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The Cochrane Database of Systematic... May 2023Chronic pain is common in adults, and often has a detrimental impact upon physical ability, well-being, and quality of life. Previous reviews have shown that certain... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic pain is common in adults, and often has a detrimental impact upon physical ability, well-being, and quality of life. Previous reviews have shown that certain antidepressants may be effective in reducing pain with some benefit in improving patients' global impression of change for certain chronic pain conditions. However, there has not been a network meta-analysis (NMA) examining all antidepressants across all chronic pain conditions.
OBJECTIVES
To assess the comparative efficacy and safety of antidepressants for adults with chronic pain (except headache).
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, AMED and PsycINFO databases, and clinical trials registries, for randomised controlled trials (RCTs) of antidepressants for chronic pain conditions in January 2022.
SELECTION CRITERIA
We included RCTs that examined antidepressants for chronic pain against any comparator. If the comparator was placebo, another medication, another antidepressant, or the same antidepressant at different doses, then we required the study to be double-blind. We included RCTs with active comparators that were unable to be double-blinded (e.g. psychotherapy) but rated them as high risk of bias. We excluded RCTs where the follow-up was less than two weeks and those with fewer than 10 participants in each arm. DATA COLLECTION AND ANALYSIS: Two review authors separately screened, data extracted, and judged risk of bias. We synthesised the data using Bayesian NMA and pairwise meta-analyses for each outcome and ranked the antidepressants in terms of their effectiveness using the surface under the cumulative ranking curve (SUCRA). We primarily used Confidence in Meta-Analysis (CINeMA) and Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) to assess the certainty of the evidence. Where it was not possible to use CINeMA and ROB-MEN due to the complexity of the networks, we used GRADE to assess the certainty of the evidence. Our primary outcomes were substantial (50%) pain relief, pain intensity, mood, and adverse events. Our secondary outcomes were moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change (PGIC), serious adverse events, and withdrawal.
MAIN RESULTS
This review and NMA included 176 studies with a total of 28,664 participants. The majority of studies were placebo-controlled (83), and parallel-armed (141). The most common pain conditions examined were fibromyalgia (59 studies); neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of RCTs was 10 weeks. Seven studies provided no useable data and were omitted from the NMA. The majority of studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. In duloxetine studies, standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that of duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. Primary efficacy outcomes Duloxetine standard dose (60 mg) showed a small to moderate effect for substantial pain relief (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.69 to 2.17; 16 studies, 4490 participants; moderate-certainty evidence) and continuous pain intensity (standardised mean difference (SMD) -0.31, 95% CI -0.39 to -0.24; 18 studies, 4959 participants; moderate-certainty evidence). For pain intensity, milnacipran standard dose (100 mg) also showed a small effect (SMD -0.22, 95% CI -0.39 to 0.06; 4 studies, 1866 participants; moderate-certainty evidence). Mirtazapine (30 mg) had a moderate effect on mood (SMD -0.5, 95% CI -0.78 to -0.22; 1 study, 406 participants; low-certainty evidence), while duloxetine showed a small effect (SMD -0.16, 95% CI -0.22 to -0.1; 26 studies, 7952 participants; moderate-certainty evidence); however it is important to note that most studies excluded participants with mental health conditions, and so average anxiety and depression scores tended to be in the 'normal' or 'subclinical' ranges at baseline already. Secondary efficacy outcomes Across all secondary efficacy outcomes (moderate pain relief, physical function, sleep, quality of life, and PGIC), duloxetine and milnacipran were the highest-ranked antidepressants with moderate-certainty evidence, although effects were small. For both duloxetine and milnacipran, standard doses were as efficacious as high doses. Safety There was very low-certainty evidence for all safety outcomes (adverse events, serious adverse events, and withdrawal) across all antidepressants. We cannot draw any reliable conclusions from the NMAs for these outcomes.
AUTHORS' CONCLUSIONS
Our review and NMAs show that despite studies investigating 25 different antidepressants, the only antidepressant we are certain about for the treatment of chronic pain is duloxetine. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Evidence for all other antidepressants was low certainty. As RCTs excluded people with low mood, we were unable to establish the effects of antidepressants for people with chronic pain and depression. There is currently no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for the safety of antidepressants for chronic pain at any time point.
