension achieving targets.Design Meta-analysis of 18 randomised controlled trials.Participants 1359 people with essential hypertension allocated to home blood pressure monitoring and 1355 allocated to the “control” group seen in the healthcare system for 2-36 months.Main outcome measures Differences in systolic (13 studies), diastolic (16 studies), or mean (3 studies) blood pressures, and proportion of patients achieving targets (6 studies), between intervention and control groups.Results Systolic blood pressure was lower in people with hypertension who had home blood pressure monitoring than in those who had standard blood pressure monitoring in the healthcare system (standardised mean difference 4.2 (95% confidence interval 1.5 to 6.9) mm Hg), diastolic blood pressure was lower by 2.4 (1.2 to 3.5) mm Hg, and mean blood pressure was lower by 4.4 (2.0 to 6.8) mm Hg. The relative risk of blood pressure above predetermined targets was lower in people with home blood pressure monitoring (risk ratio 0.90, 0.80 to 1.00). When publication bias was allowed for, the differences were attenuated: 2.2 (-0.9 to 5.3) mm Hg for systolic blood pressure and 1.9 (0.6 to 3.2) mm Hg for diastolic blood pressure.Conclusions Blood pressure control in people with hypertension (assessed in the clinic) and the proportion achieving targets are increased when home blood pressure monitoring is used rather than standard blood pressure monitoring in the healthcare system. The reasons for this are not clear. The difference in blood pressure control between the two methods is small but likely to contribute to an important reduction in vascular complications in the hypertensive population.     

Effects of statins in patients with chronic kidney disease: meta-analysis and meta-regression of randomised controlled trials

Objective To analyse the benefits and harms of statins in patients with chronic kidney disease (pre-dialysis, dialysis, and transplant populations).Design Meta-analysis.Data sources Cochrane Central Register of Controlled Trials, Medline, Embase, and Renal Health Library (July 2006).Study selection Randomised and quasi-randomised controlled trials of statins compared with placebo or other statins in chronic kidney disease.Data extraction and analysis Two reviewers independently assessed trials for inclusion, extracted data, and assessed trial quality. Differences were resolved by consensus. Treatment effects were summarised as relative risks or weighted mean differences with 95% confidence intervals by using a random effects model.Results Fifty trials (30 144 patients) were included. Compared with placebo, statins significantly reduced total cholesterol (42 studies, 6390 patients; weighted mean difference −42.28 mg/dl (1.10 mmol/l), 95% confidence interval −47.25 to −37.32), low density lipoprotein cholesterol (39 studies, 6216 patients; −43.12 mg/dl (1.12 mmol/l), −47.85 to −38.40), and proteinuria (g/24 hours) (6 trials, 311 patients; −0.73 g/24 hour, −0.95 to −0.52) but did not improve glomerular filtration rate (11 studies, 548 patients; 1.48 ml/min (0.02 ml/s), −2.32 to 5.28). Fatal cardiovascular events (43 studies, 23 266 patients; relative risk 0.81, 0.73 to 0.90) and non-fatal cardiovascular events (8 studies, 22 863 patients; 0.78, 0.73 to 0.84) were reduced with statins, but statins had no significant effect on all cause mortality (44 studies, 23 665 patients; 0.92, 0.82 to 1.03). Meta-regression analysis showed that treatment effects did not vary significantly with stage of chronic kidney disease. The side effect profile of statins was similar to that of placebo. Most of the available studies were small and of suboptimal quality; mortality data were provided by a few large trials only.Conclusion Statins significantly reduce lipid concentrations and cardiovascular end points in patients with chronic kidney disease, irrespective of stage of disease, but no benefit on all cause mortality or the role of statins in primary prevention has been established. Reno-protective effects of statins are uncertain because of relatively sparse data and possible outcomes reporting bias.     

Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled,randomised controlled trials submitted to the MHRA's safety review

Objective To investigate whether selective serotonin reuptake inhibitor (SSRI) antidepressants are associated with an increased risk of suicide related outcomes in adults.Design Meta-analysis of randomised controlled trials of SSRIs compared with placebo in adults submitted by pharmaceutical companies to the safety review of the Medicines and Healthcare products Regulatory Agency (MHRA).Participants Over 40 000 individuals participating in 477 randomised controlled trials.Main outcome measures Suicide, non-fatal self harm, and suicidal thoughts.Results An estimated 16 suicides, 172 episodes of non-fatal self harm, and 177 episodes of suicidal thoughts were reported. We found no evidence that SSRIs increased the risk of suicide, but important protective or hazardous effects cannot be excluded (odds ratio 0.85, 95% credible interval 0.20 to 3.40). We found weak evidence of an increased risk of self harm (1.57, 0.99 to 2.55). Risk estimates for suicidal thoughts were compatible with a modest protective or adverse effect (0.77, 0.37 to 1.55). The relative frequency of reported self harm and suicidal thoughts in the trials compared with suicide indicates non-fatal end points were under-recorded.Conclusion Increased risks of suicide and self harm caused by SSRIs cannot be ruled out, but larger trials with longer follow up are required to assess the balance of risks and benefits fully. Any such risks should be balanced against the effectiveness of SSRIs in treating depression. When prescribing SSRIs, clinicians should warn patients of the possible risk of suicidal behaviour and monitor patients closely in the early stages of treatment.     

Quantitative systematic review of randomised controlled trials comparing antibiotic with placebo for acute cough in adults

Objectives: To assess whether antibiotic treatment for acute cough is effective and to measure the side effects of such treatment. Design: Quantitative systematic review of randomised placebo controlled trials. Data sources: Nine trials (8 published, 1 unpublished) retrieved from a systematic search (electronic databases, contact with authors, contact with drug manufacturers, reference lists); no restriction on language. Main outcome measures: Proportion of subjects with productive cough at follow up (7-11 days after consultation with general practitioner); proportion of subjects who had not improved clinically at follow up; proportion of subjects who reported side effects from taking antibiotic or placebo. Results: Eight trials contributed to the meta-analysis. Resolution of cough was not affected by antibiotic treatment (relative risk 0.85 (95% confidence interval 0.73 to 1.00)), neither was clinical improvement at re-examination (relative risk 0.62 (0.36 to 1.09)). The side effects of antibiotic were more common in the antibiotic group when compared to placebo (relative risk 1.51 (0.86 to 2.64)). Conclusions: Treatment with antibiotic does not affect the resolution of cough or alter the course of illness. The benefits of antibiotic treatment are marginal for most patients with acute cough and may be outweighed by the side effects of treatment.

Key messages

• Acute cough, with or without sputum, is a common reason for consulting a general practitioner
• Although antibiotic treatment is common for this condition, its likely benefits and side effects have not been measured
• This systematic review reports the outcome of nine randomised controlled trials that compared antibiotic with placebo in patients with acute cough
• Resolution of cough and clinical improvement at follow up was no different in the two groups
• The benefits of antibiotic treatment seem to be marginal for most patients with acute cough and may be outweighed by the side effects of treatment

     

Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled trials

Background

Significant pain from HIV-associated sensory neuropathy (HIV-SN) affects ∼40% of HIV infected individuals treated with antiretroviral therapy (ART). The prevalence of HIV-SN has increased despite the more widespread use of ART. With the global HIV prevalence estimated at 33 million, and with infected individuals gaining increased access to ART, painful HIV-SN represents a large and expanding world health problem. There is an urgent need to develop effective pain management strategies for this condition.

Method and Findings

Objective: To evaluate the clinical effectiveness of analgesics in treating painful HIV-SN. Design: Systematic review and meta-analysis. Data sources: Medline, Cochrane central register of controlled trials, www.clinicaltrials.gov, www.controlled-trials.com and the reference lists of retrieved articles. Selection criteria: Prospective, double-blinded, randomised controlled trials (RCTs) investigating the pharmacological treatment of painful HIV-SN with sufficient quality assessed using a modified Jadad scoring method. Review methods: Four authors assessed the eligibility of articles for inclusion. Agreement of inclusion was reached by consensus and arbitration. Two authors conducted data extraction and analysis. Dichotomous outcome measures (≥30% and ≥50% pain reduction) were sought from RCTs reporting interventions with statistically significant efficacies greater than placebo. These data were used to calculate RR and NNT values.

