Novel Antibiotics May Be Noninferior but Are They Becoming Less Effective?: a Systematic Review.
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ABSTRACT:
SUBMITTER: Bai AD
PROVIDER: S-EPMC7577162 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The teaching of medicine and the expectations of trainees has changed enormously over the past two decades in parallel to changes in medical technology, advances in information technology and the provision of healthcare. With a shortened time in medical training efficient learning is ever more crucial and the skills with which to optimise and enhance our learning opportunities are discussed.
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Project description:Despite the growing threat of antimicrobial resistance, pharmaceutical and biotechnology firms are reluctant to develop novel antibiotics because of a host of market failures. This problem is complicated by public health goals that demand antibiotic conservation and equitable patient access. Thus, an innovative incentive strategy is needed to encourage sustainable investment in antibiotics. This systematic review consolidates, classifies and critically assesses a total of 47 proposed incentives. Given the large number of possible strategies, a decision framework is presented to assist with the selection of incentives. This framework focuses on addressing market failures that result in limited investment, public health priorities regarding antibiotic stewardship and patient access, and implementation constraints and operational realities. The flexible nature of this framework allows policy makers to tailor an antibiotic incentive package that suits a country's health system structure and needs.
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Project description:BackgroundFew data exist regarding pregnancy in lesbian and bisexual (LB) women.ObjectivesTo determine the likelihood of LB women becoming pregnant, naturally or assisted, in comparison with heterosexual women SEARCH STRATEGY: Systematic review of papers published 1 January 2000 to 23 June 2015.Selection criteriaStudies contained details of pregnancy rates among LB women compared with heterosexual women. No restriction on study design.Data collection and analysisInclusion decisions, data extraction and quality assessment were conducted in duplicate. Meta-analyses were carried out, with subgroups as appropriate.Main resultsOf 6859 papers identified, 104 full-text articles were requested, 30 papers (28 studies) were included. The odds ratio (OR) of ever being pregnant was 0.19 (95% CI 0.18-0.21) in lesbian women and 1.22 (95% CI 1.15-1.29) in bisexual women compared with heterosexual women. In the general population, the odds ratio for pregnancy was nine-fold lower among lesbian women and over two-fold lower among bisexual women (0.12 [95% CI 0.12-0.13] and 0.50 [95% CI 0.45-0.55], respectively). Odds ratios for pregnancy were higher for both LB adolescents (1.37 [95% CI 1.18-1.59] and 1.98 [95% CI 1.85, 2.13], respectively). There were inconsistent results regarding abortion rates. Lower rates of previous pregnancies were found in lesbian women undergoing artificial insemination (OR 0.17 [95% CI 0.11-0.26]) but there were higher assisted reproduction success rates compared with heterosexual women (OR 1.56 [95% CI 1.24-1.96]).ConclusionsHeterosexuality must not be assumed in adolescents, as LB adolescents are at greater risk of unwanted pregnancies and terminations. Clinicians should provide appropriate information to all women, without assumptions about LB patients' desire for, or rejection of, fertility and childbearing.Tweetable abstractReview of likelihood of LB women becoming pregnant: LB teenagers at greater risk of unwanted pregnancies.
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Project description:We examined whether Japanese culture has become more individualistic by investigating how the practice of naming babies has changed over time. Cultural psychology has revealed substantial cultural variation in human psychology and behavior, emphasizing the mutual construction of socio-cultural environment and mind. However, much of the past research did not account for the fact that culture is changing. Indeed, archival data on behavior (e.g., divorce rates) suggest a rise in individualism in the U.S. and Japan. In addition to archival data, cultural products (which express an individual's psyche and behavior outside the head; e.g., advertising) can also reveal cultural change. However, little research has investigated the changes in individualism in East Asia using cultural products. To reveal the dynamic aspects of culture, it is important to present temporal data across cultures. In this study, we examined baby names as a cultural product. If Japanese culture has become more individualistic, parents would be expected to give their children unique names. Using two databases, we calculated the rate of popular baby names between 2004 and 2013. Both databases released the rankings of popular names and their rates within the sample. As Japanese names are generally comprised of both written Chinese characters and their pronunciations, we analyzed these two separately. We found that the rate of popular Chinese characters increased, whereas the rate of popular pronunciations decreased. However, only the rate of popular pronunciations was associated with a previously validated collectivism index. Moreover, we examined the pronunciation variation of common combinations of Chinese characters and the written form variation of common pronunciations. We found that the variation of written forms decreased, whereas the variation of pronunciations increased over time. Taken together, these results showed that parents are giving their children unique names by pairing common Chinese characters with uncommon pronunciations, which indicates an increase in individualism in Japan.
