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OBJECTIVE The inclusion of peer-delivered services in organizations providing behavioral health care has significantly increased in recent years, and substantial resources are being directed toward implementing recovery-oriented mental health services using peer-provided programs. Previous research found that participants in such programs have improved recovery outcomes. While there are demonstrated positive associations between recovery outcomes and peer-provided services, there is limited research on the effectiveness of specific peer-provided interventions. Veteran X is a peer-led program developed in the Department of Veterans Affairs in which participants serve as a recovery team for a fictitious Veteran who faces numerous social and mental health issues. This study compared the effectiveness of the Veteran X program with treatment as usual on measures of recovery wellbeing, symptoms and functioning, and risk and protective factors for substance use disorders. METHODS Participants were recruited (N = 80) over a period of ten months, and had self-selected into treatment as usual (TAU, N = 37), or treatment as usual plus Veteran X (N = 43). RESULTS No baseline differences were found on the pretest measures. Both groups improved on all measures after 60 days of participation, however Veteran X participants improved significantly more than TAU participants on the measures of recovery wellbeing and symptoms and functioning. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE The results of this study appear to support the positive contribution of the Veteran X program in improving recovery wellbeing and symptoms and functioning among participating veterans. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background School closures and family economic instability caused by the COVID-19 lockdown measures have threatened the mental health and academic progress of adolescents. Through secondary data analysis of World Vision Asia Pacific Region’s COVID-19 response-assessments in May–June 2020, this study examined whether adolescents’ study, physical, and leisure activities, psychosocial status, and sources of COVID-19 information differed by gender. Methods The assessments used cross-sectional surveys of adolescents in poor communities served by World Vision (n = 5552 males and n = 6680 females) aged 10–18 years old in six countries. The study households of adolescents were selected either by random sampling or non-probability convenience sampling and assessed using telephone or in-person interviews. Multivariate logistic regression analyses examined the relationship between gender and psychosocial status; daily activities (e.g., play, study); and sources of information about COVID-19. Results Participation in remote education was low (range: 0.5–20.7% across countries), with gender difference found only in Vietnam. Compared to males, female adolescents were less likely to play physically with a range of AOR: 0.36–0.55 (n = 5 countries) or play video games with a range of AOR: 0.55–0.72 (n = 2 countries). Female adolescents were more likely to feel isolated or stressed (India, AOR = 1.13, 95%CI:1.00, 1.26); feel unsafe (the Philippines, AOR = 2.22, 95%CI:1.14, 4.33; Vietnam, AOR = 1.31, 95%CI:1.03, 1.47); be concerned about education (India, AOR = 1.24, 95%CI:1.09, 1.41; Myanmar, AOR = 1.59, 95%CI:1.05, 2.40); or be concerned about household income (India, AOR = 1.13, 95%CI:1.00, 1.28; Vietnam, AOR = 1.31, 95%CI:1.09, 1.58). Female adolescents were also less likely to obtain COVID-19 related information through internet/social media (Bangladesh, AOR = 0.51, 95%CI:0.41, 0.64; India, AOR = 0.84, 95%CI:0.73, 0.96; and Myanmar, AOR = 0.65, 95%CI:0.43, 0.97) and mobile call or short message (India, AOR = 0.88, 95%CI:0.80, 0.98) but more likely to get the information from friends (Vietnam, AOR = 1.18, 95%CI:1.02, 1.36) and family (Bangladesh, AOR = 1.44, 95% CI:1.21, 1.70; India, AOR = 1.29, 95% CI:1.15, 1.45). Conclusions An understanding of gender differences in the impacts of COVID-19 on adolescents' schooling, physical, and mental health can inform adolescent protection interventions. Psychosocial support during response and recovery phases needs to pay special attention to gender differences, since female adolescents’ psychosocial status is at higher risk when facing the challenges of this pandemic.

BACKGROUND: AML patients with FLT3/ITD mutations have poor response to cytarabine-based chemotherapy. FLT3 inhibitors (FLT3i) may resensitize cells to cytarabine (CYT). Improving treatment outcome of this combination may benefit from a mechanistic extrapolation approach from in vitro data. METHODS: The effects of CYT and several FLT3i on cell proliferation and cell cycle kinetics were examined in AML cell lines. The effect of FLT3i (quizartinib, midostaurin, sorafenib) on cell proliferation and cell cycle kinetics was assessed in AML cell lines with differing FLT3 status; HEL (negligible expression of wild-type FLT3), EOL1 (wild-type FLT3), MV4–11 (FLT3-ITD resulting in constitutively active isoform). Semi-mechanistic cell cycle models for CYT and FLT3i were developed. Clinical CYT and quizartinib pharmacokinetic dosage regimens were modeled. Survival of AML patients was described via a hazard model. Simulations exploring different CYT/quizartinib regimens were conducted with the goal of improving treatment outcome. RESULTS: FLT3 status was associated with sensitivity to CYT (HEL cells most sensitive > EOL1 > MV4–11 cells). This order of sensitivity is reversed for FLT3i. Cytarabine induced apoptosis in the S-phase while all FLT3i induced apoptosis and cell cycle arrest at G1 phase. Simulations of candidate clinical regimens predict better cell kill upon adding quizartinib simultaneously with or immediately after CYT exposure. Overall survival was predicted to be significantly better with quizartinib 200 mg administered every 48 h vs every 24 h in patients with FLT3 aberrations. CONCLUSION: Simultaneous administration of quizartinib and CYT every other day is a promising combination regimen for AML patients with FLT3 mutations.

BackgroundCOVID-19 was the leading cause of death in the United States over the three-month period March through May 2020. Another perspective is COVID-19’s toll in terms of years of life lost. We calculated years of life lost for COVID-19 and other leading causes of death over those three months in the US. We also predicted years of life lost for COVID-19 and ischemic heart diseases (which includes heart attacks) for March through August 2020.MethodsYears of life lost are the sum of differences between life expectancy at age of death and age at death. Average years of life lost, years of life lost divided by the number of deaths, were also calculated. We used the COVID-19 Projections Using Machine Learning model to predict years of life lost from COVID-19 through the end of August 2020.ResultsCOVID-19 caused 12,035 more deaths than ischemic heart diseases during March through May 2020 but ischemic heart diseases years of life lost were 1.5% greater than those for COVID-19. Average years of life lost were 10.8 and 12.4 for COVID-19 and ischemic heart diseases, respectively. At the end of August, COVID-19 may overtake ischemic heart diseases as the leading cause of deaths and years of life lost in the US.ConclusionEach COVID-19 death causes more than a decade of lost life in the US. We are reminded of a Danish Proverb that states “Prediction is difficult, especially when dealing with the future.” We suggest that while dying is bad, losing life is even worse.

This study investigated service use by individuals with serious and nonserious mental illness receiving mental health care in medical and mental health settings.Claims data from the New York State Medicaid Data Warehouse were examined for 8,988 patients who received at least one mental health service at an urban academic medical center during 2017 at a mental health setting, a medical setting, or both.Most patients (59%) received all of their mental health care in medical settings and from unaffiliated providers, including a large portion (16%) with serious mental illness. Despite the availability of integrated care in the medical setting and use of unaffiliated mental health providers, rates of mental health inpatient admissions were high among all patients in this setting (including those with serious and with nonserious mental illness), considerably higher than for patients treated in a mental health clinic within the system. Rates of medical and substance abuse inpatient admissions were also much higher for patients treated in the medical setting and by unaffiliated providers, compared with those treated in the system's mental health clinics.Findings suggest that when mental health services are available in medical and mental health settings within the same system, either patients with more severe physical illnesses are more likely to receive their mental health care in medical settings and from unaffiliated providers and thus have more hospitalizations of all types or affiliated mental health settings more effectively address clinical needs and thus reduce hospitalizations.