Topics: Adult; Humans; Antidepressive Agents; Chronic Pain; Duloxetine Hydrochloride; Milnacipran; Network Meta-Analysis; Pain Management; Randomized Controlled Trials as Topic
PubMed: 37160297
DOI: 10.1002/14651858.CD014682.pub2 -
The Lancet. Global Health May 2023Sub-Saharan Africa is highly endemic for hepatitis B virus (HBV); historically, most people were exposed during childhood through vertical or horizontal transmission.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sub-Saharan Africa is highly endemic for hepatitis B virus (HBV); historically, most people were exposed during childhood through vertical or horizontal transmission. Although all African countries now provide a three-dose infant hepatitis B vaccination starting at age 6-8 weeks, only a third of African countries have introduced birth dose (HepB-BD) vaccine. Adding HepB-BD is fundamental to prevent vertical transmission, but its effectiveness in preventing horizontal transmission, compared with the three-dose infant vaccination alone, is unknown. We aimed to estimate the risk of early horizontal transmission in children of hepatitis B surface antigen (HBsAg)-negative mothers in sub-Saharan Africa stratified according to the vaccination schedule.
METHODS
In this systematic review and meta-analysis we searched MEDLINE, Global Health, Embase, African Index Medicus and African Journals Online from their inception to Oct 24, 2022, for studies reporting HBsAg or HBV DNA, or both, in children (aged 0-5 years) of HBsAg-negative mothers. We excluded studies if children were only tested at birth. Two reviewers independently screened the titles and abstracts of all articles and data were extracted using a standardised pre-piloted data extraction sheet, and authors were contacted if any important information was missing. The primary outcome was the risk of HBV infection in children of HBsAg-negative mothers, stratified by vaccination schedule (no vaccination, first dose at 6-8 weeks, or first dose at birth). We pooled the child risks of HBsAg or HBV DNA-positivity from the age of 0 years to 5 years via a random-effect meta-analysis using a generalised linear mixed model. The study was registered on PROSPERO, CRD42021236203.
FINDINGS
Of 8856 articles identified, 27 studies evaluating 10 003 children of HBsAg-negative mothers were included. The pooled risks of infection were 6·16% (95% CI 3·05-12·04; 155/1407) in the no vaccination group, 0·21% (0·04-1·15; 10/3425) in children who received their first dose at 6-8 weeks, and 0·05% (0·00-1·32; 3/2902) in children who received their first dose at birth. The difference was not statistically significant in children who received their first dose at 6-8 weeks and children who received their first dose at birth after adjusting for the study period, region, and maternal HIV status (test of moderators p=0·37).
INTERPRETATION
In children of HBsAg-negative mothers, the risk of infection might be minimal even with the vaccination starting at 6-8 weeks, without clear additional benefit from HepB-BD. When births take place at home and timely administration of HepB-BD is challenging, antenatal HBsAg screening and selective HepB-BD might allow efficient allocation of resources to mother and child pairs at high risk compared with universal HepB-BD.
FUNDING
None.
TRANSLATION
For the French translation of the abstract see Supplementary Materials section.
Topics: Infant; Infant, Newborn; Child; Female; Humans; Pregnancy; Hepatitis B virus; Mothers; Hepatitis B Surface Antigens; DNA, Viral; Hepatitis B; Hepatitis B Vaccines; Infectious Disease Transmission, Vertical; Africa South of the Sahara
PubMed: 37061310
DOI: 10.1016/S2214-109X(23)00131-6 -
The Cochrane Database of Systematic... Mar 2023Zinc deficiency is prevalent in low- and middle-income countries, and is considered a significant risk factor for morbidity, mortality, and linear growth failure. The... (Review)
Review
BACKGROUND
Zinc deficiency is prevalent in low- and middle-income countries, and is considered a significant risk factor for morbidity, mortality, and linear growth failure. The effectiveness of preventive zinc supplementation in reducing prevalence of zinc deficiency needs to be assessed.
