Multiple data sources are preferred in adverse drug event (ADEs) surveillance owing to inadequacies of single source. However, analytic methods to monitor potential ADEs after prolonged drug exposure are still lacking. In this study we propose a method aiming to screen potential ADEs by combining FDA Adverse Event Reporting System (FAERS) and Electronic Medical Record (EMR). The proposed method uses natural language processing (NLP) techniques to extract treatment outcome information captured in unstructured text and adopts case-crossover design in EMR. Performances were evaluated using two ADE knowledge bases: Adverse Drug Reaction Classification System (ADReCS) and SIDER. We tested our method in ADE signal detection of conventional disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis patients. Findings showed that recall greatly increased when combining FAERS with EMR compared with FAERS alone and EMR alone, especially for flexible mapping strategy. Precision (FAERS + EMR) in detecting ADEs improved using ADReCS as gold standard compared with SIDER. In addition, signals detected from EMR have considerably overlapped with signals detected from FAERS or ADE knowledge bases, implying the importance of EMR for pharmacovigilance. ADE signals detected from EMR and/or FAERS but not in existing knowledge bases provide hypothesis for future study.

Introduction: Although pharmaceutical companies, regulatory authorities, and health technology assessment (HTA) agencies have been increasingly using decision-making frameworks, it is not certain whether these enable better quality decision making. This could be addressed by formally evaluating the quality of decision-making process within those organizations. The aim of this literature review was to identify current techniques (tools, questionnaires, surveys, and studies) for measuring the quality of the decision-making process across the three stakeholders. Methods: Using MEDLINE, Web of Knowledge, and other Internet-based search engines, a literature review was performed to systematically identify techniques for assessing quality of decision making in medicines development, regulatory review, and HTA. A structured search was applied using key words and a secondary review was carried out. In addition, the measurement properties of each technique were assessed and compared. Ten Quality Decision-Making Practices (QDMPs) developed previously were then used as a framework for the evaluation of techniques identified in the review. Due to the variation in studies identified, meta-analysis was inappropriate. Results: This review identified 13 techniques, where 7 were developed specifically to assess decision making in medicines' development, regulatory review, or HTA; 2 examined corporate decision making, and 4 general decision making. Regarding how closely each technique conformed to the 10 QDMPs, the 13 techniques assessed a median of 6 QDMPs, with a mode of 3 QDMPs. Only 2 techniques evaluated all 10 QDMPs, namely the Organizational IQ and the Quality of Decision Making Orientation Scheme (QoDoS), of which only one technique, QoDoS could be applied to assess decision making of both individuals and organizations, and it possessed generalizability to capture issues relevant to companies as well as regulatory authorities. Conclusion: This review confirmed a general paucity of research in this area, particularly regarding the development and systematic application of techniques for evaluating quality decision making, with no consensus around a gold standard. This review has identified QoDoS as the most promising available technique for assessing decision making in the lifecycle of medicines and the next steps would be to further test its validity, sensitivity, and reliability.

Objective: Consumers increasingly buy pharmaceuticals online. No scoping review has been carried out to summarize and synthesize the studies that have identified drivers of consumers' purchase intention and behavior from online pharmacies. Thus, we conducted a scoping review to explore the extent to which prior research has studied consumer purchase intentions and behavior related to online pharmacies, the drivers previously identified to explain consumers' online pharmacy purchase intentions and behavior, and how these antecedents differ between OTC and prescription medications. Then, we identified gaps in the published literature to form a comprehensive theory-based agenda for future research. Methods: We searched PubMed, Web of Science, and Scopus to retrieve relevant studies published in English in peer-reviewed journals. The search strategy identified forty-eight eligible studies. Results: We identified twelve types of factors influencing purchase intentions and behaviors from online pharmacies: demographics, convenience, availability, price, evaluations of the purchase environment, information sources, internet usage, prior experience, perceived risk, health insurance, privacy, and product. Our analysis also revealed differences between OTC and prescription medications in drivers of purchase intentions and behaviors. Conclusion: While demographic factors tended to be the most often measured influences on intentions and behavior, their role was generally inconsistent, with many contradictory results. However, other factors (e.g., convenience, availability, lower prices, and favorable evaluations toward the purchase environment) more consistently enhanced online medication purchase intentions and behavior. An extensive agenda for future research is advanced.

