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Progress has been made in the prevention and treatment of community-acquired bacterial meningitis during the past three decades but the burden of the disease remains high globally. Conjugate vaccines against the three most common causative pathogens (Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae) have reduced the incidence of disease, but with the replacement by non-vaccine pneumococcal serotypes and the emergence of bacterial strains with reduced susceptibility to antimicrobial treatment, meningitis continues to pose a major health challenge worldwide. In patients presenting with bacterial meningitis, typical clinical characteristics (such as the classic triad of neck stiffness, fever, and an altered mental status) might be absent and cerebrospinal fluid examination for biochemistry, microscopy, culture, and PCR to identify bacterial DNA are essential for the diagnosis. Multiplex PCR point-of-care panels in cerebrospinal fluid show promise in accelerating the diagnosis, but diagnostic accuracy studies to justify routine implementation are scarce and randomised, controlled studies are absent. Early administration of antimicrobial treatment (within 1 hour of presentation) improves outcomes and needs to be adjusted according to local emergence of drug resistance. Adjunctive dexamethasone treatment has proven efficacy beyond the neonatal age but only in patients from high-income countries. Further progress can be expected from implementing preventive measures, especially the development of new vaccines, implementation of hospital protocols aimed at early treatment, and new treatments targeting checkpoints of the inflammatory cascade.

Introduction The term “hidden curriculum” (HC) is a set of ethical, moral, and value-based teachings communicated in a non-explicit manner. Recent literature has described increasing awareness of the prevalence of the HC and potential negative impact on medical learners; however, this information is lacking in pharmacy resident education. Consequently, we conducted a survey study of United States pharmacy residents to learn their perceptions concerning the HC in pharmacy residency training. Methods A nationwide survey of pharmacy residents was conducted in June 2019. The survey assessed the following: presence of negative HC (score 0 to 80), cynicism (score 0 to 25), burnout via Maslach Burnout Inventory depersonalization (MBI-D) (range 0 to 30), and emotional exhaustion via Maslach Burnout Inventory emotional exhaustion (MBI-EE) (range 0 to 54). Higher scores represent increased occurrences of each domain. Results The mean HC score was 20 (SD 14.7), mean cynicism score was 9 (SD 5.5), MBI-D was 5.5 (SD 4.5), and MBI-EE was 24.2 (SD 12.4). Of those completing an MBI score, 40.4% (82/203) reported burnout in one area, while 15.8% (32/203) reported burnout in both areas. Residents reporting burnout had higher mean HC and cynicism scores. Conclusions Awareness to develop and grow cultures that minimize the presence of a negative HC is essential to improve postgraduate pharmacy training.

Introduction The phosphodiesterase inhibitors theophylline and pentoxifylline have anti‐inflammatory properties that may make them useful in COVID‐19 pneumonia. We conducted a retrospective review of hospitalized COVID‐19 patients requiring oxygen who received these drugs. Objectives To examine the potential efficacy and safety of theophylline and pentoxifylline in COVID‐19 pneumonia patients. Methods Adults with a positive test for SARS‐COV2 and were hospitalized due to pneumonia requiring either high flow nasal cannula or mechanical ventilation were included. Patients with a history of asthma or chronic obstructive pulmonary disease were preferentially given theophylline. All other patients received pentoxifylline 400 mg orally TID. A group of hospitalized COVID‐19 patients receiving standard of care acted as a comparison group. The coprimary outcomes were a change in C‐reactive protein (CRP) and ROX score between groups from day 1 to day 4 of therapy. Results Two hundred and nine inpatients were reviewed. Fifty‐eight patients received pentoxifylline/theophylline, with 151 patients serving as the comparison group. Active therapy was associated with an increase in the ROX score (mean: 2.9 (95% CI: 0.6, 5.1)) and decrease in CRP (mean: −0.7 (95% CI: −4.7, 3.2). Mortality rates were theophylline/pentoxifylline 24% and comparison group had a 26%, respectively. Conclusion In this retrospective study, theophylline and pentoxifylline were associated with an increase in ROX score and nominal decreases in CRP and mortality. Treatment was safe with few adverse reactions documented. We believe that this study could the basis for randomized‐controlled trials to further explore these drugs’ role in COVID‐19.

The relationship between obesity and glenohumeral osteoarthritis is relatively understudied. The purpose of this study was to better define this relationship by age- and gender-matching 596,874 patients across six body mass index (BMI) cohorts and determining the prevalence of glenohumeral osteoarthritis and the standardized rate of glenohumeral arthroplasty in each cohort. Individuals with a BMI over 24 were found to be at increased odds for developing glenohumeral osteoarthritis, compared to the normal BMI cohort, and individuals with a BMI over 30 were additionally found to be at increased odds for undergoing glenohumeral arthroplasty.

Introduction: Cannabis is the most widely used illicit drug in the US, and cannabis use among young adults continues to rise. Previous studies have shown that chronic administration of delta 9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, induces dependence in animal models. Because smoking is the most frequent route of THC self-administration, it is critical to investigate the effects of cannabis smoke inhalation. The goal of the current study was to develop a rat model to characterize the pharmacokinetics (PKs) of THC after cannabis smoke inhalation, and to determine if chronic cannabis smoke inhalation leads to the development of cannabis dependence. Materials and Methods: For the PK study, male Wistar rats were administered THC intravenously (1 mg/kg) or exposed to smoke from 5 or 10 sequentially smoked cannabis cigarettes (5.3% THC) in an automated smoking machine. Plasma samples were collected from 10 min to 10 hours post smoke exposure (or intravenous administration) and analyzed using liquid chromatography–mass spectrometry to characterize the PK of THC. A three-compartment PK model was used to characterize the PKs. In a separate study, three groups of male Wistar rats were trained in an intracranial self-stimulation (ICSS) procedure, and exposed to smoke from burning 5 or 10 cannabis cigarettes (or clean air control conditions), 5 days/week for 4 weeks. Discussion and Conclusions: Across exposure days, the change from baseline in ICSS thresholds for cannabis smoke-exposed groups was significantly lower and response latencies were significantly faster in the cannabis smoke-exposed groups compared to controls, suggesting that chronic cannabis smoke exposure has rewarding properties. Acute administration of the CB1 receptor antagonist rimonabant (0.3, 1.0, 3.0 mg/kg) induced a dose-dependent increase in ICSS thresholds in the smoke-exposed rats, suggestive of dependence and withdrawal. Finally, an effect compartment PK-pharmacodynamic model was used to describe the relationship between THC concentrations and changes in ICSS thresholds after cannabis smoke exposure.

