International Clinical Trials Registry Platform Research Articles

Psychological and social interventions for the promotion of mental health in people living in low- and middle-income countries affected by humanitarian crises.

Because of wars, conflicts, persecutions, human rights violations, and humanitarian crises, about 84 million people are forcibly displaced around the world; the great majority of them live in low- and middle-income countries (LMICs). People living in humanitarian settings are affected by a constellation of stressors that threaten their mental health. Psychosocial interventions for people affected by humanitarian crises may be helpful to promote positive aspects of mental health, such as mental well-being, psychosocial functioning, coping, and quality of life. Previous reviews have focused on treatment and mixed promotion and prevention interventions. In this review, we focused on promotion of positive aspects of mental health. To assess the effects of psychosocial interventions aimed at promoting mental health versus control conditions (no intervention, intervention as usual, or waiting list) in people living in LMICs affected by humanitarian crises. We searched CENTRAL, MEDLINE, Embase, and seven other databases to January 2023. We also searched the World Health Organization's (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov to identify unpublished or ongoing studies, and checked the reference lists of relevant studies and reviews. Randomised controlled trials (RCTs) comparing psychosocial interventions versus control conditions (no intervention, intervention as usual, or waiting list) to promote positive aspects of mental health in adults and children living in LMICs affected by humanitarian crises. We excluded studies that enrolled participants based on a positive diagnosis of mental disorder (or based on a proxy of scoring above a cut-off score on a screening measure). We used standard Cochrane methods. Our primary outcomes were mental well-being, functioning, quality of life, resilience, coping, hope, and prosocial behaviour. The secondary outcome was acceptability, defined as the number of participants who dropped out of the trial for any reason. We used GRADE to assess the certainty of evidence for the outcomes of mental well-being, functioning, and prosocial behaviour. We included 13 RCTs with 7917 participants. Nine RCTs were conducted on children/adolescents, and four on adults. All included interventions were delivered to groups of participants, mainly by paraprofessionals. Paraprofessional is defined as an individual who is not a mental or behavioural health service professional, but works at the first stage of contact with people who are seeking mental health care. Four RCTs were carried out in Lebanon; two in India; and single RCTs in the Democratic Republic of the Congo, Jordan, Haiti, Bosnia and Herzegovina, the occupied Palestinian Territories (oPT), Nepal, and Tanzania. The mean study duration was 18 weeks (minimum 10, maximum 32 weeks). Trials were generally funded by grants from academic institutions or non-governmental organisations. For children and adolescents, there was no clear difference between psychosocial interventions and control conditions in improving mental well-being and prosocial behaviour at study endpoint (mental well-being: standardised mean difference (SMD) 0.06, 95% confidence interval (CI) -0.17 to 0.29; 3 RCTs, 3378 participants; very low-certainty evidence; prosocial behaviour: SMD -0.25, 95% CI -0.60 to 0.10; 5 RCTs, 1633 participants; low-certainty evidence), or at medium-term follow-up (mental well-being: mean difference (MD) -0.70, 95% CI -2.39 to 0.99; 1 RCT, 258 participants; prosocial behaviour: SMD -0.48, 95% CI -1.80 to 0.83; 2 RCT, 483 participants; both very low-certainty evidence). Interventions may improve functioning (MD -2.18, 95% CI -3.86 to -0.50; 1 RCT, 183 participants), with sustained effects at follow-up (MD -3.33, 95% CI -5.03 to -1.63; 1 RCT, 183 participants), but evidence is very uncertain as the data came from one RCT (both very low-certainty evidence). Psychosocial interventions may improve mental well-being slightly in adults at study endpoint (SMD -0.29, 95% CI -0.44 to -0.14; 3 RCTs, 674 participants; low-certainty evidence), but they may have little to no effect at follow-up, as the evidence is uncertain and future RCTs might either confirm or disprove this finding. No RCTs measured the outcomes of functioning and prosocial behaviour in adults. To date, there is scant and inconclusive randomised evidence on the potential benefits of psychological and social interventions to promote mental health in people living in LMICs affected by humanitarian crises. Confidence in the findings is hampered by the scarcity of studies included in the review, the small number of participants analysed, the risk of bias in the studies, and the substantial level of heterogeneity. Evidence on the efficacy of interventions on positive mental health outcomes is too scant to determine firm practice and policy implications. This review has identified a large gap between what is known and what still needs to be addressed in the research area of mental health promotion in humanitarian settings.

Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients.

