Search

Vergleich der Wirksamkeit und Sicherheit von Biologika zur Behandlung mittelschwerer bis schwerer Plaque-Psoriasis im Kindes- und Jugendalter, soweit diese von der US Food and Drug Administration (FDA) und der European Medicines Agency (EMA) zugelassen sind.Die Datenbanken MEDLINE, Embase und Cochrane Central Register of Controlled Trials wurden im Zeitraum bis 7. Mai 2021 nach relevanten randomisierten, kontrollierten Studien (RCT, randomized controlled trials) durchsucht. Eine Fixed-Effect-Netzwerk-Metaanalyse (NMA) wurde durchgeführt, wobei für die Rangfolge die SUCRA (surface under the cumulative ranking curve) berechnet wurde. Die primären Endpunkte waren die Verbesserung des Psoriasis Area and Severity Index Score um ≥ 90 % (PASI 90) nach 12-16 Wochen sowie das Ausscheiden aufgrund von Nebenwirkungen (DAE, discontinuation owing to adverse events) im Laufe der ersten 12-16 Wochen.Fünf RCT mit insgesamt 798 pädiatrischen Psoriasis-Patienten wurden in unsere Analyse einbezogen. Sämtliche untersuchten Biologika zeigten im Vergleich zu Placebo signifikant verbesserte PASI 90-Werte, während das Risiko für DAE keinen Unterschied zu Placebo aufwies. Basierend auf der SUCRA erreichte Secukinumab in der niedrigeren Dosierung (SEC-L) das beste Ansprechen im PASI 90 (84,7 %), gefolgt von Ixekizumab (70,8 %).Unter allen eingeschlossenen Biologika konnte mit SEC-L das beste Ansprechen im PASI 90 erreicht werden, ohne das Risiko für DAE zu erhöhen. Weitere Langzeitstudien sollten folgen.

To compare the efficacy and safety of biologic treatments for moderate-to-severe pediatric psoriasis approved by the US Food and Drug Administration and European Medicines Agency.MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for relevant randomized controlled trials (RCTs) were searched for the identification of eligible RCTs until May 7, 2021. Fixed-effect frequentist network meta-analysis (NMA) was performed with the surface under the cumulative ranking curve (SUCRA) calculated for ranking. Our primary outcomes included ≥ 90 % improvement of Psoriasis Area and Severity Index score (PASI 90) at 12-16 weeks and discontinuation owing to adverse events (DAE) through the first 12-16 weeks.Five RCTs involving 798 pediatric psoriasis patients were included. Compared to placebo, all biologic regimens exhibited a significantly higher PASI 90 response but did not differ in the risk for DAE. Based on the SUCRA, secukinumab-low dose (SEC-L) ranked first in the achieved PASI 90 response (84.7 %), followed by ixekizumab (70.8 %).Among all biologic treatments, SEC-L showed the best PASI 90 response without increasing the risk for DAE. More long-term studies are warranted.

This investigation demonstrates that a series of (highly) substituted acephenanthrylenes (APs)

To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for clozapine-resistant schizophrenia (CRS).Six major electronic databases were systematically searched for RCTs published until July 10, 2021. The primary outcome was change in overall symptoms, and the secondary outcomes were positive and negative symptoms and acceptability. We performed random-effects network meta-analysis. Normalized entropy was calculated to examine the uncertainty of treatment ranking.We identified 35 RCTs (1472 patients with 23 active augmentation treatments) with a mean daily clozapine dose of 440.80 (91.27) mg for 1168.22 (710.28) days. Network meta-analysis of overall symptoms (reported as standardized mean difference; 95 % confidence interval) with consistent results indicated that mirtazapine (-4.41; -5.61, -3.21), electroconvulsive therapy (ECT) (-4.32; -5.43, -3.21), and memantine (-2.02; -3.14, -0.91) were ranked as the best three treatments. For positive symptoms, ECT (-5.18; -5.86, -4.49) was ranked the best with less uncertainty. For negative symptoms, memantine (-3.38; -4.50, -2.26), duloxetine (-3.27; -4.25, -2.29), and mirtazapine (-1.73; -2.71, -0.74) were ranked the best three treatments with less uncertainty. All antipsychotics, N-methyl d-aspartate receptor agonists, and antiepileptics were not associated with more efficacy than placebo. Compared to placebo, only amisulpride had statistically significant lower discontinuation rate (risk ratio: 0.21; 95 % CI: 0.05, 0.93).Add-on mirtazapine, ECT, and memantine were the most efficacious augmentation options for CRS. Data on other important outcomes such as cognitive functioning or quality of life were rarely reported, making further large-scale, well-designed RCTs necessary. (PROSPERO number, CRD42021262197.).