IntroductionPost-COVID-19 complications require simultaneous characterisation and management to plan policy and health system responses. We describe the 12-month experience of the first UK dedicated post-COVID-19 clinical service to include hospitalised and non-hospitalised patients.MethodsIn a single-centre, observational analysis, we report the demographics, symptoms, comorbidities, investigations, treatments, functional recovery, specialist referral and rehabilitation of 1325 individuals assessed at the University College London Hospitals post-COVID-19 service between April 2020 and April 2021, comparing by referral route: posthospitalised (PH), non-hospitalised (NH) and post emergency department (PED). Symptoms associated with poor recovery or inability to return to work full time were assessed using multivariable logistic regression.Results1325 individuals were assessed (PH: 547, 41.3%; PED: 212, 16%; NH: 566, 42.7%). Compared with the PH and PED groups, the NH group were younger (median 44.6 (35.6–52.8) years vs 58.3 (47.0–67.7) years and 48.5 (39.4–55.7) years), more likely to be female (68.2%, 43.0% and 59.9%), less likely to be of ethnic minority (30.9%, 52.7% and 41.0%) or seen later after symptom onset (median (IQR): 194 (118–298) days, 69 (51–111) days and 76 (55–128) days; all pConclusionPost-COVID-19 symptoms were significant in PH and NH patients, with significant ongoing healthcare needs and utilisation. Trials of interventions and patient-centred pathways for diagnostic and treatment approaches are urgently required.

Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic.

Soundscapes offer rich descriptions of composite acoustic environments. Characterizing marine soundscapes simply through sound levels results in incomplete descriptions, limits the understanding of unique features, and impedes meaningful comparisons. Sources that contribute to sound level metrics shift in time and space with changes in biological patterns, physical forces, and human activity. The presence of a constant or chronic source is often interwoven with episodic sounds. Further, the presence and intensity of sources can influence other sources, calling for a more integrated approach to characterizing soundscapes. Here, we illustrate this complexity using data from a national-scale effort, the Sanctuary Soundscape Monitoring Project (SanctSound), an initiative designed to support collection of biological, environmental, and human use data to compliment the interpretation of sound level measurements. Using nine examples from this diverse dataset we demonstrate the benefit of integrating source identification and site features to interpret sound levels across a diversity of shallow water marine soundscapes (

No abstract available.

Passive acoustic data collection has grown exponentially over the past decade resulting in petabytes of data that document our ocean soundscapes. This effort has resulted in two big data challenges: (1) the curation, management, and global dissemination of passive acoustic datasets and (2) efficiently extracting critical information and comparing it to other datasets in the context of ecosystem-based research and management. To address the former, the NOAA National Centers for Environmental Information recently established an archive for passive acoustic data. This fast-growing archive currently contains over 100 TB of passive acoustic audio files mainly collected from stationary recorders throughout waters in the United States. These datasets are documented with standards-based metadata and are freely available to the public. To begin to address the latter, through standardized processing and centralized stewardship and access, we provide a previously unattainable comparison of first order sound level-patterns from archived data collected across three distinctly separate long-term passive acoustic monitoring (PAM) efforts conducted at regional and national scales: NOAA/National Park Service Ocean Noise Reference Station Network, the Atlantic Deepwater Ecosystem Observatory Network, and the Sanctuary Soundscape Monitoring Project. Nine sites were selected from these projects covering the Alaskan Arctic, Northeast and Central Pacific, Gulf of Mexico, Caribbean Sea, and Mid and Northwest Atlantic. Sites could generally be categorized into those strongly influenced by anthropogenic noise (e.g., vessel traffic) and those that were not. Higher sound levels, specifically for lower frequencies (

BackgroundComplications following SARS-CoV-2 infection require simultaneous characterisation and management to plan policy and health system responses. We describe the 12-month experience of the first UK dedicated Post-COVID clinical service to include both hospitalised and non-hospitalised patients.MethodsIn a single-centre, observational analysis, we report outcomes for 1325 individuals assessed in the University College London Hospitals NHS Foundation Trust Post-COVID service between April 2020 and April 2021. Demography, symptoms, comorbidities, investigations, treatments, functional recovery, specialist referral and rehabilitation were compared by referral route (“post hospitalisation”, PH; “non-hospitalised”, NH; and “post emergency department”, PED). Symptoms associated with poor recovery or inability to return to work full-time were assessed using multivariable logistic regression.Findings1325 individuals were assessed (PH 547 [41.3%], PED 212 [16%], NH 566 [42.7%]. Compared with PH and PED groups, NH were younger (median 44.6 [35.6-52.8] vs 58.3 [47.0-67.7] and 48.5 [39.4-55.7] years), more likely to be female (68.2%, 43.0% and 59.9%), less likely to be from an ethnic minority (30.9%, 52.7% and 41.0%) and seen later after symptom onset (median [IQR]:194 [118-298], 69 [51-111] and 76 [55-128] days) (all pInterpretationSymptoms following SARS-CoV-2 infection were significant in both post- and non-hospitalised patients, with significant ongoing healthcare needs and utilisation. Trials of interventions and patient-centred pathways for diagnostic and treatment approaches are urgently required.FundingUCLH/UCL BRCResearch in contextPrevious evidenceLong COVID and post-COVID syndrome were first identified in April 2020. We searched PubMed and medrxiv for articles published up to April 30th, 2021, using the keywords “long COVID”, “post-COVID syndrome”, “persistent symptoms”, “hospitalised”, “community” and “non-hospitalised”. We identified 17 articles and 7 systematic reviews. Fifteen studies have considered symptoms, multi-organ or functional impairment but only one study to-date has considered all these variables in non-hospitalised COVID patients. No studies have compared symptom burden and management between non-hospitalised and hospitalised individuals as systematically assessed and managed in a dedicated post-COVID service.Added value of this studyFor the first time, we report the baseline characteristics, investigation and outcomes of initial assessment of all eligible patients in a dedicated multi-professional post-COVID service, including 547 post-hospitalisation, 566 non-hospitalised and 212 patients discharged from emergency department. Despite relatively low comorbidity and risk factor burden in non-hospitalised patients, we show that both non-hospitalised and hospitalised patients presenting with persistent symptoms after SARS-CoV2 infection have high rates of functional impairment, specialist referral and rehabilitation, even 6-12 months after the acute infection. These real-world data will inform models of care during and beyond the pandemic.Implications of all the available evidenceThe significant, long-lasting health and social consequences of SARS-CoV-2 infection are not confined to those who required hospitalisation. As with other long-term conditions, care of patients experiencing Long COVID or specific end-organ effects require consistent, integrated, patient-centred approaches to investigation and management. At public health and policy level, burden of post-COVID morbidity demands renewed focus on effective infection suppression for all age groups.

