Current and Potential Roles in Sports Pharmacy: A Systematic Review

(1) Background: The objective of this systematic review was to evaluate current and potential roles for pharmacists in sports medicine and to identify key themes in outcomes reported in studies. (2) Methods: EMBASE, MEDLINE, CINAHL, Scopus and the Cochrane Library were searched in January 2019. Peer-reviewed, original research articles were considered for inclusion. Articles published in a language other than English were excluded. Quality appraisal was performed independently by two authors. (3) Results: Findings of 11 eligible articles (10 observational and 1 experimental study design) were grouped into three themes: (i) doping prevention and control, (ii) injury management and first aid, and (iii) educational and curricular needs. Pharmacists were perceived as a good potential source of information about doping and are enthusiastic about counseling athletes, but lack knowledge and confidence in this area. While pharmacists were frequently consulted for advice on managing sprains and strains, their advice was not always guided by current evidence. Pharmacists and pharmacy students recalled limited opportunity for education in sports pharmacy. (4) Conclusion: Pharmacists showed a willingness and an aptitude to counsel athletes. However, lack of knowledge and confidence, and limited educational opportunities, were key barriers. More research is necessary to support pharmacists in this role

Community-onset sepsis and its public health burden : a systematic review

Background: Sepsis is a life-threatening condition and major contributor to public health and economic burden in the industrialised world. The difficulties in accurate diagnosis lead to great variability in estimates of sepsis incidence. There has been even a greater uncertainty regarding the incidence of and risk factors for community-onset sepsis (COS). We systematically reviewed the recent evidence on the incidence and risk factors of COS in high income countries. Methods: Cohort and case-control studies were eligible for inclusion. Medline and Embase databases were searched from 2002 onwards. References of relevant publications were hand searched. Two reviewers screened titles/abstracts and full-texts independently. One reviewer extracted data and appraised studies which were cross-checked by independent reviewers. Disagreements were resolved via consensus. Odds ratios (ORs) and 95 percent confidence intervals (95% CIs) were ascertained by type of sepsis (non-severe, severe, and septic shock). Results: 10 cohort and 4 case-control studies were included. There was a wide variation in the incidence (# cases per 100,000 per year) of non-severe sepsis (range: 64 - 514), severe sepsis (range: 40 - 455), and septic shock (range: 9 - 31). Heterogeneity precluded statistical pooling. Two cohort and 4 case-control studies reported risk factors for sepsis. In one casecontrol and one cohort study, older age and diabetes were associated with increased risk of sepsis. The same case-control study showed an excess risk for sepsis in participants with clinical conditions (e.g., immunosuppression, lung disease, and peripheral artery disease). In one cohort study, higher risk of sepsis was associated with being a nursing home resident (OR=2.60, 95% CI: 1.20, 5.60) and in the other cohort study with being physically inactive (OR=1.33, 95% CI: 1.13, 1.56) and smoking tobacco (OR=1.85, 95% CI: 1.54, 2.22). The evidence on sex, ethnicity, statin use, and body mass index as risk factors was inconclusive. Conclusions: The lack of a valid standard approach for defining sepsis makes it difficult to determine the true incidence of COS. Differences in case ascertainment contribute to the variation in incidence of COS. The evidence on COS is limited in terms of the number and quality of studies. This review highlights the urgent need for an accurate and standard method for identifying sepsis. Future studies need to improve the methodological shortcomings of previous research in terms of case definition, identification, and surveillance practice

Factors for Recurrent Injuries in Victims of Suspected Non-Accidental Trauma: A Retrospective Cohort Study

Background Many children who are victims of non-accidental trauma (NAT) may be repeatedly evaluated for injuries related to maltreatment. The purpose of this study was to identify risk factors for repeated injuries in children with suspected NAT. Methods We conducted a retrospective cohort study using claims data from a pediatric Medicaid accountable care organization. Children with birth claims and at least one non-birth related claim indicating a diagnosis of NAT or skeletal survey in 2007–2011 were included. Recurrent events were defined as independent episodes of care involving an urgent/emergent care setting that included a diagnosis code specific for child abuse, a CPT code for a skeletal survey, or a diagnosis code for an injury suspicious for abuse. Cox proportional hazards models were used to examine risk factors for recurrent events. Results Of the 1,361 children with suspected NAT, a recurrent NAT event occurred in 26% within 1 year and 40% within 2 years of their initial event. Independent risk factors for a recurrent NAT event included a rural residence, age \u3c 30 months old, having only 1 or 2 initially detected injuries, and having a dislocation, open wound, or superficial injury at the previous event (p ≤ 0.01 for all). Conclusions Over 25% of children who experienced a suspected NAT event had a recurrent episode within one year. These children were younger and more likely to present with “minor” injuries at their previous event

