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Trauma center mortality rates are benchmarked to expected rates of death based on patient and injury characteristics. The expected mortality rate is recalculated from pooled outcomes across a trauma system each year, obscuring system-level change across years. We hypothesized that risk-adjusted mortality would decrease over time within a state-wide trauma system.We identified adult trauma patients presenting to Level I and II Pennsylvania trauma centers, 1999-2018, using the Pennsylvania Trauma Outcomes Study. Multivariable logistic regression generated risk-adjusted models for mortality in all patients, and in key subgroups: penetrating torso injury, blunt multisystem trauma, and patients presenting in shock.Of 162,646 included patients, 123,518 (76.1%) were white and 108,936 (67.0%) were male. The median age was 49 (interquartile range [IQR] 29-70), median injury severity score was 16 (IQR 10-24), and 87.5% of injuries were blunt. Overall, 9.9% of patients died, and compared to 1999, no year had significantly higher adjusted odds of mortality. Overall mortality was significantly lower in 2007-2009 and 2011-2018. Of patients with blunt, multisystem injuries, 17.7% died, and adjusted mortality improved over time. Mortality rates were 24.9% for penetrating torso injury, and 56.9% for shock, with no significant change. Mortality improved for patients with ISS25, but not for the most severely injured.Over 20 years, Pennsylvania trauma centers demonstrated improved risk-adjusted mortality rates overall, but improvement remains lacking in high-risk groups despite numerous innovations and practice changes in this time period. Identifying change over time can help guide focus to these critical gaps.

Background: Delayed cerebral ischemia remains one of the principal therapeutic targets after aneurysmal subarachnoid hemorrhage. While large vessel vasospasm may contribute to ischemia, increasing evidence suggests that physiological impairment through disrupted impaired cerebral autoregulation (CA) and spreading depolarizations (SDs) also contribute to delayed cerebral ischemia and poor neurological outcome. This study seeks to explore the intermeasure correlation of different measures of CA, as well as correlation with SD and neurological outcome. Methods: Simultaneous measurement of 7 continuous indices of CA was calculated in 19 subjects entered in a prospective study of SD in aneurysmal subarachnoid hemorrhage undergoing surgical aneurysm clipping. Intermeasure agreement was assessed, and the association of each index with modified Rankin Scale score at 90 days and occurrence of SD was assessed. Results: There were 4102 hours of total monitoring time across the 19 subjects. In time-resolved assessment, no CA measures demonstrated significant correlation; however, most demonstrate significant correlation averaged over 1 hour. Pressure reactivity (PRx), oxygen reactivity, and oxygen saturation reactivity were significantly correlated with modified Rankin Scale score at 90 days. PRx and oxygen reactivity also were correlated with the occurrence of SD events. Across multiple CA measure reactivity indices, a threshold between 0.3 and 0.5 was most associated with intervals containing SD. Conclusions: Different continuous CA indices do not correlate well with each other on a highly time-resolved basis, so should not be viewed as interchangeable. PRx and oxygen reactivity are the most reliable indices in identifying risk of worse outcome in patients with aneurysmal subarachnoid hemorrhage undergoing surgical treatment. SD occurrence is correlated with impaired CA across multiple CA measurement techniques and may represent the pathological mechanism of delayed cerebral ischemia in patients with impaired CA. Optimization of CA in patients with aneurysmal subarachnoid hemorrhage may lead to decreased incidence of SD and improved neurological outcomes. Future studies are needed to evaluate these hypotheses and approaches.

Objectives Prone positioning is widely used in mechanically ventilated patients with COVID-19; however, the specific clinical scenario in which the individual is most poised to benefit is not fully established. In patients with COVID-19 respiratory failure requiring mechanical ventilation, how effective is prone positioning in improving oxygenation and can that response be predicted? Design This is a retrospective observational study from two tertiary care centers including consecutive patients mechanically ventilated for COVID-19 from 3/1/2020 – 7/1/2021. The primary outcome is improvement in oxygenation as measured by PaO2/FiO2. We describe oxygenation before, during and after prone episodes with a focus on identifying patient, respiratory or ventilator variables that predict prone positioning success. Setting 2 Tertiary Care Academic Hospitals Patients 125 patients mechanically ventilated for COVID-19 respiratory failure. Interventions Prone positioning Main Results One hundred twenty-five patients underwent prone positioning a total of 309 times for a median duration of 23 hours IQR (14 – 49). On average, PaO2/FiO2 improved 19%: from 115 mm Hg (80 – 148) immediately before proning to 137 mm Hg (95 – 197) immediately after returning to the supine position. Prone episodes were more successful if the pre-prone PaO2/FiO2 was lower and if the patient was on inhaled epoprostenol (iEpo). For individuals with severe acute respiratory distress syndrome (ARDS) (PaO2/FiO2 < 100 prior to prone positioning) and on iEpo, the median improvement in PaO2/FiO2 was 27% in both instances. Conclusions Prone positioning in mechanically ventilated patients with COVID-19 is generally associated with sustained improvements in oxygenation, which is made more likely by the concomitant use of iEpo and is more impactful in those who are more severely hypoxemic prior to prone positioning.

This is a report of the survey results from the International Dermatology Outcome Measures (IDEOM) actinic keratosis (AK) workgroup. The purpose of the survey was to compile a list of gaps within AK care and management that require refinement. The results were discussed at the IDEOM annual meeting held virtually on October 23ndash;24, 2020. This built a framework with which the AK workgroup, which consisted of physicians, patients, and pharmaceutical scientists, discussed at length in their breakout session at the meeting. The electronic survey was distributed to patients, pharmaceutical scientists, and leading physician experts in the field via email on September 22, 2020, with a deadline of October 2, 2020. The survey consisted of three open-ended prompts concerning key gaps and/or unmet needs in (1) the care of AKs, (2) outcome measurement of AKs in clinical trials and, (3) the measurement of AKs in clinical practice. The results were qualitative, with a response rate of 47%. Responses included reform of outcome measures for clinical trials, a methodology for evaluating the efficacy of preventative measures, and a comparison of treatments to establish a treatment protocol, among other efforts. This paper will also provide a brief overview of the current state of the AK outcome measures, emphasizing the heterogeneity of the measures and detailing the AK workgroup's future efforts to create a reliable and applicable core outcome measure set. J Drugs Dermatol. 2022;21(2):128-134. doi:10.36849/JDD.6360.

Aim: The first Plan-Do-Study-Act cycle for the Veterans Affairs Pharmacogenomic Testing for Veterans pharmacogenomic clinical testing program is described. Materials & methods: Surveys evaluating implementation resources and processes were distributed to implementation teams, providers, laboratory and health informatics staff. Survey responses were mapped to the Consolidated Framework for Implementation Research constructs to identify implementation barriers. The Expert Recommendation for Implementing Change strategies were used to address implementation barriers. Results: Survey response rate was 23–73% across personnel groups at six Veterans Affairs sites. Nine Consolidated Framework for Implementation Research constructs were most salient implementation barriers. Program revisions addressed these barriers using the Expert Recommendation for Implementing Change strategies related to three domains. Conclusion: Beyond providing free pharmacogenomic testing, additional implementation barriers need to be addressed for improved program uptake.