Purpose We describe the use of liposomal amphotericin B and amphotericin B deoxycholate in a critically ill patient with pulmonary blastomycosis receiving both venovenous extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). Summary A 50-year-old African American man presented for dyspnea and cough and was noted to have blastomycosis on bronchoscopy. He developed respiratory failure and acute kidney injury, requiring mechanical ventilation, ECMO, and CRRT. After 4 days of liposomal amphotericin, the transmembrane pressure gradient on the membrane oxygenator increased dramatically without visualization of a clot, requiring a circuit exchange. A trough amphotericin B level taken the day before the exchange was undetectable for amphotericin B. After the circuit exchange, the patient was switched to amphotericin B deoxycholate. A subsequent trough level was 3.8 μg/mL. The patient improved and was able to be decannulated. However, he did require tracheostomy and long-term hemodialysis. Conclusion In our case we believe that liposomal amphotericin B was significantly removed by ECMO and was responsible for the failure of the ECMO circuit. We would suggest amphotericin B deoxycholate be used in such patients preferentially and that serum levels of the drug be assessed when possible.

BACKGROUND Left common iliac vein (LCIV) compression by the right or left common iliac artery (RCIA, LCIA) is known to cause venous thromboembolism (VTE), but the extent to which occult LCIV compression synergizes with lower extremity orthopedic surgery is unknown. We hypothesize that occult LCIV compression is associated with increased VTE risk following total hip or knee arthroplasty (THA, TKA). METHODS This case-control study involves all patients at our institution who underwent primary or revision THA or TKA from 2009 to 2017 who had computed tomography or magnetic resonance imaging of the abdomen or pelvis available preoperatively. VTE cases (pulmonary embolism or left-sided deep vein thrombosis) within 30 days of surgery were matched to a control by age, gender, body mass index, Charlson Comorbidity Index, surgical site, and hypercoagulable risk factors. LCIV compression by the right common iliac artery and/or the left common iliac artery was measured in a blinded fashion and was considered present at 50% diameter reduction. RESULTS One hundred twelve patients (22 cases, 90 controls) were included for analysis. Nineteen (86.4%) cases and 46 (51.1%) controls demonstrated LCIV compression. The overall sample odds ratio of postoperative VTE in the presence of LCIV compression was 5.97 (95% confidence interval 1.59-33.67, P = .003). In patients who underwent THA (n = 75), LCIV compression was highly predictive of VTE (odds ratio ∞, 95% confidence interval 2.83-∞, P < .001). Compression in the TKA patients did not significantly predict VTE. CONCLUSION Compression of the LCIV significantly increases odds of developing postoperative VTE following THA. This effect may suggest a new method of stratifying VTE risk in the orthopedic population to reduce VTE-associated morbidity and mortality.

SUMMARYIn their recent paper ‘On-farm trials for development impact? The organization of research and the scaling of agricultural technologies’, de Roo, Andersson and Krupnik report on three case studies, each undertaken by one of the authors, of projects conducting on-farm research. They reach conclusions on the limitations of the projects themselves and the effects of ‘donor dependency’, and propose a strategy to overcome these issues. However, the description of the philosophy, strategies and conduct of the projects reviewed in the southern African case study is incomplete and misleading, and shows that the case study author did not understand or overlooked important project components. Due to this the conclusions reached, insofar as this case study is concerned, are largely either invalid or already contemplated in the project activities. Here, we describe more fully the philosophy and strategies followed by the series of projects on which the case study was conducted, which were designed to facilitate, through the upscaling of project methodologies, the eventual outscaling and widespread adoption of more sustainable farming systems by smallholder farmers in eastern and southern Africa. We propose these methodologies as a valid comprehensive approach to the organization of agricultural research for development for the successful development, scaling-up and scaling-out of agricultural technologies.

BACKGROUND: People with the human immunodeficiency virus (PWHIV) have improved survival because of the advent of antiretroviral therapy. Consequently, PWHIV experience higher rates of non-acquired immunodeficiency syndrome-defining malignancies (NADMs). Previous studies have demonstrated worsened cancer-specific survival in PWHIV, partly because of advanced cancer stage at diagnosis. The objective of the current systematic review was to evaluate screening disparities for NADMs among PWHIV. METHODS: The PubMed, Cochrane, EMBASE, and ClinicalTrials.gov databases were searched from January 1, 1996 through April 10, 2018 to identify studies related to screening disparities for NADMs among PWHIV. Eligibility criteria included any study performed in a high-income country that compared screening for NADMs by HIV status. After title/abstract screening and full-text review, articles that met eligibility criteria were analyzed. RESULTS: Of 613 unique articles identified through the search, 9 studies were analyzed. Three studies addressed breast cancer screening, 4 addressed colorectal cancer screening, and 2 addressed prostate cancer screening. Five of the reviewed studies demonstrated that PWHIV were less likely to receive indicated cancer screenings compared with the general population, whereas 3 indicated that screening proportions were higher among PWHIV, and 1 demonstrated that screening proportions were comparable. In most of the studies, PWHIV who had regular access to health care were more likely to undergo cancer screening. CONCLUSIONS: The available evidence does not uniformly confirm that PWHIV are less likely to receive cancer screening. Social determinants of health (insurance status, access to health care, education, income level) were associated with the receipt of appropriate cancer screening, suggesting that these barriers need to be addressed to improve cancer screening in PWHIV.