Breastfeeding, the use of docosahexaenoic acid-fortified formulas in infancy and neuropsychological function in childhood

OBJECTIVE: To investigate the relation between breastfeeding, use of docosahexaenoic acid (DHA)-fortified formula and neuropsychological function in children. DESIGN: Prospective cohort study. SETTING: Southampton, UK. SUBJECTS: 241 children aged 4 years followed up from birth. MAIN OUTCOME MEASURES: IQ measured by the Wechsler Pre-School and Primary Scale of Intelligence (3rd edn), visual attention, visuomotor precision, sentence repetition and verbal fluency measured by the NEPSY, and visual form-constancy measured by the Test of Visual-Perceptual Skills (Non-Motor). RESULTS: In unadjusted analyses, children for whom breast milk or DHA-fortified formula was the main method of feeding throughout the first 6 months of life had higher mean full-scale and verbal IQ scores at age 4 years than those fed mainly unfortified formula. After adjustment for potential confounding factors, particularly maternal IQ and educational attainment, the differences in IQ between children in the breast milk and unfortified formula groups were severely attenuated, but children who were fed DHA-fortified formula had full-scale and verbal IQ scores that were respectively 5.62 (0.98 to 10.2) and 7.02 (1.56 to 12.4) points higher than children fed unfortified formula. However, estimated total intake of DHA in milk up to age 6 months was not associated with subsequent IQ or with score on any other test. CONCLUSIONS: Differences in children's intelligence according to type of milk fed in infancy may be due more to confounding by maternal or family characteristics than to the amount of long-chain polyunsaturated fatty acids they receive in milk

The human ankyrin 1 promoter insulator sustains gene expression in a β-globin lentiviral vector in hematopoietic stem cells.

Lentiviral vectors designed for the treatment of the hemoglobinopathies require the inclusion of regulatory and strong enhancer elements to achieve sufficient expression of the β-globin transgene. Despite the inclusion of these elements, the efficacy of these vectors may be limited by transgene silencing due to the genomic environment surrounding the integration site. Barrier insulators can be used to give more consistent expression and resist silencing even with lower vector copies. Here, the barrier activity of an insulator element from the human ankyrin-1 gene was analyzed in a lentiviral vector carrying an antisickling human β-globin gene. Inclusion of a single copy of the Ankyrin insulator did not affect viral titer, and improved the consistency of expression from the vector in murine erythroleukemia cells. The presence of the Ankyrin insulator element did not change transgene expression in human hematopoietic cells in short-term erythroid culture or in vivo in primary murine transplants. However, analysis in secondary recipients showed that the lentiviral vector with the Ankyrin element preserved transgene expression, whereas expression from the vector lacking the Ankyrin insulator decreased in secondary recipients. These studies demonstrate that the Ankyrin insulator may improve long-term β-globin expression in hematopoietic stem cells for gene therapy of hemoglobinopathies

Balanced impacts of fitness and drug pressure on the evolution of PfMDR1 polymorphisms in Plasmodium falciparum.