The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis to prevent the clinical syndrome associated with CMV infection. This is an update of a review first published in 2005 and updated in 2008 and 2013. To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause death in solid organ transplant recipients. We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 5 February 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. We included randomised controlled trials (RCTs) and quasi-RCTs comparing antiviral medications with placebo or no treatment, comparing different antiviral medications or different regimens of the same antiviral medications for CMV prophylaxis in recipients of any solid organ transplant. Studies examining pre-emptive therapy for CMV infection are studied in a separate review and were excluded from this review. Two authors independently assessed study eligibility, risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. This 2024 update found four new studies, bringing the total number of included studies to 41 (5054 participants). The risk of bias was high or unclear across most studies, with a low risk of bias for sequence generation (12), allocation concealment (12), blinding (11) and selective outcome reporting (9) in fewer studies. There is high-certainty evidence that prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment is more effective in preventing CMV disease (19 studies: RR 0.42, 95% CI 0.34 to 0.52), all-cause death (17 studies: RR 0.63, 95% CI 0.43 to 0.92), and CMV infection (17 studies: RR 0.61, 95% CI 0.48 to 0.77). There is moderate-certainty evidence that prophylaxis probably reduces death from CMV disease (7 studies: RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduces the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but probably makes little to no difference to fungal infection, acute rejection or graft loss. No apparent differences in adverse events with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment were found. There is high certainty evidence that ganciclovir, when compared with aciclovir, is more effective in preventing CMV disease (7 studies: RR 0.37, 95% CI 0.23 to 0.60). There may be little to no difference in any outcome between valganciclovir and IV ganciclovir compared with oral ganciclovir (low certainty evidence). The efficacy and adverse effects of valganciclovir or ganciclovir were probably no different to valaciclovir in three studies (moderate certainty evidence). There is moderate certainty evidence that extended duration prophylaxis probably reduces the risk of CMV disease compared with three months of therapy (2 studies: RR 0.20, 95% CI 0.12 to 0.35), with probably little to no difference in rates of adverse events. Low certainty evidence suggests that 450 mg/day valganciclovir compared with 900 mg/day valganciclovir results in little to no difference in all-cause death, CMV infection, acute rejection, and graft loss (no information on adverse events). Maribavir may increase CMV infection compared with ganciclovir (1 study: RR 1.34, 95% CI: 1.10 to 1.65; moderate certainty evidence); however, little to no difference between the two treatments were found for CMV disease, all-cause death, acute rejection, and adverse events at six months (low certainty evidence). Prophylaxis with antiviral medications reduces CMV disease and CMV-associated death, compared with placebo or no treatment, in solid organ transplant recipients. These data support the continued routine use of antiviral prophylaxis in CMV-positive recipients and CMV-negative recipients of CMV-positive organ transplants.

Associations of dietary patterns with objective and subjective sleep duration and sleep quality in a population-based cohort study

ObjectiveTo examine cross-sectional and longitudinal associations of various types of dietary patterns with self-reported sleep quality and with actigraphy-estimated sleep parameters in the prospective, population-based Rotterdam Study. MethodsFor each participant, scores for five different dietary patterns were derived based on food frequency questionnaires; two pre-defined scores developed to estimate adherence to the Dutch dietary guidelines and to the Mediterranean diet; and three data-driven scores indicating a prudent, unhealthy and typical Dutch diet. In 2,589 participants (median age 56.9 years; 58% female), self-rated sleep quality was assessed with the Pittsburgh Sleep Quality Index. In 533 participants, actigraphs were worn for an average of 6.8 days (SD: 0.7) to estimate total sleep time, sleep onset latency, wake after sleep onset, and sleep efficiency. Sleep parameters were measured at baseline and 3-6 years later. Multiple linear regression was used to assess cross-sectional and longitudinal associations. ResultsNo statistically significant associations between dietary patterns and total sleep time, sleep onset latency, wake after sleep onset, sleep efficiency and subjective sleep quality were observed in cross-sectional or longitudinal analyses. To illustrate, the effect estimate for sleep duration was 2.7 minutes per night (95% CI -2.1, 7.5) per 5 point increase in Mediterranean diet score in the cross-sectional analyses. Furthermore, in longitudinal analyses, the effect estimate for sleep duration was -1.0 minutes per night (95% CI -5.2, 3.1) per SD increase in the prudent diet. ConclusionsOur results suggest that dietary patterns are not associated with sleep in this population-based cohort study. Trial registrationNetherlands National Trial Register and WHO International Clinical Trials Registry Platform (ICTRP; https://apps.who.int/trialsearch/. Klik of tik als u deze koppeling vertrouwt.">https://apps.who.int/trialsearch/) shared catalogue number NL6645 / NTR6831. Registered November 13th, 2017

Effectiveness of intrathecal dexmedetomidine vs fentanyl as additives to hyperbaric bupivacaine for postoperative analgesia in women undergoing cesarean section: a systematic review protocol.

The aim of this review is to compare the effectiveness of intrathecal dexmedetomidine vs fentanyl as additives to hyperbaric bupivacaine in providing postoperative analgesia in patients undergoing cesarean section. Pain following cesarean section remains a challenge, with limited treatment options due to potential undesirable parturient and neonatal side effects. Intrathecal dexmedetomidine has emerged as a favorable alternative to opioid additives to hyperbaric bupivacaine in prolonging postoperative analgesia, but its effectiveness requires further investigation. The review will evaluate studies of patients who underwent cesarean section under spinal anesthesia where dexmedetomidine and fentanyl were compared as intrathecal additives to hyperbaric bupivacaine for postoperative analgesia. This review will consider randomized controlled trials, non-randomized controlled trials, and prospective cohort studies for inclusion. No limits regarding publication date or language will be applied. A preliminary search of PubMed and Cochrane Central Register of Controlled Trials has been conducted to identify relevant index terms and keywords, which will be applied in a second search across PubMed, Cochrane CENTRAL, Scopus, and Embase. Google Scholar, National Library of Medicine (Clinicaltrials.gov), and the World Health Organization International Clinical Trial Registry Platform will be searched to identify unpublished literature. Full-text studies will be subjected to an assessment of methodological quality, and data extraction will be performed independently by 2 reviewers. The results will be presented in both tabular and narrative format and, where possible, pooled into a meta-analysis. A Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Summary of Findings will be created to grade the certainty of evidence of the reported outcomes. PROSPERO CRD42022364815.