Numerous preclinical studies show that acute cannabinoid administration impairs cognitive performance. Almost all of this research has employed cannabinoid injections, however, whereas smoking is the preferred route of cannabis administration in humans. The goal of these experiments was to systematically determine how acute exposure to cannabis smoke affects working memory performance in a rat model. Adult male (n = 15) and female (n = 16) Long-Evans rats were trained in a food-motivated delayed response working memory task. Prior to test sessions, rats were exposed to smoke generated by burning different numbers of cannabis or placebo cigarettes, using a within-subjects design. Exposure to cannabis smoke had no effect on male rats’ performance, but surprisingly, enhanced working memory accuracy in females, which tended to perform less accurately than males under baseline conditions. In addition, cannabis smoke enhanced working memory accuracy in a subgroup of male rats that performed comparably to the worst-performing females. Exposure to placebo smoke had no effect on performance, suggesting that the cannabinoid content of cannabis smoke was critical for its effects on working memory. Follow-up experiments showed that acute administration of either Δ9-tetrahydrocannabinol (0.0, 0.3, 1.0, 3.0 mg/kg) or the cannabinoid receptor type 1 antagonist rimonabant (0.0, 0.2, 0.6, 2.0 mg/kg) impaired working memory performance. These results indicate that differences in the route, timing, or dose of cannabinoid administration can yield distinct cognitive outcomes, and highlight the need for further investigation of this topic.

Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery.This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy.Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51-19.97) than planned admissions (OR: 2.32, 95% CI: 1.43-3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8-51.9%, P0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI.After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.

Highlights • Mucorales known to cause opportunistic infections in immunocompromised hosts. • This is the 2nd reported case of cutaneous mucormycosis in a patient on ibrutinib. • Amphotericin B is typical 1st line therapy. • We report successful completion of treatment of cutaneous mucormycosis with posaconazole., Background Mucorales is a zygomycete fungi known to cause opportunistic infections in immunosuppressed hosts. Spores may be inhaled, causing rhinocerebral or pulmonary infections, or gastrointestinal infections if swallowed. Less often, cutaneous mucormycosis develops after inoculation via broken skin. Presentation A 72-year old male on ibrutinib and prednisone for chronic lymphocytic leukemia (CLL) presented with localized, right forearm cutaneous mucormycosis at the site of a dog-scratch sustained three weeks prior. The patient failed to respond to cephalexin as an outpatient, prompting biopsy showing ribbon-like pseudo septate hyphae and possible vascular invasion suggestive of Mucorales. Treatment course included liposomal amphotericin B 5 mg/kg IV every 24 h for ten days followed by a 90-day course of posaconazole 300 mg daily after general surgery consultation was sought. Conclusion We outline the second reported case of localized cutaneous mucormycosis arising in the setting of ibrutinib use. Because the combination of immunosuppressed states, ibrutinib and skin trauma may serve as a nidus for mucormycosis, practitioners should be vigilant of thorough skin evaluations in these patients and appropriate anti-fungal treatment. Although amphotericin B has been well studied as first line therapy, oral posaconazole has been shown as an efficacious second-line treatment.

Passive acoustic monitoring is a well-established tool for researching the occurrence, movements, and ecology of a wide variety of marine mammal species. Advances in hardware and data collection have exponentially increased the volumes of passive acoustic data collected, such that discoveries are now limited by the time required to analyze rather than collect the data. In order to address this limitation, we trained a deep convolutional neural network (CNN) to identify humpback whale song in over 187,000 h of acoustic data collected at 13 different monitoring sites in the North Pacific over a 14-year period. The model successfully detected 75 s audio segments containing humpback song with an average precision of 0.97 and average area under the receiver operating characteristic curve (AUC-ROC) of 0.992. The model output was used to analyze spatial and temporal patterns of humpback song, corroborating known seasonal patterns in the Hawaiian and Mariana Islands, including occurrence at remote monitoring sites beyond well-studied aggregations, as well as novel discovery of humpback whale song at Kingman Reef, at 5∘ North latitude. This study demonstrates the ability of a CNN trained on a small dataset to generalize well to a highly variable signal type across a diverse range of recording and noise conditions. We demonstrate the utility of active learning approaches for creating high-quality models in specialized domains where annotations are rare. These results validate the feasibility of applying deep learning models to identify highly variable signals across broad spatial and temporal scales, enabling new discoveries through combining large datasets with cutting edge tools.

Recently Boreskie and colleagues published an editorial in the Journal of Frailty and Aging on Preventing Frailty Progression During the COVID-19 Pandemic (1). In it they proposed the SAVE programme (Socialization, Adequate nutrition, Vitamin D, Exercise) to prevent frailty. They concluded that creative thinking and concerted efforts would be needed to disseminate health recommendations to maintain the health of pre-frail and frail older adults in unprecedented times, such as those posed by the COVID-19 pandemic.

BackgroundMortality from bacterial meningitis, predominately caused by Streptococcus pneumoniae, exceeds 50% in sub-Saharan African countries with high HIV prevalence. Underlying causes of high mortality are poorly understood. We examined the host and pathogen proteome in the CSF of adults with proven pneumococcal meningitis (PM), testing if there was an association between differentially expressed proteins and outcome.Materials/MethodsCSF proteomes were analyzed by quantitative Mass-Spectrometry. Spectra were identified using the Swissprot human and TIGR4 pneumococcal protein libraries. Proteins were quantitated and analyzed against mortality. Unique proteins in PM were identified against published normal CSF proteome. Random-Forest models were used to test for protein signatures discriminating outcome. Proteins of interest were tested for their effects on growth and neutrophil opsonophagocytic killing of S. pneumoniae.ResultsCSF proteomes were available for 57 Adults with PM (median age 32 years, 60% male, 70% HIV-1 co-infected, mortality 63%). Three hundred sixty individual human and 23 pneumococcal proteins were identified. Of the human protein hits, 30% were not expressed in normal CSF, and these were strongly associated with inflammation and primarily related to neutrophil activity. No human protein signature predicted outcome. However, expression of the essential S. pneumoniae protein Elongation Factor Tu (EF-Tu) was significantly increased in CSF of non-survivors [False Discovery Rate (q) -correlated against expression of Neutrophil defensin (r 0.4 p p < 0.002), but not against complement proteins C3 or Factor H. In vitro, addition of EF-Tu protein impaired S. pneumoniae neutrophil killing in CSF.ConclusionsExcessive S. pneumoniae EF-Tu protein in CSF was associated with reduced survival in meningitis in a high HIV prevalence population. We show EF-Tu may inhibit neutrophil mediated killing of S. pneumoniae in CSF. Further mechanistic work is required to better understand how S. pneumoniae avoids essential innate immune responses during PM through production of excess EF-Tu.