Despite the significant health impacts of adverse events associated with drug-drug interactions, no standard models exist for managing and sharing evidence describing potential interactions between medications. Minimal information models have been used in other communities to establish community consensus around simple models capable of communicating useful information. This paper reports on a new minimal information model for describing potential drug-drug interactions. A task force of the Semantic Web in Health Care and Life Sciences Community Group of the World-Wide Web consortium engaged informaticians and drug-drug interaction experts in in-depth examination of recent literature and specific potential interactions. A consensus set of information items was identified, along with example descriptions of selected potential drug-drug interactions (PDDIs). User profiles and use cases were developed to demonstrate the applicability of the model. Ten core information items were identified: drugs involved, clinical consequences, seriousness, operational classification statement, recommended action, mechanism of interaction, contextual information/modifying factors, evidence about a suspected drug-drug interaction, frequency of exposure, and frequency of harm to exposed persons. Eight best practice recommendations suggest how PDDI knowledge artifact creators can best use the 10 information items when synthesizing drug interaction evidence into artifacts intended to aid clinicians. This model has been included in a proposed implementation guide developed by the HL7 Clinical Decision Support Workgroup and in PDDIs published in the CDS Connect repository. The complete description of the model can be found at https://w3id.org/hclscg/pddi.

Objective: Telavancin is approved to treat complicated skin and skin structure infections, hospital-acquired, and ventilator-associated bacterial pneumonia caused by Staphylococcus aureus. A previous meta-analysis of randomized controlled trials suggested that it might be an alternative to vancomycin in cases of difficult-to-treat meticillin-resistant S. aureus infections. We did a meta-analysis including one new trial to access the efficacy and safety of telavancin. Methods: We searched PubMed, Cochrane Central Register of Controlled Trials, EMBASE and ClinicalTrials.gov up to December 30, 2015 to identify randomized controlled trials that assessed the clinical efficacy, eradication efficiency, adverse events and laboratory abnormalities of telavancin vs. other antibiotic agents for bacterial infection. Meta-analysis was performed using Review Manager 5.3.0. Results: Five studies (3790 participants) were included in the meta-analysis. There was no significant difference in treatment success with telavancin than with control antibiotic agents. The pooled pathogen eradication for the telavancin group was numerically higher than that for the control groups, but there was no significant difference. While all-cause mortalities and serious adverse events were comparable between telavancin and control antibiotic agents, adverse event-related withdrawals (OR 1.47, 95% CI 1.13-1.91) were higher in telavancin group. The total number adverse events were more in the telavancin group than in the control groups, especially in the digestive system (OR 1.57, 95% CI 1.37-1.79), nervous system (OR 2.14, 95% CI 1.86-2.47) and urogenital system (OR 2.54, 95% CI 1.99-3.25). Serum creatinine increase (OR 2.25, 95% Cl 1.78-2.85) and hypokalemia (OR 1.74, 95% CI 1.19-2.53) occurred more frequently in telavancin group compared to control groups. Conclusion: Telavancin may be as effective as but no better than the comparison therapy for S. aureus infection. However, because of the high risk of adverse event-related withdrawals and potential nephrotoxicity, prudence with the clinical use of telavancin in infections is required.