A systematic review and meta-analysis of the impacts of germline pharmacogenomics on severe toxicity and symptom burden in adult patients with cancer.

The clinical application of Pharmacogenomics (PGx) has improved patient safety. However, comprehensive PGx testing has not been widely adopted in clinical practice, and significant opportunities exist to further optimize PGx in cancer care. This systematic review and meta-analysis aim to evaluate the safety outcomes of reported PGx-guided strategies (Analysis 1) and identify well-studied emerging pharmacogenomic variants that predict severe toxicity and symptom burden (Analysis 2) in patients with cancer. We searched MEDLINE, EMBASE, CENTRAL, clinicaltrials.gov, and International Clinical Trials Registry Platform from inception to January 2023 for clinical trials or comparative studies evaluating PGx strategies or unconfirmed pharmacogenomic variants. The primary outcomes were severe adverse events (SAE; ≥ grade 3) or symptom burden with pain and vomiting as defined by trial protocols and assessed by trial investigators. We calculated pooled overall relative risk (RR) and 95% confidence interval (95%CI) using random effects models. PROSPERO, registration number CRD42023421277. Of 6811 records screened, six studies were included for Analysis 1, 55 studies for Analysis 2. Meta-analysis 1 (five trials, 1892 participants) showed a lower absolute incidence of SAEs with PGx-guided strategies compared to usual therapy, 16.1% versus 34.0% (RR = 0.72, 95%CI 0.57-0.91, p = 0.006, I2 = 34%). Meta-analyses 2 identified nine medicine(class)-variant pairs of interest across the TYMS, ABCB1, UGT1A1, HLA-DRB1, and OPRM1 genes. Application of PGx significantly reduced rates of SAEs in patients with cancer. Emergent medicine-variant pairs herald further research into the expansion and optimization of PGx to improve systemic anti-cancer and supportive care medicine safety and efficacy.

Growth and body composition of infants born moderate-to-late preterm fed a protein- and mineral-enriched postdischarge formula compared with a standard term formula ≤6 months corrected age, a randomized controlled trial

BackgroundInfants born moderate-to-late preterm (i.e., 32 wk–35 wk 6 d gestation) are, analogous to those born very preterm, at risk of later obesity, hypertension, and diabetes. Appropriate early life nutrition is key for ensuring optimal growth and body composition, thereby mitigating potential cardiometabolic risks. ObjectivesWe aimed to compare growth and body composition between infants born moderate-to-late preterm fed isocaloric but protein- and mineral-enriched postdischarge formula (PDF) or standard term formula (STF) until 6 mo corrected age (CA; i.e., after term equivalent age [TEA]). MethodsAfter enrollment (≤7 d postpartum), infants received PDF if (fortified) mother’s own milk (MOM) was insufficient. At TEA, those receiving >25% of intake as formula were randomized to either continue the same PDF (n = 47) or switch to STF (n = 50); those receiving ≥75% of intake as MOM (n = 60) served as references. At TEA and 6 mo CA, we assessed anthropometry and body composition using both dual-energy x-ray absorptiometry (DXA) and air displacement plethysmography (ADP). ResultsFeeding groups had similar gestational age (median [25th percentile;75th percentile]: 34.3 [33.5; 35.1] wk), birthweight (mean ± standard deviation [SD]: 2175 ± 412 g), anthropometry, and body composition at TEA. At 6 mo CA, infants fed PDF had slightly, but significantly, greater length (67.6 ± 2.5 and 66.9 ± 2.6 cm, P < 0.05) and larger head circumference (43.9 ± 1.3 and 43.4 ± 1.5 cm, P < 0.05) compared to infants fed STF. Also, infants fed PDF had higher lean mass (LM) and bone mineral content estimated by DXA (4772 ± 675 and 4502 ± 741 g; 140 ± 20 and 131 ± 23 g, respectively; P < 0.05). ADP estimates, however, were not statistically different between feeding groups. ConclusionsInfants born moderate-to-late preterm demonstrated modest increases in length, head circumference, LM, and bone mineral content when fed PDF compared to STF for 6 mo after TEA.This trial was registered at the International Clinical Trial Registry Platform as NTR5117 and NTR NL4979.

Effectiveness of combining prevention psychological interventions with interventions that address the social determinants of mental health in low and middle-income countries: protocol of a systematic review and meta-analysis

IntroductionCommon mental health conditions (CMHCs), including depression, anxiety and post-traumatic stress disorder (PTSD), are highly prevalent in low and middle-income countries (LMICs). Preventive strategies combining psychological interventions with interventions addressing...

Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis

ObjectiveTo determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs.DesignSystematic review and meta-analysis.Data sourcesFive electronic databases of published literature (Cochrane Central Register of Controlled Trials,...