Dermatologists have been pioneers in the development and refinement of liposuction using local anesthesia. Although other specialties routinely use general anesthesia for liposuction, the safety profile of liposuction using local anesthesia is impressive. This article traces the history and development of liposuction by dermatologists in the United States. J Drugs Dermatol. 2022;21(9):997-1000. doi:10.36849/JDD.6952.

The Accreditation Council for Graduate Medical Education (ACGME) granted accreditation to the first 5 Procedural Dermatology Fellowship Training Programs in 2004. The name of the training program was changed from Procedural Dermatology to Micrographic Surgery and Dermatologic Oncology by the ACGME/Residency Review Committee for Dermatology in 2014. The American Board of Dermatology/American Board of Medical Specialties conducted the first certification examination in Micrographic Dermatology Surgery in October 2021. This article chronicles the history and development of the subspecialty. J Drugs Dermatol. 2022;21(8):861-863.: doi:10.36849/JDD.6933.

Background Microalbuminuria is an independent risk factor for cardiovascular and kidney disease and a predictor of end organ damage, both in the general population and in persons with HIV (PWH). Microalbuminuria is also an important risk factor for mortality in PWH treated with antiretroviral therapy (ART). In the ongoing Renal Risk Reduction (R3) study in Nigeria, we identified a high prevalence of microalbuminuria confirmed by two measurements 4–8 weeks apart in ART-experienced, virologically suppressed PWH. Although Stage 1 or 2 hypertension and exposure to potentially nephrotoxic antiretroviral medications were common in R3 participants, other traditional risk factors for albuminuria and kidney disease, including diabetes, APOL1 high-risk genotype, and smoking were rare. Co-infection with endemic pathogens may also be significant contributors to albuminuria, but co-infections were not evaluated in the R3 study population. Methods In Aim 1, we will cross-sectionally compare the prevalence of albuminuria and established kidney disease risk factors in a cohort of PWH to age- and sex-matched HIV-negative adults presenting for routine care at the Aminu Kano Teaching Hospital in Kano, Nigeria. We will leverage stored specimens from 2500 R3 participants and enroll an additional 500 PLWH recently initiated on ART (≤ 24 months) and 750 age- and sex-matched HIV-negative adults to determine the contribution of HIV, hypertension, and other comorbid medical conditions to prevalent albuminuria. In Aim 2, we will follow a cohort of 1000 HIV-positive, ART-treated and 500 HIV-negative normoalbuminuric adults for 30 months to evaluate the incidence and predictors of albuminuria. Discussion The findings from this study will support the development of interventions to prevent or address microalbuminuria in PWH to reduce kidney and cardiovascular morbidity and mortality. Such interventions might include more intensive monitoring and treatment of traditional risk factors, the provision of renin-angiotensin aldosterone system or sodium-glucose cotransporter-2 inhibitors, consideration of changes in ART regimen, and screening and treatment for relevant co-infections.

Hemorrhage, and particularly noncompressible torso hemorrhage (NCTH) remains a leading cause of potentially preventable prehospital death from trauma in the United States and globally. A subset of severely-injured patients either die in the field or develop irreversible hemorrhagic shock before they can receive hospital definitive care, resulting in poor outcomes. The focus of this opinion paper is to delineate (a) the need for existing trauma systems to adapt so that potentially life-saving advanced resuscitation and truncal hemorrhage control interventions can be delivered closer to the point-of-injury in select patients, and (b) a possible mechanism through which some trauma systems can train and incorporate select prehospital advanced resuscitative care teams to deliver those interventions.

Background The electronic health record (EHR) has become increasingly ubiquitous. At the same time, health professionals have been turning to this resource for access to data that is needed for the delivery of health care and for clinical research. There is little doubt that the EHR has made both of these functions easier than earlier days when we relied on paper-based clinical records. Coupled with modern database and data warehouse systems, high-speed networks, and the ability to share clinical data with others are large number of challenges that arguably limit the optimal use of the EHR Objectives Our goal was to provide an exhaustive reference for those who use the EHR in clinical and research contexts, but also for health information systems professionals as they design, implement, and maintain EHR systems. Methods This study includes a panel of 24 biomedical informatics researchers, information technology professionals, and clinicians, all of whom have extensive experience in design, implementation, and maintenance of EHR systems, or in using the EHR as clinicians or researchers. All members of the panel are affiliated with Penn Medicine at the University of Pennsylvania and have experience with a variety of different EHR platforms and systems and how they have evolved over time. Results Each of the authors has shared their knowledge and experience in using the EHR in a suite of 20 short essays, each representing a specific challenge and classified according to a functional hierarchy of interlocking facets such as usability and usefulness, data quality, standards, governance, data integration, clinical care, and clinical research. Conclusion We provide here a set of perspectives on the challenges posed by the EHR to clinical and research users.

In a large health system in the United States, investigators examined whether mortality, receipt of mechanical ventilation, and patient acuity changed over time among adult patients with COVID-19–related critical illness admitted to intensive care units., Visual Abstract. COVID-19–Related Critical Illness In a large health system in the United States, investigators examined whether mortality, receipt of mechanical ventilation, and patient acuity changed over time among adult patients with COVID-19–related critical illness admitted to intensive care units. Visual Abstract. COVID-19–Related Critical Illness In a large health system in the United States, investigators examined whether mortality, receipt of mechanical ventilation, and patient acuity changed over time among adult patients with COVID-19–related critical illness admitted to intensive care units., Background: The coronavirus disease 2019 (COVID-19) pandemic continues to surge in the United States and globally. Objective: To describe the epidemiology of COVID-19–related critical illness, including trends in outcomes and care delivery. Design: Single–health system, multihospital retrospective cohort study. Setting: 5 hospitals within the University of Pennsylvania Health System. Patients: Adults with COVID-19–related critical illness who were admitted to an intensive care unit (ICU) with acute respiratory failure or shock during the initial surge of the pandemic. Measurements: The primary exposure for outcomes and care delivery trend analyses was longitudinal time during the pandemic. The primary outcome was all-cause 28-day in-hospital mortality. Secondary outcomes were all-cause death at any time, receipt of mechanical ventilation (MV), and readmissions. Results: Among 468 patients with COVID-19–related critical illness, 319 (68.2%) were treated with MV and 121 (25.9%) with vasopressors. Outcomes were notable for an all-cause 28-day in-hospital mortality rate of 29.9%, a median ICU stay of 8 days (interquartile range [IQR], 3 to 17 days), a median hospital stay of 13 days (IQR, 7 to 25 days), and an all-cause 30-day readmission rate (among nonhospice survivors) of 10.8%. Mortality decreased over time, from 43.5% (95% CI, 31.3% to 53.8%) to 19.2% (CI, 11.6% to 26.7%) between the first and last 15-day periods in the core adjusted model, whereas patient acuity and other factors did not change. Limitation: Single–health system study; use of, or highly dynamic trends in, other clinical interventions were not evaluated, nor were complications. Conclusion: Among patients with COVID-19–related critical illness admitted to ICUs of a learning health system in the United States, mortality seemed to decrease over time despite stable patient characteristics. Further studies are necessary to confirm this result and to investigate causal mechanisms. Primary Funding Source: Agency for Healthcare Research and Quality.