Oral non-steroidal anti-inflammatory drugs (NSAIDs) are known to be associated with an increased risk of bleeding. The NSAID, flurbiprofen, in the form of 8.75 mg lozenge or oromucosal spray is indicated for the symptomatic relief of sore throat. Despite the low dose as compared to alternative flurbiprofen preparations, concerns have been raised regarding its safety in terms of haemorrhagic events. This systematic review was conducted to identify existing evidence on the risk of haemorrhagic events with flurbiprofen 8.75 mg dose (any formulation), particularly where this may be due to potential interactions with other medicinal products. The systematic review examined studies reporting haemorrhagic events in patients receiving flurbiprofen 8.75 mg dose. Six individual electronic databases were searched up to 28th April 2020. Records were initially screened for relevance followed by further review of potentially eligible studies. Data extraction was performed for eligible studies and risk of bias in studies was assessed. The search strategy identified 1093 individual records. Of these, 1038 records were excluded after initial review; the majority of these records related to flurbiprofen in alternative formulations with alternative doses (e.g., eye drops, skin patches, oral tablets) thus were not considered relevant for further review. The 55 remaining records related to flurbiprofen 8.75 mg dose (any formulation) or flurbiprofen lozenge/oromucosal spray where the dose was not specified. After further review, 52 of these records were not considered eligible. Thus, only three records were included in this systematic review. The three studies reported a total of five haemorrhagic events in patients taking flurbiprofen 8.75 mg lozenge; the corresponding risk in each of the studies was 8.33, 1.98 and 1.96%. Where possible, comparison of flurbiprofen 8.75 mg lozenge to placebo produced risk ratios of 0.96 (95% CI 0.07, 13.25) and 2.00 (95% CI 0.10, 118.0). This systematic review found limited evidence on the risk of haemorrhagic events with flurbiprofen when used at a dose of 8.75 mg. Counts were low across all studies and results comparing flurbiprofen and placebo treatment arms were non-significant. However, scarcity of studies and low certainty of evidence for the outcome of haemorrhagic events limits the conclusions of this systematic review.

Objective: To systematically review and compare the efficacy and posttreatment resistance of ceftazidime-avibactam therapy and ceftazidime-avibactam-based combination therapy in patients with Gram-negative pathogens. Methods: PubMed, Embase, Web of Science, CNKI, and Wanfang Data databases were searched from their inception up to March 31, 2021, to obtain studies on ceftazidime-avibactam therapy versus ceftazidime-avibactam-based combination therapy in patients with carbapenem-resistant Gram-negative pathogens. The primary outcome was mortality rate, and the second outcomes were microbiologically negative, clinical success, and the development of resistance after ceftazidime-avibactam treatment. Results: Seventeen studies representing 1,435 patients (837 received ceftazidime-avibactam-based combination therapy and 598 received ceftazidime-avibactam therapy) were included in the meta-analysis. The results of the meta-analysis showed that no statistically significant difference was found on mortality rate (Petos odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.79-1.34), microbiologically negative (OR = 0.99, 95% CI 0.54-1.81), and clinical success (OR =0.95, 95% CI 0.64-1.39) between ceftazidime-avibactam-based combination therapy and ceftazidime-avibactam therapy. Although there was no difference in posttreatment resistance of ceftazidime-avibactam (OR = 0.65, 95% CI 0.34-1.26) in all included studies, a trend favoring the combination therapy was found (according to the pooled three studies, OR = 0.18, 95% CI 0.04-0.78). Conclusions: The current evidence suggests that ceftazidime-avibactam-based combination therapy may not have beneficial effects on mortality, microbiologically negative, and clinical success to patients with carbapenem-resistant Gram-negative pathogens. A trend of posttreatment resistance occurred more likely in ceftazidime-avibactam therapy than the combination therapy. Due to the limited number of studies that can be included, additional high-quality studies are needed to verify the above conclusions.

Background: Immune checkpoint inhibitors (ICIs) have made a significant breakthrough in the treatment of solid tumors; however, their use also generates unique immune-related adverse effects (irAEs). Here, we performed a systematic review and meta-analysis to assess the risk of immune-related liver dysfunction between in patients treated by programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors exclusively and chemotherapy. Methods: A comprehensive search of multiple databases identified eligible studies, including randomized controlled trials (RCTs) with PD-1/PD-L1 inhibitors exclusively and chemotherapy in patients with different solid tumors was carried out. The elevations of alanine aminotransferase (ALT) and aspartic aminotransferase (AST) were used to evaluate liver dysfunction. The relative risk (RR) and 95% confidence intervals (CI) were calculated and analyzed by Review Manager 5.3 and STATA version 12.0 statistical software. Results: After screening and eligibility assessment, a total of 5638 patients from 12 RCTs were included in our meta-analysis. In comparison with chemotherapy, patients treated with PD-1/PD-L1 inhibitors exclusively showed an increased incidence of all-grade ALT/AST elevations (ALT: RR, 1.52, 95% CI, 1.09-2.13; p = 0.01; AST: RR, 1.96, 95% CI, 1.37-2.81; p = 0.0002). Patients receiving PD-1 inhibitors showed the significantly higher risk of all-grade ALT/AST elevations incidence than those receiving chemotherapy (ALT: RR, 1.47; 95% CI, 1.05-2.07; p = 0.03; AST: RR, 1.90, 95% CI, 1.32-2.73; p = 0.0005). However, no significant difference was found between PD-L1 inhibitor and chemotherapy group. Moreover, for non-small cell lung cancer (NSCLC) and urothelial carcinoma (UC), patients treated with PD-1/PD-L1 inhibitors exclusively exhibited a significant higher risk of all-grade ALT elevation incidence (NSCLC: RR, 1.92; 95% CI, 1.23-3.02; p = 0.004; UC: RR, 3.36; 95% CI, 1.12-10.06, p = 0.03) and all-grade AST elevation incidence (NSCLC: RR, 2.37; 95% CI, 1.45-3.87, p = 0.0005; UC: RR, 4.47; 95% CI, 1.30-15.38, p = 0.02) than chemotherapy. Conclusions: The meta-analysis confirms that PD-1/PD-L1 inhibitors exclusive pose an increased risk of immune-related liver dysfunction than chemotherapy. PD-1/PD-L1 blockade in NSCLC and UC increase the risk of immune-related liver dysfunction, but not in melanoma (MM) and head-neck squamous cell carcinoma (HNSCC).