Current Evidence in the Management of Central Skull Base Osteomyelitis: A Systematic Review

Objectives Based on current evidence, this systematic review focuses on various gray areas related to these patients' diagnosis, management, and follow-up in central skull base osteomyelitis (CSBO). Study Design A systematic review of all case reports and observational studies. Methods We systematically searched PubMed, Scopus database, Cochrane database, U.K. clinicaltrails.gov registry, and World Health Organization International Clinical Trials Registry Platform and included all reports as per our inclusion criteria. Data was analyzed systematically, and we made essential observations. Results Out of 179 articles, 25 were selected according to inclusion criteria and quality assessment. Among the 44 patients, refractory headache (95%) was the most common presentation, followed by cranial nerve paralysis (82%) and Pseudomonas (32%) as the most common bacteria. Contrary to the available literature the disease cure was worse in those who underwent targeted biopsy (64% vs. 36%, p = 0.023) and surgical debridement (61% vs. 39%, p = 0.013) in the late stages of the disease. Conclusion Otogenic osteomyelitis can spread to central skull bones in the absence of obvious ear symptoms. Early diagnosis and intervention of CSBO before progression to late stages can help decrease significant morbidity and mortality.

Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease.

Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease.

A scoping review to investigate recruitment and retention of people with dementia in clinical trials

Abstract Introduction The literature acknowledges difficulties in recruiting people with dementia (PwD) to research studies. Despite efforts of researchers and policymakers to improve participant recruitment and retention in clinical studies,[1] challenges remain.[2] Further work is needed to describe recruitment and retention of PwD in clinical studies and strategies used to promote these activities. Aim This scoping review aimed to investigate recruitment and retention of PwD in clinical trials focused on evaluating the pharmacological management of cognitive symptoms of dementia. Methods Five electronic databases (Medline, Embase, PsychINFO, Scopus, Web of Science) and the International Clinical Trials Registry Platform were searched using a variety of search terms to identify articles published in English from date of inception until July 2023. All registered, unregistered, published, and unpublished randomised controlled trials that evaluated pharmacological treatments for cognitive symptom management among PwD, with a mean age ≥65 years and dementia of any sub-type or stage were included; studies were not excluded based on setting. Two reviewers independently reviewed full texts of potentially eligible records. Data were extracted by one reviewer using a table constructed in Microsoft Excel; a 10% subset was checked by a second reviewer. Findings were summarised using frequencies and percentages and/or narratively presented in tables. Results In total, 3,253 records were found, with 2,953 records remaining after removal of duplicates. Following title/abstract screening, 229 full-text articles were assessed for eligibility. A total of 129 records met the inclusion criteria for this review. Fifty-eight studies (45.0%) recruited community dwelling PwD. Common reasons for participants to be excluded from trials were having no carer present (n=128 studies, 99.2%), using specific medications such as anticholinergic medications (n=28 studies, 21.7%), and being unable to swallow tablets without crushing (n=10 studies, 7.7%). A limited number of studies (n=45, 34.9%) provided details about how they recruited participants. A variety of different recruitment sites were used including clinical research facilities (n=16, 12.4%), memory clinics (n=17, 13.2%), general practices (n=2, 1.6%), nursing homes (n=2, 1.6%), hospitals (n=2, 1.6%). Few studies recruited through advertisements in local newspapers/radio stations (n=2, 1.6%). Only one study reported that PwD and their carers were supported by research/clinical staff throughout the trial to improve participant retention. The mean sample size was 439 participants, and the mean retention rate was 73.5%. On average, 99 participants per study withdrew from the clinical trials, with common reasons for withdrawal being adverse events (n=45 participants per study), carer no longer available (n=37 participants per study), and death (n=12 participants per study). Conclusion This study has provided important evidence on recruitment and retention of PwD in clinical studies. The findings highlight how poorly recruitment is described in the literature and it is unclear what strategies were used to promote recruitment and retention. Researchers working in this field should consider this when disseminating their work. Whilst a quality assessment of included studies was not undertaken, this is acceptable in scoping reviews. Future research should focus on enhancing transparency of reporting recruitment and retention of PwD in clinical research.

Care home staff interventions to optimise pain assessment and management in people with advanced dementia in long-term care settings: a systematic review

