Anticandidal synergistic activity of Ocimum sanctum and fluconazole of azole resistance strains of clinical isolates

Candida albicans is the most prevalent fungal pathogen in humans. It is the causative agent and most associated with serious fungal infection, accounting for more than 90% of cases. It is a most common cause of deep mycoses and vulvovaginal candidiasis. In the present study we found that methanolic extract of O. sanctum in combination of fluconazole shows higher zone of inhibition and lesser MIC values as compared to methanolic extract of leaves of O. sanctum or fluconazole when used alone. Synergistic antimicrobial activity was found when methanolic extract of leaves of O. sanctum was used in combination with fluconazole against C. albicans azole resistance strains isolated from catheter tip (CT) and high vaginal swab (HVS) (FIC ≤ 0.5). Partial synergistic activity was observed against urine (U). Methanolic extract of stem of O. sanctum in combination with fluconazole gave indifferent antifungal results (FIC = 1.0–4.0). Benzene extract of the leaf and stem of O. sanctum in combination with fluconazole showed indifferent antifungal results (FIC = 1.0–4.0). Aqueous extract of leaves of O. sanctum in combination with fluconazole showed partial synergistic antimicrobial activity against catheter tip (CT) and high vaginal swab (HVS) and urine (U) (FIC = 0.5–1.0). In the present study we evaluate the synergism of C. albicans against azole resistant clinical isolates. This study indicates clear evidence supporting the traditional use of O. sanctum in treating Candida infectious diseases.     

Epidemiology of Clostridium difficile infection in a large teaching hospital in Singapore

AIMS: We undertook this study to define the incidence of toxigenic Clostridium difficile in our hospital and to characterise the isolates. METHODS: All unformed stool was tested for the presence of Toxin A (TcdA) and Toxin B (TcdB), and cultured for C. difficile. Culture filtrates were also tested for TcdA and TcdB. Detection of tcdA and tcdB genes was carried out for A(-)B(+) strains by polymerase chain reaction (PCR).The minimum inhibitory concentrations (MICs) of metronidazole, vancomycin and clindamycin for all isolates were tested using the Etest. PCR ribotyping was carried out on all isolates. RESULTS: The incidence of Clostridium difficile associated disease (CDAD) was 3.2 cases per 1000 admissions or discharges and 53.8 cases per 100 000 patient days. Most cases occurred in renal and haematology patients. CDAD was more common in patients aged over 50 years and of male gender. The Indian population was under-represented. Fourteen (11.8%) isolates were A(-)B(+). All strains were susceptible to metronidazole but one strain showed intermediate resistance to vancomycin. Only 12.8% of the isolates were susceptible to clindamycin. Thirty-five isolates had PCR ribotype A, of which 29 (83%) had a clindamycin MIC >256 mg/L. Thirty-three had PCR ribotype B, of which only one (3%) had a clindamycin MIC >256 mg/L. The 14 A(-)B(+) strains were all PCR ribotype C, and had a range of MICs for clindamycin from 2 to >256 mg/L. CONCLUSIONS: The incidence of CDAD in our hospital is relatively low. Isolates remain susceptible to metronidazole and vancomycin.     