OBJECTIVES
To assess the effects of zinc supplementation for preventing mortality and morbidity, and for promoting growth, in children aged 6 months to 12 years.
SEARCH METHODS
A previous version of this review was published in 2014. In this update, we searched CENTRAL, MEDLINE, Embase, five other databases, and one trials register up to February 2022, together with reference checking and contact with study authors to identify additional studies.
SELECTION CRITERIA
Randomized controlled trials (RCTs) of preventive zinc supplementation in children aged 6 months to 12 years compared with no intervention, a placebo, or a waiting list control. We excluded hospitalized children and children with chronic diseases or conditions. We excluded food fortification or intake, sprinkles, and therapeutic interventions.
DATA COLLECTION AND ANALYSIS
Two review authors screened studies, extracted data, and assessed the risk of bias. We contacted study authors for missing information and used GRADE to assess the certainty of evidence. The primary outcomes of this review were all-cause mortality; and cause-specific mortality, due to all-cause diarrhea, lower respiratory tract infection (LRTI, including pneumonia), and malaria. We also collected information on a number of secondary outcomes, such as those related to diarrhea and LRTI morbidity, growth outcomes and serum levels of micronutrients, and adverse events.
MAIN RESULTS
We included 16 new studies in this review, resulting in a total of 96 RCTs with 219,584 eligible participants. The included studies were conducted in 34 countries; 87 of them in low- or middle-income countries. Most of the children included in this review were under five years of age. The intervention was delivered most commonly in the form of syrup as zinc sulfate, and the most common dose was between 10 mg and 15 mg daily. The median duration of follow-up was 26 weeks. We did not consider that the evidence for the key analyses of morbidity and mortality outcomes was affected by risk of bias. High-certainty evidence showed little to no difference in all-cause mortality with preventive zinc supplementation compared to no zinc (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.84 to 1.03; 16 studies, 17 comparisons, 143,474 participants). Moderate-certainty evidence showed that preventive zinc supplementation compared to no zinc likely results in little to no difference in mortality due to all-cause diarrhea (RR 0.95, 95% CI 0.69 to 1.31; 4 studies, 132,321 participants); but probably reduces mortality due to LRTI (RR 0.86, 95% CI 0.64 to 1.15; 3 studies, 132,063 participants) and mortality due to malaria (RR 0.90, 95% CI 0.77 to 1.06; 2 studies, 42,818 participants); however, the confidence intervals around the summary estimates for these outcomes were wide, and we could not rule out a possibility of increased risk of mortality. Preventive zinc supplementation likely reduces the incidence of all-cause diarrhea (RR 0.91, 95% CI 0.90 to 0.93; 39 studies, 19,468 participants; moderate-certainty evidence) but results in little to no difference in morbidity due to LRTI (RR 1.01, 95% CI 0.95 to 1.08; 19 studies, 10,555 participants; high-certainty evidence) compared to no zinc. There was moderate-certainty evidence that preventive zinc supplementation likely leads to a slight increase in height (standardized mean difference (SMD) 0.12, 95% CI 0.09 to 0.14; 74 studies, 20,720 participants). Zinc supplementation was associated with an increase in the number of participants with at least one vomiting episode (RR 1.29, 95% CI 1.14 to 1.46; 5 studies, 35,192 participants; high-certainty evidence). We report a number of other outcomes, including the effect of zinc supplementation on weight and serum markers such as zinc, hemoglobin, iron, copper, etc. We also performed a number of subgroup analyses and there was a consistent finding for a number of outcomes that co-supplementation of zinc with iron decreased the beneficial effect of zinc.
AUTHORS' CONCLUSIONS
Even though we included 16 new studies in this update, the overall conclusions of the review remain unchanged. Zinc supplementation might help prevent episodes of diarrhea and improve growth slightly, particularly in children aged 6 months to 12 years of age. The benefits of preventive zinc supplementation may outweigh the harms in regions where the risk of zinc deficiency is relatively high.