Abstract Introduction As a person’s dementia symptoms worsen, they become increasingly frail and dependent on others for support,[1] which often necessitates moving into long-term care (LTC). Pain is often poorly recognised and undertreated in people with advanced dementia.[2] Aim To identify and evaluate the effectiveness of care home staff interventions involving pain assessment and management in people with advanced dementia in LTC settings. Methods This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022355487). Nine databases (Medline, Scopus, The Cochrane Library, EMBASE, Web of Science, International Pharmaceutical Abstracts, PsycINFO, CINAHL, World Health Organisation International Clinical Trials Registry Platform) were searched. The search strategy was developed in Medline and adapted as appropriate for the other databases; it comprised the following search terms: ‘dementia’, ‘Alzheimer’s disease’, ‘pain assessment’, ‘pain management’, ‘pain intervention’, ‘care home’, and ‘nursing home’. The selection of studies was limited to randomised controlled trials (RCTs) in which ≥50% of participants had advanced (moderate-severe) dementia and published in English. Electronic databases were searched from date of inception to May 2023. Two reviewers independently assessed potentially relevant articles for inclusion, completed data extraction and assessed risk of bias using the Cochrane Risk of Bias (RoB) 2.0 tool. A third reviewer was consulted when consensus could not be reached. A narrative analysis was undertaken due to the heterogeneity of outcome measures. Results In total, 3504 articles were identified, with 998 records remaining after duplicate removal. This left 2456 studies for title/abstract screening, and 22 full-text studies were assessed for eligibility; five studies met the inclusion criteria. A total of 1363 participants (mean age 83-88 years) and 123 care homes were included in the studies. The studies reported that these interventions were shown to be effective compared to control groups: the Pain recognition and Treatment (PRT) protocol in China, regular use of the PACSLAC pain assessment tool in Canada, the use of a Comprehensive Observational Pain Management Protocol in Hong Kong, the COSMOS intervention in Norway, and the STA OP stepwise multidisciplinary intervention in the Netherlands. Primary outcomes concerning pain scores measured by PACSLAC (n=2 studies), PAINAD (n=2 studies), and MOBID-2 (n=1 study) showed a statistically significant decrease. Secondary outcomes measured included several clinical outcomes associated with pain, depression, presence of neuropsychiatric symptoms and nursing staff stress. Four of the included studies were judged to be at ‘some concerns of bias’ according to RoB 2.0, due to unclear information in two or more domains (randomisation process, deviations from intended interventions, and measurement of the outcomes); one study was judged as having a ‘low risk of bias’. Conclusion The use of pain assessment tools decreased pain scores in people with advanced dementia in LTC. A limitation of this review is the exclusion of non-English language studies. Further, the clinical and methodological heterogeneity of included studies made a quantitative comparison difficult, thus, the findings are based on narrative analysis.

Psychosocial and medication interventions to stop or reduce alcohol consumption during pregnancy.

Despite the known harms, alcohol consumption is common in pregnancy. Rates vary between countries, and are estimated to be 10% globally, with up to 25% in Europe. To assess the efficacy of psychosocial interventions and medications to reduce or stop alcohol consumption during pregnancy. We searched the Cochrane Drugs and Alcohol Group Specialised Register (via CRSLive), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, Web of Science, and PsycINFO, from inception to 8 January 2024. We also searched for ongoing and unpublished studies via ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). All searches included non-English language literature. We handsearched references of topic-related systematic reviews and included studies. We included randomised controlled trials that compared medications or psychosocial interventions, or both, to placebo, no intervention, usual care, or other medications or psychosocial interventions used to reduce or stop alcohol use during pregnancy. Our primary outcomes of interest were abstinence from alcohol, reduction in alcohol consumption, retention in treatment, and women with any adverse event. We used standard Cochrane methodological procedures. We included eight studies (1369 participants) in which pregnant women received an intervention to stop or reduce alcohol use during pregnancy. In one study, almost half of participants had a current diagnosis of alcohol use disorder (AUD); in another study, 40% of participants had a lifetime diagnosis of AUD. Six studies took place in the USA, one in Spain, and one in the Netherlands. All included studies evaluated the efficacy of psychosocial interventions; we did not find any study that evaluated the efficacy of medications for the treatment of AUD during pregnancy. Psychosocial interventions were mainly brief interventions ranging from a single session of 10 to 60 minutes to five sessions of 10 minutes each. Pregnant women received the psychosocial intervention approximately at the end of the first trimester of pregnancy, and the outcome of alcohol use was reassessed 8 to 24 weeks after the psychosocial intervention. Women in the control group received treatment as usual (TAU) or similar treatments such as comprehensive assessment of alcohol use and advice to stop drinking during pregnancy. Globally, we found that, compared to TAU, psychosocial interventions may increase the rate of continuously abstinent participants (risk ratio (RR) 1.34, 95% confidence interval (CI) 1.14 to 1.57; I2 =0%; 3 studies; 378 women; low certainty evidence). Psychosocial interventions may have little to no effect on the number of drinks per day, but the evidence is very uncertain (mean difference -0.42, 95% CI -1.13 to 0.28; I2 = 86%; 2 studies; 157 women; very low certainty evidence). Psychosocial interventions probably have little to no effect on the number of women who completed treatment (RR 0.98, 95% CI 0.94 to 1.02; I2 = 0%; 7 studies; 1283 women; moderate certainty evidence). None of the included studies assessed adverse events of treatments. We downgraded the certainty of the evidence due to risk of bias and imprecision of the estimates. Brief psychosocial interventions may increase the rate of continuous abstinence among pregnant women who report alcohol use during pregnancy. Further studies should be conducted to investigate the efficacy and safety of psychosocial interventions and other treatments (e.g. medications) for women with AUD. These studies should provide detailed information on alcohol use before and during pregnancy using consistent measures such as the number of drinks per drinking day. When heterogeneous populations are recruited, more detailed information on alcohol use during pregnancy should be provided to allow future systematic reviews to be conducted. Other important information that would enhance the usefulness of these studies would be the presence of other comorbid conditions such as anxiety, mood disorders, and the use of other psychoactive substances.