Results

Of 44 studies identified, 19 were RCTs. Of these, 14 fulfilled the inclusion criteria. Interventions demonstrating greater efficacy than placebo were smoked cannabis NNT 3.38 95%CI(1.38 to 4.10), topical capsaicin 8%, and recombinant human nerve growth factor (rhNGF). No superiority over placebo was reported in RCTs that examined amitriptyline (100mg/day), gabapentin (2.4g/day), pregabalin (1200mg/day), prosaptide (16mg/day), peptide-T (6mg/day), acetyl-L-carnitine (1g/day), mexilitine (600mg/day), lamotrigine (600mg/day) and topical capsaicin (0.075% q.d.s.).

Conclusions

Evidence of efficacy exists only for capsaicin 8%, smoked cannabis and rhNGF. However,rhNGF is clinically unavailable and smoked cannabis cannot be recommended as routine therapy. Evaluation of novel management strategies for painful HIV-SN is urgently needed.     

Efficacy of topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials

Objective To assess the efficacy of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of osteoarthritis.Data sources Medline, Embase, Scientific Citation Index, CINAHL, Cochrane Library, and abstracts from conferences.Review methods Inclusion criterion was randomised controlled trials comparing topical NSAIDs with placebo or oral NSAIDs in osteoarthritis. Effect size was calculated for pain, function, and stiffness. Rate ratio was calculated for dichotomous data such as clinical response rate and adverse event rate. Number needed to treat to obtain the clinical response was estimated. Quality of trial was assessed, and sensitivity analyses were undertaken.Results Topical NSAIDs were superior to placebo in relieving pain due to osteoarthritis only in the first two weeks of treatment. Effect sizes for weeks 1 and 2 were 0.41 (95% confidence interval, 0.16 to 0.66) and 0.40 (0.15 to 0.65), respectively. No benefit was observed over placebo in weeks 3 and 4. A similar pattern was observed for function, stiffness, and clinical response rate ratio and number needed to treat. Topical NSAIDs were inferior to oral NSAIDs in the first week of treatment and associated with more local side effects such as rash, itch, or burning (rate ratio 5.29, 1.14 to 24.51).Conclusion Randomised controlled trials of short duration only (less than four weeks) have assessed the efficacy of topical NSAIDs in osteoarthritis. After two weeks there was no evidence of efficacy superior to placebo. No trial data support the long term use of topical NSAIDs in osteoarthritis.     

Effect of preventive treatment for tuberculosis in adults infected with HIV: systematic review of randomised placebo controlled trials

Objective: To determine whether preventive treatment for tuberculosis in adults infected with HIV reduces the frequency of tuberculosis and overall mortality. Design: Systematic review and data synthesis of randomised placebo controlled trials. Main outcome measures: Active tuberculosis, mortality, and adverse drug reaction requiring cessation of the study regimen. Outcomes stratified by status of purified protein derivative skin test. Results: Four trials comprising 4055 adults from Haiti, Kenya, the United States, and Uganda were included. All compared isoniazid (6-12 months) with placebo, and one trial also compared multidrug treatment for 3 months with placebo. Mean follow up was 15-33 months. Overall, frequency of tuberculosis (relative risk 0.57, 95% confidence interval 0.41 to 0.79) was reduced in those receiving preventive treatment compared with placebo: mortality was not significantly reduced (0.93, 0.83 to 1.05). In subjects positive for purified protein derivative receiving preventive treatment, the risk of tuberculosis was reduced substantially (0.32, 0.19 to 0.51) and the risk of death was reduced moderately (0.73, 0.57 to 0.95) compared with those taking placebo. In adults negative for purified protein derivative receiving preventive treatment, the risk of tuberculosis (0.82, 0.50 to 1.36) and the risk of death (1.02, 0.89 to 1.17) were not reduced significantly. Adverse drug reactions were more frequent, but not significantly so, in patients receiving drug compared with placebo (1.45, 0.98 to 2.14). Conclusions: Preventive treatment given for 3-12 months protects against tuberculosis in adults infected with HIV, at least in the short to medium term. Protection is greatest in subjects positive for purified protein derivative, in whom death is also less frequent. Long term benefits remain to be shown.