Topics: Child; Child, Preschool; Humans; Diarrhea; Dietary Supplements; Iron; Malaria; Malnutrition; Minerals; Morbidity; Respiratory Tract Infections; Zinc
PubMed: 36994923
DOI: 10.1002/14651858.CD009384.pub3 -
BMJ Medicine 2023To determine the effect of covid-19 vaccination, given before and after acute infection with the SARS-CoV-2 virus, or after a diagnosis of long covid, on the rates and...
OBJECTIVE
To determine the effect of covid-19 vaccination, given before and after acute infection with the SARS-CoV-2 virus, or after a diagnosis of long covid, on the rates and symptoms of long covid.
DESIGN
Systematic review.
DATA SOURCES
PubMed, Embase, and Cochrane covid-19 trials, and Europe PubMed Central (Europe PMC) for preprints, from 1 January 2020 to 3 August 2022.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Trials, cohort studies, and case-control studies reporting on patients with long covid and symptoms of long covid, with vaccination before and after infection with the SARS-CoV-2 virus, or after a diagnosis of long covid. Risk of bias was assessed with the ROBINS-I tool.
RESULTS
1645 articles were screened but no randomised controlled trials were found. 16 observational studies from five countries (USA, UK, France, Italy, and the Netherlands) were identified that reported on 614 392 patients. The most common symptoms of long covid that were studied were fatigue, cough, loss of sense of smell, shortness of breath, loss of taste, headache, muscle ache, difficulty sleeping, difficulty concentrating, worry or anxiety, and memory loss or confusion. 12 studies reported data on vaccination before infection with the SARS-CoV-2 virus, and 10 showed a significant reduction in the incidence of long covid: the odds ratio of developing long covid with one dose of vaccine ranged from 0.22 to 1.03; with two doses, odds ratios were 0.25-1; with three doses, 0.16; and with any dose, 0.48-1.01. Five studies reported on vaccination after infection, with odds ratios of 0.38-0.91. The high heterogeneity between studies precluded any meaningful meta-analysis. The studies failed to adjust for potential confounders, such as other protective behaviours and missing data, thus increasing the risk of bias and decreasing the certainty of evidence to low.
CONCLUSIONS
Current studies suggest that covid-19 vaccines might have protective and therapeutic effects on long covid. More robust comparative observational studies and trials are needed, however, to clearly determine the effectiveness of vaccines in preventing and treating long covid.
PROTOCOL REGISTRATION
Open Science Framework https://osf.io/e8jdy.
PubMed: 36936268
DOI: 10.1136/bmjmed-2022-000385 -
Advances in Therapy May 2023The objective of this systematic literature review was to evaluate the available literature concerning the clinical, economic, and patient-reported benefits of insulin...
INTRODUCTION
The objective of this systematic literature review was to evaluate the available literature concerning the clinical, economic, and patient-reported benefits of insulin pen platforms, including connected insulin pens/caps/sleeves and insulin platforms, as well as mobile apps capable of receiving near real-time insulin dosing information.
METHODS
Medline and Embase databases and the Cochrane Library were searched for published literature between January 2015 and May 2021, and manual searches for conference abstracts from 2018 to May 2021 were performed. These searches were supplemented by internet searches for relevant literature and clinical trials. Study selection involved the population, intervention, comparator, outcomes, time frame, and study design outline. Included studies investigated connected insulin systems or connected caps/sleeves enabling pens to be connected, or apps able to connect to these systems, in individuals of all ages with type 1 or type 2 diabetes mellitus.
RESULTS
Searches identified a total of 26 publications (mostly observational studies and conference abstracts) for inclusion, representing ten unique, predominantly small studies. Evidence in this field is still in its early stages, and only two randomized controlled trials met our inclusion criteria. Available results showed that connected insulin pens and their systems potentially helped reduce suboptimal insulin use and may therefore improve glycemic control. Satisfaction of people with diabetes with the technologies used was high, and economic benefits were noted. Features of effective connected insulin pen devices include simplicity of use and data upload/sharing, useful "point-of-care" alerts, and simple and understandable data presentation to facilitate more effective consultations.
CONCLUSIONS
Connected insulin pen systems could be increasingly considered as part of routine clinical care for insulin-treated persons with diabetes who must manage the complexity of their daily insulin routine. Future research focusing on the way data obtained from these devices can be most effectively used alongside other information is urgently needed.