| S-EPMC4613833 | biostudies-literature
Project description:BackgroundSurgical innovation is different from the introduction of novel pharmaceuticals. To help address this, in 2009 the IDEAL Collaboration (Idea, Development, Exploration, Assessment, Long-term follow-up) introduced the five-stage framework for surgical innovation. To evaluate the framework feasibility for novel neurosurgical procedure introduction, two innovative surgical procedures were examined: the endoscopic endonasal approach for skull base meningiomas (EEMS) and the WovenEndobridge (WEB device) for endovascular treatment of intracranial aneurysms.MethodsThe published literature on EEMS and WEB devices was systematically reviewed. Identified studies were classified according to the IDEAL framework stage. Next, studies were evaluated for possible categorization according to the IDEAL framework.ResultsFive hundred seventy-six papers describing EEMS were identified of which 26 papers were included. No prospective studies were identified, and no studies reported on ethical approval or patient informed consent for the innovative procedure. Therefore, no clinical studies could be categorized according to the IDEAL Framework. For WEB devices, 6229 articles were screened of which 21 were included. In contrast to EEMS, two studies were categorized as 2a and two as 2b.ConclusionThe results of this systematic review demonstrate that both EEMS and WEB devices were not introduced according to the (later developed in the case of EEMS) IDEAL framework. Elements of the framework such as informed consent, ethical approval, and rigorous outcomes reporting are important and could serve to improve the quality of neurosurgical research. Alternative study designs and the use of big data could be useful modifications of the IDEAL framework for innovation in neurosurgery.
| S-EPMC5590028 | biostudies-literature
Project description:Homelessness remains a societal problem. Compiled evidence of predictors for becoming homeless and exiting homelessness might be used to inform policy-makers and practitioners in their work to reduce homeless-related problems. We examined individual-level predictors for becoming homeless and exiting homelessness by searching PubMed, EMBASE, PsycINFO, and Web of Science up to January 2018. Becoming homeless and exiting homelessness were the outcomes. Observational studies with comparison groups from high-income countries were included. The Newcastle Ottawa Quality Assessment Scale was used for bias assessment. Random effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). We included 116 independent studies of risk factors for becoming homeless and 18 for exiting homelessness. We found evidence of adverse life events as risk factors for homelessness, e.g., physical abuse (OR 2.9, 95% CI 1.8-4.4) and foster care experiences (3.7, 1.9-7.3). History of incarceration (3.6, 1.3-10.4), suicide attempt (3.6, 2.1-6.3), and psychiatric problems, especially drug use problems (2.9, 1.5-5.1), were associated with increased risk of homelessness. The heterogeneity was substantial in most analyses (I2 >?90%). Female sex (1.5, 1.1-1.9; I2 =?69%) and having a partner (1.7, 1.3-2.1; I2 =?40%) predicted higher chances whereas relationship problems (0.6, 0.5-0.8), psychotic disorders (0.4, 0.2-0.8; I2 =?0%), and drug use problems (0.7, 0.6-0.9; I2 =?0%) reduced the chances for exiting homelessness. In conclusion, sociodemographic factors, adverse life events, criminal behaviour, and psychiatric problems were individual-level predictors for becoming homeless and/or exiting homelessness. Focus on individual-level vulnerabilities and early intervention is needed. PROSPERO registration number: CRD42014013119 .
| S-EPMC6814700 | biostudies-literature
Project description:Antibiotics are a medical wonder, but an increasing frequency of resistance among most human pathogens is rendering them ineffective. If this trend continues, the consequences for public health and for the general community could be catastrophic. The current clinical pipeline, however, is very limited and is dominated by derivatives of established classes, the "me too" compounds. Here, we have exploited our recent identification of a bacterial toxin to transform it into antibiotics active on multidrug-resistant (MDR) gram-positive and -negative bacterial pathogens. We generated a new family of peptidomimetics-cyclic heptapseudopeptides-inspired from a natural bacterial peptide. Out of the 4 peptides studied, 2 are effective against methicillin-resistant Staphylococcus aureus (MRSA) in mild and severe sepsis mouse models without exhibiting toxicity on human erythrocytes and kidney cells, zebrafish embryos, and mice. These new compounds are safe at their active doses and above, without nephrotoxicity. Efficacy was also demonstrated against Pseudomonas aeruginosa and MRSA in a mouse skin infection model. Importantly, these compounds did not result in resistance after serial passages for 2 weeks and 4 or 6 days' exposure in mice. Activity of heptapseudopeptides was explained by the ability of unnatural amino acids to strengthen dynamic association with bacterial lipid bilayers and to induce membrane permeability, leading to bacterial death. Based on structure determination, we showed that cationic domains surrounded by an extended hydrophobic core could improve bactericidal activity. Because 2 peptide analogs, Pep 16 and Pep19, are effective against both MRSA and P. aeruginosa in severe sepsis and skin infection models, respectively, we believe that these peptidomimetics are promising lead candidates for drug development. We have identified potential therapeutic agents that can provide alternative treatments against antimicrobial resistance. Because the compounds are potential leads for therapeutic development, the next step is to start phase I clinical trials.