Impact of vaccination on antibiotic usage: a systematic review and meta-analysis

BackgroundVaccines may reduce antibiotic use and the development of resistance.ObjectivesTo provide a comprehensive, up-to-date assessment of the evidence base relating to the effect of vaccines on antibiotic use.Data sourcesOvid MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and WHO Trials Registry.Study eligibility criteriaRandomized controlled trials (RCTs) and observational studies published from January 1998 to March 2018.ParticipantsAny population.InterventionsVaccines versus placebo, no vaccine or another vaccine.MethodsTitles, abstracts and full-texts were screened independently by two reviewers. Certainty of RCT evidence was assessed using GRADE.ResultsIn all, 4980 records identified; 895 full-text reports assessed; 96 studies included (24 RCTs, 72 observational). There was high-certainty evidence that influenza vaccine reduces days of antibiotic use among healthy adults (one RCT; n = 4253; rate reduction 28·1%; 95% CI 16·0–38·4); moderate-certainty evidence that influenza vaccines probably reduce antibiotic use in children aged 6 months to 14 years (three RCTs; n = 610; ratio of means 0·62; 95% CI 0·54–0·70) and probably reduce community antibiotic use in children aged 3–15 years (one RCT; n = 10 985 person-seasons; risk ratio 0·69, 95% CI 0·58–0·83); and moderate-certainty evidence that pneumococcal vaccination probably reduces antibiotic use in children aged 6 weeks to 6 years (two RCTs; n = 47 945; rate ratio 0·93, 95% CI 0·87–0·99) and reduces illness episodes requiring antibiotics in children aged 12–35 months (one RCT; n = 264; rate ratio 0·85, 95% CI 0·75–0·97). Other RCT evidence was of low or very low certainty, and observational evidence was affected by confounding.ConclusionsThe evidence base is poor. Although some vaccines may reduce antibiotic use, collection of high-quality data in future vaccine trials is needed to improve the evidence base.PROSPERO registrationCRD42018103881.     

四川地区200例随机临床分枝杆菌分离株耐药状况的分析研究

目的 了解四川地区分枝杆菌的耐药状况,为临床用药提供参考依据.方法 采用罗氏绝对浓度法对我院2009年6月-2010年12月间的200株分枝杆菌随机临床分离株进行9种抗结核药物的敏感性试验,并同步进行微量药敏(MIC)检测.结果 200株分枝杆菌临床分离株中192株(96.0％)为结核分枝杆菌(MTB),8株(4.0％)为非结核分枝杆菌(NTM),两种分群方法结果一致.192株MTB中108株对9种抗结核药物全部敏感,对≥1种药物耐药者84株,总耐药率为43.7％ (84/192),多重耐药( MDR)23株(12.0％),广泛耐药4株(2.1％),全耐药2株(1.0％).耐9种不同抗结核药物的顺位由高到低依次为:丙硫异烟胺(PTA,33.3％)、异烟肼(INH,20.8％)、利福平(RFP,17.2％)、硫酸链霉素( SM,16.7％)、硫酸阿米卡星注射液(AMK,16.7％)、力克肺疾(PI,16.1％)、乙胺丁醇(EMB,10.9％)、左氧氟沙星( LFX,8.8％)、硫酸卷曲霉素(CPM,6.2％);单一耐1、2、3、4、5、6、7、8和9种药物耐药率分别为12.5％、7.3％、6.2％、4.7％、4.2％、3.6％、3.1％、1.0％和1.0％.对≥2种药物耐药者60株(31.2％);对≥4种药物耐药者34株(17.7％).M DR-TB对另外7种药物的罗氏药敏耐药率从高到底依次为:PI(78.3％)、EMB(69.6％)、SM(65.2％)、PTA (65.2％)、LFX (39.1％)、AMK( 30.4％)、CPM(8.7％).结论 四川地区耐药性结核病仍处于全国较高水平,特别是同时耐多种(≥4种)药物的耐药率较高,应引起重视.     

Exposure to World Health Organization's AWaRe antibiotics and isolation of multidrug resistant bacteria: a systematic review and meta-analysis