BackgroundIt has been suggested that many of those who died from COVID-19 were older, had more comorbidities, and would have died within a short period anyway. We estimated the number and percent of excess deaths due to COVID-19 In April 2020 in the United States, New York City, and Michigan.MethodsFor each locale we calculated attributable fractions in the exposed comparing observed COVID-19 deaths and expected deaths. In addition, we estimated the number of months it would take for the excess deaths to occur without the virus and the proportions of the populations that were infected leading to the April deaths. We compared the excess deaths from the attributable fraction method to those obtained by comparing weekly deaths in 2019 and 2020.ResultsUsing an assumed infection fatality rate of 1%, the percentages of excess deaths were 95%, 97%, and 95% in the US, NYC, and MI equivalent to 54,560; 14,951; and 3,338 deaths, respectively. Absent the virus these deaths would have occurred over 21.0, 29.2, and 18.4 months in the respective locations. An estimated 1.7% of the US population was infected between March 13 and April 10, 2020. Nearly 19% were infected in NYC.ConclusionsOver 75% of COVID-19 deaths in April 2020 were excess deaths meaning they would not have occurred in April without SARS-CoV-2 but would have been spread out over the ensuing 18 to 29 months. Confirmed cases in the US under-report the actual number of infections by at least an order of magnitude. Excess death numbers calculated using the attributable fraction in the exposed are similar to those obtained from weekly mortality reports.

In April 2020, Vietnam initiated a country-wide lockdown to curb the spread of COVID-19. This secondary data analysis evaluates whether NGO-supported households (n = 3,431) reporting to be severely impacted by the lockdowns differ from those reporting a lesser impact, regarding food availability within households and at markets and affordability. 19.2% of respondents indicated that the pandemic had severely impacted their livelihoods. In the severely impacted group, there was a higher percentage of urban residents (25.3 vs. 8.6%; p < 0.001), households reporting decreased income (85.4 vs. 39.9%), and females (56.4 vs. 45.6%; p < 0.001) than in the less impacted group. Both groups reported similar availabilities of staple food groups at the household-level, but the availability of green vegetables was lower in the severely affected group (Adjusted OR [aOR] = 0.62, 95% CI: 0.38, 1.00) than in the less affected group. However, local market availability of hygiene items (aOR = 1.64, 95% CI: 1.13, 2.39) and essential medicines (aOR = 1.80, 95% CI: 1.29, 2.50) were higher for the more impacted group relative to the less impacted group. While the self-reported livelihood impact of COVID-19 was associated with a loss of income, the association of indicators of food availability within households and at markets, and essential item affordability, did not frequently differ. Self-determination of a severe economic impact may represent a relative change in the household's socioeconomic status from before the pandemic.

Endoscope reprocessing is often ineffective, and microbes frequently remain on endoscopes after the use of high-level disinfectants (HLDs). Several factors impact reprocessing effectiveness, including non-adherence to guidelines, use of damaged endoscopes, use of insoluble products during endoscopy, insufficient cleaning, contaminated rinse water, and inadequate drying before storage. Our team suspected that issues with HLD chemistries and monitoring could also contribute to reprocessing failures. We conducted a mixed-methods analysis of published literature, our interviews with frontline personnel, and evidence from our previous studies. The evidence showed that reusable HLDs commonly failed tests for minimum effective concentration (MEC) before their maximum usage periods. MEC tests also detected failures associated with single-use HLDs that did not fully deploy. These failures were due to product issues, process complexities, and personnel non-adherence with guidelines and manufacturer instructions. HLDs will likely continue to be used for the foreseeable future. More research is needed to assess real-world practice patterns related to the high-level disinfection step and MEC testing and to establish more realistic usage periods for reusable HLD chemistries. Manufacturers and researchers should evaluate the ability of technological solutions and engineered safeguards to overcome human error. Recognition of the need for quality improvement is growing, and infection preventionists should take action to build on this momentum and collaborate with manufacturers, endoscopists, and reprocessing personnel to improve the effectiveness of high-level disinfection.

The paper discusses the etiology, pathogenesis, pathomorphology and pathophysiology of osteoarthritis of large joints from the perspective of evidencebased medicine. The processes occurring in the tissues of the joints during the development of the pathological process at various stages are described in detail; the features of diagnosis and treatment in sports medicine are described in detail. The characteristic of drugs used to treat osteoarthritis is described, with a description of the positive effect and negative effect on particular organs and systems. A preparation Alflutop was comprehensively analysed regarding its effectiveness in terms of safety and impact on the development of the pathological process. It was shown that Alflutop is a drug of choice in the treatment of joint destruction.

Key Points Dasatinib and dexamethasone induction then allogeneic hematopoietic cell transplantation was feasible and effective for untreated Ph+ ALL.Treatment failure was associated with BCR-ABL1 T315I mutation, the p210 BCR-ABL1 isoform, or isolated CNS relapse., Visual Abstract, Post-remission strategies after dasatinib-corticosteroid induction in adult Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL) are not well studied. We evaluated dasatinib and dexamethasone induction then protocol-defined post-remission therapies, including hematopoietic cell transplantation (HCT). Adults (N = 65) with Ph-positive ALL received dasatinib-dexamethasone induction, methotrexate-based central nervous system (CNS) prophylaxis, reduced-intensity conditioning (RIC) allogeneic HCT, autologous HCT, or chemotherapy alone, and dasatinib-based maintenance. Key end points were disease-free survival (DFS) and overall survival (OS). The median age was 60 years (range, 22-87 years). The complete remission rate was 98.5%. With a median follow-up of 59 months, 5-year DFS and OS were 37% (median, 30 months) and 48% (median, 56 months), respectively. For patients receiving RIC allogeneic HCT, autologous HCT, or chemotherapy, 5-year DFS were 49%, 29%, and 34%, and 5-year OS were 62%, 57%, and 46%, respectively. Complete molecular response rate after CNS prophylaxis was 40%. Relative to the p190 isoform, p210 had shorter DFS (median 10 vs 34 months, P = .002) and OS (median 16 months vs not reached, P = .05). Relapse occurred in 25% of allogeneic HCT, 57% of autologous HCT, and 36% of chemotherapy patients. T315I mutation was detected in 6 of 8 marrow relapses. Dasatinib CNS concentrations were low. Dasatinib-dexamethasone followed by RIC allogeneic HCT, autologous HCT, or chemotherapy was feasible and efficacious, especially with RIC allogeneic HCT. Future studies should address the major causes of failure: T315I mutation, the p210 BCR-ABL1 isoform, and CNS relapse. This study was registered at www.clinicaltrials.gov as #NCT01256398.