Imatinib mesylate (IM) is the standard treatment for advanced, metastatic gastrointestinal stromal tumors (GISTs) and chronic myeloid leukemia (CML) with a fixed daily standard dosage via the oral route. Interindividual and intraindividual variability in plasma concentrations have been closely linked to the efficacy of IM therapy. Therefore, this review identifies and describes the key factors influencing the plasma concentration of IM in patients with GISTs and CML. We used the following keywords to search the PubMed, EMBASE, Ovid, Wangfang, and CNKI databases to identify published reports: IM, plasma concentration, GISTs, CML, drug combination/interaction, pathology, and genotype/genetic polymorphism, either alone or in combination. This literature review revealed that only 10 countries have reported the mean concentrations of IM in GISTs or CML patients and the clinical outcomes in different ethnic groups and populations. There were totally 24 different gene polymorphisms, which were examined for any potential influence on the steady-state plasma concentration of IM. As a result, some genotype locus made discrepant conclusion. Herein, the more sample capacity, multicenter, long-term study was worthy to carry out. Eleven reports were enumerated on clinical drug interactions with IM, while there is not sufficient information on the pharmacokinetic parameters altered by drug combinations with IM that could help in investigating the actual drug interactions. The drug interaction with IM should be paid more attention in the future research.

Patients receive information about their medication from different sources, including prescription labels. These labels are physically attached to each package dispensed to patients and contain the most important instructions on how to use the medication correctly. However, many patients experience difficulties in understanding and applying the instructions on these labels correctly, especially patients with limited health literacy. The aim of this study is to investigate the comprehensibility of prescription label instructions among patients with adequate and limited health literacy skills, and to implement improvements in primary health care.

Introduction: At the initial part of the gastrointestinal tract, multiple tissues serve the normal function of food delivery. Periodontal structures are integral elements of these. When they deteriorate, it is extremely challenging to regenerate and reconstruct them. The conventional intervention for periodontal disease is scaling and root planning with the aim of reducing pathogenic bacteria. However, periodontal pathogens can rapidly recolonize treated areas. Probiotics have been proposed as novel tools for managing oral health by suppressing pathogenic bacteria through their anti-inflammatory effect, but the available data are controversial. Aim: Therefore, we performed a meta-analysis to study the effect of probiotics on periodontal pathogenic bacteria. Methods: The study was registered in PROSPERO under registration number CRD42018094903. A comprehensive literature search from four electronic databases (PubMed, Cochrane CENTRAL, Embase, and Web of Science) yielded nine eligible records for statistical analysis. Studies measuring bacterial counts in saliva and supra- and subgingival plaque were included. Bacterial counts were analyzed using standard mean difference (SMD) and by a random effects model with the DerSimonian-Laird estimation. Results: The results showed a significant decrease in the overall count of Aggregatibacter actinomycetemcomitans in the probiotic-treated group compared to the control at 4 weeks (SMD: -0.28; 95% CI: -0.56--0.01; p = 0.045) but not later. Analyzing the bacterial counts in subgroups, namely, in saliva and supra- and subgingival plaque, separately, yielded no significant difference. Probiotics had no significant effect on the overall count of Porphyromonas gingivalis at 4 weeks (SMD: -0.02; 95% CI: -0.35-0.31; p = 0.914) or later. Subgroup analysis also revealed no significant difference between treatment and control groups nor did probiotics significantly decrease the overall and subgroup bacterial counts of Prevotella intermedia, Tannerella forsythia, and Fusobacterium nucleatum. Conclusion: Our data support the beneficial effect of probiotics in reducing A. actinomycetemcomitans counts, but not of other key periodontal pathogenic bacteria in periodontal disease patients. However, due to the complex mechanism associated with periodontal disease and the limitations of the available studies, there is a further need for well-designed randomized clinical trials to assess the efficacy of probiotics.