Topics: Humans; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Randomized Controlled Trials as Topic; Insulin; Hypoglycemic Agents; Mobile Applications; Point-of-Care Systems; Injections, Subcutaneous; Cost-Benefit Analysis
PubMed: 36928495
DOI: 10.1007/s12325-023-02478-1 -
The Cochrane Database of Systematic... Mar 2023Systematic reviews showed that systemic postnatal corticosteroids reduce the risk of bronchopulmonary dysplasia (BPD) in preterm infants. However, corticosteroids have... (Review)
Review
BACKGROUND
Systematic reviews showed that systemic postnatal corticosteroids reduce the risk of bronchopulmonary dysplasia (BPD) in preterm infants. However, corticosteroids have also been associated with an increased risk of neurodevelopmental impairment. It is unknown whether these beneficial and adverse effects are modulated by differences in corticosteroid treatment regimens related to type of steroid, timing of treatment initiation, duration, pulse versus continuous delivery, and cumulative dose.
OBJECTIVES
To assess the effects of different corticosteroid treatment regimens on mortality, pulmonary morbidity, and neurodevelopmental outcome in very low birth weight infants.
SEARCH METHODS
We conducted searches in September 2022 of MEDLINE, the Cochrane Library, Embase, and two trial registries, without date, language or publication- type limits. Other search methods included checking the reference lists of included studies for randomized controlled trials (RCTs) and quasi-randomized trials.
SELECTION CRITERIA
We included RCTs comparing two or more different treatment regimens of systemic postnatal corticosteroids in preterm infants at risk for BPD, as defined by the original trialists. The following comparisons of intervention were eligible: alternative corticosteroid (e.g. hydrocortisone) versus another corticosteroid (e.g. dexamethasone); lower (experimental arm) versus higher dosage (control arm); later (experimental arm) versus earlier (control arm) initiation of therapy; a pulse-dosage (experimental arm) versus continuous-dosage regimen (control arm); and individually-tailored regimens (experimental arm) based on the pulmonary response versus a standardized (predetermined administered to every infant) regimen (control arm). We excluded placebo-controlled and inhalation corticosteroid studies.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed eligibility and risk of bias of trials, and extracted data on study design, participant characteristics and the relevant outcomes. We asked the original investigators to verify if data extraction was correct and, if possible, to provide any missing data. We assessed the following primary outcome: the composite outcome mortality or BPD at 36 weeks' postmenstrual age (PMA). Secondary outcomes were: the components of the composite outcome; in-hospital morbidities and pulmonary outcomes, and long-term neurodevelopmental sequelae. We analyzed data using Review Manager 5 and used the GRADE approach to assess the certainty of the evidence.
MAIN RESULTS
We included 16 studies in this review; of these, 15 were included in the quantitative synthesis. Two trials investigated multiple regimens, and were therefore included in more than one comparison. Only RCTs investigating dexamethasone were identified. Eight studies enrolling a total of 306 participants investigated the cumulative dosage administered; these trials were categorized according to the cumulative dosage investigated, 'low' being < 2 mg/kg, 'moderate' being between 2 and 4 mg/kg, and 'high' > 4 mg/kg; three studies contrasted a high versus a moderate cumulative dose, and five studies a moderate versus a low cumulative dexamethasone dose. We graded the certainty of the evidence low to very low because of the small number of events, and the risk of selection, attrition and reporting bias. Overall analysis of the studies investigating a higher dose versus a lower dosage regimen showed no differences in the outcomes BPD, the composite outcome death or BPD at 36 weeks' PMA, or abnormal neurodevelopmental outcome in survivors assessed. Although there was no evidence of a subgroup difference for the higher versus lower dosage regimens comparisons (Chi = 2.91, df = 1 (P = 0.09), I = 65.7%), a larger effect was seen in the subgroup analysis of moderate-dosage regimens versus high-dosage regimens for the outcome cerebral palsy in survivors. In this subgroup analysis, there was an increased risk of cerebral palsy (RR 6.85, 95% CI 1.29 to 36.36; RD 0.23, 95% CI 0.08 to 0.37; P = 0.02; I² = 0%; NNTH 5, 95% CI 2.6 to 12.7; 2 studies, 74 infants). There was evidence of subgroup differences for higher versus lower dosage regimens comparisons for the combined outcomes death or cerebral palsy, and death and abnormal neurodevelopmental outcomes (Chi = 4.25, df = 1 (P = 0.04), I = 76.5%; and Chi = 7.11, df = 1 (P = 0.008), I = 85.9%, respectively). In the subgroup analysis comparing a high dosage