Rasburicase can markedly and rapidly decrease uric acid (UA) levels, thereby preventing and treating tumor lysis syndrome. However, rasburicase is expensive, especially when used as per the manufacturer's recommended dosage of 0.2 mg/kg/day for up to 5 days. Numerous reports have shown that lower, and even single doses are effective in lowering UA levels but prospective randomized studies comparing low doses have not been performed.To prospectively determine the efficacy and safety of two single low doses of rasburicase in adult patients (pts) with acute leukemia and elevated plasma UA.Eligible pts aged ≥ 18 years old with acute leukemia and UA ≥ 7.5 mg/dL were randomized to receive an initial single dose of rasburicase 1.5 mg (Arm A) or 3 mg (Arm B) on day 1 in an unblinded fashion. All pts received allopurinol 300 mg daily on days 1-6.Twenty-four pts (median age 69 years; 14 males and 10 females) were enrolled in this phase 2 study (12 on each arm). Twenty pts had acute myeloid leukemia while 3 had acute lymphoblastic leukemia, and 1 had acute promyelocytic leukemia. Median initial UA level was 9.8 mg/dL. Eighty-three percent of pts in both arms achieved UA7.5 mg/dL by 24 h after therapy. Five pts (21 %; 2 from Arm A and 3 from Arm B) required additional doses of rasburicase. The majority (23/24) of pts achieved UA goals after 1-2 doses of rasburicase. None had worsening renal function. Both doses were well tolerated, and no treatment related adverse events were reported.Single doses of rasburicase (as low as 1.5-3 mg) used in addition to allopurinol were well tolerated and highly efficacious (83 % response rate) in decreasing UA levels within 24 h of administration in adult acute leukemia pts with hyperuricemia.

Venous thromboembolism (VTE) is the fourth most commonly reported complication in trauma patients. For these patients, thromboprophylaxis is a standard of care. Patient compliance with sequential compression devices (SCDs), a form of mechanical VTE prophylaxis, has been a focus of efforts to improve patient safety. At our institution, a baseline audit in July 2020 revealed that patients admitted to the trauma floors have poor compliance with the use of SCDs. In this quality improvement project, we developed a patient education intervention to improve SCD compliance. We distributed an informational flyer to patients and led short educational sessions on VTE risk factors and proper SCD use. Our aim was to increase our SCD compliance rate by 30% in 4 weeks. We used three plan-do-study-act (PDSA) cycles to implement and refine our intervention. We measured SCD compliance during morning and afternoon patient observations and generated run charts to understand how our cycles were leading to change. After a 4-week period, we did not achieve our aim, but increased our overall compliance from 45% to 60% and sustained this improvement throughout our PDSA cycles. Morning compliance was lower than afternoon compliance both at baseline (45% vs 48.5%) and at the end the project (45% vs 53%). Our results suggest that patient education should be coupled with interventions that address other barriers to SCD compliance.

Background Malaria was the leading cause of post-neonatal deaths in Mozambique in 2017. The use of long-lasting insecticidal nets (LLINs) is recognized as one of the most effective ways to reduce malaria morbidity and mortality, especially in children. In 2015, Mozambique committed to the expansion of LLIN coverage nationwide, culminating in the first countrywide campaign in 2017, reaching 95% of registered households. Between 2012 and 2019, more than 34 million LLINs were distributed. No previous analyses have estimated changes in mortality attributable to the scale-up of LLINs, accounting for provincial differences in mortality rates and coverage of health interventions. Methods From 2012 to 2020, the population-based model NetCALC was used to predict provincial household LLIN coverage based upon the number of LLINs distributed annually. NetCALC also projected how many LLINs are needed to maintain universal coverage in 10 provinces from 2021 to 2025. Based upon the annual provincial coverage of LLINs, the Lives Saved Tool (LiST), a multi-cause mathematical model, estimated under-5 lives saved, and reductions in under-5 mortality attributable to LLIN expansion in 10 provinces of Mozambique between 2012 and 2020, and projected lives saved from 2021 to 2025 if universal coverage of LLINs is sustained. Results Results from the LiST models estimate that 64,470 child deaths were averted between 2012 and 2019. If currently planned quantities of LLINs are distributed in 2020, and universal coverage is maintained from 2021 to 2025, an additional 68,695 child deaths could be averted. From 2011 to 2020, the percent reduction in all-cause child mortality was 19.2%, from 114.5 per 1,000 to 93.2 per 1000 in the LLIN distribution model compared to 9.5% in the baseline model. If universal coverage continues through 2025, this reduction will be sustained. Conclusions LiST and NetCALC used together are useful in estimating lives saved and mortality in countries such as Mozambique where vital registration data to measure changes in mortality are not consistently available. Universal coverage of LLINs can save a substantial number of child lives and reduce child mortality in Mozambique but will require resource mobilization. Without continued investment, thousands of avoidable child deaths will occur.

Background Recent outbreaks of duodenoscope-associated multidrug-resistant organisms (MDROs) have brought attention to the infection risk from procedures performed with duodenoscopes. Prior to these MDRO outbreaks, procedures with duodenoscopes were considered safe and low risk for exogenous infection transmission, provided they were performed in strict accordance with manufacturer instructions for use and multisociety reprocessing guidelines. The attention and efforts of the scientific community, regulatory agencies, and the device industry have deepened our understanding of factors responsible for suboptimal outcomes. These include instrument design, reprocessing practices, and surveillance strategies for detecting patient and instrument colonization. Various investigations have made it clear that current reprocessing methods fail to consistently deliver a pathogen-free instrument. The magnitude of infection transmission has been underreported due to several factors. These include the types of organisms responsible for infection, clinical signs presenting in sites distant from ERCP inoculation, and long latency from the time of acquisition to infection. Healthcare providers remain hampered by the ill-defined infectious risk innate to the current instrument design, contradictory information and guidance, and limited evidence-based interventions or reprocessing modifications that reduce risk. Therefore, the objectives of this narrative review included identifying outbreaks described in the peer-reviewed literature and comparing the findings with infections reported elsewhere. Search strategies included accessing peer-reviewed articles, governmental databases, abstracts for scientific conferences, and media reports describing outbreaks. This review summarizes current knowledge, highlights gaps in traditional sources of evidence, and explores opportunities to improve our understanding of actual risk and evidence-based approaches to mitigate risk.

Background Cutaneous leishmaniasis (CL) is a neglected tropical disease causing an estimated 1 million new cases annually. While antimonial compounds are the standard of care worldwide, they are associated with significant adverse effects. Miltefosine, an oral medication, is United States (US) Food and Drug Administration approved to treat CL caused by Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis. Evidence of efficacy in other species and side-effect profiles in CL has been limited. Methods Twenty-six patients with CL were treated with miltefosine at the US National Institutes of Health. Species included L. braziliensis (n = 7), L. panamensis (n = 5), Leishmania mexicana (n = 1), Leishmania infantum (n = 3), Leishmania aethiopica (n = 4), Leishmania tropica (n = 2), Leishmania major (n = 1), and unspeciated (n = 3). Demographic and clinic characteristics of the participants, response to treatment, and associated adverse events were analyzed. Results Treatment with miltefosine resulted in cure in 77 % (20/26) of cases, with cures among all species. Common adverse events included nausea/vomiting (97%) and lack of appetite (54%). Clinical management or dose reduction was required in a third of cases. Gout occurred in 3 individuals with a prior history of gout. Most laboratory abnormalities, including elevated creatinine and aminotransferases, were mild and normalized after treatment. Conclusions Our data suggest that miltefosine has good but imperfect efficacy to a wide variety of Leishmania species. While side effects were common and mostly mild to moderate, some resulted in discontinuation of therapy. Due to oral administration, broad efficacy, and manageable toxicities, miltefosine is a viable alternative treatment option for CL, though cost and lack of local availability may limit its widespread use.