Objective: This study aims to determine the efficacy of the Acacia arabica (Lam.) Willd. and Cinnamomum camphora (L.) J. Presl. vaginal suppository in addressing heavy menstrual bleeding (HMB) and their impact on participants' health-related quality of life (HRQoL) analyzed using machine learning algorithms. Method: A total of 62 participants were enrolled in a double-dummy, single-center study. They were randomly assigned to either the suppository group (SG), receiving a formulation prepared with Acacia arabica gum (Gond Babul) and camphor from Cinnamomum camphora (Kafoor) through two vaginal suppositories (each weighing 3,500 mg) for 7 days at bedtime along with oral placebo capsules, or the tranexamic group (TG), receiving oral tranexamic acid (500 mg) twice a day for 5 days and two placebo vaginal suppositories during menstruation at bedtime for three consecutive menstrual cycles. The primary outcome was the pictorial blood loss assessment chart (PBLAC) for HMB, and secondary outcomes included hemoglobin level and SF-36 HRQoL questionnaire scores. Additionally, machine learning algorithms such as k-nearest neighbor (KNN), AdaBoost (AB), naive Bayes (NB), and random forest (RF) classifiers were employed for analysis. Results: In the SG and TG, the mean PBLAC score decreased from 635.322 ± 504.23 to 67.70 ± 22.37 and 512.93 ± 283.57 to 97.96 ± 39.25, respectively, at post-intervention (TF3), demonstrating a statistically significant difference (p < 0.001). A higher percentage of participants in the SG achieved normal menstrual blood loss compared to the TG (93.5% vs 74.2%). The SG showed a considerable improvement in total SF-36 scores (73.56%) compared to the TG (65.65%), with a statistically significant difference (p < 0.001). Additionally, no serious adverse events were reported in either group. Notably, machine learning algorithms, particularly AB and KNN, demonstrated the highest accuracy within cross-validation models for both primary and secondary outcomes. Conclusion: The A. arabica and C. camphora vaginal suppository is effective, cost-effective, and safe in controlling HMB. This botanical vaginal suppository provides a novel and innovative alternative to traditional interventions, demonstrating promise as an effective management approach for HMB.

Background: The vaccine against the rotavirus is an effective measure in reducing hospitalizations and mortality caused by the virus. However, its use can result in serious adverse effects. The available evidence on Kawasaki disease has not yet been reported in the literature. This study investigated the risk of developing Kawasaki disease with the use of rotavirus vaccines in children. Methods: This is a systematic review of data collected from studies retrieved on the following databases: Cochrane, MEDLINE, Embase, CINAHL, Scopus, Web of Science, HealthSTAR, Lilacs, Clinical trial.gov, and International Clinical Trials Registry Platform, up to the 15th of August 2018, with no restrictions on language or date of publication. The outcomes measured were incidence of Kawasaki disease, risk of developing the disease, and rate of discontinuation of the vaccination schedule. Four reviewers independently selected the studies, performed data extraction, and assessed the quality of evidence. A meta-analysis of random effects was performed. Results: A total of 13 publications were included, with a population of 164,434 children included in the meta-analysis. The incidence of Kawasaki disease (24 cases per 100,000, 95% CI = 11.98-48.26) in the vaccinated children was low. No difference between the vaccines was found in the prevalence rate of adverse effects (RR = 1.55, 95% CI = 0.41-5.93). Use of the vaccines was not associated with risk of developing Kawasaki disease (low-quality evidence). None of the studies reported the rate of discontinuation of the vaccination schedule. Conclusions: The vaccines were associated with a low incidence of developing Kawasaki disease, showing no association with this serious adverse effect.