Previous studies have suggested that the topical mechanistic target of rapamycin (mTOR) inhibitors may be effective in treating facial angiofibromas in patients with tuberous sclerosis complex (TSC). Various concentrations of topical sirolimus for TSC have been tested, but their comparative efficacy and safety remained unclear. To assess the effects of topical mTOR inhibitors in treating facial angiofibromas, we conducted a systematic review and network meta-analysis (NMA) and searched MEDLINE, Embase, and Cochrane Library for relevant randomized controlled trials on 14 February 2022. The Cochrane Collaboration tool was used to assess the risk of bias of included trials. Our outcomes were clinical improvement and severe adverse events leading to withdrawal. We included three trials on 261 TSC patients with facial angiofibromas. The NMA found when compared with placebo, facial angiofibromas significantly improved following the application of various concentrations of topical sirolimus (risk ratio being 3.87, 2.70, 4.43, and 3.34 for 0.05%, 0.1%, 0.2%, and 1%, respectively). When compared with placebo, all concentrations of topical sirolimus did not differ in severe adverse events leading to withdrawal. The ranking analysis suggested topical sirolimus 0.2% as the most effective drug. In conclusion, topical sirolimus 0.05–1% are effective and safe in treating facial angiofibromas in patients with TSC, with topical sirolimus 0.2% being the most effective.

ObjectivesTo compare cognitive effects and acceptability of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) in patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI), and to determine whether cognitive training (CT) during rTMS or tDCS provides additional benefits.MethodsElectronic search of PubMed, Medline, Embase, the Cochrane Library and PsycINFO up to 5 March 2020. We enrolled double-blind, randomised controlled trials (RCTs). The primary outcomes were acceptability and pre–post treatment changes in general cognition measured by Mini-Mental State Examination, and the secondary outcomes were memory function, verbal fluency, working memory and executive function. Durability of cognitive benefits (1, 2 and ≥3 months) after brain stimulation was examined.ResultsWe included 27 RCTs (n=1070), and the treatment components included high-frequency rTMS (HFrTMS) and low-frequency rTMS, anodal tDCS (atDCS) and cathodal tDCS (ctDCS), CT, sham CT and sham brain stimulation. Risk of bias of evidence in each domain was low (range: 0%–11.1%). HFrTMS (1.08, 9, 0.35–1.80) and atDCS (0.56, 0.03–1.09) had short-term positive effects on general cognition. CT might be associated with negative effects on general cognition (−0.79, –2.06 to 0.48) during rTMS or tDCS. At 1-month follow-up, HFrTMS (1.65, 0.77–2.54) and ctDCS (2.57, 0.20–4.95) exhibited larger therapeutic responses. Separate analysis of populations with pure AD and MCI revealed positive effects only in individuals with AD. rTMS and tDCS were well tolerated.ConclusionsHFrTMS is more effective than atDCS for improving global cognition, and patients with AD may have better responses to rTMS and tDCS than MCI.

The last decade has witnessed the increasing use of biologics for the treatment of ankylosing spondylitis (AS). Drug survival is an outcome incorporating real-world effectiveness and safety. However, the drug survival of biologics in treating AS is unclear. The aim was to assess the drug survival of biologics (tumor necrosis factor inhibitors and anti-interleukin-17 monoclonal antibodies) in treating AS. We conducted a systematic review and meta-analysis and searched the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase databases up to 13th May 2020. Studies that analyzed the drug survival of biologics for AS and reported the respective annual data for each biologic for at least 1 year were included. Two authors independently screened and selected studies and assessed their risk of bias. A third author was available for arbitrating discrepancies. The Newcastle–Ottawa Scale was employed to evaluate the risk of bias of included studies. We conducted a random-effects model meta-analysis to obtain pooled drug survival from year 1 to 5. We performed subgroup analyses for biologic-naive patients, first-line versus second- and third-line biologics, discontinuation due to loss of effectiveness and adverse effects, and high-quality studies. We included 39 studies with 32,493 patients. The drug survival decreased from 76% at year 1 to 51% at year 5 for etanercept, from 75 to 51% for adalimumab, from 76 to 53% for infliximab, from 72 to 49% for golimumab, and from 63 to 57% for certolizumab pegol. The drug survival rate for secukinumab was 0.77 (95% confidence interval 0.64‒0.90) at year 1. Subgroup analyses on biologic-naive patients and discontinuation due to adverse effects found no differences in the drug survival of various biologics except for a lower drug survival of infliximab in biologic-naive patients. The drug survival for first-line biologics was higher than for second- and third-line biologics. To the best of our knowledge, this study is the first systematic review and meta-analysis on the drug survival of biological therapies for AS patients. The drug survival of all biologics in treating AS appeared comparable, but is higher in first-line biologics than second- and third-line biologics. To date there are scarce data on the drug survival of newly available biologics, for example, anti-interleukin-17 biologics. CRD42018114204.