Objective The aim of this observational study was to determine the optimal timing of interleukin-6 receptor inhibitor (IL6ri) administration for coronavirus disease 2019 (COVID-19). Methods Patients with COVID-19 were given an IL6ri (sarilumab or tocilizumab) based on iteratively reviewed guidelines. IL6ri were initially reserved for critically ill patients, but after review, treatment was liberalized to patients with lower oxygen requirements. Patients were divided into two groups: those requiring ≤45% fraction of inspired oxygen (FiO2) (termed stage IIB) and those requiring >45% FiO2 (termed stage III) at the time of IL6ri administration. The main outcomes were all-cause mortality, discharge alive from hospital, and extubation. Results A total of 255 COVID-19 patients were treated with IL6ri (149 stage IIB and 106 stage III). Patients treated in stage IIB had lower mortality than those treated in stage III (adjusted hazard ratio (aHR) 0.24, 95% confidence interval (CI) 0.08–0.74). Overall, 218 (85.5%) patients were discharged alive. Patients treated in stage IIB were more likely to be discharged (aHR 1.43, 95% CI 1.06–1.93) and were less likely to be intubated (aHR 0.43, 95% CI 0.24–0.79). Conclusions IL6ri administration prior to >45% FiO2 requirement was associated with improved COVID-19 outcomes. This can guide clinical management pending results from randomized controlled trials.

During the past twenty years Open Educational Resources (OER) and Open Educational Practices (OEP) have increased educational access and affordability worldwide. The OER-OEP synergy reflects one of the most promising strategies for increasing access to education globally. Despite significant progress, emerging research suggests the need for a more concerted focus on moving from awareness raising to implementation. This article analyses the current status of OER and OEP in concert with the recent educational response to COVID-19 by educational providers with complimentary mini-case studies from Africa, Brazil, Canada, China, Sweden, and Turkey. The ICDE Ambassadors for the global advocacy of OER, and members of ICDE OER Advocacy Committee (authors) argue that in the six countries studied, there is a greater need and greater receptivity to expand access to education through OER and OEP. To better address the immediate needs of the COVID-19 educational crisis, and to make longer term educational improvements, countries should harness the policy supports and actionable steps offered by the UNESCO OER Recommendation. Currently, we see an opportunity to move OER-OEP to resilient sustainable education and the international policy framework to support such work. The article concludes with some general observations for the way forward.

Background BRCA1/2 deleterious variants account for most of the hereditary breast and ovarian cancer cases. Prediction models and guidelines for the assessment of genetic risk rely heavily on criteria with high variability such as family cancer history. Here we investigated the efficacy of MRI (magnetic resonance imaging) texture features as a predictor for BRCA mutation status. Methods A total of 41 female breast cancer individuals at high genetic risk, sixteen with a BRCA1/2 pathogenic variant and twenty five controls were included. From each MRI 4225 computer-extracted voxels were analyzed. Non-imaging features including clinical, family cancer history variables and triple negative receptor status (TNBC) were complementarily used. Lasso-principal component regression (L-PCR) analysis was implemented to compare the predictive performance, assessed as area under the curve (AUC), when imaging features were used, and lasso logistic regression or conventional logistic regression for the remaining analyses. Results Lasso-selected imaging principal components showed the highest predictive value (AUC 0.86), surpassing family cancer history. Clinical variables comprising age at disease onset and bilateral breast cancer yielded a relatively poor AUC (~ 0.56). Combination of imaging with the non-imaging variables led to an improvement of predictive performance in all analyses, with TNBC along with the imaging components yielding the highest AUC (0.94). Replacing family history variables with imaging components yielded an improvement of classification performance of ~ 4%, suggesting that imaging compensates the predictive information arising from family cancer structure. Conclusions The L-PCR model uncovered evidence for the utility of MRI texture features in distinguishing between BRCA1/2 positive and negative high-risk breast cancer individuals, which may suggest value to diagnostic routine. Integration of computer-extracted texture analysis from MRI modalities in prediction models and inclusion criteria might play a role in reducing false positives or missed cases especially when established risk variables such as family history are missing.

BackgroundWeinberger and colleagues estimated that 27,065 of the 122,300 excess deaths in the United States between March 1 and May 30, 2020 did not have a COVID-19 cause of death.MethodsThe Centers for Disease Control and Prevention (CDC) post weekly data on mortality for 13 causes of death from the most prevalent comorbid conditions reported on death certificates where COVID-19 was listed as a cause of death. The 2015-2019 data for weeks 10 through 22 were used to forecast the number of deaths from the 13 causes in the absence of COVID-19 during 2020. The forecast was subtracted from the observed number of deaths for each cause during the period March 1 to May 30, 2020.ResultsThe total of the differences for each of the 13 causes of death, 18,489 deaths, accounts for over two-thirds of the 27,065 excess deaths not due to COVID-19.ConclusionCombining the 95,235 reported COVID-19 deaths with the 18,489 from the 13 most frequent comorbid conditions reported on death certificates where COVID-19 was a cause suggests that as many as 93% of the excess deaths were due to COVID-19 and implies that COVID-19 deaths were undercounted. Ongoing assessment of excess deaths and causes of death is needed to provide a better understanding of the pandemic’s dynamics.

Background: Adequate patient selection is the key to successful lung volume reduction in patients with pulmonary emphysema. Computed tomography (CT) enables a reliable detection of pulmonary emphysema and allows an accurate quantification of the severity. Our goal was to investigate the usefulness and reliability of color-coded (CC) CT images in classification of emphysema and preoperative lung volume reduction planning. Methods: Fifty patients undergoing lung volume reduction surgery at our institution between September 2015 and February 2016 were retrospectively investigated. Three readers visually assessed the amount and distribution patterns of pulmonary emphysema on axial, multi-planar and CC CT images using the Goddard scoring system and a surgically oriented grading system (bilateral markedly heterogenous, bilateral intermediately heterogenous, bilateral homogenous and unilateral heterogenous emphysema). Observer dependency was investigated by using Fleiss’ kappa (κ) and the intraclass correlation coefficient (ICC). Results were compared to quantitative results from densitometry measurements and lung perfusion scintigraphy by using Spearman correlation. Recommendations for lung volume reduction sites based on emphysema amount and distribution of all readers were compared to removal sites from the surgical reports. Results: Inter-rater agreement for emphysema distribution rating was substantial for CC images (κ=0.70; 95% CI, 0.64–0.80) and significantly better compared to axial and multiplanar images (P≤0.001). The inter-rater agreement for recommended segment removal was moderate for CC images (κ=0.56; 95% CI, 0.49–0.63) and significantly better compared to axial and multiplanar images (P

Background Infections have been linked to inadequately reprocessed flexible bronchoscopes, and recent investigations determined that pathogen transmission occurred even when bronchoscope cleaning and disinfection practices aligned with current guidelines. This multisite, prospective study evaluated the effectiveness of real-world bronchoscope reprocessing methods, using a systematic approach. Methods This study involved direct observation of reprocessing methods for flexible bronchoscopes, multifaceted evaluations performed after manual cleaning and after high-level disinfection, and assessments of storage conditions. Visual inspections of ports and channels were performed using lighted magnification and borescopes. Contamination was detected using microbial cultures and tests for protein, hemoglobin, and adenosine triphosphate (ATP). Researchers assessed reprocessing practices, and storage cabinet cleanliness was evaluated by visual inspection and ATP tests. Results Researchers examined 24 clinically used bronchoscopes. After manual cleaning, 100% of bronchoscopes had residual contamination. Microbial growth was found in 14 fully reprocessed bronchoscopes (58%), including mold, Stenotrophomonas maltophilia, and Escherichia coli/Shigella species. Visible irregularities were observed in 100% of bronchoscopes, including retained fluid; brown, red, or oily residue; scratches; damaged insertion tubes and distal ends; and filamentous debris in channels. Reprocessing practices were substandard at two of three sites. Conclusions Damaged and contaminated bronchoscopes were in use at all sites. Inadequate reprocessing practices may have contributed to bioburden found on bronchoscopes. However, even when guidelines were followed, high-level disinfection was not effective. A shift toward the use of sterilized bronchoscopes is recommended. In the meantime, quality management programs and updated reprocessing guidelines are needed.