BACKGROUND: Anti-malarial drug resistance may be limited by decreased fitness in resistant parasites. Important contributors to resistance are mutations in the Plasmodium falciparum putative drug transporter PfMDR1. METHODS: Impacts on in vitro fitness of two common PfMDR1 polymorphisms, N86Y, which is associated with sensitivity to multiple drugs, and Y184F, which has no clear impact on drug sensitivity, were evaluated to study associations between resistance mediators and parasite fitness, measured as relative growth in competitive culture experiments. NF10 P. falciparum lines engineered to represent all PfMDR1 N86Y and Y184F haplotypes were co-cultured for 40 days, and the genetic make-up of the cultures was characterized every 4 days by pyrosequencing. The impacts of culture with anti-malarials on the growth of different haplotypes were also assessed. Lastly, the engineering of P. falciparum containing another common polymorphism, PfMDR1 D1246Y, was attempted. RESULTS: Co-culture results were as follows. With wild type (WT) Y184 fixed (N86/Y184 vs. 86Y/Y184), parasites WT and mutant at 86 were at equilibrium. With mutant 184 F fixed (N86/184F vs. 86Y/184F), mutants at 86 overgrew WT. With WT N86 fixed (N86/Y184 vs. N86/184F), WT at 184 overgrew mutants. With mutant 86Y fixed (86Y/Y184 vs. 86Y/184F), WT and mutant at 86 were at equilibrium. Parasites with the double WT were in equilibrium with the double mutant, but 86Y/Y184 overgrew N86/184F. Overall, WT N86/mutant 184F parasites were less fit than parasites with all other haplotypes. Parasites engineered for another mutation, PfMDR1 1246Y, were unstable in culture, with reversion to WT over time. Thus, the N86 WT is stable when accompanied by the Y184 WT, but incurs a fitness cost when accompanied by mutant 184F. Culturing in the presence of chloroquine favored 86Y mutant parasites and in the presence of lumefantrine favored N86 WT parasites; piperaquine had minimal impact. CONCLUSIONS: These results are consistent with those for Ugandan field isolates, suggest reasons for varied haplotypes, and highlight the interplay between drug pressure and fitness that is guiding the evolution of resistance-mediating haplotypes in P. falciparum

Energy loss after daily role stress and work incivility: caring for oneself with emotional wellness

The present study seeks to build on burnout research by examining daily fuctuations of role stress and work incivility, and their impact on employees’ energy loss. Optimism and recovery (i.e., psychological detachment and relaxation), two mechanisms that allow workers’ self-care and self-defence from these toxic conditions when faced by these job stressors, were included. In a daily study, 117 service sector workers completed surveys three times a day, over a period of one working week. Hierarchical linear modeling revealed work incivility as predictor of daily emotional exhaustion. Optimism and recovery play diferent roles in protecting workers from daily energy loss. Daily optimism increased employees’energy and decreased emotional exhaustion and negative afect at night. It also moderated the relationship between work incivility and positive afect at night. The results on psychological detachment supported the stressor-detachment model (Sonnentag, 2010), in which psychological detachment from work during nonworking time is not only a direct predictor of increased energy, but could similarly bufer the negative impact of role stress and work incivility. Relaxation basically showed main efects in predicting emotional exhaustion (inversely) and positive afect (directly). Our fndings suggest two main implications: (1) the necessity for implemention of workplace policies to prevent role stress and work incivility in reducing daily loss of energy. (2) Training workers in self-care programmes focusing on optimism and recovery can provide early steps toward organizational change and employee daily well-beingThis research was supported by a project from the Spanish Ministry of Economy and Competitiveness (PSI2015-68011-R). Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Natur

The Evolution of Galaxy Mergers and Morphology at z<1.2 in the Extended Groth Strip

We present the quantitative rest-frame B morphological evolution and galaxy merger fractions at 0.2 < z < 1.2 as observed by the All-wavelength Extended Groth Strip International Survey (AEGIS). We use the Gini coefficent and M_20 to identify major mergers and classify galaxy morphology for a volume-limited sample of 3009 galaxies brighter than 0.4 L_B^*, assuming pure luminosity evolution of 1.3 M_B per unit redshift. We find that the merger fraction remains roughly constant at 10 +/- 2% for 0.2 < z < 1.2. The fraction of E/S0/Sa increases from 21+/- 3% at z ~ 1.1 to 44 +/- 9% at z ~ 0.3, while the fraction of Sb-Ir decreases from 64 +/- 6% at z ~ 1.1 to 47 +/- 9% at z ~ 0.3. The majority of z 10^11 L_sun are disk galaxies, and only ~ 15% are classified as major merger candidates. Edge-on and dusty disk galaxies (Sb-Ir) are almost a third of the red sequence at z ~ 1.1, while E/S0/Sa makeup over 90% of the red sequence at z ~ 0.3. Approximately 2% of our full sample are red mergers. We conclude (1) the galaxy merger rate does not evolve strongly between 0.2 < z < 1.2; (2) the decrease in the volume-averaged star-formation rate density since z ~ 1 is a result of declining star-formation in disk galaxies rather than a disappearing population of major mergers; (3) the build-up of the red sequence at z < 1 can be explained by a doubling in the number of spheroidal galaxies since z ~ 1.2.Comment: 24 pages, including 3 tables and 18 color figures; accepted to the Astrophysical Journal; high resolution version available at http://www.noao.edu/noao/staff/lotz/lotz_mergers.pd