Background: Patients over 65 years of age taking multiple medications face several risks, and pharmaceutical interventions can be useful to improve quality of care and reduce those risks. However, there is still no consensus on the effectiveness of these interventions aimed at promoting changes in clinical, epidemiological, economic, and humanistic outcomes for various service delivery, organizational, financial, and implementation-based interventions. The objective of this overview of systematic reviews was to summarize evidence on the effectiveness of community-level pharmaceutical interventions to reduce the risks associated with polypharmacy in the population over 65 years of age. Method: This overview used a previously described protocol to search for systematic review articles, with and without meta-analysis, and economic evaluations, without any language or time restrictions, including articles published up to May 2018. The following databases were searched: the Cochrane Library, Epistemonikos, Health Evidence, Health Systems Evidence, Virtual Health Library, and Google Scholar. The basic search terms used were "elderly," "polypharmacy," and "pharmaceutical interventions." The findings for outcomes of interest were categorized using a taxonomy for health policies and systems. Equity-related questions were also investigated. The studies were evaluated for methodological quality and produced a narrative synthesis. Results: A total of 642 records were retrieved: 50 from Health Evidence, 197 from Epistemonikos, 194 from Cochrane, 116 from Health Systems Evidence, and 85 from the Virtual Health Library. Of these, 16 articles were selected: 1 overview of systematic reviews, 12 systematic reviews, and 3 economic evaluations. There is evidence of improvement in clinical, epidemiological, humanistic, and economic outcomes for various types of community-level pharmaceutical interventions, but differences in observed outcomes may be due to study designs, primary study sample sizes, risk of bias, difficulty in aggregating data, heterogeneity of indicators and quality of evidence included in the systematic reviews that were assessed. It is necessary to optimize the methodological designs of future primary and secondary studies. Conclusion: Community-level pharmaceutical interventions can improve various clinical, epidemiological, humanistic and economic outcomes and potentially reduce risks associated with polypharmacy in the elderly population.

Background: Ulinastatin has been prescribed to treat sepsis. However, there is doubt regarding the extent of any improvement in outcomes to guide future decision making. Objectives: To evaluate the effects of ulinastatin on mortality and related outcomes in sepsis patients. Methods: Thirteen randomized controlled trials and two prospective studies published before September 1, 2018, that included 1358 patients with sepsis, severe sepsis, or septic shock were evaluated. The electronic databases searched in this study were PubMed, Medline, Embase, and China National Knowledge Infrastructure (CNKI) for Chinese Technical Periodicals. Results: Ulinastatin significantly decreased the all-cause mortality {odds ratio (OR) = 0.48, 95% confidence interval (CI) [0.35-0.66], p < 0.00001, I2 = 13%}, Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score {mean difference (MD) = -2.40, 95% CI [-4.37, -0.44], p = 0.02, I2 = 66%}, and reduced the incidence of multiple organ dysfunction syndrome (MODS) (OR = 0.3, 95% CI [0.18, 0.49], p < 0.00001, I2 = 0%). Ulinastatin also decreased the serum levels of IL-6 (MD = -88.5, 95% CI [-123.97, -53.04], p < 0.00001), TNF-α (MD = -56.22, 95% CI [-72.11, -40.33], p < 0.00001), and increased the serum levels of IL-10 (MD = 37.73, 95% CI [16.92, 58.54], p = 0.0004). Ulinastatin administration did not lead to any difference in the occurrence of adverse events. Conclusions: Ulinastatin improved all-cause mortality and other related outcomes in patients with sepsis or septic shock. The results of this meta-analysis suggest that ulinastatin may be an effective treatment for sepsis and septic shock.