Background: Published findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence. Methods: Principal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users. Findings: During prospective follow-up, 108 647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55 575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1–4 (oestrogen-progestagen RR 1·60, 95% CI 1·52–1·69; oestrogen-only RR 1·17, 1·10–1·26), and were twice as great during years 5–14 (oestrogen-progestagen RR 2·08, 2·02–2·15; oestrogen-only RR 1·33, 1·28–1·37). The oestrogen-progestagen risks during years 5–14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21–2·40 vs 1·93, 1·84–2·01; heterogeneity p Interpretation: If these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great.

Prolongation of the QT interval is associated with adverse cardiac events specifically Torsades de pointes (TdP). There are multiple mediations that have a known, possible, or conditional risk for prolonged QT interval, but general practitioners' knowledge of these medications is unknown. We conducted a survey to assess internal medicine (IM) providers' knowledge of risk factors and medications associated with prolonged QT as well as provider experience and comfort when treating patients with prolonged QT. A 17-question, anonymous survey was constructed in 2019 and distributed to IM providers and residents at a tertiary care center. Questions included demographic information, 6 Likert-scale questions gauging provider experience with prolonged QT, and 10 multiple choice clinical vignettes to assess clinical knowledge. Data was analyzed descriptively. Knowledge was assessed via clinical vignettes and compared by level of training. Forty-one responses were received out of a total of 87 possible respondents (47.1% response rate). About 70% of respondents see patients with acquired prolonged QT once monthly or more. 95% rarely see congenital prolonged QT. When presented with QTc drug issues, 73% of providers seldom or sometimes consulted pharmacy, but about half used online resources. The average correct score on the clinical vignettes was 5.59/10, with the highest scores seen in attending physicians in their first five years of practice (6.96/10). Our survey suggests that IM providers commonly encounter QT prolonging drugs. Educational efforts to improve knowledge of drug and patient risk factors for TdP may be needed.

Objective We conducted this study to evaluate the reproducibility of a new classification system for Blount's disease and assess its correlation with established radiological measures used to evaluate the severity of this disorder. Materials and Methods This is a retrospective review of children with Blount’s disease that were younger than 10 years of age. Recurrence was defined as the need for a second corrective surgery. Radiographs immediately pre-surgery and at final follow-up were used to measure mechanical axis (MA), tibial metaphyseal-diaphyseal angle (TMDA), epiphyseal-metaphyseal angle (EMA), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA). Patients were stratified according to the new classification (Type A, B, or C). Results Sixty-five limbs from 16 males and 24 females met our inclusion criteria. The average follow-up was 4.2 years. Twelve patients (with 22 Type-A extremities) underwent bracing with a success rate of 54%. Thirty-four patients (53 extremities) underwent surgical correction. The recurrence rate was 35.8%. Group C had a recurrence rate of 62%, higher than that of Group B (33%), and Group A (23%) (P = 0.026). In addition, irrespective of reoperation, patients in Group C had the least change in the MA (62%, P = 0.046) and the most severe values of MPTA and TMDA initially and after the operation (P < 0.05). Conclusion The new classification system for Blount’s disease holds validity for predicting recurrence. The severity of the grades is correlated with the TMDA, MPTA, and varus reversibility. This can aid physicians and families in making an informed decision and setting treatment goals.

Toxic exposures with serious outcomes have increased over the last decade. Limited data exists on the pattern and outcomes of overdose-exposure patients requiring intensive care unit (ICU) admission. The primary objective of this study was to characterize the causes, treatments, and outcomes of toxic exposures in a mid-sized Midwestern health system. The secondary objective was to report cumulative economic costs associated with these patients. Data were obtained from medical records of patients 18 years or older with a diagnosis code of overdose admitted to the ICU at 2 teaching hospitals between August 1, 2012, and July 31, 2014. There were 470 (10%) of the 4,495 total ICU admissions that met inclusion criteria during the study period. Average patient age was 39 (SD = 14.2) years, with 64% females. Intentional overdose exposure was the cause of 87% of admissions. The majority (70%) of exposures involved multiple pharmacological agents, including ethanol. Most patients did not require therapeutic maneuvers, nor used decontamination methods. Primary substance classes included analgesics, benzodiazepines, ethanol, selective serotonin reuptake inhibitor antidepressants, and methamphetamine. Two hundred sixty-five (56%) patients were ICU to direct home discharges, whereas 198 (42%) were transferred to a lower level of care. The mortality rate in the sample was 1%. Average hospital charges per admission were $20,375 and average ICU charges were $5,284, which summed to more than $2 million in total charges. Causes, treatments, and outcomes of toxic exposures admitted to the ICU in a mid-sized Midwestern city reveal a potential ICU burden. Financial health care costs associated with these toxic exposures were substantial. Greater public health efforts are needed to attempt to minimize preventable admissions and better understand antecedents.

Passive acoustic data collection has grown exponentially over the past decade resulting in petabytes of data that document our ocean soundscapes. This effort has resulted in two big data challenges: the curation, management, and global dissemination of passive acoustic datasets and efficiently extracting critical information and comparing it to other datasets in the context of ecosystem-based research and management. To address the former, the NOAA National Centers for Environmental Information established a passive acoustic data archive, which contains over 100 TB of audio files mainly collected from stationary recorders throughout waters in the U.S. These datasets are documented with standards-based metadata and are freely available to the public. To begin to address the latter, through standardized processing and centralized stewardship and access, we will present a previously unattainable comparison of first order sound level-patterns from archived data collected across three distinctly separate long-term passive acoustic monitoring efforts conducted at regional and national scales: NOAA/National Park Service Ocean Noise Reference Station Network, the NOPP-funded Atlantic Deepwater Ecosystem Observatory Network, and the NOAA-Navy Sanctuary Soundscape Monitoring Project. Further, we will propose the next frontier for scalable data stewardship, access, and processing flow to help the community collaboratively move forward.

Background: Intravenous (IV) iron sucrose can be used for iron deficiency anemia (IDA), but little information exists on total dose infusion (TDI) of this drug. At a tertiary hospital, an iron sucrose TDI protocol was implemented with staff pharmacists aiding physicians in appropriate dosing. Objectives: We sought to define the safety and efficacy of this protocol in adults ≥18 years old with IDA. Methods: We conducted a retrospective chart review of patients who received iron sucrose TDI. Inclusion criteria included patients ≥18 years old who were hospitalized and received iron sucrose in doses ≥300 mg. We reviewed the medical record for adverse reactions to any TDI of iron sucrose as well as pre-TDI and post-TDI hemoglobin (Hgb) levels to assess efficacy. Results: A total of 238 patients received iron sucrose TDI for IDA during the study period. One hundred ninety-three (81%) patients were female, and the mean age in our cohort was 60.6 years. Mean pre-TDI Hgb was 8.76 g/dL. The mean total dose of iron sucrose in the total cohort was 680 mg (range: 300-2500 mg). Adverse effects attributable to iron sucrose were reported in 15 patients, with nausea being the most common effect (7/238, 2.9%). When matching patients’ preadmission and postadmission records, a Hgb increase of 2.1 g/L was found ( P < .001). No increase in liver function tests was found in any patient. Conclusions: A pharmacist-assisted iron sucrose TDI protocol for patients with IDA successfully increased serum Hgb and was well tolerated. Anaphylaxis was not reported.