Does clinical management improve outcomes following self-Harm? Results from the multicentre study of self-harm in England

Background Evidence to guide clinical management of self-harm is sparse, trials have recruited selected samples, and psychological treatments that are suggested in guidelines may not be available in routine practice. Aims To examine how the management that patients receive in hospital relates to subsequent outcome. Methods We identified episodes of self-harm presenting to three UK centres (Derby, Manchester, Oxford) over a 10 year period (2000 to 2009). We used established data collection systems to investigate the relationship between four aspects of management (psychosocial assessment, medical admission, psychiatric admission, referral for specialist mental health follow up) and repetition of self-harm within 12 months, adjusted for differences in baseline demographic and clinical characteristics. Results 35,938 individuals presented with self-harm during the study period. In two of the three centres, receiving a psychosocial assessment was associated with a 40% lower risk of repetition, Hazard Ratios (95% CIs): Centre A 0.99 (0.90–1.09); Centre B 0.59 (0.48–0.74); Centre C 0.59 (0.52–0.68). There was little indication that the apparent protective effects were mediated through referral and follow up arrangements. The association between psychosocial assessment and a reduced risk of repetition appeared to be least evident in those from the most deprived areas. Conclusion These findings add to the growing body of evidence that thorough assessment is central to the management of self-harm, but further work is needed to elucidate the possible mechanisms and explore the effects in different clinical subgroups

Cost-effectiveness of routine mediastinoscopy in computed tomography– and positron emission tomography–screened patients with stage I lung cancer

ObjectiveAccurate preoperative staging is essential for the optimal management of patients with lung cancer. An important goal of preoperative staging is to identify mediastinal lymph node metastasis. Computed tomography and positron emission tomography may identify mediastinal lymph node metastasis with sufficient sensitivity to allow omission of mediastinoscopy. This study utilizes our experience with patients with clinical stage I lung cancer to perform a decision analysis addressing whether mediastinoscopy should be performed in clinical stage I lung cancer patients staged by computed tomography and positron emission tomography.MethodsWe retrospectively reviewed our thoracic surgery database for cases between May 1999 and May 2004. Patients deemed clinical stage I by computed tomography and positron emission tomography were chosen for further study. Individual computed tomography, positron emission tomography, and operative and pathology reports were reviewed. The postresection pathologic staging and long-term survival were recorded. A decision model was created using TreeAgePro software and our observed data for the prevalence of mediastinal lymph node metastases and for the rate of benign nodules. Data reported in the literature were also utilized to complete the decision analysis model. A sensitivity analysis of key variables was performed.ResultsA total of 248 patients with clinical stage I lung tumors were identified. One hundred seventy-eight patients (72%) underwent mediastinoscopy before resection, and 5/178 (3%) showed N2 disease. An additional 9 patients were found to have N2 metastasis in the final resected specimen, resulting in a total of 14/248 patients (5.6%) with occult mediastinal lymph node metastases. Benign nodules were found in 19/248 (8%) of patients. Decision analysis determined that mediastinoscopy added 0.008 years of life expectancy at a cost of $250,989 per life-year gained. The outcome was sensitive to the prevalence of N2 disease in the population and the benefit of induction versus adjuvant therapy for N2 lung cancer. If the prevalence of N2 disease exceeds 10$100,000 per life-year gained.ConclusionPatients with clinical stage I lung cancer staged by computed tomography and positron emission tomography benefit little from mediastinoscopy. The survival advantage it confers is very small and is dependent on the prevalence of N2 metastasis and the unproven superiority of induction therapy over adjuvant therapy