Background Torsade de pointes (TdP) is a potentially fatal cardiac arrhythmia that is often drug induced. Clinical decision support (CDS) may help minimize TdP risk by guiding decision making in patients at risk. CDS has been shown to decrease prescribing of high‐risk medications in patients at risk of TdP, but alerts are often ignored. Other risk‐management options can potentially be incorporated in TdP risk CDS. Our goal was to evaluate actions clinicians take in response to a CDS advisory that uses a modified Tisdale QT risk score and presents management options that are easily selected (eg, single click). Methods and Results We implemented an inpatient TdP risk advisory systemwide across a large health care system comprising 30 hospitals. This CDS was programmed to appear when prescribers attempted ordering medications with a known risk of TdP in a patient with a QT risk score ≥12. The CDS displayed patient‐specific information and offered relevant management options including canceling offending medications and ordering electrolyte replacement protocols or ECGs. We retrospectively studied the actions clinicians took within the advisory and separated by drug class. During an 8‐month period, 7794 TdP risk advisories were issued. Antibiotics were the most frequent trigger of the advisory (n=2578, 33.1%). At least 1 action was taken within the advisory window for 2700 (34.6%) of the advisories. The most frequent action taken was ordering an ECG (n=1584, 20.3%). Incoming medication orders were canceled in 793 (10.2%) of the advisories. The frequency of each action taken varied by drug class ( P Conclusions A modified Tisdale QT risk score–based CDS that offered relevant single‐click management options yielded a high action/response rate. Actions taken by clinicians varied depending on the class of the medication that evoked the TdP risk advisory, but the most frequent was ordering an ECG.

The emergence of biofilms on dry hospital surfaces has led to the development of numerous models designed to challenge the efficacious properties of common antimicrobial agents used in cleaning. This is in spite of limited research defining how dry surfaces are able to facilitate biofilm growth and formation in such desiccating and nutrient-deprived environments. While it is well established that the phenotypical response of biofilms is dependent on the conditions in which they are formed, most models incorporate a nutrient-enriched, hydrated environment dissimilar to the clinical setting. In this study, we piloted a novel culture medium, artificial human sweat (AHS), which is perceived to be more indicative of the nutrient sources available on hospital surfaces, particularly those in close proximity to patients. AHS was capable of sustaining the proliferation of four clinically relevant multidrug-resistant pathogens (Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa) and achieved biofilm formation at concentration levels equivalent to those found in situ (average, 6.00 log10 CFU/cm2) with similar visual characteristics upon microscopy. The AHS model presented here could be used for downstream applications, including efficacy testing of hospital cleaning products, due to its resemblance to clinical biofilms on dry surfaces. This may contribute to a better understanding of the true impact these products have on surface hygiene. IMPORTANCE Precise modeling of dry surface biofilms in hospitals is critical for understanding their role in hospital-acquired infection transmission and surface contamination. Using a representative culture condition which includes a nutrient source is key to developing a phenotypically accurate biofilm community. This will enable accurate laboratory testing of cleaning products and their efficacy against dry surface biofilms.

The United States has not yet decided to ensure that every citizen has access to health care services at reasonable cost. The United States spends more on health care than any other country by far. Yet the health status of the US population, when compared with that of like nations, remains poor. The US system does not operate efficiently, fares poorly in terms of health equity, and has an illness and injury care industry with many uncoordinated "systems" focused on treating individuals rather than on improving health status. There are lessons for us in Cuba's health system.

Basal cell carcinoma (BCC) is the most common malignancy in fair-skinned populations. Most cases are successfully treated with surgery, but in advanced BCCmdash;including locally advanced BCC and metastatic BCCmdash;surgery is likely to result in substantial morbidity or unlikely to be effective. In those patients, the systemic Hedgehog inhibitors (HHIs) sonidegib and vismodegib are the only approved pharmacologic treatment option. Although a number of clinical studies highlight the similarities and differences between the two HHIs, no head-to-head clinical comparison is available. Results from the pivotal BOLT and ERIVANCE clinical studies for sonidegib and vismodegib, respectively, demonstrate similar efficacy measured by objective response rate, complete response rate, and histologic tumor subtype. Safety results for both studies are comparable with similar common adverse events reported for muscle spasms, alopecia, and dysgeusia. A notable difference between sonidegib and vismodegib is their respective pharmacokinetic profiles with sonidegib reaching peak concentration in plasma within 2ndash;4 hours of dosing and steady state in plasma achieved by week 17 of treatment, while vismodegib reaches peak plasma concentration approximately 2 days after a single dose and steady state within 21 days of repeated dosing. This review compares efficacy, safety, and pharmacokinetics of sonidegib and vismodegib based on published literature to date. J Drugs Dermatol. 2021;20(2):156-165. doi:10.36849/JDD.5657 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Incorporating the advanced practice provider (APP) in the delivery of tele critical care medicine (teleCCM) addresses the critical care provider shortage. However, the current literature lacks details of potential workflows, deployment difficulties and implementation outcomes while suggesting that expanding teleCCM service may be difficult. Here, we demonstrate the implementation of a telemedicine APP (eAPP) pilot service within an existing teleCCM program with the objective of determining the feasibility and ease of deployment. The goal is to augment an existing tele-ICU system with a balanced APP service to assess the feasibility and potential impact on the ICU performance in several hospitals affiliated within a large academic center. A REDCap survey was used to assess eAPP workflows, expediency of interventions, duration of tasks, and types of assignments within different service locations. Between 02/01/2021 and 08/31/2021, 204 interventions (across 133 12-h shift) were recorded by eAPP (nroutine = 109 (53.4%); nurgent = 82 (40.2%); nemergent = 13 (6.4%). The average task duration was 10.9 ± 6.22 min, but there was a significant difference based on the expediency of the task (F [2; 202] = 3.89; p p

HIV develops single nucleotide polymorphisms (SNPs), some of which lead to drug resistance mutations (DRMs) that prevent therapeutic viral suppression. Genomic sequencing enables healthcare professionals to select effective combination antiretroviral therapy (ART) to achieve and maintain viral suppression. However, sequencing technologies, which are resource-intensive, are limited in their availability. This report describes the first step toward a highly specific ligation-based SNP discrimination method with endpoint PCR detection, which is more suitable for resource-limited clinics. The approach is based on magnetic bead processing to maximize reaction product transfer and minimize the carryover of incompatible buffer for three consecutive enzymatic reactions─reverse transcription (RT), oligonucleotide ligation assay (OLA), and PCR. The method improved PCR detection following RT → OLA by 8.06 cycles (∼250-fold) compared to direct pipette processing and detected between 10