Key messages

• One third of the world’s population is infected with Mycobacterium tuberculosis
• People infected with HIV are at much increased risk of developing active tuberculosis
• Short term preventive drug treatment given to people infected with HIV reduces the occurrence of active tuberculosis
• The benefit is greatest in people with latent infection, as shown by a positive skin test for tuberculosis, and this group also exhibits a survival benefit

     

Selenium supplementation decreases CRP and IL-6 and increases TNF-alpha: A systematic review and meta-analysis of randomized controlled trials

Inflammation is an initiating cause of infectious and non-infectious diseases. Studies have shown that selenium (Se) has anti-inflammatory effects. However, its’ effects on serum c-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) plasma concentrations are equivocal. Therefore, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs), evaluating the effects of per oral (PO) and intravenous (IV) Se supplementation on CRP, TNF-α, and IL-6. A systematic search was conducted using four databases, including PubMed, Google Scholar, Cochrane Library, and Scopus to find randomized clinical trials, published up to April 2023. From 19476 papers, after screening and removing duplicate articles, 24 studies were analyzed in the present meta-analysis. In the pooled analysis, PO Se administration showed no significant effect on CRP (WMD: 0.12; 95 % CI −0.11, 0.38; P-value= 0.30). However, IV Se supplementation had a significant negative association with CRP concentration (−2.24; 95 % CI: −4.24, −0.24; p-value: 0.02). Se administration had no significant association with TNF-α plasma concentration (9.64, 95 % CI: −0.59, 19.88, p-value= 0.06; and heterogeneity: 98 %). However, a significant positive association was present between Se and plasma TNF-α concentrations (0.15, 95 % CI: 0.14, 0.17, P-value<0.0001). Moreover, Se supplementation had a significant negative correlation with IL-6 plasma concentration in PO (−0.54; 95 % CI: −1.61, 0.52; P-value = 0.31) and IV administrations (−4.77; 95 % CI: −7.61, −1.93; P-value<0.0001), respectively. This study demonstrated that IV Se administration reduced CRP and IL-6 plasma concentrations. Conversely, IV Se supplementation increased TNF-α plasma concentration. It is evident that further, well-controlled clinical trials are required.     

Combined resynchronisation and implantable defibrillator therapy in left ventricular dysfunction: Bayesian network meta-analysis of randomised controlled trials

Objective To review the evidence base from randomised controlled trials of combined cardiac resynchronisation therapy and implantable cardioverter defibrillator therapy in left ventricular impairment and symptomatic heart failure.Design Bayesian network meta-analysis.Data sources Medline, Embase, and Cochrane databases up to June 2006.Review methods Two reviewers independently assessed trial eligibility and quality. Included trials compared cardiac resynchronisation therapy, implantable cardioverter defibrillator therapy, combined resynchronisation and implantable defibrillator therapy, and medical therapy alone, in patients with impaired left ventricular systolic function. Bayesian random effects network models were used to examine overall number of deaths.Results 12 studies including 1636 events in 8307 patients were identified. Combined cardiac resynchronisation and implantable cardioverter defibrillator therapy reduced the number of deaths by one third compared with medical therapy alone (odds ratio 0.57, 95% credible interval 0.40 to 0.80) but did not further improve survival when compared with implantable defibrillator therapy (0.82, 0.57 to 1.18) or resynchronisation (0.85, 0.60 to 1.22) therapy alone.Conclusion Evidence from randomised controlled trials is insufficient to show the superiority of combined cardiac resynchronisation and implantable cardioverter defibrillator therapy over cardiac resynchronisation therapy alone in patients with left ventricular impairment.     

Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence

Objective To examine the effectiveness of parenteral corticosteroids for the relief of acute severe migraine headache and prevention of recurrent headaches.Design Meta-analysis.Data sources Electronic databases (Cochrane Central Register of Controlled Trials, Medline, Embase, LILACS, and CINAHL), conference proceedings, clinical practice guidelines, contacts with industry, and correspondence with authors.Selection criteria Randomised controlled trials in which corticosteroids (alone or combined with standard abortive therapy) were compared with placebo or any other standard treatment for acute migraine in adults.Review methods Two reviewers independently assessed relevance, inclusion, and study quality. Weighted mean differences and relative risks were calculated and are reported with 95% confidence intervals.Results From 666 potentially relevant abstracts, seven studies met the inclusion criteria. All included trials used standard abortive therapy and subsequently compared single dose parenteral dexamethasone with placebo, examining pain relief and recurrence of headache within 72 hours. Dexamethasone and placebo provided similar acute pain reduction (weighted mean difference 0.37, 95% confidence interval −0.20 to 0.94). Dexamethasone was, however, more effective than placebo in reducing recurrence rates (relative risk 0.74, 95% confidence interval 0.60 to 0.90). Side effect profiles between dexamethasone and placebo groups were similar.Conclusion When added to standard abortive therapy for migraine headache, single dose parenteral dexamethasone is associated with a 26% relative reduction in headache recurrence (number needed to treat=9) within 72 hours.     