BackgroundAntibiotic use drives antibiotic resistance.ObjectivesTo systematically review the literature and estimate associations between prior exposure to antibiotics across World Health Organization's (WHO) AWaRe categories (Access, Watch, Reserve) and isolation of critical and high-priority multidrug resistant organisms (MDROs) on the WHO priority pathogen list.Data SourcesEmbase, Ovid Medline, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov (from inception to 20/08/2020).Study eligibility criteriaCase-control, cohort, or experimental studies that assessed the risk of infection/colonization with MDROs.ParticipantsInpatients or outpatients of any age and sex.InterventionsPrior exposure to antibiotics that could be categorized into the AWaRe framework.Data analysisTailored design-specific checklists applied to each included study. For each antibiotic/class, crude odds ratios (ORs) were pooled through random-effects meta-analyses, both overall and by MDRO. Heterogeneity was examined.ResultsWe identified 349 eligible studies. All were observational, prone to bias due to design and lack of adjustment for confounding, and not primarily designed to compare associations across AWaRe categories. We found statistically significant associations between prior exposure to almost all antibiotics/classes across AWaRe categories and colonization/infection with any MDRO. We observed higher ORs for Watch and Reserve antibiotics than with Access antibiotics. First generation cephalosporins (Access) had the least association with any MDRO colonization/infection (58 studies; OR = 1.2 [95% CI: 1.0–1.4]), whereas strongest associations were estimated for linezolid (Reserve) (22 studies; OR = 2.6 [95% CI: 2.1–3.1]), followed by carbapenems (Watch) (237 studies; OR = 2.3 [95% CI: 2.1–2.5]). There was high heterogeneity for all antibiotic/MDRO associations.ConclusionsOptimising use of Access antibiotics is likely to reduce the selection of MDROs and global antibiotic resistance. Despite data limitations, our study offers a strong rationale for further adoption of AWaRe as an important tool to improve antibiotic use globally.     

The association between antimicrobial resistance and HIV infection: a systematic review and meta-analysis

ObjectivesPeople living with HIV (PLWH) are at increased risk of infections with resistant organisms due to more frequent healthcare utilization. Our objective was to investigate the association between HIV and antimicrobial resistance (AMR).MethodsWe searched MEDLINE, EMBASE, Web of Science, LILACS and African Journals Online. Studies were eligible if they reported on AMR for colonization or infection with bacterial pathogens (excluding mycobacteria and bacteria causing sexually transmitted infections) and were stratified by HIV status, species and antimicrobials tested. Pooled odds ratios were used to evaluate the association between HIV and resistance.ResultsIn total, 92 studies published between 1995 and 2020 were identified. The studies included the following organisms: Staphylococcus aureus (n = 47), Streptococcus pneumoniae (n = 28), Escherichia coli (n = 6) and other Gram-negative bacteria. PLWH had a 2.12 (95%CI 1.36–3.30) higher odds for colonization and 1.90 (95%CI 1.45–2.48) higher odds for infection with methicillin-resistant S. aureus, a 2.28 (95%CI 1.75–2.97) higher odds of infection with S. pneumoniae with decreased penicillin susceptibility, and a 1.59 (95%CI 0.83-3.05) higher odds of resistance to third-generation cephalosporins in E. coli and Klebsiella pneumoniae.ConclusionThis review shows an increased risk of AMR in PLWH across a range of bacterial pathogens and multiple drug classes. The lack of laboratory capacity for identifying AMR, and limited access to alternative treatment options in countries with the highest burden of HIV, highlight the need for more research on AMR in PLWH. Overall, the quality of studies was moderate or low, which may impact the findings of this review.     

阿奇霉素对泌尿生殖道沙眼衣原体临床株的单独和联合药物敏感性检测

目的 检测本地区近年来泌尿生殖道沙眼衣原体临床分离株对阿奇霉素的药物敏感性,筛查耐药株,以及体外阿奇霉素与莫西沙星、多西环素、米诺环素和利福平的相互作用情况.方法 将经McCoy细胞培养法检测出的41例沙眼衣原体临床株,传代培养至感染率达90%以上,收集标本进行阿奇霉素、莫西沙星、多西环素、米诺环素和利福平5种抗菌药物的药敏试验,采用棋盘稀释法测定阿奇霉素与莫西沙星、阿奇霉素与多西环素、阿奇霉素与米诺环素、阿奇霉素与利福平4组抗菌药物联合后的体外相互作用情况.结果 阿奇霉素最低抑菌浓度(MIC)结果为0.063～0.5μg/ml.阿奇霉素与莫西沙星、多西环素和利福平体外联合时对分别对51.22%、53.66%和58.54%的菌株为协同或相加作用,统计结果显示3组之间差异无统计学意义(P＞0.05);阿奇霉素与米诺环素联合时对90.24%的菌株为拮抗作用.结论 在体外,阿奇霉素与莫西沙星、多西环素或利福平联用,能够提高各自的抗菌活性,可能对治疗沙眼衣原体反复感染或持续感染患者的疗效优于单用一种抗菌药物;相反,阿奇霉素与米诺环素联合应用时,它们之间的拮抗作用将极大地降低各自的抗菌活性.联合药敏试验在一定程度上能够弥补单独药敏实验的一些不足.     