Appendectomy versus antibiotic treatment for acute appendicitis.

Acute appendicitis is one of the most common emergency general surgical conditions worldwide. Uncomplicated/simple appendicitis can be treated with appendectomy or antibiotics. Some studies have suggested possible benefits with antibiotics with reduced complications, length of hospital stay, and the number of days off work. However, surgery may improve success of treatment as antibiotic treatment is associated with recurrence and future need for surgery. To assess the effects of antibiotic treatment for uncomplicated/simple acute appendicitis compared with appendectomy for resolution of symptoms and complications. We searched CENTRAL, MEDLINE, Embase, and two trial registers (World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov) on 19 July 2022. We also searched for unpublished studies in conference proceedings together with reference checking and citation search. There were no restrictions on date, publication status, or language of publication. We included parallel-group randomised controlled trials (RCTs) only. We included studies where most participants were adults with uncomplicated/simple appendicitis. Interventions included antibiotics (by any route) compared with appendectomy (open or laparoscopic). We used standard methodology expected by Cochrane. We used GRADE to assess the certainty of evidence for each outcome. Primary outcomes included mortality and success of treatment, and secondary outcomes included number of participants requiring appendectomy in the antibiotic group, complications, pain, length of hospital stay, sick leave, malignancy in the antibiotic group, negative appendectomy rate, and quality of life. Success of treatment definitions were heterogeneous although mainly based on resolution of symptoms rather than incorporation of long-term recurrence or need for surgery in the antibiotic group. We included 13 studies in the review covering 1675 participants randomised to antibiotics and 1683 participants randomised to appendectomy. One study was unpublished. All were conducted in secondary care and two studies received pharmaceutical funding. All studies used broad-spectrum antibiotic regimens expected to cover gastrointestinal bacteria. Most studies used predominantly laparoscopic surgery, but some included mainly open procedures. Six studies included adults and children. Almost all studies aimed to exclude participants with complicated appendicitis prior to randomisation, although one study included 12% with perforation. The diagnostic technique was clinical assessment and imaging in most studies. Only one study limited inclusion by sex (male only). Follow-up ranged from hospital admission only to seven years. Certainty of evidence was mainly affected by risk of bias (due to lack of blinding and loss to follow-up) and imprecision. Primary outcomes It is uncertain whether there was any difference in mortality due to the very low-certainty evidence (Peto odds ratio (OR) 0.51, 95% confidence interval (CI) 0.05 to 4.95; 1 study, 492 participants). There may be 76 more people per 1000 having unsuccessful treatment in the antibiotic group compared with surgery, which did not reach our predefined level for clinical significance (risk ratio (RR) 0.91, 95% CI 0.87 to 0.96; I2 = 69%; 7 studies, 2471 participants; low-certainty evidence). Secondary outcomes At one year, 30.7% (95% CI 24.0 to 37.8; I2 = 80%; 9 studies, 1396 participants) of participants in the antibiotic group required appendectomy or, alternatively, more than two-thirds of antibiotic-treated participants avoided surgery in the first year, but the evidence is very uncertain. Regarding complications, it is uncertain whether there is any difference in episodes of Clostridium difficile diarrhoea due to very low-certainty evidence (Peto OR 0.97, 95% CI 0.24 to 3.89; 1 study, 1332 participants). There may be a clinically significant reduction in wound infections with antibiotics (RR 0.25, 95% CI 0.09 to 0.68; I2 = 16%; 9 studies, 2606 participants; low-certainty evidence). It is uncertain whether antibiotics affect the incidence of intra-abdominal abscess or collection (RR 1.58, 95% CI 0.61 to 4.07; I2 = 19%; 6 studies, 1831 participants), or reoperation (Peto OR 0.13, 95% CI 0.01 to 2.16; 1 study, 492 participants) due to very low-certainty evidence, mainly due to rare events causing imprecision and risk of bias. It is uncertain if antibiotics prolonged length of hospital stay by half a day due to the very low-certainty evidence (MD 0.54, 95% CI 0.06 to 1.01; I2 = 97%; 11 studies, 3192 participants). The incidence of malignancy was 0.3% (95% CI 0 to 1.5; 5 studies, 403 participants) in the antibiotic group although follow-up was variable. Antibiotics probably increased the number of negative appendectomies at surgery (RR 3.16, 95% CI 1.54 to 6.49; I2 = 17%; 5 studies, 707 participants; moderate-certainty evidence). Antibiotics may be associated with higher rates of unsuccessful treatment for 76 per 1000 people, although differences may not be clinically significant. It is uncertain if antibiotics increase length of hospital stay by half a day. Antibiotics may reduce wound infections. A third of the participants initially treated with antibiotics required subsequent appendectomy or two-thirds avoided surgery within one year, but the evidence is very uncertain. There were too few data from the included studies to comment on major complications.