regimen of dexamethasone versus a moderate cumulative-dosage regimen, there was an increased risk of death or cerebral palsy (RR 3.20, 95% CI 1.35 to 7.58; RD 0.25, 95% CI 0.09 to 0.41; P = 0.002; I² = 0%; NNTH 5, 95% CI 2.4 to 13.6; 2 studies, 84 infants; moderate-certainty evidence), and death or abnormal neurodevelopmental outcome (RR 3.41, 95% CI 1.44 to 8.07; RD 0.28, 95% CI 0.11 to 0.44; P = 0.0009; I² = 0%; NNTH 4, 95% CI 2.2 to 10.4; 2 studies, 84 infants; moderate-certainty evidence). There were no differences in outcomes between a moderate- and a low-dosage regimen. Five studies enrolling 797 infants investigated early initiation of dexamethasone therapy versus a moderately early or delayed initiation, and showed no significant differences in the overall analyses for the primary outcomes. The two RCTs investigating a continuous versus a pulse dexamethasone regimen showed an increased risk of the combined outcome death or BPD when using the pulse therapy. Finally, three trials investigating a standard regimen versus a participant-individualized course of dexamethasone showed no difference in the primary outcome and long-term neurodevelopmental outcomes. We assessed the GRADE certainty of evidence for all comparisons discussed above as moderate to very low, because the validity of all comparisons is hampered by unclear or high risk of bias, small samples of randomized infants, heterogeneity in study population and design, non-protocolized use of 'rescue' corticosteroids and lack of long-term neurodevelopmental data in most studies.
AUTHORS' CONCLUSIONS
The evidence is very uncertain about the effects of different corticosteroid regimens on the outcomes mortality, pulmonary morbidity, and long term neurodevelopmental impairment. Despite the fact that the studies investigating higher versus lower dosage regimens showed that higher-dosage regimens may reduce the incidence of death or neurodevelopmental impairment, we cannot conclude what the optimal type, dosage, or timing of initiation is for the prevention of BPD in preterm infants, based on current level of evidence. Further high quality trials would be needed to establish the optimal systemic postnatal corticosteroid dosage regimen.
Topics: Infant, Newborn; Infant; Humans; Glucocorticoids; Dexamethasone; Bronchopulmonary Dysplasia; Cerebral Palsy; Infant, Premature
PubMed: 36912887
DOI: 10.1002/14651858.CD010941.pub3 -
Molecular Psychiatry May 2023In schizophrenia, it is currently thought that stigma experience is increased by psychotic and depressive symptomatology, exposure to stigma at the workplace, and that...
In schizophrenia, it is currently thought that stigma experience is increased by psychotic and depressive symptomatology, exposure to stigma at the workplace, and that self-stigma levels vary across countries without knowing the factors explaining these variations. The aim of the present meta-analysis was to synthetize the data of observational studies comprehensively exploring multiple self-stigma dimensions and associated factors. A systematic literature search without language or time restrictions was conducted in Medline, Google Scholar, and Web of Science for studies, last 09/2021. Eligible studies that included ≥80% of patients diagnosed with schizophrenia-spectrum disorders and used a validated scale measuring self-stigma dimensions were meta-analysed using random-effects models, followed by subgroup and meta-regression analyses. Study registration: PROSPERO CRD42020185030. Overall, 37 studies (n = 7717) from 25 countries (5 continents) published between 2007 and 2020 were included, with 20 studies conducted in high-income countries. These studies used two scales with total scores ranging 1-4. The mean estimate of perceived stigma was 2.76 [95% confidence interval (CI) = 2.60-2.94], experienced stigma 2.29 [95% CI = 2.18, 2.41], alienation 2.40 [95% CI = 2.29, 2.52], stereotype endorsement 2.14 [95% CI = 2.03, 2.27], social withdrawal 2.28 [95% CI = 2.17, 2.39] and stigma resistance 2.53 [95% CI = 2.43, 2.63]). Self-stigma levels did not reduce over time. Living outside urban areas, low-income, singleness, unemployment, high antipsychotic dose and low functioning were associated with different stigma dimensions. Some stigma dimensions were lower in studies carried out in Europe compared to other regions. Most studies published since 2007 report that self-stigma is a particular concern for a specific subgroup of patients. This subgroup is characterized by unemployment, high antipsychotic dose and low functioning. We identified important other missing factors that should be explored to improve the effectiveness of public policies and personalized interventions to reduce self-stigma. Importantly, classical illness severity indices (psychotic severity, age at illness onset, illness duration) and sociodemographic variables (age, sex and education) were not associated with self-stigma, moderating previous findings.