Neuropsychological correlates of schizotypy: a systematic review and meta-analysis of cross-sectional studies

Introduction: Cognitive deficits can precede the onset of psychotic episodes and predict the onset of the illness in individuals with schizotypy traits. In some studies, high levels of schizotypy were associated with impairments in memory, attention, executive functions, and verbal fluency. This review provides a more comprehensive understanding of cognitive impairments related to schizoytpy.

Methods: A systematic review of “schizotypy and neuropsychological measures” was conducted, and it retrieved 67 studies. All papers with case-control design showing means and standard deviations from neuropsychological measures were included in a meta-analysis (n = 40). A comparison between our finding and another metaanalysis with patients with schizophrenia-spectrum disorders [Fatouros-Bergman, H., Cervenka, S., Flyckt, L., Edman, G., & Farde, L. (2014). Meta-analysis of cognitive performance in drugnaive patients with schizophrenia. Schizophrenia Research. doi:10.1016/j.schres.2014.06.034] was performed to study the similarities on the MATRICS domains between the two disorders.

Results: We found evidence of worse functioning of verbal and visual-spatial working memory, and of language in people with schizotypy or with schizotypal traits. Working memory deficit is present in both schizotypy and schizophrenia with larger effect sizes compared to other domains.

Conclusions:?Working memory deficit might be a cognitive marker of the risk of psychosis. Interventions targeting cognitive deficits early may be crucial to the prevention of psychosis.     

Proton pump inhibitor use and risk for recurrent Clostridioides difficile infection: a systematic review and meta-analysis

ObjectivesProton pump inhibitor (PPI) therapy is a potentially modifiable risk factor for recurrent Clostridioides difficile infection (CDI). Citing an absence of clinical trials, many guidelines do not provide recommendations for addressing PPI management. Our aim was to perform an updated systematic review and meta-analysis evaluating the association between PPI use and recurrent CDI addressing prior methodological limitations.MethodsData sources were MEDLINE and EMBASE. Eligible studies were cohort and case–control studies; there were no restrictions on study setting or duration of follow-up. Participants were adults with prior CDI who did or did not receive PPI therapy and were assessed for recurrent CDI. Summary (unadjusted) odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model. Prespecified subgroup analyses were performed to explore heterogeneity including study design, study quality, duration of follow-up, adjustment for confounders, and outcome definition.ResultsSixteen studies were included in the meta-analysis, comprising 57 477 patients with CDI, of whom 6870 (12%) received PPIs. The rate of recurrent CDI was 24% in patients treated with PPIs versus 18% in those who were not. A meta-analysis that pooled unadjusted odds ratios demonstrated higher odds of recurrent CDI in patients who received PPIs (OR 1.69, 95%CI 1.46–1.96) versus those who did not. There was moderate heterogeneity between studies (I² 56%); however, a sensitivity analysis restricted to studies with 56 days of follow-up substantially reduced the heterogeneity (OR 1.59, 95%CI 1.36–1.85; I² 12%). An analysis restricted to multivariate studies that combined adjusted ORs also demonstrated higher odds of recurrent CDI in patients who received PPIs (OR 1.49, 95%CI 1.12–2.00). No publication bias was identified.ConclusionsWe found significantly higher odds of recurrent CDI among users of PPIs that persisted across multiple sensitivity analyses. These results support stronger recommendations for PPI stewardship at CDI diagnosis.     