Endoscopy-associated infection transmission is frequently linked to inadequate reprocessing. Residual organic material and moisture may foster biofilm development inside endoscopes. This study evaluated the effectiveness of endoscope drying and storage methods and assessed associations between retained moisture and contamination.Endoscope reprocessing, drying, and storage practices were assessed at 3 hospitals. Researchers performed visual examinations and tests to detect fluid and contamination on patient-ready endoscopes.Fluid was detected in 22 of 45 (49%) endoscopes. Prevalence of moisture varied significantly by site (5%; 83%; 85%; P .001). High adenosine triphosphate levels were found in 22% of endoscopes, and microbial growth was detected in 71% of endoscopes. Stenotrophomonas maltophilia, Citrobacter freundii, and Lecanicillium lecanii/Verticillium dahliae were found. Retained fluid was associated with significantly higher adenosine triphosphate levels (P .01). Reprocessing and drying practices conformed with guidelines at 1 site and were substandard at 2 sites. Damaged endoscopes were in use at all sites.Inadequate reprocessing and insufficient drying contributed to retained fluid and contamination found during this multisite study. More effective methods of endoscope reprocessing, drying, and maintenance are needed to prevent the retention of fluid, organic material, and bioburden that could cause patient illness or injury.

OBJECTIVE: Prospective studies have not identified a viable pharmacologic strategy for secondary prevention of posttraumatic stress disorder (PTSD). The authors examined whether preventive intervention via early and short-term administration of a selective serotonin reuptake inhibitor (SSRI), within 1 month of exposure to a traumatic event (before diagnosis of PTSD could be made), may reduce the severity of PTSD symptoms according to DSM-IV at 13 months' follow-up. METHODS: Over 25,000 screening calls to patients referred to an emergency department for a traumatic event performed between June 2006 and December 2008 yielded 353 participants who were recruited within the month following a traumatic event. Participants were randomly assigned in a double-blind design to escitalopram (n = 176) or placebo (n = 177). The per-protocol analysis comprised 198 participants (escitalopram, n = 102; placebo, n = 96) who received treatment for 12 to 24 weeks and were available for follow-up at week 56. RESULTS: The primary outcome measure, the Clinician Administered PTSD Scale (CAPS), revealed no prevention effect. However, a secondary outcome, the Pittsburgh Sleep Quality Inventory (PSQI), showed better results for the SSRI group than for the placebo group. For a subset of participants who experienced intentional trauma (missile attacks, rape, or physical assault; n = 50), the prevention effect was found on both primary and secondary measures (CAPS, PSQI and measures of depression and global illness severity). CONCLUSIONS: Early and short-term administration of escitalopram was not shown to prevent PTSD, although it did improve sleep quality. In a subgroup of participants who experienced intentional trauma, however, this early-treatment approach may be effective as secondary prevention. This large study is the first to investigate the preventive effect of early administration of escitalopram on PTSD. It highlights the relevance of the type of trauma (intentional vs unintentional) to the outcome. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00300313​. Language: en

Subsequent recall is improved if students try to recall target material during study (self-testing) versus simply re-reading it. This effect is consistent with the notion of “desirable difficulties.” If the learning experience involves difficulties that induce extra effort, then retention may be improved. Not all difficulties are desirable, however. Difficult-to-read ( disfluent) typefaces yield inconsistent results. A new disfluent font, Sans Forgetica, was developed and alleged to promote deeper processing and improve learning. Although it would be invaluable if changing the font could enhance learning, the few studies on Sans Forgetica have been inconsistent, and focused on short retention intervals (0–5 minutes). We investigated a 1-week interval to increase practical relevance and because some benefits only manifest after a delay. A testing-effect manipulation was also included. Students ( N = 120) learned two passages via different methods (study then re-study vs. study then self-test). Half the students saw the passages in Times New Roman and half in Sans Forgetica. Recall test scores were higher for passages learned via self-testing than restudying, but the effect of font and the interaction were nonsignificant. We suggest that disfluency increases the local (orthographic) processing effort on each word but slowed reading might impair relational processing across words. In contrast, testing and generation effect manipulations often engage relational processing (question: answer; cue: target)—yielding subsequent benefits on cued-recall tests. We elaborate this suggestion to reconcile conflicting results across studies.

Background: Military service members and veterans face health issues related to traumatic brain injury (TBI), especially during combat, use of heavy equipment, and exposures to environmental hazards and explosives. There were 400,000 TBIs reported in deployed U.S. troops in 2012. Athletes are also subject to TBI. Studies have indicated that some manual therapies could be helpful for treating patients who have post-concussive syndrome. Objective: This case series report describes the effects of CranioSacral Therapy (CST), Visceral Manipulation (VM), and Neural Manipulation (NM) modalities for treating patients who have post-concussion syndrome. The goal of this study was to evaluate these effects on immobility, pain intensity, quality of life, sleep disorders, and cognition in these patients. Materials and Methods: This single-blinded case series was conducted at the Upledger Institute, in West Palm Beach, FL. The patients were 11 male retired professional football players from the National Football League and the Canadian Football League who had been medically diagnosed with post-concussion syndrome. Each participant received a morning and afternoon 2-hour session of these three specific manual therapies, which were capable of accessing and addressing the structural, vascular, and neurologic tissues of the cranium and brain—as well addressing far-reaching ramifications throughout the body following trauma. The main outcome measures were scores on the: Impact Neurocognitive Test; Dynavisiontm Test; Short Form–36 Quality of Life Survey, Headache Impact Test, Dizziness Handicap Inventory; a numeric pain rating scale; orthopedic range of motion tests (ROM); and vestibular testing. Hours of sleep were also checked. These outcome measures were registered at baseline, after treatment, and after a 3-month follow up. Results: Statistically significant differences were seen with a decrease in overall pain rating scale scores (P = 0.0448), and cervicogenic pain levels decreased (P = 0.0486). There were statistically significant increases in Dynavision Average Reaction Time (P = 0.0332), Memory Test (P = 0.0156) scores, and cervical ROM scores (P = 0.0377). Hours of sleep averaged 2 hours on the first day of treatment and increased to 4.0 hours at the end of treatment and were continuing to increase, as noted at a 3-month evaluation. Conclusions: Ten sessions of specific CST/VM/NM therapy resulted in statistically greater improvements in pain intensity, ROM, memory, cognition, and sleep in concussed patients.

Background There are no guidelines or quality benchmarks specific to ureteroscope reprocessing, and patient injuries and infections have been linked to ureteroscopes. This prospective study evaluated ureteroscope reprocessing effectiveness. Methods Reprocessing practices at 2 institutions were assessed. Microbial cultures, biochemical tests, and visual inspections were conducted on sterilized ureteroscopes. Results Researchers examined 16 ureteroscopes after manual cleaning and sterilization using hydrogen peroxide gas. Every ureteroscope had visible irregularities, such as discoloration, residual fluid, foamy white residue, scratches, or debris in channels. Tests detected contamination on 100% of ureteroscopes (microbial growth 13%, adenosine triphosphate 44%, hemoglobin 63%, and protein 100%). Contamination levels exceeded benchmarks for clean gastrointestinal endoscopes for hemoglobin (6%), adenosine triphosphate (6%), and protein (100%). A new, unused ureteroscope had hemoglobin and high protein levels after initial reprocessing, although no contamination was found before reprocessing. Conclusions Flexible ureteroscope reprocessing methods were insufficient and may have introduced contamination. The clinical implications of residual contamination and viable microbes found on sterilized ureteroscopes are unknown. Additional research is needed to evaluate the prevalence of suboptimal ureteroscope reprocessing, identify sources of contamination, and determine clinical implications of urinary tract exposure to reprocessing chemicals, organic residue, and bioburden. These findings reinforce the need for frequent audits of reprocessing practices and the routine use of cleaning verification tests and visual inspection as recommended in reprocessing guidelines.