Mentor Mothers (MM) provide peer support to pregnant and postpartum women living with HIV (PPWH) and their infants with perinatal HIV exposure (IPE) throughout the cascade of prevention of vertical transmission (PVT) services. MM were implemented in Zambézia Province, Mozambique starting in August 2017. This evaluation aimed to determine the effect of MM on PVT outcomes.A retrospective interrupted time series analysis was done using routinely collected aggregate data from 85 public health facilities providing HIV services in nine districts of Zambézia. All PPWH (and their IPE) who initiated antiretroviral therapy (ART) from August 2016 through April 2019 were included. Outcomes included the proportion per month per district of: PPWH retained in care 12 months after ART initiation, PPWH with viral suppression and IPE with HIV DNA PCR test positivity by 9 months of age. The effect of MM on outcomes was assessed using logistic regression.The odds of 12-month retention increased 1.5% per month in the pre-MM period, compared to a monthly increase of 7.6% with-MM (35-61% pre-MM, 56-72% with-MM; p0.001). The odds of being virally suppressed decreased by 0.9% per month in the pre-MM period, compared to a monthly increase of 3.9% with-MM (49-85% pre-MM, 59-80% with-MM; p0.001). The odds of DNA PCR positivity by 9 months of age decreased 8.9% per month in the pre-MM period, compared to a monthly decrease of 0.4% with-MM (0-14% pre-MM, 4-10% with-MM; p0.001). The odds of DNA PCR uptake (the proportion of IPE who received DNA PCR testing) by 9 months of age were significantly higher in the with-MM period compared to the pre-MM period (48-100% pre-MM, 87-100% with-MM; p0.001).MM services were associated with improved retention in PVT services and higher viral suppression rates among PPWH. While there was ongoing but diminishing improvement in DNA PCR positivity rates among IPE following MM implementation, this might be explained by increased uptake of HIV testing among high-risk IPE who were previously not getting tested. Additional efforts are needed to further optimize PVT outcomes, and MM should be one part of a comprehensive strategy to address this critical need.

Background: When a patient arrives in the emergency department following a stroke, a traumatic brain injury, or sudden cardiac arrest, there is no therapeutic drug available to help protect their jeopardized neurons. One crucial reason is that we have not identified the molecular mechanisms leading to electrical failure, neuronal swelling, and blood vessel constriction in newly injured gray matter. All three result from a process termed spreading depolarization (SD). Because we only partially understand SD, we lack molecular targets and biomarkers to help neurons survive after losing their blood flow and then undergoing recurrent SD. Methods: In this review, we introduce SD as a single or recurring event, generated in gray matter following lost blood flow, which compromises the Na/K pump. Electrical recovery from each SD event requires so much energy that neurons often die over minutes and hours following initial injury, independent of extracellular glutamate. Results: We discuss how SD has been investigated with various pitfalls in numerous experimental preparations, how overtaxing the Na/K ATPase elicits SD. Elevated K or glutamate are unlikely natural activators of SD. We then turn to the properties of SD itself, focusing on its initiation and propagation as well as on computer modeling. Conclusions: Finally, we summarize points of consensus and contention among the authors as well as where SD research may be heading. In an accompanying review, we critique the role of the glutamate excitotoxicity theory, how it has shaped SD research, and its questionable importance to the study of early brain injury as compared with SD theory., This work was supported by grants from the Heart and Stroke Foundation of Canada and the National Science and Engineering Research Council of Canada to RDA, an NIH grant (NS106901) to CWS, a National Research, Development and Innovation Office of Hungary grant (K1343777) and EU Horizon 2020 research and innovation program (739953) to EF and from DFG Deutsche Forschungsgemeinschaft (German Research Council) (DFG DR 323/5-1), DFG DR 323/10-1, and BMBF Bundesministerium fuer Bildung und Forschung (EraNet Neuron EBio2, with funds from BMBF 01EW2004) to JPD.

Advances in combat casualty care have improved combat survivability over the past two decades. However, these outcomes remain incompletely framed in the broader context of combat casualty outcomes over the past eighty years. We hypothesized that starting with World War II, combat survival worsened at the beginning of each new conflict but then improved over time. To evaluate long-term trends in combat casualty outcomes, monthly combat injuries and deaths during World War II, the Korean conflict, the Vietnam conflict, Operation Iraqi Freedom (OIF), and Operation Enduring Freedom (OEF) were collated. From these numbers, we calculated the monthly case fatality rate (CFR), the killed in action rate (%KIA), and the died of wounds rate (%DOW). We analyzed these metrics for significant trends during and between each conflict using linear and Loess regression. We then simulated alternate outcome scenarios by eliminating outcome variability. In this comprehensive analysis, CFR decreased over the study period in parallel with a decrease in %KIA. When examining individual conflicts, however, several unfavorable trends emerged including a spike in all fatality measures at the end of Vietnam and a rise in %DOW over the course of Korea and OIF. In comparing CFR at the beginning of each conflict to the best CFR from the prior conflict, high mortality outliers occurred in every conflict after a period of relative peace, and a clear "peacetime effect" occurred in both World War II and Vietnam. Eliminating these negative trends and the attendant preventable deaths would have reduced combat fatalities over the course of eighty years by 107,256 (39.7%). In summary, although combat mortality rates have generally improved since World War II, closer examination indicates several unfavorable trends both during and between conflicts. Identifying factors behind these trends will reveal further opportunities to improve combat casualty outcomes in the future. LEVEL OF EVIDENCE: III, Epidemiological.

Support of human immunodeficiency virus (HIV) and tuberculosis (TB) testing and treatment supported by President's Emergency Plan for AIDS Relief (PEPFAR) in Africa requires immense quantities of tests and medications. We sought to use central pharmacy supply data of Mozambique's rural Zambézia Province (2017 population ≈5.11 million persons; ≈12.6% adult HIV prevalence in 2016) to examine shortages, stockouts, and trends in availability. Using stock surveillance for 60 weeks in 2014–2015, we assessed availability of 36 medications [4 classes: adult antiretroviral (ARV) medications, pediatric ARVs, anti-TB medications, and antibiotics] and diagnostic test kits (2 rapid tests for HIV; 1 each for malaria and syphilis). We contrasted these to 2018–2019 data. We modeled pharmacy data using ordinal logistic regression, characterizing weekly product availability in four categories: good, adequate, shortage, or complete stockout. We found 166 (7(.)7%) stockouts and 150 (6.9%) shortages among 2,160 weekly records. Earlier calendar time was associated with reduced medication supplies (p