Mortality and clinical cure rates for pneumonia: a systematic review,meta-analysis,and trial sequential analysis of randomized control trials comparing bactericidal and bacteriostatic antibiotic treatments

BackgroundBactericidal antibiotics are generally assumed to be superior to bacteriostatic antibiotics as first-line treatment for pneumonia.ObjectivesWe performed a systematic review, meta-analysis, and trial sequential analysis (TSA) of randomized controlled trials (RCTs) of bactericidal versus bacteriostatic antibiotics to ascertain clinical superiority. Clinical cure rate was the primary outcome. Secondary outcomes included all-cause mortality, microbiological eradication, treatment failure, and relapse rates.Data sourcesPubMed, Cochrane Library, Embase, and MedRxivStudy eligibility criteriaRandomized control trials.ParticiapantsAdult patients with bacterial pneumonia treated with antibiotics in the community or in-hospital.InterventionsBacteriostatic versus bactericidal antibiotics.Assessment of risk of biasThe Cochrane Collaboration assessing risk of bias 2 tool.Methods of data synthesisData on dichotomous outcomes are presented as risk ratio (RR). A random-effects model with the generic Mantel–Haenszel method was used for integrating RRs for generalizability of findings. The I² method was used to assess the magnitude of variation secondary to heterogeneity.ResultsForty-three RCTs involving 10 752 patients met the eligibility criteria. The clinical cure rate (42 studies, 10 312 patients; RR: 1.02; 95% CI, 0.99–1.05; I²: 37%; TSA-adjusted CI, 0.99–1.05), all-cause mortality (25 studies, 8302 patients; RR: 1.07; 95% CI, 0.81–1.42; I²: 57%), microbiological eradication (24 studies, 2776 patients; RR: 1.00; 95% CI, 0.97–1.03; I²: 0%), treatment failure (31 studies, 7296 patients; RR: 0.96; 95% CI, 0.83–1.11; I²: 42%), and relapse rate (5 studies, 1111 patients; RR: 1.15; 95% CI, 0.50–2.63; I²: 0%) were similar between bactericidal and bacteriostatic antibiotic treatments.ConclusionsBactericidal agents are not associated with any statistical difference in clinical cure rates, mortality, microbiological eradication, treatment failure, or relapse rates compared with bacteriostatic antibiotics in the treatment of pneumonia.     

Predictors of failure after fecal microbiota transplantation for recurrent Clostridioides difficile infection: a systematic review and meta-analysis

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI), with ~15% 1-year recurrence rate. Small studies have identified variable risk factors associated with FMT failure. We, therefore, performed a systematic review and meta-analysis to evaluate the predictors of FMT failure. A systematic search of Medline, Embase, and Web of Science was performed from January 2013 up to June 2020. Meta-analyses were performed using random-effects models and pooled adjusted odds ratios for risk factors reported in ≥2 studies were calculated. Overall, 2671 patients with recurrent CDI who underwent FMT in 12 studies were included. FMT failure occurred in 454 patients (16.9%) with median follow-up of 3 months (range 2–7.7 months). A total of 9 risk factors were identified in ≥2 studies. Meta-analysis showed that use of non- CDI antibiotics, presence of inflammatory bowel disease, poor quality of bowel preparation, CDI-related hospitalization before FMT, inpatient FMT, and severe CDI were associated with statistically significant increased risk of failure after FMT. Increasing age, female gender, and immunocompromised status were not associated with increased risk for FMT failure. Several risk factors (both modifiable and non-modifiable) are associated with FMT failure. Lower use of antibiotics in the post-FMT period and good bowel preparation at the time of FMT are associated with lower risk of failure after FMT. Additionally, patients with non-modifiable risk factors should be counseled to be particularly alert about recurrent symptoms after FMT.