Background: Long-term maintenance therapy with proton pump inhibitors (PPIs) is a common treatment strategy for acid-related gastrointestinal diseases. However, concerns have been raised about the potential increased risk of gastric cancer and related precancerous lesions with long-term PPI use. This systematic review and meta-analysis aimed to evaluate this potential risk. Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials published before 1 March 2023, with no language restrictions. The primary endpoint was the occurrence and progression of gastric mucosal atrophy, intestinal metaplasia, Enterochromaffin-like (ECL) cell hyperplasia, gastric polyps, and gastric cancer during the trial and follow-up. Data were analysed using a random effects model. Results: Of the 4,868 identified studies, 10 met the inclusion criteria and were included in our analysis, comprising 27,283 participants. Compared with other treatments, PPI maintenance therapy for more than 6 months was associated with an increased risk of ECL cell hyperplasia (OR 3.01; 95% CI 1.29 to 7.04; p = 0.01). However, no significant increase was found in the risk of gastric mucosal atrophy (OR 1.01; 95% CI 0.55 to 1.85; p = 0.97), intestinal metaplasia (OR 1.14; 95% CI 0.49 to 2.68; p = 0.76), gastric polyps (OR 1.13; 95% CI 0.68 to 1.89; p = 0.64), or gastric cancer (OR 1.06; 95% CI 0.79 to 1.43; p = 0.71). Conclusion: This systematic review and meta-analysis does not support an increased risk of gastric cancer or related precancerous lesions with long-term PPI maintenance therapy. However, long-term PPI use should be monitored for potential complications such as ECL cell hyperplasia. Further studies are needed to confirm these findings and evaluate the safety of PPI maintenance therapy for acid-related gastrointestinal diseases. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, Identifier: PROSPERO (CRD42022379692).

Our current 24-h society requires an increasing number of employees to work nightshifts with millions of people worldwide working during the evening or night. Clear associations have been found between shiftwork and the risk to develop metabolic health problems, such as obesity. An increasing number of studies suggest that the underlying mechanism includes disruption of the rhythmically organized body physiology. Normally, daily 24-h rhythms in physiological processes are controlled by the central clock in the brain in close collaboration with peripheral clocks present throughout the body. Working schedules of shiftworkers greatly interfere with these normal daily rhythms by exposing the individual to contrasting inputs, i.e., at the one hand (dim)light exposure at night, nightly activity and eating and at the other hand daytime sleep and reduced light exposure. Several different animal models are being used to mimic shiftwork and study the mechanism responsible for the observed correlation between shiftwork and metabolic diseases. In this review we aim to provide an overview of the available animal studies with a focus on the four most relevant models that are being used to mimic human shiftwork: altered timing of (1) food intake, (2) activity, (3) sleep, or (4) light exposure. For all studies we scored whether and how relevant metabolic parameters, such as bodyweight, adiposity and plasma glucose were affected by the manipulation. In the discussion, we focus on differences between shiftwork models and animal species (i.e., rat and mouse). In addition, we comment on the complexity of shiftwork as an exposure and the subsequent difficulties when using animal models to investigate this condition. In view of the added value of animal models over human cohorts to study the effects and mechanisms of shiftwork, we conclude with recommendations to improve future research protocols to study the causality between shiftwork and metabolic health problems using animal models.

The World Health Organization recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria to improve the therapeutic efficacy and limit the choice of drug-resistant parasites. This systematic review and meta-analysis aimed to evaluate the comparative efficacy and safety of artemisinin-piperaquine (AP) in the treatment of uncomplicated malaria relative to other commonly used ACTs.

Cognitive impairment is a central feature of schizophrenia and has shown to play a crucial role in the psychosocial function of the disorder. Over the past few years, several cognitive remediation (CR) interventions have been developed for schizophrenia, whose effectiveness has also been widely demonstrated by systematic reviews and meta-analysis studies. Despite these evidences, many questions remain open. In particular, the identification of CR response predictors in patients with schizophrenia is still a topic with equivocal findings and only a few studies have looked for the relationship between CR response or resistance and the biological, socio-demographic, clinical and cognitive features in schizophrenia. The current knowledge on positive or negative response predictors to CR treatment in schizophrenia include: age, duration of illness, premorbid adjustment, baseline cognitive performance, intrinsic motivation, hostility, disorganized symptoms, neurobiological reserve, genetic polymorphisms, the amounts of antipsychotics, the type of CR, etc. The aim of this review is to identify neurobiological, psychopathological, cognitive, and functional predictors of CR response or resistance in schizophrenia, taking into account both cognitive and functional outcome measures. The information obtained could be very useful in planning integrated and personalized interventions, also with a better use of the available resources.

To explore the short-term efficacy and tolerability of paroxetine in the treatment of panic disorder in adults.