OBJECTIVEMost patients with chronic subdural hematoma (cSDH) recover after surgical evacuation with a straightforward course. There is a subset of patients who develop transient and fluctuating deficits not explained by seizures, stroke, or mass effect after evacuation. The objective of this study was to investigate whether these postoperative neurological deficits may be related to temporary brain dysfunction caused by cortical spreading depolarizations (SDs).METHODSThe authors conducted a prospective observational study of 40 patients who underwent cSDH evacuation. At the time of surgery, a 1 × 6 subdural electrode strip was placed on the cortex parallel to the subdural drain. Clinical outcomes were assessed utilizing the Markwalder Grading Scale, need for clinical EEG for new deficit, and presence of new deficits.RESULTSDefinitive SD was detected in 6 (15%) of 40 patients. Baseline and cSDH characteristics did not differ between patients with and without SD. More patients experienced postoperative neurological deterioration if they had SD (50%) compared to those without SD (8.8%; p = 0.03). Only 2 patients in the entire cohort demonstrated early neurological deterioration, both of whom had SD. One of these cases demonstrated a time-locked new focal neurological deficit (aphasia) at the start of a series of multiple clusters of SD.CONCLUSIONSThis is the first observation of SD occurring after cSDH evacuation. SD occurred at a rate of 15% and was associated with neurological deterioration. This may represent a novel mechanism for otherwise unexplained fluctuating neurological deficit after cSDH evacuation. This could provide a new therapeutic target, and SD-targeted therapies should be evaluated in prospective clinical trials.

The opioid epidemic is a recent focus of national initiatives to reduce opioid misuse and related addiction. As interstitial cystitis (IC) is a chronic pain state at risk for narcotic use, we sought to assess opioid prescription use in patients with IC. Data were accessed from the Virginia All Payers Claims Database. We identified female patients diagnosed with IC from 2011 to 2016 using International Classification of Disease codes. A patient identifier was used to link diagnoses with outpatient prescription claims for opioids using generic product identifiers. We then analyzed opioid prescriptions within 30 days of a claim with a diagnosis of IC. A total of 6,884 patients with an IC diagnosis were identified. The median number of IC claims per patient was 2 (IQR 1 to 4). Mean patient age was 47.8. Twenty-eight percent of patients received at least 1 opioid prescription, with a median of 2 (IQR 1, 4) per patient. Among those receiving opioids, 185 (9.5%) had more than 10 opioid prescriptions, with a maximum of 129. The most common prescriptions were hydrocodone (n = 2,641, 32.3%), oxycodone (n = 2,545, 31.2%), and tramadol (n = 1,195, 14.6%). There was a decline in opioid prescriptions per month for IC, although the rate per IC diagnosis remained stable. A significant number of patients with IC are treated with opioids. Although the overall number of opioid prescriptions associated with IC had declined, the prescription rate per IC diagnosis had not. As part of the national initiative to reduce opioid use, our data suggest that IC treatment strategies should be examined.

Numerous surgical advances have resulted from exchanges between military and civilian surgeons. As part of the U.S. National Library of Medicine Michael E. DeBakey Fellowship in the History of Medicine, we conducted archival research to shed light on the lessons that civilian surgery has learned from the military system and vice-versa. Several historical case studies highlight the need for immersive programs where surgeons from the military and civilian sectors can gain exposure to the techniques, expertise, and institutional knowledge the other domain provides. Our findings demonstrate the benefits and promise of structured programs to promote reciprocal learning between military and civilian surgery.

Microscopic interpretation of frozen tissue sections is fundamental to Mohs micrographic surgery. Mohs surgeons spend a significant portion of their day at the microscope. Eye strain and fatigue, in addition to musculoskeletal strain, may increase the risk of interpretation errors as well as musculoskeletal injury.3,4,5,7 Advances in microscope systems have allowed for more efficient and reliable reading of slides as well as decreased physical strain. In particular, the advent of super wide field (SWF) microscopy, which includes lower power objective lenses as well as wider eyepieces, allows for a much larger area to be viewed, decreasing eye strain.2,5 Also, more ergonomically designed systems help to decrease musculoskeletal fatigue and injury.7 In an update to an article from Goldsberry et al, that compared older SWF microscope systems,1 we review three newer systems for comparison: Leica DM2500, Nikon Ci-L, and Olympus Bx53 (Figure 1.) Each system reviewed demonstrates ergonomic design and super wide fields of view, allowing for efficient interpretation of tissue and decreased eye strain and musculoskeletal strain compared to older systems. The Nikon Ci-L had the largest possible VFA at 490.87 mm2, 40% more area than the Olympus and 56% more area than the Leica. J Drugs Dermatol. 2021;20(10):1093-1095, doi:10.36849/JDD.6083.

ImportanceThe burden of firearm violence in US cities continues to rise. The role of access to trauma center care as a trauma system measure with implications for firearm injury mortality has not been comprehensively evaluated.ObjectiveTo evaluate the association between geospatial access to care and firearm injury mortality in an urban trauma system.Design, Setting, and ParticipantsRetrospective cohort study of all people 15 years and older shot due to interpersonal violence in Philadelphia, Pennsylvania, between January 1, 2015, and August 9, 2021.ExposuresGeospatial access to care, defined as the predicted ground transport time to the nearest trauma center for each person shot, derived by geospatial network analysis.Main Outcomes and MeasuresRisk-adjusted mortality estimated using hierarchical logistic regression. The population attributable fraction was used to estimate the proportion of fatalities attributable to disparities in geospatial access to care.ResultsDuring the study period, 10 105 people (910 [9%] female and 9195 [91%] male; median [IQR] age, 26 [21-28] years; 8441 [84%] Black, 1596 [16%] White, and 68 other [Conclusions and RelevanceThese findings indicate that geospatial access to care may be an important trauma system measure, improvements to which may result in reduced deaths from gun violence in US cities.

INTRODUCTION Few structured mentoring programs target early-stage investigators in Africa, creating a gap in mentorship skills where HIV burden is greatest. We describe findings from a Nigeria-based workshop for early-career physician scientists to build mentoring and leadership capacity in HIV and noncommunicable disease research. METHODS Baseline surveys captured participant demographics, confidence in implementing mentoring competencies, and perceived importance of workshop training domains. The workshop included didactic presentations, small group activities, and interactive discussions. Daily surveys evaluated sessions, and postworkshop surveys solicited overall course impressions. RESULTS Of the 33 participants, most were male (n = 21, 63.6%) and from medicine, laboratory sciences, and surgical specialties. "Building mentees' confidence" and "setting mentees' research goals" were ranked as areas where participants most believed they needed training. Sessions were rated favorably across five areas. Greatest improvements in mean scores were for confidence in identifying personal temperament styles, describing mentoring and leadership theories/frameworks, and developing mentoring plans. Additional identified workshop strengths were content relevance, leadership case series, interactive nature, and collegial atmosphere. All respondents indicated learning something new/useful/helpful in each session. At 6-month postworkshop, most respondents (25 of 26, 96%) had replicated or plan to replicate parts of the workshop in their departments/institutions. DISCUSSION Effective mentoring training initiatives targeting future academic leaders have the potential to create skilled academicians who can impart mentoring skills and competencies to their mentees.