RATIONALE: Cannabis use is common among adolescents and some research suggests that adolescent cannabis use increases the risk for depression, anxiety, and cognitive impairments in adulthood. In human studies, however, confounds may affect the association between cannabis use and the development of brain disorders. OBJECTIVES: These experiments investigated the effects of adolescent exposure to either cannabis smoke or THC on anxiety- and depressive-like behavior and cognitive performance in adulthood in Long-Evans rats. METHODS: Adolescent rats of both sexes were exposed to either cannabis smoke from postnatal days (P) 29-49 or ascending doses of THC from P35-45. When the rats reached adulthood (P70), anxiety-like behavior was investigated in the large open field and elevated plus maze, depressive-like behavior in the sucrose preference and forced swim tests, and cognitive function in the novel object recognition test. RESULTS: Despite sex differences on some measures in the open field, elevated plus maze, forced swim, and novel object recognition tests, there were no effects of either adolescent cannabis smoke or THC exposure, and only relatively subtle interactions between exposure conditions and sex, such that sex differences on some performance measures were slightly attenuated. CONCLUSION: Neither cannabis smoke nor THC exposure during adolescence produced robust alterations in adult behavior after a period of abstinence, suggesting that adverse effects associated with adolescent cannabis use might be due to non-cannabinoid concomitants of cannabis use.

The Second International Consensus Meeting on Orthopedic Infections was held in Philadelphia, Pennsylvania, in July 2018. A multidisciplinary team of international experts from all 9 subspecialties of orthopedic surgery and allied fields of infectious disease, microbiology, and epidemiology was assembled to form the International Consensus Group. The following consensus proceedings from the International Consensus Meeting involve 30 questions pertaining to the management of periprosthetic shoulder infection.

Outcomes from pneumococcal meningitis (PM) are worse than meningococcal meningitis (MM), particularly in settings with high HIV-1 prevalence, but the reasons are unknown. We compared inflammatory responses between PM and MM in Malawian adults.As compared to MM (n=27, 67% HIV-infected, mortality 11%), patients with PM (n=440, 84% HIV-infected, mortality 54%) were older, had strikingly lower CSF WCC, higher pro-inflammatory cytokine concentrations and higher mortality. PM is characterized by significantly lower CSF WCC, but greater inflammation and higher mortality compared to MM. Mechanistic understanding of blunting of the CSF leukocyte response in PM in-vivo is required.

Purpose The purpose of this article is to offer practical guidance for pharmacists to successfully implement penicillin allergy skin testing (PAST). Summary Less than 10% of patients labeled as having a penicillin allergy are confirmed as present upon skin testing. This labeling results in use of alternative antibiotics and thus unwanted adverse consequences including potentiated antimicrobial resistance, increased costs, and worse clinical outcomes. Stewardship guidelines recommend PAST to enhance use of first-line agents; however, this was a weak recommendation with low-quality evidence. Recent efforts and subsequent research since publication of guidelines have demonstrated beneficial effects from increasing use of PAST among stewardship programs to improve outcomes. A number of different models exist demonstrating successful implementation of PAST at various healthcare facilities. There are important logistical factors to consider during implementation of PAST such as target population, optimal preparation, leadership structure, resource availability, and state regulations. Pharmacists as leaders of antimicrobial stewardship teams and experts in drug allergies are a natural fit to help implement PAST in healthcare settings to improve overall outcomes. This article offers guidance to institutions considering implementation of PAST. Conclusion PAST is rapidly becoming an effective, long-term antimicrobial stewardship tool to optimize antimicrobial prescribing in both the inpatient and outpatient settings. Pharmacists have demonstrated significant benefit as providers of PAST services in a variety of healthcare settings with a number of different healthcare professionals.

Background: Improving outcomes from pneumococcal meningitis (PM), particularly in populations with high HIV prevalence, requires better understanding of host inflammatory responses to infection. Methods: We compared the transcriptome in pre-antibiotic cerebrospinal fluid (CSF) and blood from Malawian adults with PM using RNA sequencing. We used network analyses and cellular/process deconvolution of the transcriptome to identify important patho-physiological associations with outcome. Findings: Blood transcriptional profiles were obtained in 28 patients (21 HIV co-infected; median age 33 years [26-66]; median CSF WCC 28 cells/mm3 [0-3660]; median bacterial load 4.7x106 copies/ml CSF [671-2x109]; in-hospital mortality 64%), paired CSF profiles were obtained in 13. Marked differences in gene expression by outcome were confined to the CSF. In non-survivors, differentially expressed genes in the CSF were co-correlated in a network of pro-inflammatory gene-clusters enriched for collagen degradation and platelet degranulation. In contrast, CSF gene expression networks from surviving patients were dominated by DNA repair, transcriptional regulation and immunological signalling. CSF expression of gene response-modules for IL-17, Type 1 interferons and IL-10 were enriched in non-survivors, expression of cell-specific response-modules did not differ by outcome. However, genes for neutrophil chemotaxis and persistence were highly over-expressed in non-survivors. Interpretation: These data suggest poor outcome in PM is associated with over-expression of IL-17 and T1-IFN associated pro-inflammatory responses in the CSF and suggest a role for neutrophil-mediated inflammation. These responses are unlikely to be effected by current adjunctive treatments. Improving poor outcomes from PM will require better-targeted interventions. Registration Number: (Current Controlled Trials registration ISRCTN96218197). Funding Statement: This study was funded by a Clinical Lecturer Starter Grant from the Academy of Medical Sciences (UK), by a PhD Fellowship in Global Health to EW from the Wellcome Trust (089671/B/09/Z) and by a Postdoctoral Clinical Research Fellowship to GP from the Wellcome Trust (WT101766). The Malawi-Liverpool-Wellcome Trust Clinical Research Programme is supported by a core grant from the Wellcome Trust (101113/Z/13/Z). This work was undertaken at UCLH/UCL who received a proportion of funding from the National Institute for Health Research University College London Hospitals Department of Health’s NIHR Biomedical Research Centre. JSB, MN and CV are supported by the Centre’s funding scheme. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data and the final responsibility to submit for publication. Declaration of Interests: All authors have no conflicts of interest to declare. Ethics Approval Statement: All participants or nominated guardians gave written informed consent for inclusion. Ethical approval for the transcriptomics study was granted by both the College of Medicine Research and Ethics Committee (COMREC), University of Malawi, (P.01/10/980, January 2011), and the Liverpool School of Tropical Medicine Research Ethics Committee, UK (P10.70, November 2010) Committee, Liverpool, UK