PubMed: 36890299
DOI: 10.1038/s41380-023-02003-4 -
Frontiers in Psychiatry 2023Psychedelic-assisted therapy [e.g., with lysergic acid diethylamide (LSD)] has shown promising results as treatment for substance use disorders (SUDs). Previous...
BACKGROUND
Psychedelic-assisted therapy [e.g., with lysergic acid diethylamide (LSD)] has shown promising results as treatment for substance use disorders (SUDs). Previous systematic reviews assessing the efficacy of psilocybin in SUDs only included clinical trials conducted in the last 25 years, but they may have missed clinical trials assessing the efficacy of psilocybin that were conducted before the 1980s, given much research has been done with psychedelics in the mid-20th century. In this systematic review, we specifically assessed the efficacy of psilocybin in patients with a SUD or non-substance-related disorder with no publication date restrictions in our search strategy.
METHODS
A systematic literature search was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines from the earliest published manuscript up to September 2, 2022, in seven electronic databases, including clinical trials in patients with a SUD or non-substance-related disorder evaluating the efficacy of psilocybin.
RESULTS
A total of four studies (six articles, of which two articles were long-term follow-up results from the same trial) were included in this systematic review. Psilocybin-assisted therapy was administered to = 151 patients in a dose ranging from 6 to 40 mg. Three studies focused on alcohol use disorder, and one study on tobacco use disorder. In a pilot study ( = 10), the percentage of heavy drinking days decreased significantly between baseline and weeks 5-12 (mean difference of 26.0, 95% CI = 8.7-43.2, = 0.008). In another single-arm study ( = 31), 32% (10/31) became completely abstinent from alcohol (mean duration of follow-up 6 years). In a double-blind, placebo-controlled randomized controlled trial (RCT, = 95), the percentage of heavy drinking days during the 32-week double-blind period was significantly lower for psilocybin compared to placebo (mean difference of 13.9, 95% CI = 3.0-24.7, = 0.01). In a pilot study ( = 15), the 7-day point prevalence of smoking abstinence at 26 weeks was 80% (12/15), and at 52 weeks 67% (10/15).
CONCLUSION
Only one RCT and three small clinical trials were identified assessing the efficacy of psilocybin combined with some form of psychotherapy in patients with alcohol and tobacco use disorder. All four clinical trials indicated a beneficial effect of psilocybin-assisted therapy on SUD symptoms. Larger RCTs in patients with SUDs need to evaluate whether psilocybin-assisted therapy is effective in patients with SUD.