Background An accurate system to predict mortality in patients requiring intubation for COVID-19 could help to inform consent, frame family expectations and assist end-of-life decisions. Research objective To develop and validate a mortality prediction system called C-TIME (COVID-19 Time of Intubation Mortality Evaluation) using variables available before intubation, determine its discriminant accuracy, and compare it to acute physiology and chronic health evaluation (APACHE IVa) and sequential organ failure assessment (SOFA). Methods A retrospective cohort was set in 18 medical-surgical ICUs, enrolling consecutive adults, positive by SARS-CoV 2 RNA by reverse transcriptase polymerase chain reaction or positive rapid antigen test, and undergoing endotracheal intubation. All were followed until hospital discharge or death. The combined outcome was hospital mortality or terminal extubation with hospice discharge. Twenty-five clinical and laboratory variables available 48 hours prior to intubation were entered into multiple logistic regression (MLR) and the resulting model was used to predict mortality of validation cohort patients. Area under the receiver operating curve (AUROC) was calculated for C-TIME, APACHE IVa and SOFA. Results The median age of the 2,440 study patients was 66 years; 61.6 percent were men, and 50.5 percent were Hispanic, Native American or African American. Age, gender, COPD, minimum mean arterial pressure, Glasgow Coma scale score, and PaO2/FiO2 ratio, maximum creatinine and bilirubin, receiving factor Xa inhibitors, days receiving non-invasive respiratory support and days receiving corticosteroids prior to intubation were significantly associated with the outcome variable. The validation cohort comprised 1,179 patients. C-TIME had the highest AUROC of 0.75 (95%CI 0.72–0.79), vs 0.67 (0.64–0.71) and 0.59 (0.55–0.62) for APACHE and SOFA, respectively (Chi2 P Conclusions C-TIME is the only mortality prediction score specifically developed and validated for COVID-19 patients who require mechanical ventilation. It has acceptable discriminant accuracy and goodness-of-fit to assist decision-making just prior to intubation. The C-TIME mortality prediction calculator can be freely accessed on-line at https://phoenixmed.arizona.edu/ctime.

PURPOSE OF REVIEW: Clinical trials represent a bedrock for measuring efficacy of interventions in biomedical research, but recruitment into clinical trials remains a challenge. Few data have focused on recruitment strategies from the perspective of clinical trial teams, especially in low- and middle-income countries (LMIC), where HIV is most prevalent. RECENT FINDINGS: We summarized data from the literature and our experience with recruitment for the Renal Risk Reduction trial, aimed at reducing risk of kidney complications among people living with HIV in Nigeria. Using an implementation science framework, we identified strategies that contributed to successful clinical trial recruitment. For strategies that could not be categorized by this framework, we summarized key features according to selected action, actor, target, context, and time. We identified how these identified strategies could map to subsequent implementation outcomes at the patient and provider/health system level, as well as capacity-building efforts to meet needs identified by LMIC partners, which is a priority for success. SUMMARY: Our experience highlights the importance of considering implementation outcomes, and the strategies necessary to achieve those outcomes early, in the planning and execution of clinical trials. Clinical trial recruitment can be optimized via methodologies grounded in implementation science.

Chronic subdural hematoma (cSDH) is a common neurosurgical condition responsible for excess morbidity, particularly in the geriatric population. Recovery after evacuation is complicated by fluctuating neurological deficits in a high proportion of patients. We previously demonstrated that spreading depolarizations (SDs) may be responsible for some of these events. In this study, we aim to determine candidate risk factors for probable SD and assess the influence of probable SD on outcome. We used two cohorts who underwent surgery for cSDH. The first cohort (n = 40) had electrocorticographic monitoring to detect SD. In the second cohort (n = 345), we retrospectively identified subjects with suspected SD based on the presence of transient neurological symptoms not explained by structural etiology or ictal activity on electroencephalography. We extracted standard demographic and outcome variables for comparisons and modeling. Of 345 subjects, 80 (23%) were identified in the retrospective cohort as having probable SD. Potential risk factors included history of hypertension, worse clinical presentation on the Glasgow Coma Scale, and lower Hounsfield unit density and volume of the preoperative subdural hematoma. Probable SD was associated with multiple worse-outcome measures, including length of stay and clinical outcomes, but not increased mortality. On a multivariable analysis, probable SD was independently associated with worse outcome, determined by the Glasgow Outcome Scale score at the first clinic follow-up (odds ratio 1.793, 95% confidence interval 1.022–3.146) and longer hospital length of stay (odds ratio 7.952, 95% confidence interval 4.062–15.563). Unexplained neurological deficits after surgery for cSDH occur in nearly a quarter of patients and may be explained by SD. We identified several potential candidate risk factors. Patients with probable SD have worse outcomes, independent of other baseline risk factors. Further data with gold standard monitoring are needed to evaluate for possible predictors of SD to target therapies to a high-risk population.

Apathy is a common and impairing sequela of traumatic brain injury (TBI). Yet, little is known about the neural mechanisms determining in which patients apathy does or does not develop post-TBI. We aimed to elucidate the impact of TBI on motivational neural circuits and how this shapes apathy over the course of TBI recovery. Resting-state functional magnetic resonance imaging data were collected in patients with subacute mild TBI (n = 44), chronic mild-to-moderate TBI (n = 26), and nonbrain-injured control participants (CTRL; n = 28). We measured ventromedial prefrontal cortex (vmPFC) functional connectivity (FC) as a function of apathy, using an a priori vmPFC seed adopted from a motivated decision-making study in an independent TBI study cohort. Patients reported apathy using a well-validated tool for assaying apathy in TBI. The vmPFC-to-wholebrain FC was contrasted between groups, and we fit regression models with apathy predicting vmPFC FC. Subacute and chronic TBI caused increased apathy relative to CTRL, replicating previous work suggesting that apathy has an enduring impact in TBI. The vmPFC was functionally connected to the canonical default network, and this architecture did not differ between subacute TBI, chronic TBI, and CTRL groups. Critically, in TBI, increased apathy scores predicted decreased vmPFC-dorsal anterior cingulate cortex (dACC) FC. Last, we subdivided the TBI group based on patients above versus below the threshold for “clinically significant apathy,” finding that TBI patients with clinically significant apathy demonstrated comparable vmPFC-dACC FC to CTRLs, whereas TBI patients with subthreshold apathy scores demonstrated vmPFC-dACC hyperconnectivity relative to both CTRLs and patients with clinically significant apathy. Post-TBI vmPFC-dACC hyperconnectivity may represent an adaptive compensatory response, helping to maintain motivation and enabling resilience to the development of apathy after neurotrauma. Given the role of vmPFC-dACC circuits in value-based decision making, rehabilitation strategies designed to improve this ability may help to reduce apathy and improve functional outcomes in TBI.