Effects of dual-task resistance exercise on cognition, mood, depression, functional fitness, and activities of daily living in older adults with cognitive impairment: a single-blinded, randomized controlled trial

BackgroundRegular exercise is emphasized for the improvement of functional capacity and independence of older adults. This study aimed to compare the effects of a dual-task resistance exercise program and resistance exercise on cognition, mood, depression, physical function, and activities of daily living (ADL) in older adults with cognitive impairment.MethodsA total of 44 older adults participated in the study. Participants were randomly allocated to an experimental group (n = 22) performing a dual-task resistance exercise program for cognitive function improvement and a control group (n = 22) performing a resistance exercise program. Both groups performed the exercise for 40 min per session, three times a week, for 6 weeks (18 sessions). Cognition, mood, depression, functional fitness, and ADL were quantified before and after the intervention using the Mini-Mental State Examination (MMSE), profile of mood states (POMS), geriatric depression scale (GDS), senior fitness test (SFT), and Korean version of ADL, respectively.ResultsThere was a significant time and group interaction on the MMSE (p = 0.044). There were no significant time and group interactions in the POMS, GDS, SFT, or ADL. Cognitive function (p < 0.001), mood (p < 0.001), depression (p < 0.001), functional fitness (p < 0.001), and ADL (p < 0.001) significantly improved after dual-task resistance exercise, and cognitive function (p < 0.001), mood (p < 0.001), depression (p < 0.001), functional fitness (p < 0.001), and ADL (p < 0.001) significantly improved after resistance exercise.ConclusionsDual-task resistance exercise is more effective than resistance exercise in improving cognitive function in older adults with cognitive impairment. Both dual-task resistance exercise and resistance exercise improves mood, depression, functional fitness, and ADL after the intervention. We propose using dual-task resistance exercises for cognitive and physical health management in the older adults with cognitive impairment.Trial registrationThis study was registered with the Clinical Research Information Service (WHO International Clinical Trials Registry Platform) (Registration ID, KCT0005389; Registration date, 09/09/2020).

Exploring the cessation efficacy and harm reduction potential of heated tobacco and nicotine pouch products in smokers and smokeless tobacco users: study protocol of a 6-month randomized controlled switching trial

Background: Despite decades of research on pharmacological and behavioural smoking cessation treatments, current quit aids are of limited success. The introduction of new, combustion-free nicotine and tobacco products extended the tool kit for people who smoke to switch away from their risky habit. We performed a systematic review including 120 studies resulting in several recommendations for a robust study design to determine the cessation efficacy of a new nicotine or tobacco product. Consequently, we prepared this study protocol to assess the cessation efficacy of heated tobacco products (HTPs) and nicotine pouches (NPs). Methods: 250 subjects (125 exclusive smokers and 125 exclusive smokeless tobacco (SLT) users) will be recruited and offered a choice of HTPs in case of smokers and a choice of NPs in case of SLT users in order to switch. Subjects will undergo four visits (baseline, 1, 3, and 6 months) to collect biospecimens and for physical examinations. Use behaviour and questionnaires will be monitored on a regular basis by means of a smartphone-app. We describe a sensitive and specific compliance monitoring using suitable biomarkers of exposure. The sample size of 250 subjects and duration of 6 months will allow the quit rates to be assessed with sufficient statistical power. Finally, the choice between different products shall reflect the individuals’ preferences. Conclusions: This protocol can be applied generically, providing a robust determination of a products’ cessation efficacy. Trial Registration: The trial will be registered in the International Clinical Trials Registry Platform.

Palliative procedures for malignant gastric outlet obstruction: A network meta-analysis.

The optimal treatment for malignant gastric outlet obstruction (GOO) remains uncertain. The aim of this systematic review was to comprehensively investigate the efficacy and safety of four palliative treatments for malignant GOO: gastrojejunostomy (GJ), endoscopic ultrasound-guided gastroenterostomy (EGE), stomach-partitioning gastrojejunostomy (PGJ), and endoscopic stenting (ES). We searched the PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases; ClinicalTrials.gov; and the World Health Organization International Clinical Trials Registry Platform for randomized controlled trials (RCTs) and cohort studies comparing the aforementioned treatments for malignant GOO. We included studies that reported at least one of the following clinical outcomes: clinical success, 30-day mortality, reintervention rate, or length of hospital stay. Evidence from RCTs and non-RCTs was naïve combined to perform network meta-analysis through the frequentist approach using an inverse variance model. Treatments were ranked by P-score. This network meta-analysis included 3417 patients from 4 RCTs, 4 prospective cohort studies, and 32 retrospective cohort studies. PGJ was the optimal approach in terms of clinical success and reintervention (P-scores: 0.95 and 0.90, respectively). EGE had the highest probability of being the optimal treatment in terms of 30-day mortality and complications (P-scores: 0.82 and 0.99, respectively). Cluster ranking to combine the P-scores for 30-day mortality and reintervention indicated the benefits of PGJ and EGE (cophenetic correlation coefficient: 0.94; PGJ and EGE were in the same cluster). PGJ and EGE are recommended for malignant GOO. PGJ could be the alternative choice in centers with limited resources or cases unsuitable for EGE.

Post-kala-azar dermal leishmaniasis (PKDL) drug efficacy study landscape: A systematic scoping review of clinical trials and observational studies to assess the feasibility of establishing an individual participant-level data (IPD) platform.

Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis which can occur after successful treatment of visceral leishmaniasis (VL) and is a public health problem in VL endemic areas. We conducted a systematic scoping review to assess the characteristics of published PKDL clinical studies, understand the scope of research and explore the feasibility and value of developing a PKDL individual patient data (IPD) platform. A systematic review of published literature was conducted to identify PKDL clinical studies by searching the following databases: PubMed, Scopus, Ovid Embase, Web of Science Core Collection, WHO Global Index Medicus, PASCAL, Clinicaltrials.gov, Ovid Global Health, Cochrane Database and CENTRAL, and the WHO International Clinical Trials Registry Platform. Only prospective studies in humans with PKDL diagnosis, treatment, and follow-up measurements between January 1973 and March 2023 were included. Extracted data includes variables on patient characteristics, treatment regimens, diagnostic methods, geographical locations, efficacy endpoints, adverse events and statistical methodology. A total of 3,418 records were screened, of which 56 unique studies (n = 2,486 patients) were included in this review. Out of the 56 studies, 36 (64.3%) were from India (1983-2022), 12 (21.4%) from Sudan (1992-2021), 6 (10.7%) were from Bangladesh (1991-2019), and 2 (3.6%) from Nepal (2001-2007). Five (8.9%) studies were published between 1981-1990 (n = 193 patients), 10 (17.9%) between 1991-2000 (n = 230 patients), 10 (17.9%) between 2001-2010 (n = 198 patients), and 31 (55.4%) from 2011 onwards (n = 1,865 patients). Eight (14.3%) were randomised clinical trials, and 48 (85.7%) were non-randomised studies. The median post-treatment follow-up duration was 365 days (range: 90-540 days) in 8 RCTs and 360 days (range: 28-2,373 days) in 48 non-randomised studies. Disease diagnosis was based on clinical criterion in 3 (5.4%) studies, a mixture of clinical and parasitological methods in 47 (83.9%) and was unclear in 6 (10.7%) studies. Major drugs used for treatment were miltefosine (n = 636 patients), liposomal amphotericin B (L-AmB) (n = 508 patients), and antinomy regimens (n = 454 patients). Ten other drug regimens were tested in 270 patients with less than 60 patients per regimen. Our review identified studies with very limited sample size for the three major drugs (miltefosine, L-AmB, and pentavalent antimony), while the number of patients combined across studies suggest that the IPD platform would be valuable. With the support of relevant stakeholders, the global PKDL community and sufficient financing, a PKDL IPD platform can be realised. This will allow for exploration of different aspects of treatment safety and efficacy, which can potentially guide future healthcare decisions and clinical practices.

Prevalence of Drug Fever among Cases of Nosocomial Fever: A Systematic Review and Meta-analysis.

Objective Drug fever is defined as a fever that temporally coincides with the start of a culprit drug and disappears after discontinuation of the drug. It is a common cause of nosocomial fever, which refers to a fever that develops beyond the first 48 h after hospital admission. However, the exact prevalence of drug fever among cases of nosocomial fever is unclear, as is the variation in prevalence depending on the clinical setting and most common causative drugs. Methods PubMed MEDLINE, Dialog EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov were systematically searched. Studies that reported the prevalence of drug fever in patients with nosocomial fever were included. Two of the four reviewers conducted independent assessments of the inclusion, data extraction, and quality. Pooled adjusted odds ratios were generated using a random-effects model and presented with 95% confidence intervals (CIs). Results Fifteen meta-analysis from 15 studies were included. Ten studies did not report the definition of drug fever or excluded febrile patients who were admitted to the hospital within 24-48 h. The pooled prevalence of drug fever among cases of nosocomial fever was 3.0% (95% CI, 0.6-6.8%), which was largely consistent across the settings, except for at oriental medicine hospital. Only four studies reported the causative agents, and antibiotics were the most frequently reported. Conclusions The prevalence of drug fever is low in patients with nosocomial fever. Clinicians should recognize that drug fever is a diagnosis of exclusion, even in cases of nosocomial fever.

Botulinum Toxin Injections for Psychiatric Disorders: A Systematic Review of the Clinical Trial Landscape.

Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of negative emotions. We conducted a systematic review of past and ongoing efficacy trials of BONT-A therapy for psychiatric disorders to identify relevant trends in the field and discuss the refinement of therapeutic techniques. A comprehensive search for published clinical trials using BONT-A injections for psychiatric disorders was performed on 4 May 2023 through OVID databases (MEDLINE, Embase, APA PsycINFO). Unpublished clinical trials were searched through the ClinicalTrials.gov and International Clinical Trial Registry Platform public registries. The risk of bias was assessed using the JBI Critical Appraisal tools for use in systematic reviews. We identified 21 studies (17 published, 4 unpublished clinical trials) involving 471 patients. The studies focused on evaluating the efficacy of BONT-A for major depressive, borderline personality, social anxiety, and bipolar disorders. BONT-A was most commonly injected into the glabellar area, with an average dose ranging between 37.75 U and 44.5 U in published studies and between 32.7 U and 41.3 U in unpublished trials. The results indicated significant symptom reductions across all the studied psychiatric conditions, with mild adverse effects. Thus, BONT-A appears to be safe and well-tolerated for psychiatric disorders of negative affectivity. However, despite the clinical focus, there was a noted shortage of biomarker-related assessments. Future studies should focus on pursuing mechanistic explorations of BONT-A effects at the neurobiological level.