The focus of predictive modeling or predictive analytics is to use statistical techniques to predict outcomes and/or the results of an intervention or observation for patients that are conditional on a specific set of measurements taken on the patients prior to the outcomes occurring. Statistical methods to estimate these models include using such techniques as Bayesian methods; data mining methods, such as machine learning; and classical statistical models of regression such as logistic (for binary outcomes), linear (for continuous outcomes), and survival (Cox proportional hazards) for time-to event outcomes. A Bayesian approach incorporates a prior estimate that the outcome of interest is true, which is made prior to data collection, and then this prior probability is updated to reflect the information provided by the data. In principle, data mining uses specific algorithms to identify patterns in data sets and allows a researcher to make predictions about outcomes. Regression models describe the relations between 2 or more variables where the primary difference among methods concerns the form of the outcome variable, whether it is measured as a binary variable (i.e., success/ failure), continuous measure (i.e., pain score at 6 months postop), or time to event (i.e., time to surgical revision). The outcome variable is the variable of interest, and the predictor variable(s) are used to predict outcomes. The predictor variable is also referred to as the independent variable and is assumed to be something the researcher can modify in order to see its impact on the outcome (i.e., using one of several possible surgical approaches). Survival analysis investigates the time until an event occurs. This can be an event such as failure of a medical device or death. It allows the inclusion of censored data, meaning that not all patients need to have the event (i.e., die) prior to the study’s completion.

Background: The impact of interleukin-6 receptor inhibitors (IL6ri) on Coronavirus disease 2019 (Covid-19) outcomes remains uncertain. Methods: Patients with severe and critical Covid-19 were given an IL6ri (sarilumab or tocilizumab) based on pragmatic and iteratively reviewed guidelines at a safety net hospital with a diverse population. IL6ri were initially reserved for critically ill patients, but after review, treatment was liberalized to patients requiring >4 liters/minute of oxygen or having an alveolar-arterial gradient >50 mmHg and elevated inflammatory markers (C-reactive protein >100 mg/L or lactate dehydrogenase >450 units/L). Patients were divided into 2 groups, those requiring ≤ 45% fraction of inspired oxygen (FiO2) (termed stage IIB) and those requiring >45% FiO2 (termed stage III) at the time of IL6ri administration. Main outcomes were all-cause mortality, discharge alive from hospital, and extubation. Findings: Prior to treatment, 255 consecutive Covid-19 patients treated with IL6ri (149 stage IIB and 106 stage III) had hypoxemia requiring supplemental oxygen and had elevated inflammatory markers. Patients treated in stage IIB had lower mortality than the stage III group (adjusted hazard ratio [aHR]: 0.20; 95% confidence interval [CI] 0.07-0.60). Overall, 218 (85.5%) patients were discharged alive. Patients treated in stage IIB were more likely to be discharged (aHR: 2.04; 95% CI 1.53 – 2.73) and to have intubation-free survival (HR: 0.39; 95% CI: 0.20-0.74). Interpretation: Our finding that early IL6ri were associated with reduced mortality from severe Covid-19 can guide current clinical management while we await definitive results from randomized controlled trials. Funding Statement: This work was supported by National Institutes of Health grants K24-AI145661 and 5T32AI052074-13. Declaration of Interests: None to declare Ethics Approval Statement: All activities associated with this project were approved by the Boston University Medical Center Institutional Review Board (IRB)

Among the different existing types of bacterial meningitis, the one caused by Neisseria meningitidis is the main presentation of invasive meningococcal disease (IMD). IMD is a significant public health concern and has a reported incidence rate in Argentina of 0.44 cases per 100 000 inhabitants in 2015. However, the actual incidence is thought to be higher as passive surveillance systems neither report nor identify 100% of all cases. The aim of this study is to develop an estimation of the burden of IMD in Argentina closer to reality by adjusting/correcting several limitations observed in the surveillance data available. A retrospective observational study has been performed using four Argentinean national databases recording the number of IMD cases and deaths, serogroups of N. meningitidis and ages, between 2007 to 2016. The reported data were adjusted to account for underreporting and to also integrate the cases missed due to well-known limitations associated with the diagnosis of N. meningitidis detection methods. Data were further analysed by serogroups of N. meningitidis and by age groups. After these adjustments, the potential numbers of IMD cases and IMD-related deaths are estimated to be 3.1 and 1.9 higher than reported, respectively. The study corrects the previous underestimation of the disease burden and provides expectedly more robust estimates aligned with international evidence and highlights the importance of active surveillance, with high-quality methods, for a better definition of preventive strategies against IMD in Argentina.

Subarachnoid neurocysticercosis (SUBNCC) is usually caused by an aberrant proliferative form of Taenia solium causing mass effect and arachnoiditis. Thirty of 34 SUBNCC patients were treated with extended cysticidal and anti-inflammatory regimens and followed up a median of 4.2 years posttreatment (range: 15 for ≥ 4 years, 20 ≥ 2 years, 26 > 1 year, and 3 < 1 year). The median ages at the time of first symptom, diagnosis, and enrollment were 29.7, 35.6, and 37.9 years, respectively; 58.8% were male and 82.4% were Hispanic. The median time from immigration to symptoms (minimum incubation) was 10 years and the estimated true incubation period considerably greater. Fifty percent also had other forms of NCC. Common complications were hydrocephalus (56%), shunt placement (41%), infarcts (18%), and symptomatic spinal disease (15%). Thirty patients (88.2%) required prolonged treatment with albendazole (88.2%, median 0.55 year) and/or praziquantel (61.8%; median 0.96 year), corticosteroids (88.2%, median 1.09 years), methotrexate (50%, median 1.37 years), and etanercept (34.2%, median 0.81 year), which led to sustained inactive disease in 29/30 (96.7%) patients. Three were treated successfully for recurrences and one has continuing infection. Normalization of cerebral spinal fluid parameters and cestode antigen levels guided treatment decisions. All 15 patients with undetectable cestode antigen values have sustained inactive disease. There were no deaths and moderate morbidity posttreatment. Corticosteroid-related side effects were common, avascular necrosis of joints being the most serious (8/33, 24.2%). Prolonged cysticidal treatment and effective control of inflammation led to good clinical outcomes and sustained inactive disease which is likely curative.

Background Glucocorticoids (GC) are considered first-line therapy for most patients with hypereosinophilic syndrome (HES). Although response rates are generally high, many patients require moderate to high doses for control of eosinophilia and symptoms, and up to 15% of patients do not respond at all. Despite this, little is known about the mechanisms of GC resistance in patients with HES. Objective To explore the aetiology of GC resistance in HES. Methods Clinical data and samples from 26 patients with HES enrolled on a prospective study of GC responsiveness and 23 patients with HES enrolled on a natural history study of eosinophilia for whom response to GC was known were analysed retrospectively. Expression of GC receptor isoforms was assessed by quantitative RT-PCR in purified eosinophils. Serum cytokine levels were quantified by suspension array assay in multiplex. Results Despite an impaired eosinophil response to GC after 7 days of treatment, the expected rise in absolute neutrophil count was seen in 7/7 GC-resistant patients, suggesting that GC resistance in HES is not a global phenomenon. Eosinophil mRNA expression of glucocorticoid receptor (GR) isoforms (α, β, and P) was similar between GC-sensitive (n = 20) and GC-resistant (n = 9) patients with HES. Whereas geometric mean serum levels were also comparable between GC-r (n = 11) and GC-s (n = 19) for all cytokines tested, serum IL-5 levels were >100 pg/mL only in GC-r patients. Conclusions and clinical relevance These data suggest that the mechanism of GC resistance in HES is not due to a global phenomenon affecting all lineages, but may be due, at least in some patients, to impairment of eosinophil apoptosis by increased levels of IL-5.