     

The clinical effectiveness of counselling in primary care: a systematic review and meta-analysis

BACKGROUND: Counselling is frequently used in the management of common mental disorders (such as anxiety and depression) in primary care. However, there are concerns over the clinical effectiveness of counselling, both in comparison with usual general practitioner care, and with other treatments such as alternative psychological therapies and antidepressant treatment. This study used systematic review methodology to assess the current evidence-base. METHOD: A systematic literature review located seven trials of relevance, comparing counselling with usual general practitioner care, cognitive-behaviour therapy and antidepressant medication. Data on internal and external validity were examined using a standardized quality rating scheme. Data concerning the impact of counselling on symptoms of anxiety and depression were pooled using meta-analytical procedures. RESULTS: The main analyses showed significantly greater clinical effectiveness of counselling compared with usual general practitioner care in the short-term (standardized mean difference -0.28, 95% CI -0.43 to -0.13, N=741, six trials) but not the long-term (standardized mean difference -0.07, 95% CI -0.26 to 0.12, N=447, four trials). Sensitivity analyses were undertaken to test the robustness of the results. CONCLUSION: Counselling is associated with modest improvement in short-term outcome compared with usual general practitioner care, and thus may be a useful addition to mental health services in primary care.     

Amphotericin B for treatment of visceral leishmaniasis: systematic review and meta-analysis of prospective comparative clinical studies including dose-ranging studies

ObjectivesTo evaluate the evidence for use of different formulations of amphotericin B (AmB), minimum effective dose for each formulation and its comparative efficacy against other drugs in achieving definitive cure of visceral leishmaniasis.MethodsThis systematic review and meta-analysis included following data sources: PubMed, Embase, Scopus, Web of Science and CINAHL. Controlled prospective clinical trials (randomized or nonrandomized, including dose-ranging studies) conducted between 1996 and 2017 with at least one treatment group receiving AmB were included (published data only). The primary outcome was definitive cure at 6 months. Adverse events and mortality were assessed as secondary outcomes. The PROSPERO registration number for this review is CRD42017067488.ResultsThirty-one studies (26 from India) that enrolled 6903 patients into 84 study groups met the selection criteria. In India, liposomal AmB was not inferior to AmB deoxycholate (relative risk 1.00, 95% confidence interval (CI) 0.96–1.03, two randomized controlled trials (RCTs), 514 participants, high-quality evidence), and a single dose of the earlier formulation as low as 3.75 mg/kg achieved a cure rate of over 89% (95% CI 70.6–97.2). AmB deoxycholate was as effective as miltefosine (relative risk 0.99, 95% CI 0.95–1.03, two trials, 523 participants, high-quality evidence) and may be better than paromomycin (relative risk 1.04, 95% CI 1.02–1.07, one trial, 667 participants, low-quality evidence) in achieving definitive cure.ConclusionsAmB is an efficacious drug in the Indian subcontinent. Further evidence is needed from prospective clinical trials in other endemic geographical regions.     

Patient-related determinants of antibiotic use: a systematic review

Objectives

We aimed to assess patient-related determinants potentially influencing antibiotic use.

Association between nonverbal communication during clinical interactions and outcomes: a systematic review and meta-analysis

Objective

To conduct a systematic review and meta-analysis of studies reporting associations between patients’ and clinicians’ nonverbal communication during real clinical interactions and clinically relevant outcomes.

Methods

We searched 10 electronic databases, reference lists, and expert contacts for English-language studies examining associations between nonverbal communication measured through direct observation and either clinician or patient outcomes in adults. Data were systematically extracted and random effects meta-analyses were performed.

Results

26 observational studies met inclusion criteria. Meta-analysis was performed for patient satisfaction, which was assessed in 65% of studies. Mental and physical health status were evaluated in 23% and 19% of included studies, respectively. Both clinician warmth and clinician listening were associated with greater patient satisfaction (p < 0.001 both). Physician negativity was not related to patient satisfaction (p = 0.505), but greater nurse negativity was associated with less patient satisfaction (p < 0.001). Substantial differences in study design and nonverbal measures existed across studies.

Conclusion

Greater clinician warmth, less nurse negativity, and greater clinician listening were associated with greater patient satisfaction. Additional studies are needed to evaluate the impact of nonverbal communication on patients’ mental and physical health.

Practice implications

Communication-based interventions that target clinician warmth and listening and nurse negativity may lead to greater patient satisfaction.     