PubMed: 36846225
DOI: 10.3389/fpsyt.2023.1134454 -
Nutrients Feb 2023Vitamin D is a nutrient potentially beneficial in the treatment of depression. The study aimed to carry out a systematic review of the studies assessing the influence of... (Review)
Review
Vitamin D is a nutrient potentially beneficial in the treatment of depression. The study aimed to carry out a systematic review of the studies assessing the influence of vitamin D supplementation on depression within Randomized Controlled Trials (RCTs). The systematic review was prepared on the basis of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42020155779). The peer-reviewed studies available within PubMed or Web of Science databases until September 2021 were taken into account. The number of screened records was 8514, and 8 records were included. Two independent researchers conducted screening, including, reporting, and risk of bias assessment using the revised Cochrane risk-of-bias tool for randomized trials. The included studies presented a population of patients with major depressive disorders or general depression, as well as bipolar depression or postpartum depression. The majority of included studies were conducted for 8 weeks or 12 weeks, while one study was conducted for 6 months. Within the large number of included studies, a daily dose of 1500 IU, 1600 IU, or 2800 IU was applied, while within some studies, a vitamin D dose of 50,000 IU was applied weekly or biweekly. Among applied psychological measures of depression, there were various tools. In spite of the fact that the majority of included studies (five studies) supported the positive effect of vitamin D supplementation for the psychological measure of depression, for three studies the positive influence was not supported. A medium risk of bias was indicated for six studies, while a high risk of bias was defined for only two studies, due to deviations from the intended interventions and in measurement of the outcome, as well as for one study, also arising from the randomization process and due to missing outcome data. Based on conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of the medium risk of bias, while two studies of a medium risk of bias did not support it. Taking this into account, the conducted systematic review is not a strong confirmation of the effectiveness of vitamin D supplementation in the treatment of depression.
Topics: Female; Adult; Humans; Dietary Supplements; Randomized Controlled Trials as Topic; Vitamin D; Vitamins; Vitamin D Deficiency
PubMed: 36839310
DOI: 10.3390/nu15040951 -
Journal of the International AIDS... Feb 2023Tenofovir alafenamide (TAF) is approved for paediatric use in fixed-dose combination tablets, but efficacy and safety data in children are limited. We conducted a... (Review)
Review
INTRODUCTION
Tenofovir alafenamide (TAF) is approved for paediatric use in fixed-dose combination tablets, but efficacy and safety data in children are limited. We conducted a systematic review on the efficacy/effectiveness and safety of TAF in infants, children and adolescents living with HIV.
METHODS
We searched MEDLINE, Embase, the Cochrane Library, clinical trial registries, reference lists and relevant conferences to identify literature published January 2009-March 2021. We included clinical trials and observational studies assessing the efficacy/effectiveness or safety of TAF through ≥6 months of treatment in participants aged 0-19 years.
RESULTS AND DISCUSSION
Overall 3626 abstracts and 371 full papers were screened. Four single-arm, innovator-funded trials (341 participants) and a pooled analysis of those trials were identified. All four trials included treatment-experienced and virally suppressed children or adolescents. One trial also included treatment-naïve adolescents with baseline viral load >1000 copies/ml. The risk of bias was rated as low in one study and unclear in the other three owing to missing data on study design (all conference presentations). At 48 weeks, 92% (46/50) of treatment-naïve participants were virally suppressed (one trial). Among treatment-experienced participants with viral load at 48 weeks, 214 of 224 participants were virally suppressed. Across the studies, one grade 3/4 adverse event was considered drug-related (intermediate uveitis). There were three discontinuations for adverse events (grade 2 anxiety and insomnia, grade 1 iridocyclitis [drug-related] and grade 1 pulmonary tuberculosis [unrelated to treatment]). One accidental death occurred across the four studies. In the pooled analysis of 223 participants, the median change in bone mineral density z-score (height- and age-adjusted) from baseline to 48 weeks was -0.12 (interquartile range [IQR] -0.46, 0.17) to 0.05 (IQR not reported) for spine, and -0.09 (IQR -0.33, 0.07) to 0.09 (IQR not reported) for total body less head. Weight-for-age z-scores increased by 0.25 from baseline to 48 weeks.
CONCLUSIONS
Four single-arm trials were identified in this systematic review, with initial evidence suggesting good viral suppression and no obvious safety concerns in children and adolescents on TAF-containing regimens over 24-48 weeks. However, further comparative and longer-term safety data are needed in children and adolescents, including on weight and metabolic changes.
Topics: Infant; Humans; Child; Adolescent; Tenofovir; HIV Infections; Anti-HIV Agents; HIV-1; Adenine; Emtricitabine
PubMed: 36823283
DOI: 10.1002/jia2.26037