Background Studies have revealed the efficacy of home-based environmental interventions on reduction of asthma symptoms as a strategy for managing asthma in children. A focus on education and behavior change alone is generally too limited to reduce exposure to asthma triggers that exist because of adverse housing conditions. Objective To demonstrate that housing conditions as a focus of a health intervention should be considered more widely as an effective means of addressing serious health problems such as asthma. Methods Residences of 41 families of children identified with some of the highest rates of asthma-related hospital visits were assessed for the presence of asthma triggers. Results The intervention had a positive effect on lessening the effect of the child's asthma on the family's lives and activities. Reductions in frequency of negative effects of children's asthma on sleeping, job or work around the house, and family activity plans, fewer worries or concerns about children getting enough sleep and performing normal daily activities, and fewer adverse effects of children's asthma medications were reported. Reduced use of asthma medication, medication applications, and health visits were noted. Households with return visits had 50% lower hospital bills for childhood asthma treatment. Conclusion Home environment conditions that lead to or exacerbate asthma may be reduced or eliminated by making minor repairs and introducing reasonable cleaning regimens that address sources of asthma triggers. This can produce greater awareness on the part of families about the presence of asthma triggers and motivate future action to address the conditions associated with these triggers.

Lymphangiomas are most commonly described as a small painless mass in the neck or a vesicular rash in an infant patient. Ninety per cent of cases are diagnosed before the age of 2. Treatment usually involves surgical resection. Intra-abdominal lymphangiomas and mesenteric lymphangiomas, as described in our case report, represent a rare pathology. The exact prevalence of this condition is unclear but it has been suggested in the literature that there have been as few as 820 cases since the 16th century. The clinical presentation is usually subacute and diagnosis made incidentally during a workup of chronic gastrointestinal symptoms. Acute abdominal symptoms, as in our case presentation, are unusual but may be explained by the mass effect of a large intra-abdominal lesion. Cross-sectional imaging is key in preoperative workup and operative planning. Complete surgical resection is recommended and curative in the majority of cases with a low risk of local recurrence.

OBJECTIVEIn addition to the rising burden of surgical disease globally, infrastructure and human resources for health remain a great challenge for low- and middle-income countries, especially in Uganda. In this study, the authors aim to explore the trends of neurosurgical care at a regional referral hospital in Uganda and assess the long-term impact of the institutional collaboration between Mulago National Referral Hospital and Duke University.METHODSAn interrupted time series is a quasi-experimental design used to evaluate the effects of an intervention on longitudinal data. The authors applied this design to evaluate the trends in monthly mortality rates for neurosurgery patients at Mbarara Regional Referral Hospital (MRRH) from March 2013 to October 2015. They used segmented regression and autoregressive integrated moving average models for the analysis.RESULTSOver the study timeframe, MRRH experienced significant increases in referrals received (from 117 in 2013 to 211 in 2015), neurosurgery patients treated (from 337 in 2013 to 625 in 2015), and operations performed (from 61 in 2013 to 173 in 2015). Despite increasing patient volumes, the hospital achieved a significant reduction in hospital mortality during 2015 compared to prior years (p value = 0.0039).CONCLUSIONSThis interrupted time series analysis study showed improving trends of neurosurgical care in Western Uganda. There is a steady increase in volume accompanied by a sharp decrease in mortality through the years. Multiple factors are implicated in the significant increase in volume and decrease in mortality, including the addition of a part-time neurosurgeon, improvement in infrastructure, and increased experience. Further in-depth prospective studies exploring seasonality and long-term outcomes are warranted.