Molecular characterization,toxin detection and resistance testing of human clinical Clostridium difficile isolates from Lebanon

Clostridium (Clostridioides) difficile is the main cause for nosocomial diarrhoea in industrialised nations. Epidemiologic data on the pathogen’s occurrence in other world regions are still scarce. In this context we characterized with phenotypic and molecular genetic methods C. difficile isolates stemming from hospitalised patients with diarrhoea in Lebanon.From 129 stool samples of symptomatic patients at a tertiary care University hospital in Lebanon, a total of 107 C. difficile strains were cultivated and underwent ribotyping, toxin gene detection and antibiotic resistance testing.Ribotype 014 (RT014, 16.8%) predominated, followed by RT002 (9.3%), RT106 (8.4%) and RT070 (6.5%). Binary toxin gene-positive isolates (RT023, RT078 and RT126) were rarely detected and RT027 was absent. Interestingly, within one isolate only the toxin A gene (tcdA) was detected. Multiple-locus variable-number tandem repeat analysis (MLVA) revealed strong strain diversity in most RTs. The isolates were sensitive to metronidazole and vancomycin, and only a small proportion of strains displayed resistance against moxifloxacin, rifampicin, and clarithromycin (5.6%, 1.9%, and 2.8%), respectively.The data indicate that the genetic strain composition of Lebanese strains differs markedly from the situation seen in Europe and North America. Especially the epidemic RTs seen in the latter regions were almost absent in Lebanon. Interestingly, most strains showed almost no resistance to commonly used antibiotics that are suspected to play a major role in the development of C. difficile infection, despite frequent use of these antibiotics in Lebanon. Thus, the role of antimicrobial resistance as a major driving force for infection development remains uncertain in this area.     

Self-directed interventions to promote weight loss: a systematic review and meta-analysis

Many self-directed weight-loss interventions have been developed using a variety of delivery formats (e.g., internet and smartphone) and change techniques. Yet, little research has examined whether self-directed interventions can exclusively promote weight loss. MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Library were systematically reviewed for randomised controlled trials evaluating self-directed interventions in relation to weight-loss outcomes in adults. Standardised mean differences (SMD) and 95% confidence intervals (CI) were calculated using a random effects model. Twenty-seven trials incorporating 36 comparisons met our inclusion criteria. Participants using self-directed interventions lost significantly more weight (MD?=??1.56?kg, CI ?2.25, ?0.86 ranging from 0.6 to 5.3?kg) compared to those in the minimal intervention or no-treatment groups (3.1-month follow-up median). The majority of interventions were internet based (18 evaluations) and these were effective at 3 months (MD?=??1.74?kg, CI ?2.65, ?0.82 ranging from 0.6 to 4.8?kg) (SMD?=??0.48, 95% CI ?0.72, ?0.24, I²?=?82%; p?I²?=?76%; p?=?.004; 4 evaluations). Self-directed weight-loss interventions can generate modest weight loss for up to 6 months but may need to be supplemented by other interventions to achieve sustained and clinically meaningful weight loss.     

Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis

Blood phenylalanine (Phe) levels provide a practical and reliable method for the diagnosis and monitoring of metabolic status in patients with phenylketonuria (PKU). To assess the reliability of blood Phe levels as a predictive biomarker of clinical outcomes in the development of treatments for PKU, a systematic literature review and meta-analysis of published trials of PKU, which included Phe level and neurological and dietary compliance outcome measures, was conducted. Within-study correlations between Phe level and intelligence quotient (IQ) were extracted from 40 studies. Significant, proportional correlations were found during critical periods (from 0 to 12 years of age) for early-treated patients with PKU (r=-0.35; 95% confidence interval [CI]: -0.44 to -0.27), where each 100 micromol/l increase in Phe predicted a 1.3- to 3.1-point reduction in IQ. Similar significant correlations were observed between IQ and mean lifetime Phe level for early-treated patients (r=0.34; 95% CI: -0.42 to -0.25), where each 100 micromol/l increase in Phe predicted a 1.9- to 4.1-point reduction in IQ. Moderate correlations were found between concurrent Phe level and IQ for early-treated patients. In conclusion, these results confirm a significant correlation between blood Phe level and IQ in patients with PKU, and support the use of Phe as a predictive biomarker for IQ in clinical trials.