Background The first pillar of the UNAIDS 90-90-90 goal seeks to accurately identify persons living with HIV (PLHIV), a process that is predicated on facilities having the necessary HIV tests available to perform the task. In many rural settings, the identification of PLHIV is accomplished through a two-step process involving the sequential use of 2 separate rapid diagnostic tests (RDTs). Inadequate inventory of either test has ramifications for the success of HIV-related programs. The purpose of this study was to evaluate the inventory levels of HIV RDT kits at specific healthcare facilities in Zambézia province, Mozambique. Methods Using facility-level pharmacy stock surveillance data from October 2015 through September 2016, we assessed the inventory levels of HIV RDTs at 75 health facilities in 8 districts within Zambézia province, Mozambique. Using programmatically established categories (good, sufficient, threatened, or stockout), defined in conjunction with the provincial health authorities, descriptive statistics were performed to determine inventory control of HIV RDTs at the district and health facility levels. Monthly proportions of adequate (good + sufficient) inventory were calculated for each district to identify inventory trends over the evaluation period. To assess whether the proportion of inadequate stocks differed between RDT, a mixed-effects logistic regression was conducted, with inadequate inventory status as the outcome of interest. Results When viewed as a whole, the inventory of each test kit was reported as being at adequate levels more than 89% of the time across the 75 facilities. However, disaggregated analysis revealed significant variability in the inventory levels of HIV RDTs at the district level. Specifically, the districts of Inhassunge, Namacurra, and Pebane reported inadequate inventory levels (threatened + stockout), of one or both test kits, for more than 10% of the study period. In addition, a disparity between inventory levels of each test kit was identified, with the odds of reporting inadequate inventory levels of the confirmatory test (Uni-Gold™) being approximately 1.8-fold greater than the initial test (Determine™) (odds ratio: 1.82, 95% CI: 1.40-2.38). Conclusion As Test and Treat programs evolve, a significant emphasis should be placed on the “test” component of the strategy, beginning with assurances that health facilities have the adequate inventory of RDT necessary to meet the needs of their community. As national policy-makers rely predominantly on data from the upstream arm of the supply chain, it is unlikely the disparity between inventory levels of HIV RDTs identified at individual districts and specific health facilities would have been recognized. Moving forward, our findings point to a need for (1) renewed efforts reinforcing appropriate downstream forecasting of essential medicines and diagnostic tests in general and for Uni-Gold™ test kits specifically, and (2) simple metrics that may be routinely collected at all health facilities and which may then easily and quickly flow upstream so that policy-makers may optimally allocate resources.

The Covid-19 pandemic required rapid scale of telemedicine as well as other digital workflows to maintain access to care while reducing infection risk. Both patients and clinicians who hadn't used telemedicine before were suddenly faced with a multi-step setup process to log into a virtual meeting. Unlike in-person examination rooms, locking a virtual meeting room was more error-prone and posed a risk of multiple patients joining the same online session. There was administrative burden on the practice staff who were generating and manually sending links to patients, and educating patients on device set up was time-consuming and unsustainable. A solution had to be deployed rapidly system-wide, without the usual roll out across months. Our answer was to design and implement a novel EHR-integrated web application called the Switchboard, in just two weeks. The Switchboard leverages a commercial, cloud-based video meeting platform and facilitates an end-to-end virtual care encounter workflow, from pre-visit reminders to post-visit SMS text message-based measurement of patient experience, with tools to extend contact-less workflows to in-person appointments. Over the first 11 months of the pandemic, the in-house platform has been adopted across 6 hospitals and >200 practices, scaled to 8,800 clinicians who at their peak conducted an average of 30,000 telemedicine appointments/week, and enabled over 10,000-20,000 text messages/day to be exchanged through the platform. Furthermore, it enabled our organization to convert from an average of 75% of telehealth visits being conducted via telephone to 75% conducted via video within weeks.

Background and Objective: Electrocorticographic (ECoG) measurement of spreading depolarization (SD) has led to significant advances in understanding of injury progression in neuro ICU patients. Ho...

Background Public health measures were instituted to reduce COVID-19 spread. A decrease in total emergency department volume followed, but the impact on injury is unknown. With lockdown and social distancing potentially increasing domicile discord, we hypothesized that intentional injury increased during COVID-19, driven primarily by an increase in penetrating trauma. Study Design A retrospective review of acute adult patient care in an urban Level I trauma center assessed injury patterns. Presenting patient characteristics and diagnoses from 6 weeks pre to 10 weeks post statewide stay-at-home orders (March 16, 2020) were compared, as well as with 2015-2019. Subsets were defined by intentionality (intentional vs nonintentional) and mechanism of injury (blunt vs penetrating). Fisher exact and Wilcoxon tests were used to compare proportions and means. Results There were 357 trauma patients that presented pre stay-at-home order and 480 that presented post stay-at-home order. Pre and post groups demonstrated differences in sex (35.6% vs 27.9% female; p = 0.02), age (47.4 ± 22.1 years vs 42 ± 20.3 years; p = 0.009), and race (1.4% vs 2.3% Asian; 63.3% vs 68.3% Black; 30.5% vs 22.3% White; and 4.8% vs 7.1% other; p = 0.03). Post stay-at-home order mechanism of injury revealed more intentional injury (p = 0.0008). Decreases in nonintentional trauma after adoption of social isolation paralleled declines in daily emergency department visits. Compared with earlier years, 2020 demonstrated a significantly greater proportion of intentional violent injury during the peripandemic months, especially from firearms. Conclusions Unprecedented social isolation policies to address COVID-19 were associated with increased intentional injury, especially gun violence. Meanwhile, emergency department and nonintentional trauma visits decreased. Pandemic-related public health measures should embrace intentional injury prevention and management strategies.

Despite being nearly 10 months into the COVID-19 (coronavirus disease 2019) pandemic, the definitive animal host for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causal agent of COVID-19, remains unknown. Unfortunately, similar problems exist for other betacoronaviruses, and no vouchered specimens exist to corroborate host species identification for most of these pathogens., Despite being nearly 10 months into the COVID-19 (coronavirus disease 2019) pandemic, the definitive animal host for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causal agent of COVID-19, remains unknown. Unfortunately, similar problems exist for other betacoronaviruses, and no vouchered specimens exist to corroborate host species identification for most of these pathogens. This most basic information is critical to the full understanding and mitigation of emerging zoonotic diseases. To overcome this hurdle, we recommend that host-pathogen researchers adopt vouchering practices and collaborate with natural history collections to permanently archive microbiological samples and host specimens. Vouchered specimens and associated samples provide both repeatability and extension to host-pathogen studies, and using them mobilizes a large workforce (i.e., biodiversity scientists) to assist in pandemic preparedness. We review several well-known examples that successfully integrate host-pathogen research with natural history collections (e.g., yellow fever, hantaviruses, helminths). However, vouchering remains an underutilized practice in such studies. Using an online survey, we assessed vouchering practices used by microbiologists (e.g., bacteriologists, parasitologists, virologists) in host-pathogen research. A much greater number of respondents permanently archive microbiological samples than archive host specimens, and less than half of respondents voucher host specimens from which microbiological samples were lethally collected. To foster collaborations between microbiologists and natural history collections, we provide recommendations for integrating vouchering techniques and archiving of microbiological samples into host-pathogen studies. This integrative approach exemplifies the premise underlying One Health initiatives, providing critical infrastructure for addressing related issues ranging from public health to global climate change and the biodiversity crisis.