Effects of zinc supplementation on inflammatory biomarkers and oxidative stress in adults: A systematic review and meta-analysis of randomized controlled trials

Background & ObjectiveCurrent evidence is debatable regarding the feasible effects of zinc supplementation on the inflammation and oxidative stress status of adults. This systematic review and meta-analysis aimed to clarify this inconclusiveness.Materials and MethodsLiterature search was conducted via online databases such as PubMed, Scopus, ISI Web of Science, Cochrane Library, and Google Scholar until June 2020. The overall effect was presented as the weighted mean difference (WMD) at 95 % confidence interval (CI) in a random-effects meta-analysis model. Publication bias was also assessed using Egger’s and Begg’s statistics.ResultsIn total, 25 clinical trials (n = 1428) were reviewed, which indicated that zinc supplementation significantly affects the concentration of C- reactive protein (WMD: -0.03 mg/l; 95 % CI: -0.06, 0.0; P = 0.029), interlukin-6 (WMD: -3.81 pg/mL; 95 % CI: -6.87, -0.76; P = 0.014), malondialdehyde (WMD: -0.78 μmol/l; 95 % CI: -1.14, -0.42; P < 0.001), and total antioxidant capacity (WMD: 95.96 mmol/l; 95 % CI: 22.47, 169.44; P = 0.010). In addition, a significant between-study heterogeneity and a non-significant increment was reported in nitric oxide (WMD: 1.47 μmol/l; 95 % CI: -2.45, 5.40; P = 0.461) and glutathione (WMD: 34.84 μmol/l; 95 % CI: -5.12, 74.80; P = 0.087).ConclusionAccording to the results, zinc supplementation may have beneficial anti-inflammatory and anti-oxidative effects in adults.     

Effect of L-Carnosine in children with autism spectrum disorders: a systematic review and meta-analysis of randomised controlled trials

Autism spectrum disorders (ASD) are an emerging health problem worldwide. So far, no definite cure for ASD exists. L-Carnosine is an amino acid containing β-alanine and L-histidine which has been proposed to have neuroprotective, antioxidant and anti-convulsive properties that may benefit affected children with this disorder. This review aimed to assess the effect of L-Carnosine in the management of ASD in children. We systematically reviewed randomised controlled trials (RCTs) which documented the effect of L-Carnosine in children with ASD. A literature search was performed in PubMed, Cochrane Library, Google Scholar, ClinicalTrials.gov, Clinical Trial Registry-India databases from inception to December 20, 2020. Articles were selected based on pre-set inclusion/exclusion criteria. The primary outcomes were changes in social, communication and behavioural responses and the secondary outcomes were improvement in sleep disorders, gastrointestinal problems, oxidative stress markers and adverse effects. Jadad scale was used to assess the quality of RCTs and modified Cochrane risk of bias tool was used to check the risk of bias of the included studies. The meta-analysis was reported based on the fixed-effects model. Four double-blinded, placebo-controlled, RCTs and one open label trial with a total of 215 participants were selected for the review. All the trials were methodological of high quality according to the Jadad scale. The modified Cochrane risk of bias tool showed a low to high risk of bias. Results from the meta-analysis of three studies showed no significant difference between L-Carnosine and placebo groups in the Gilliam autism rating scale (GARS) (MD = − 2.57; 95% CI − 10.30, 5.16, p = 0.52) and in its socialisation (MD = − 1.51; 95% CI − 6.16, 3.14, p = 0.53), behaviour (MD = − 0.48; 95% CI − 4.82, 3.87, p = 0.83) and communication (MD = − 3.94; 95% CI − 10.00, 2.11, p = 0.20) subscales as well as the childhood autism rating scale (CARS) (MD = − 0.88; 95% CI − 6.96, 5.20; p = 0.78). Current data do not support the use of L-Carnosine in the management of children with ASD due to a low number of studies and sample size available. Further studies are warranted to know the effect of L-Carnosine for ASD management.