Background Every day children and adults die from acute community-acquired bacterial meningitis, particularly in low-income countries, and survivors risk deafness, epilepsy and neurological disabilities. Osmotic therapies may attract extra-vascular fluid and reduce cerebral oedema, and thus reduce death and improve neurological outcomes. This is an update of a Cochrane Review first published in 2013. Objectives To evaluate the effects of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults on mortality, deafness and neurological disability. Search methods We searched CENTRAL (2017, Issue 1), MEDLINE (1950 to 17 February 2017), Embase (1974 to 17 February 2017), CINAHL (1981 to 17 February 2017), LILACS (1982 to 17 February 2017) and registers of ongoing clinical trials (ClinicalTrials.com, WHO ICTRP) (21 February 2017). We also searched conference abstracts and contacted researchers in the field (up to 12 December 2015). Selection criteria Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis. Data collection and analysis Two review authors independently screened the search results and selected trials for inclusion. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. We used the GRADE approach to assess the certainty of the evidence. Main results We included five trials with 1451 participants. Four trials evaluated glycerol against placebo, and one evaluated glycerol against 50% dextrose; in addition three trials evaluated dexamethasone and one trial evaluated acetaminophen (paracetamol) in a factorial design. Stratified analysis shows no effect modification with steroids; we present aggregate effect estimates. Compared to placebo, glycerol probably has little or no effect on death in people with bacterial meningitis (RR 1.08, 95% CI 0.90 to 1.30; 5 studies, 1272 participants; moderate-certainty evidence), but may reduce neurological disability (RR 0.73, 95% CI 0.53 to 1.00; 5 studies, 1270 participants; low-certainty evidence). Glycerol may have little or no effect on seizures during treatment for meningitis (RR 1.08, 95% CI 0.90 to 1.30; 4 studies, 1090 participants; low-certainty evidence). Glycerol may reduce the risk of subsequent deafness (RR 0.64, 95% CI 0.44 to 0.93; 5 studies, 922 participants; low to moderate-certainty evidence). Glycerol probably has little or no effect on gastrointestinal bleeding (RR 0.93, 95% CI 0.39 to 2.19; 3 studies, 607 participants; moderate-certainty evidence). The evidence on nausea, vomiting and diarrhoea is uncertain (RR 1.09, 95% CI 0.81 to 1.47; 2 studies, 851 participants; very low-certainty evidence). Authors' conclusions Glycerol was the only osmotic therapy evaluated, and data from trials to date have not demonstrated an effect on death. Glycerol may reduce neurological deficiency and deafness. Osmotic therapies added to antibiotics for acute bacterial meningitis What is the aim of this review? The aim of this Cochrane Review is to collect and analyse trials evaluating osmotic therapies given orally or intravenously to people with acute bacterial meningitis. Cochrane authors collected and analysed all relevant studies to answer this question; they found five relevant studies. Key messages Giving glycerol, an osmotic diuretic, probably has little or no effect on death (moderate-certainty evidence), but may reduce subsequent deafness (moderate-certainty evidence) or neurological disability (low-certainty evidence). The evidence is current to 17 February 2017. What was studied in the review? In meningitis, the cerebrospinal fluid that surrounds the brain and spinal cord is infected, usually as a result of spread from the blood. Any form of meningitis can result in death or severe disability, but acute bacterial meningitis is rapidly fatal without treatment. Even with antibiotics, 10% to 15% of children with bacterial meningitis die in high-income countries with much higher rates in low-income settings. The infection causes the brain to swell, and this is thought to contribute to death and to long-term brain damage in survivors. Osmotic therapies increase the concentration of the blood by exerting an osmotic pressure across a semi-permeable membrane (such as a cell wall or blood vessel lining in the brain). This draws water from the brain into the blood, thereby reducing pressure in the brain. Potentially osmotic therapies could increase the rate of survival, or they could do harm. What are the main results of the review? We included five trials that compared glycerol with placebo in a total of 1451 patients with bacterial meningitis. In the studies steroids were often given as well, but this did not appear to modify any of the effects seen with glycerol. This review detected no benefit from glycerol relating to death. There appeared to be marginal protection against deafness and against neurological disability. No effect on epileptic seizures at follow-up was noted. Glycerol was not associated with any severe adverse effects. The number of trials included was small and only two tested a large number of participants. All trials were from different healthcare settings and examined either adults or children.

To introduce the challenges in addressing irreparable rotator cuff tears and examine the surgical options, specifically interposition grafting and superior capsule reconstruction. Interposition grafting of rotator cuff tears shows promising results in reducing pain and improving function postoperatively and one study demonstrated that it performs significantly better than partial repair alone. Superior capsule reconstruction has become popular rapidly, but given the novelty of the procedure, there is currently a paucity of outcomes data to review. Irreparable rotator cuff tears are a challenging condition with a variety of surgical options available. Two such options—interposition and superior capsule reconstruction—both employ grafts in an attempt to restore joint stability and function. In the past 3 years, literature discussing interposition grafting has explored the different types of grafts, and mostly employed pre-post analysis. The recent superior capsule reconstruction articles strictly used human dermal allograft and offer a variety of surgical techniques without quantitative data.

Thiopurine drugs, including azathioprine and 6-mercaptopurine, are used commonly in patients with inflammatory bowel disease for maintenance of remission. Although generally well tolerated, adverse effects lead to discontinuation in a significant minority of patients. Pharmacogenomic studies have suggested that metabolic breakdown of azathioprine in an individual is genetically determined. Coupled with the fact that certain thiopurine metabolites, notably 6-thioguanine nucleotide and 6-methylmercaptopurine, are associated with antiinflammatory effects and adverse effects, respectively, some investigators have examined intentionally shunting the metabolism of azathioprine toward increasing 6-thioguanine nucleotide levels by using low doses of the xanthine oxidoreductase inhibitor allopurinol to improve efficacy and decrease toxicity of azathioprine in patients with inflammatory bowel disease. We performed a search of the MEDLINE and Embase databases for basic and clinical research reports of this modality. Pertinent articles were retrieved, reviewed, and assessed by the authors. Case series, cohort studies, and one randomized trial have investigated adding allopurinol to azathioprine therapy in patients with inflammatory bowel disease. Most reports primarily examined metabolite levels in these patients. In general, the literature suggests that this modality was successful at significantly increasing 6-thioguanine nucleotide levels while decreasing 6-methylmercaptopurine levels. Several small reports have suggested that patients with increased 6-thioguanine nucleotide levels had improved symptoms or symptom remission. Adverse effects and discontinuation rates remained similar or were improved in patients who were taking a thiopurine and started allopurinol. In conclusion, the addition of allopurinol may be an option for optimizing thiopurine metabolite production in select patients with low 6-thioguanine nucleotide levels. Appropriate care and monitoring of these patients are mandatory to prevent neutropenia or other adverse effects.

Quantification and comparison of the dewatering characteristics of fifteen sewage sludges from a range of digestion scenarios are described. The method proposed uses laboratory dewatering measurements and integrity analysis of the extracted material properties. These properties were used as inputs into a model of filtration, the output of which provides the dewatering comparison. This method is shown to be necessary for quantification and comparison of dewaterability as the permeability and compressibility of the sludges varies by up to ten orders of magnitude in the range of solids concentration of interest to industry. This causes a high sensitivity of the dewaterability comparison to the starting concentration of laboratory tests, thus simple dewaterability comparison based on parameters such as the specific resistance to filtration is difficult. The new approach is demonstrated to be robust relative to traditional methods such as specific resistance to filtration analysis and has an in-built integrity check. Comparison of the quantified dewaterability of the fifteen sludges to the relative volatile solids content showed a very strong correlation in the volatile solids range from 40 to 80%. The data indicate that the volatile solids parameter is a strong indicator of the dewatering behaviour of sewage sludges.

Objective We report a project that utilized pharmacy students to increase pneumococcal vaccination rates in patients aged 19-64 years with high-risk medical conditions within urgent care clinics. The study also sought to better identify the number of patients previously vaccinated for pneumococcal disease. A total of 1,178 patients were considered eligible for pneumococcal vaccination during the study period, 287 (24.4%) of whom were determined to be previously vaccinated through chart assessment or patient interview. Of the remaining 891 patients, chart documentation of pneumococcal vaccination administered at the time of the urgent care visit was present for 96 patients (10.7%) in the intervention clinics compared with 6 patients in 2 control clinics who received the usual standard of care (P