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Project description:IntroductionTotal hip arthroplasty (THA) surgeries are expected to exponentially increase in the upcoming years, likely because of the overall broader indication of THAs. With these developments, an increasing number of younger (< 50 years) and active patients will receive surgical interventions, and expectations for an active lifestyle will accordingly increase. In addition, surgeons now have a growing array of techniques and implant materials to choose from. Despite these developments, evidence to provide the best standard-of-care to patients with high expectations for return to sports (RTS) is scarce and urgently needed. What recommendations do arthroplasty surgeons currently make to patients with high return to sports expectations, what factors may influence their recommendations and what surgical techniques and implant specifications are considered favorable in the treatment of patients with a more active lifestyle? This study was conducted to analyze the current recommendations, patient assessment, and patient counseling after THA to identify trends and relevant factors for surgical decision-making in patients with high-RTS expectations.Material and methodsWe designed a questionnaire comprising five general items and 19 specific items that included 46 sub-items for hip arthroplasty and conducted a survey among 300 German surgeons specialized in arthroplasty at the German Arthroplasty Society (AE) to assess expert opinions, recommendations, surgical decision-making, and patient counseling for patients with high expectations for RTS after THA.ResultsThe majority of surgeons (81.9%) were in favor of RTS after THA. Risks associated with sports after THA were considered minimal (1%), with periprosthetic fractures ranking highest, followed by hip dislocation and polyethylene wear. Some surgical decision-making was influenced by high-RTS expectations in regard to implant fixation, stem type, femoral head diameter, and bearing-surface tribology. We observed an increasingly liberal counseling of patients for high-impact sports.ConclusionWith the improvement of implants and surgical techniques, surgeons are more willing to encourage patients to adopt a more active lifestyle. However, the true long-term limitations need further investigation in future studies.Level of evidence5 Expert opinions.
| S-EPMC7899958 | biostudies-literature
Project description:For decades, there is an unresolved debate about adequate prescription of antibiotics for patients suffering from exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this systematic review was to analyse randomised controlled trials investigating the clinical benefit of antibiotics for COPD exacerbations.We conducted a systematic review of randomised, placebo-controlled trials assessing the effects of antibiotics on clinically relevant outcomes in patients with an exacerbation. We searched bibliographic databases, scrutinized reference lists and conference proceedings and asked the pharmaceutical industry for unpublished data. We used fixed-effects models to pool results. The primary outcome was treatment failure of COPD exacerbation treatment.We included 13 trials (1557 patients) of moderate to good quality. For the effects of antibiotics on treatment failure there was much heterogeneity across all trials (I(2) = 75%) [corrected] Meta-regression revealed severity of exacerbation as significant explanation for this heterogeneity (p = 0.038) [corrected] Antibiotics did not reduce treatment failures in outpatients with mild to moderate exacerbations (pooled odds ratio 1.81, 95% CI 0.55-1.18, I(2) = 13%) [corrected] Inpatients with severe exacerbations had a substantial benefit on treatment failure rates (pooled odds ratio of 0.25, 95% CI 0.16-0.39, I2 = 0%; number-needed to treat of 4, 95% CI 3-5) and on mortality (pooled odds ratio of 0.20, 95% CI 0.06-0.62, I2 = 0%; number-needed to treat of 14, 95% CI 12-30).Antibiotics effectively reduce treatment failure and mortality rates in COPD patients with severe exacerbations. For patients with mild to moderate exacerbations, antibiotics may not be generally indicated and further research is needed to guide antibiotic prescription in these patients.
| S-EPMC1853091 | biostudies-other
Project description:The evolutionary origin of the striking genome size variations found in eukaryotes remains enigmatic. The effective size of populations, by controlling selection efficacy, is expected to be a key parameter underlying genome size evolution. However, this hypothesis has proved difficult to investigate using empirical data sets. Here, we tested this hypothesis using 22 de novo transcriptomes and low-coverage genomes of asellid isopods, which represent 11 independent habitat shifts from surface water to resource-poor groundwater. We show that these habitat shifts are associated with higher transcriptome-wide [Formula: see text] After ruling out the role of positive selection and pseudogenization, we show that these transcriptome-wide [Formula: see text] increases are the consequence of a reduction in selection efficacy imposed by the smaller effective population size of subterranean species. This reduction is paralleled by an important increase in genome size (25% increase on average), an increase also confirmed in subterranean decapods and mollusks. We also control for an adaptive impact of genome size on life history traits but find no correlation between body size, or growth rate, and genome size. We show instead that the independent increases in genome size measured in subterranean isopods are the direct consequence of increasing invasion rates by repeat elements, which are less efficiently purged out by purifying selection. Contrary to selection efficacy, polymorphism is not correlated to genome size. We propose that recent demographic fluctuations and the difficulty of observing polymorphism variation in polymorphism-poor species can obfuscate the link between effective population size and genome size when polymorphism data are used alone.
| S-EPMC5453316 | biostudies-literature