Background Previous studies have suggested that biologic therapy for psoriasis might relate to body weight gain. Objective To assess the changes in body weight and body mass index (BMI) in psoriasis patients after receiving various biologics. Methods We conducted a systematic review and network meta-analysis to evaluate the changes in body weight and BMI in psoriasis patients receiving biologics. On March 1, 2019, we searched Medline, Embase, and Cochrane Central Register of Controlled Trials for relevant studies. The Newcastle-Ottawa scale was used to assess the risk of bias. Results We included 6 studies with 862 psoriasis patients. Compared with conventional systemic treatments, treatment with tumor necrosis factor α inhibitors was associated with a significant increase in body weight (mean difference 1.40 kg, 95% confidence interval 0.88-1.93 kg) and BMI (0.39 kg/m2, 95% confidence interval 0.24-0.54 kg/m2). In contrast, no significant increase in body weight or BMI was found among patients receiving anti-interleukin (IL)-12/23 or anti-IL-17 biologics. Limitations Only 1 study reported body weight and BMI for patients receiving the anti-IL-17 biologic. Conclusion Tumor necrosis factor α inhibitor treatment appears to be associated with an increase in body weight and BMI, and treatment with anti-IL-12/23 and anti-IL-17 biologics do not. This association should be considered before initiating biologics for overweight and obese patients.

Preliminary meta-analyses suggested that fluvoxamine was effective in treating COVID-19 infection. However, the reliability of this evidence has not yet been examined. MEDLINE, CENTRAL, EMBASE, PsycINFO, and ClinicalTrials.gov were searched to identify any randomized controlled trials (RCTs) from the inception of the databases to 5 February 2023. We used trial sequential analysis (TSA) to examine the reliability of the current existing evidence on the benefits of fluvoxamine on COVID-19 infection. The primary outcome was clinical deterioration, as defined in the original study (reported as odds ratio (OR), with 95% confidence intervals), and the secondary outcome was hospitalization. In the TSA, we used the relative risk reduction thresholds of 10, 20, and 30%. The updated meta-analysis of the five RCTs showed that fluvoxamine was not associated with lower odds of clinical deterioration when compared with a placebo (OR: 0.81; 0.59–1.11). The effect of fluvoxamine lay within the futility boundary (i.e., lack of effect) when using a 30% relative risk reduction threshold. The effect estimates lay between the superiority and futility boundary using the 10% and 20% threshold, and the required size of information was not reached for these two thresholds. The effect of fluvoxamine on the odds of hospitalization was not statistically significant (0.76; 0.56–1.03). In conclusion, there is no reliable evidence that fluvoxamine, when compared to a placebo, reduces the relative risk of clinical deterioration among adult patients with COVID-19 infection by 30%, and a relative risk reduction of 20% or 10% is still uncertain. The role of fluvoxamine as a COVID-19 treatment cannot be justified.

QuestionAre antipsychotic dose equivalents between acute mania and schizophrenia the same?Study selection and analysisSix databases were systematically searched (from inception to 17 September 2022) to identify blinded randomised controlled trials (RCTs) that used a flexible-dose oral antipsychotic drug for patients with acute mania. The mean and SD of the effective dose and the pre–post changes in manic symptoms were extracted. A network meta-analysis (NMA) under a frequentist framework was performed to examine the comparative efficacy between the antipsychotics. A classic mean dose method (sample size weighted) was used to calculate each antipsychotic dose equivalent to 1 mg/day olanzapine for acute mania. The antipsychotic dose equivalents of acute mania were compared with published data for schizophrenia.FindingsWe included 42 RCTs which enrolled 11 396 participants with acute mania. The NMA showed that risperidone was superior to olanzapine (reported standardised mean difference: −022, 95% CI −0.41 to –0.02), while brexpiprazole was inferior to olanzapine (standardised mean difference: 0.36, 95% CI 0.08 to 0.64). The dose equivalents to olanzapine (with SD) were 0.68 (0.23) for haloperidol, 0.32 (0.07) for risperidone, 0.60 (0.11) for paliperidone, 8.00 (1.41) for ziprasidone, 41.46 (5.98) for quetiapine, 1.65 (0.32) for aripiprazole, 1.23 (0.20) for asenapine, 0.53 (0.14) for cariprazine and 0.22 (0.03) for brexpiprazole. Compared with the olanzapine dose equivalents for schizophrenia, those of acute mania were higher for quetiapine (pConclusionsAntipsychotic drugs have been considered first-line treatment for acute mania, warranting specific dose equivalence for scientific and clinical purposes.