Flexible endoscopes are exposed to blood, mucus, and other secretions during procedures. Single-use sheaths are designed to prevent contact between contaminants and reusable endoscope components. This systematic review examined findings from 22 studies that assessed endoscopic sheath use during urologic, gastrointestinal, or respiratory procedures. The evidence showed that sheaths were durable and yielded faster endoscope turnover times because their reusable components did not require high-level disinfection or sterilization. After a brief learning period, health care providers successfully assembled and maneuvered sheathed endoscopes. Patients generally did not experience greater discomfort during procedures in which sheaths were used. Microbial cultures of sheathed endoscopes were negative or similar to unsheathed endoscopes. More research is needed to evaluate the potential effect of disposable sheaths on infection risks. The evidence suggests that sheaths are a viable option for reliably providing a barrier between endoscopes and patients without affecting the quality of endoscopic procedures.

BACKGROUND: Hypereosinophilic syndrome is a group of diseases defined by marked eosinophilia in blood or tissue and eosinophil-related clinical manifestations. Benralizumab is a monoclonal antibody against interleukin-5 receptor α, which is expressed on human eosinophils. METHODS: In this randomized, double-blind, placebo-controlled, phase 2 trial, we administered a series of three monthly subcutaneous injections of either benralizumab (at a dose of 30 mg) or placebo in 20 symptomatic patients who had PDGFRA-negative hypereosinophilic syndrome and an absolute eosinophil count of at least 1000 cells per cubic millimeter; all the patients were receiving stable therapy (drugs or dietary changes) for this disease. This regimen was followed by an open-label phase, during which the patient’s background therapy could be tapered as tolerated, and an extension phase. The primary end point of the randomized phase was a reduction of at least 50% in the absolute eosinophil count at week 12. RESULTS: During the randomized phase, the primary end point occurred in more patients in the benralizumab group than in the placebo group (9 of 10 patients [90%] vs. 3 of 10 patients [30%], P = 0.02). During the open-label phase, clinical and hematologic responses were observed in 17 of 19 patients (89%) and were sustained for 48 weeks in 14 of 19 patients (74%); in the latter group, in 9 of 14 patients (64%), background therapies could be tapered. Bone marrow and tissue eosinophilia were also suppressed with benralizumab therapy. The most common drug-related adverse events, headache and an elevated lactate dehydrogenase level, occurred in 32% of the patients after the first dose of benralizumab and resolved within 48 hours in all patients. Other adverse events occurred with similar frequency in the two groups. Of the many potential predictors of response that were examined, only clinical disease subtype appeared to be associated with the initial response or relapse. CONCLUSIONS: In this small phase 2 trial, patients with PDGFRA-negative hypereosinophilic syndrome who received benralizumab for 12 weeks had lower absolute eosinophil counts than those who received placebo. During the open-label phase, clinical and hematologic responses were sustained for 48 weeks in 74% of the patients. Adverse events did not limit treatment. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov numbers, NCT00001406 and NCT02130882.)

Background Low adult immunization rates leave adults at risk from infectious disease, and the resulting complications of vaccine-preventable diseases. Standing orders protocols (SOPs) for adult immunization have not been implemented widely in clinics serving adult patients. Our purpose was to evaluate the impact of SOPs on adult immunization rates and identify challenges to sustaining adult immunization coverage rates after implementation of SOPs. Methods Baseline adult vaccination rates were calculated for the year prior to SOPs implementation in 5 diverse clinics. Vaccines included in the implemented standing orders included Tdap, influenza, pneumococcal, human papillomavirus, herpes zoster, and hepatitis B. Adult vaccination rates were tracked for 1 year after SOPs implementation. Results Sites generally sustained modest gains in coverage rates (4%-8% increase) after SOP implementation, but greater success was found in practices that used SOPs as a foundation on which additional interventions were built. Challenges to increasing coverage rates included prioritization of acute and chronic conditions over adult vaccination, Medicare Part D reimbursement policies, electronic medical record issues related to data reporting and programming for patient alerts, and the lack of interoperability between the state immunization information system (missing patient vaccination history) and electronic medical record. Conclusions SOPs may provide a good starting point for increasing adult immunization coverage rates. Using additional interventions, quality-based metrics, or incentives could lead to sustained adult immunization prioritization.

Background Although previous investigators have established an association between blood transfusion and adverse outcomes, the relative frequency of different morbid events and the association with transfusion dose are not well understood. Questions/Purposes The purpose of the study is to characterize the relationship between blood transfusion and different types of morbidity after posterior spine fusion. Methods We retrospectively analyzed electronic medical records for 963 patients who underwent posterior spinal fusion surgery at a single institution, of which 603 (62.6%) received an allogeneic blood transfusion. Then, we assessed patient and surgical characteristics in a risk-adjusted fashion to identify various morbid event rates and independent predictors in these adverse outcomes. Results Compared to the non-transfused patients, transfused patients had a higher incidence of any morbid event (9.1 vs. 2.5%. P

Background Flexible endoscopes are currently reused following cleaning and high-level disinfection. Contamination has been found on endoscopes, and infections have been linked to gastrointestinal, respiratory, and urologic endoscopes. Methods This longitudinal study involved visual inspections with a borescope, microbial cultures, and biochemical tests for protein and adenosine triphosphate to identify endoscopes in need of further cleaning or maintenance. Three assessments were conducted over a 7-month period. Control group endoscopes reprocessed using customary practices were compared with intervention group endoscopes subjected to more rigorous reprocessing. Results At final assessment, all endoscopes (N = 20) had visible irregularities. Researchers observed fluid (95%), discoloration, and debris in channels. Of 12 (60%) endoscopes with microbial growth, 4 had no growth until after 48 hours. There were no significant differences in culture results by study group, assessment period, or endoscope type. Similar proportions of control and intervention endoscopes (~20%) exceeded postcleaning biochemical test benchmarks. Adenosine triphosphate levels were higher for gastroscopes than colonoscopes (P = .014). Eighty-five percent of endoscopes required repair due to findings. Conclusions More rigorous reprocessing was not consistently effective. Seven-day incubation allowed identification of slow-growing microbes. These findings bolster the need for routine visual inspection and cleaning verification tests recommended in new reprocessing guidelines.

Anthracyclines constitute the backbone of intensive adult acute myeloid leukemia (AML) therapy. Cardiotoxicity is one of its most serious adverse effects, and its incidence increases with cumulative dose. Dexrazoxane is a cardioprotective agent used in conjunction with anthracycline therapy. There is limited data of its usage in adult AML patients. We report the outcomes of six older adults at high risk of anthracycline-induced cardiotoxicity who received dexrazoxane during induction/re-induction therapy. Five had preserved left-ventricular function while two proceeded onto stem-cell transplantation. Additional investigation of dexrazoxane in adult leukemia therapy is warranted, particularly in older patients at highest risk for cardiovascular mortality.