The prevention of joint deformity is among the most important treatment goals of psoriatic arthritis. Some biologics disease-modifying antirheumatic drugs (bDMARDs) have been demonstrated to be effective for both the skin and joints, as well as for slowing radiographic progression. However, there has been a lack of direct comparisons of bDMARDs. To evaluate the comparative effects of bDMARDs in preventing radiographic progression in psoriatic arthritis, we conducted a systematic review and network meta-analysis. On March 7 2022, a search for relevant randomized trials was conducted on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Our outcomes included radiographic non-progression, a mean change in the total radiographic score, and adverse events leading to discontinuation (DAE) at week 24. We included 11 trials on 10 bDMARDs, involving 4010 participants. Most bDMARDs were more effective than placebos in achieving radiographic non-progression, including adalimumab (odds ratio (OR) 4.7, 95% confidence interval (CI) 2.66–8.29), etanercept (OR 4.19, 95% CI 1.65–10.61), certolizumab pegol (OR 2.83, 95% CI 1.55–5.2), secukinumab 300 mg (OR 2.63, CI 1.62–4.27), infliximab (OR 2.54, CI 1.13–5.69), ixekizumab (OR 2.22, 95% CI 1.06–4.65), golimumab (OR 2.21, 95% CI 1.24–3.93), and abatacept (OR 1.54, 95% CI 1.03–2.28). A significant reduction in the total radiographic score was found in infliximab (standardized mean difference (SMD) −0.59, 95% CI −0.87, −0.3), etanercept (SMD −0.51, 95% CI −0.78, −0.23), adalimumab (SMD −0.45, 95% CI −0.64, −0.26), ixekizumab (SMD −0.37, 95% CI −0.62, −0.12), secukinumab 300 mg (SMD −0.33, 95% CI −0.50, −0.15), golimumab (SMD −0.33, 95% CI −0.58, −0.09), secukinumab 150 mg (SMD −0.25, 95% CI −0.43, −0.07), certolizumab pegol (SMD −0.23, 95% CI −0.44, −0.03), and ustekinumab (SMD −0.19, 95% CI −0.35, −0.33). No significant differences in DAE were detected between bDMARDs. In conclusion, anti-tumor necrosis factor agents (adalimumab, infliximab, and etanercept) may be preferred for treating psoriatic arthritis for their superiority in preventing radiographic progression.

Smoking cessation is a public health priority to reduce smoking-related morbidity and mortality. However, weight gain is a known primary reason for not trying to quit smoking. The aim of the current study was to investigate differences in weight gain associated with different pharmacological smoking cessation interventions. Randomized controlled trials (RCTs) that reported weight gain related to pharmacologic treatments for smoking cessation were analysed using network meta-analysis with a random effects model. Thirty-one RCTs with 5650 participants were included. Ten drugs and 22 regimens were identified. Nicotine patches plus fluoxetine, topiramate with/without nicotine patches, nicotine patches plus methylphenidate, nicotine spray/gum/lozenges, high-dose nicotine patches (42 mg/21 mg), naltrexone with/without nicotine patches, or bupropion with/without nicotine patches were associated with less weight gain than the placebo/control arm. Nicotine patches plus fluoxetine were associated with the least weight gain of all smoking cessation treatments. In addition, the nicotine patch plus topiramate and nicotine inhaler was associated with the best success rate and the least dropout rate, respectively. Overall, the nicotine patch 14 mg plus fluoxetine 40 mg, nicotine patch 14 mg plus fluoxetine 20 mg, and topiramate 200 mg would be the three best pharmacologic treatments based upon both weight gain effect and success rate.

Background: People with dementia die prematurely. Identifying differences in mortality rates between different types of dementia might aid in the development of preventive interventions for the most vulnerable populations. The aim of this study was to compare the difference in mortality rates between individuals without dementia and individuals with various types of dementia. Methods: For this systematic review and meta-analysis, we did a systematic search of MEDLINE, PubMed, Embase, and Cochrane Library from inception to July 11, 2020, for cross-sectional or cohort studies that assessed mortality and survival-related outcomes among people with different types of dementia compared with people without dementia. Single-arm studies without comparison groups and autopsy studies or family studies that used a selected sample were excluded. The Newcastle-Ottawa Scale was used by two authors (D-JL and C-SC) independently to measure the methodological quality of included studies, and two authors (F-CY and P-TT) independently extracted data. We assessed differences in all-cause mortality rate and survival time from dementia diagnosis between individuals without dementia, individuals with Alzheimer's disease, and individuals with non-Alzheimer's disease dementias. The secondary outcomes were age at death and survival time from disease onset. Random-effects meta-analyses were done. Effect sizes included hazard ratios (HRs) and mean differences (MDs) with 95% CIs. Potential moderators, including age-associated moderators, were identified through meta-regression and subgroup analyses. This study is registered with PROSPERO, CRD42020198786. Findings: Our database search identified 11 973 records, and we included 78 eligible studies in our analyses, encompassing 63 125 individuals with dementia and 152 353 controls. Individuals with any type of dementia had a higher mortality rate than individuals without dementia (HR 5·90, 95% CI 3·53 to 9·86), and the HR for all-cause mortality was highest for Lewy body dementia (17·88, 5·87 to 54·46). After diagnosis, the mean survival time for people with Alzheimer's disease was 5·8 years (SD 2·0). Compared with people with Alzheimer's disease, a diagnosis of any non-Alzheimer's disease dementia was associated with a higher risk of all-cause mortality (HR 1·33, 1·21 to 1·46), a shorter survival time from diagnosis (MD −1·12 years, 95% CI −1·52 to −0·72), and a younger age at death (−1·76 years, −2·66 to −0·85). Survival time from disease onset was also shorter in people with non-Alzheimer's dementia, across types, compared with people with Alzheimer's disease, but the subgroup analysis revealed that this difference was only significant for vascular dementia (MD −1·27 years, −1·90 to −0·65) and dementia with Lewy bodies (MD −1·06 years, −1·68 to −0·44). The interactions between age and several survival-related outcomes were significant. 39 (50%) of the 78 included studies were rated as good quality, and large heterogeneity (I 2>75%) was observed for most of the study outcomes. Interpretation: Alzheimer's disease is the most common type of dementia and one of the major causes of mortality worldwide. However, the findings from the current study suggest that non-Alzheimer's disease dementias were associated with higher morality rates and shorter life expectancy than Alzheimer's disease. Developing tailored treatment and rehabilitation programmes for different types of dementia is important for mental health providers, patients, and their families. Funding: None.

Background: People with dementia die prematurely. Identifying differences in mortality rates between different types of dementia may aid in the development of preventive interventions for these most vulnerable populations. Methods: A systematic search of the MEDLINE, PubMed, EMBASE, and Cochrane Library from inception to May 31, 2020 was conducted for case-control or cohort studies providing mortality and survival-related outcomes among people with different types of dementia. The primary outcomes were the all-cause mortality rate and survival time from dementia diagnosis between the general population, people with Alzheimer’s disease (AD), and those with non-AD dementias. The secondary outcomes were age at death and survival time from disease onset. Random-effects meta-analyses were conducted. Effect sizes included hazard ratios (HRs) and mean differences (MDs) with 95% confidence intervals (CIs). Potential moderators were identified through meta-regression and subgroup analyses. The Newcastle Ottawa Scale was used to measure the methodological quality of eligible studies. Heterogeneity was assessed with the I2 statistic and sensitivity analyses were undertaken. Findings: Data were extracted from 78 eligible studies encompassing 152,353 controls and 63,125 cases of dementia. All-cause mortality occurred in 20,927 of 152,174 controls and in 2,684 of 8,102 cases of dementia during a median 5-year follow-up. After diagnosis, the median survival time for people with AD was 4·4 (range, 1·3, 10) years. Compared to controls, the HR of all-cause mortality was highest for Lewy body dementia (17·88; 95% CI, 5·87, 54·46). Compared to AD, a diagnosis of any non-AD dementia was associated with a higher risk of all-cause mortality (HR, 1·33; 95% CI, 1·21, 1·46), a shorter survival time from diagnosis (MD, -1·12; 95% CI, -1·52, -0·72), and a younger age at death (MD, -1·76; 95% CI, -2·67, -0·85). However, group differences between distinct subtypes of non-AD dementia were not significant. Interpretation: AD is the most common type of dementia and the leading cause of mortality world-wide, but non-AD dementias have a worse prognosis in terms of mortality and survival. Funding: None to declare. Declaration of Interest: None to declare