Background During a study designed to assess endoscope reprocessing effectiveness, a borescope was used to examine lumens and ports. Cloudy, white, viscous fluid was observed inside fully reprocessed gastroscopes and colonoscopes. This fluid resembled simethicone, which is commonly administered to reduce foam and bubbles that impede visualization during gastrointestinal endoscopy. This article describes methods used to determine whether the observed fluid contained simethicone. Methods Photographs of residual fluid were taken using a borescope. Sterile cotton-tipped swabs were used to collect samples of fluid observed in 3 endoscope ports. Samples were evaluated using Fourier transform infrared spectroscopy (FTIR)–attenuated total reflection analysis. Results Residual fluid was observed inside 19 of 20 endoscopes. Fluid photographed in 8 endoscopes resembled simethicone solutions. FTIR analysis confirmed the presence of simethicone in 2 endoscopes. Conclusions Fluid containing simethicone remained inside endoscopes despite reprocessing. Simethicone is an inert, hydrophobic substance that may reduce reprocessing effectiveness. Simethicone solutions commonly contain sugars and thickeners, which may contribute to microbial growth and biofilm development. Studies are needed to assess the prevalence of residual moisture and simethicone in endoscopes and determine the impact on reprocessing effectiveness. We recommend minimizing the use of simethicone pending further research into its safety.

Most cancers evolve over time as patients initially responsive to therapy acquire resistance to the same drugs at relapse. Cancer stem cells have been postulated to represent a therapy-refractory reservoir for relapse, but formal proof of this model is lacking. We prospectively characterized leukemia stem cell populations (LSCs) from a well-defined cohort of patients with acute myelogenous leukemia (AML) at diagnosis and relapse to assess the effect of the disease course on these critical populations. Leukemic samples were collected from patients with newly diagnosed AML before therapy and after relapse, and LSC frequency was assessed by limiting dilution analyses. LSC populations were identified using fluorescent-labeled cell sorting and transplantation into immunodeficient NOD/SCID/interleukin 2 receptor γ chain null mice. The surface antigen expression profiles of pretherapy and postrelapse LSCs were determined for published LSC markers. We demonstrate a 9- to 90-fold increase in LSC frequency between diagnosis and relapse. LSC activity at relapse was identified in populations of leukemic blasts that did not demonstrate this activity before treatment and relapse. In addition, we describe genetic instability and exceptional phenotypic changes that accompany the evolution of these new LSC populations. This study is the first to characterize the evolution of LSCs in vivo after chemotherapy, identifying a dramatic change in the physiology of primitive AML cells when the disease progresses. Taken together, these findings provide a new frame of reference by which to evaluate candidate AML therapies in which both disease control and the induction of more advanced forms of disease should be considered.

The United States and China have committed to enact “nearly complete bans” on the import and export of elephant ivory, including putting in place significant and timely restrictions on the import of ivory as hunting trophies, and taking swift steps to halt their domestic ivory trade. Unlike the United States, China has to move forward on its commitment to further restrict its domestic commercial trade. This is primarily due to China's existing certificated ivory manufacturers and retailers who own huge legal ivory stockpiles. We propose that the Chinese government use its eco-compensation funds to purchase back all legal ivory from the market. This “decommodification” could help save the elephant population worldwide. Alternatively, China could enact a domestic ban with a short phase-in period (a similar approach has been adopted by several U.S. States) to allow legal ivory merchants to sell their stockpiles. A hybrid of these two approaches could also be considered.

There is an urgent need for the development of an antigonococcal vaccine due to the increasing drug resistance found in this pathogen. The U.S. Centers for Disease Control (CDC) have identified multidrug-resistant gonococci (GC) as among 3 “urgent” hazard-level threats to the U.S. population. In light of this, on 29 to 30 June 2015, the National Institute for Allergy and Infectious Diseases (NIAID) sponsored a workshop entitled “Gonorrhea Vaccines: the Way Forward.” The goal of the workshop was to gather leaders in the field to discuss several key questions on the current status of gonorrhea vaccine research and the path forward to a licensed gonorrhea vaccine. Representatives from academia, industry, U.S. Government agencies, and a state health department were in attendance. This review summarizes each of the 4 scientific sessions and a series of 4 breakout sessions that occurred during the one and a half days of the workshop. Topics raised as high priority for future development included (i) reinvigoration of basic research to understand gonococcal infection and immunity to allow intervention in processes essential for infection; (ii) clinical infection studies to establish parallels and distinctions between in vitro and animal infection models versus natural human genital and pharyngeal infection and to inform in silico modeling of vaccine impact; and (iii) development of an integrated pipeline for preclinical and early clinical evaluation and direct comparisons of potential vaccine antigens and adjuvants and routes of delivery.

Experts have recommended microbiologic surveillance by external reference laboratories for certain flexible endoscopes. There is currently insufficient evidence on the feasibility and utility of cultures. Researchers evaluated a preassembled toolkit for collecting and processing samples from endoscopes.A pilot study was performed in a large academic medical center. A toolkit was used to aseptically sample biopsy ports and suction/biopsy channels of 5 gastroscopes, 5 colonoscopes, and 5 bronchoscopes after full reprocessing. Blinded specimens were packaged and transported on icepacks to a reference laboratory that used standard methodologies for microbial cultures.The laboratory detected bacteria in samples from 60% of patient-ready endoscopes, including gram-positive and gram-negative species. Viable microbes (10 CFU) were recovered from 2 gastroscopes, 3 colonoscopes, and 4 bronchoscopes. Stenotrophomonas maltophilia and Delftia acidovorans were recovered from all 3 endoscope types. Subsequent environmental testing detected S maltophilia in the reprocessing rinse water.A preassembled toolkit facilitated the aseptic collection of samples for culturing by a reference laboratory that detected viable microbes on fully reprocessed endoscopes. Speciation allowed identification of potential pathogens and a possible common contamination source, demonstrating that microbial cultures may have value even when colony counts are low.

So far, associations between serotonergic neurotransmission pathways and suicidality have been reported. The aim of our study was to investigate the role of genetic polymorphisms and gene-gene interactions of the 5-HTR1A and the 5-HTR2A gene on suicide risk and/or a personal history of suicide attempts. A total of 374 major depressive disorder patients, adequately treated with antidepressants for at least 4 weeks, were collected in the context of a European multicentre study on treatment-resistant depression. We assessed suicidality using the Mini International Neuropsychiatric Interview and the Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D17 and remission as HAM-D7 after 4 weeks of adequate antidepressant treatment. The 5-HTR1A rs6295 (C-1019G) single nucleotide polymorphism (SNP) and the 5-HTR2A rs7997012, rs6313, rs643627 and rs17288723 SNPs were selected for genotyping. Using logistic regression analyses, no association (P

Background Current methods for reprocessing flexible endoscopes do not consistently eliminate organic soil. The off-label use of simethicone as a defoaming agent may contribute to reprocessing failures, and endoscope manufacturers have cautioned against its use. Methods We sought evidence of simethicone use by interviewing hospital personnel, conducting audits, inspecting endoscopes, and conducting tests. Results Researchers examined 69 fully reprocessed endoscopes in 4 hospitals. Microbial cultures were positive for ≥50% of endoscopes. Researchers observed cloudy, shimmery fluid resembling simethicone inside channels and under a duodenoscope elevator mechanism. Crystallized white fragments were observed protruding from a gastroscope water jet outlet. Oily, sticky residue was found on endoscopes, and a 3-dimensional mass was found inside an endoscopic ultrasound endoscope. Hospital personnel reported the use of simethicone, cooking oil and silicone sprays, and tissue glue during endoscopy. Discussion The off-label use of defoaming agents, lubricants, and tissue glue is common and many endoscopists consider these products essential. Our findings suggest these substances are not removed during reprocessing and may impact reprocessing effectiveness. Conclusions Infection preventionists should determine whether these products are used in their institutions and evaluate methods for removing them. New policies may be needed to support procedural success and effective endoscope reprocessing.