Leukocyte inflammatory responses require integrin cell-adhesion molecule signaling through spleen tyrosine kinase (Syk), a non-receptor kinase that binds directly to integrin β-chain cytoplasmic domains. Here, we developed a high-throughput screen to identify small molecule inhibitors of the Syk-integrin cytoplasmic domain interactions. Screening small molecule compound libraries identified the β-lactam antibiotics cefsulodin and ceftazidime, which inhibited integrin β-subunit cytoplasmic domain binding to the tandem SH2 domains of Syk (IC50 range, 1.02–4.9 µM). Modeling suggested antagonist binding to Syk outside the pITAM binding site. Ceftazidime inhibited integrin signaling via Syk, including inhibition of adhesion-dependent upregulation of interleukin-1β and monocyte chemoattractant protein-1, but did not inhibit ITAM-dependent phosphorylation of Syk mediated by FcγRI signaling. Our results demonstrate a novel means to target Syk independent of its kinase and pITAM binding sites such that integrin signaling via this kinase is abrogated but ITAM-dependent signaling remains intact. As integrin signaling through Syk is essential for leukocyte activation, this may represent a novel approach to target inflammation.

HIV-positive adults are at risk for various kidney diseases, and apolipoprotein 1 (APOL1) high-risk genotypes increase this risk. This study aimed to determine the prevalence and ethnic distribution of APOL1 risk genotypes among a cohort of HIV-positive Nigerian adults and explore the relationship between APOL1 risk variant status with albuminuria and estimated glomerular filtration rate (eGFR). We conducted a cross-sectional study among 2 458 persons living with HIV who attended an HIV clinic in northern Nigeria and had received antiretroviral therapy for a minimum of six months. We collected two urine samples four-eight weeks apart to measure albumin excretion, and blood samples to measure eGFR and determine APOL1 genotype. The frequency of APOL1 high-risk genotype was 6.2%, which varied by ethnic group: Hausa/Fulani (2.1%), Igbo (49.1%), and Yoruba (14.5%). The prevalence of microalbuminuria (urine/albumin creatinine ratio 30 – 300 mg/g) was 37%, and prevalence of macroalbuminuria (urine/albumin creatinine ratio over 300 mg/g) was 3%. The odds of microalbuminuria and macroalbuminuria were higher for participants with the APOL1 high-risk genotype compared to those carrying the low-risk genotype ((adjusted odds ratio 1.97, 95% confidence interval 1.37-2.82) and (3.96, 1.95-8.02) respectively)). APOL1 high-risk genotype participants were at higher risk of having both an eGFR under 60 ml/min/1.73m(2) and urine/albumin creatinine ratio over 300 mg/g (5.56, 1.57-19.69). Thus, we found a high proportion of HIV-positive, antiretroviral therapy-experienced, and largely virologically suppressed adults had microalbuminuria. Hence, although the high-risk APOL1 genotype was less prevalent than expected, it was strongly associated with some level of albuminuria.

Background: Inhaled pulmonary vasodilators are used as adjunctive therapies for the treatment of refractory hypoxemia. Available evidence suggest they improve oxygenation in a subset of patients without changing long-term trajectory. Given the differences in respiratory failure due to COVID-19 and “traditional” ARDS, we sought to identify their physiologic impact. Methods: This is a retrospective observational study of patients mechanically ventilated for COVID-19, from the ICUs of 2 tertiary care centers, who received inhaled epoprostenol (iEpo) for the management of hypoxemia. The primary outcome is change in PaO2/FiO2. Additionally, we measured several patient level features to predict iEpo responsiveness (or lack thereof). Results: Eighty patients with laboratory confirmed SARS-CoV2 received iEpo while mechanically ventilated and had PaO2/FiO2 measured before and after. The median PaO2/FiO2 prior to receiving iEpo was 92 mmHg and interquartile range (74 – 122). The median change in PaO2/FiO2 was 9 mmHg (-9 – 37) corresponding to a 10% improvement (-8 – 41). Fifty-percent (40 / 80) met our a priori definition of a clinically significant improvement in PaO2/FiO2 (increase in 10% from the baseline value). Prone position and lower PaO2/FiO2 when iEpo was started predicted a more robust response, which held after multivariate adjustment. For proned individuals, improvement in PaO2/FiO2 was 14 mmHg (-6 to 45) vs. 3 mmHg (-11 – 20), p = 0.04 for supine individuals; for those with severe ARDS (PaO2/FiO2 < 100, n = 49) the median improvement was 16 mmHg (-2 – 46). Conclusion: Fifty percent of patients have a clinically significant improvement in PaO2/FiO2 after the initiation of iEpo. This suggests it is worth trying as a rescue therapy; although generally the benefit was modest with a wide variability. Those who were prone and had lower PaO2/FiO2 were more likely to respond.

Introduction: Actinic keratosis (AK) is a skin condition arising from chronic exposure to ultraviolet light and may lead to the development of malignancies. This trial aimed to evaluate efficacy and safety of ingenol disoxate gel (IngDsx, 0.018% for face/chest [FC]; 0.037% for scalp [S]), versus vehicle. Methods: Four identical phase 3 trials in patients with AK on the full face/up to 250cm2 of chest or full balding scalp, with an initial 8-week period and 12-month follow-up, were conducted. FC and S trials were pooled for analysis. The primary endpoint was complete clearance at Week 8. Results: Across trials, 616 patients were randomized to FC and 626 to S, with 410 and 420 assigned to receive IngDsx, respectively. In the FC and S trials, 25.9% and 24.5% of patients in the IngDsx group, respectively, achieved the primary endpoint. IngDsx was relatively well tolerated. During extended follow-up, there were more identified non-melanoma skin malignancies in the IngDsx group than vehicle group; HR: 2.38 (95% CI: 1.28, 4.41). Conclusion: Treatment with IngDsx was superior to vehicle on all clinical endpoints, patient-reported and cosmetic outcomes. During the 12-month follow-up, slightly increased skin malignancies in the treatment area were identified, potentially due to unintentional detection bias.

Importance Serious illness conversations (SICs) are structured conversations between clinicians and patients about prognosis, treatment goals, and end-of-life preferences. Interventions that increase the rate of SICs between oncology clinicians and patients may improve goal-concordant care and patient outcomes. Objective To determine the effect of a clinician-directed intervention integrating machine learning mortality predictions with behavioral nudges on motivating clinician-patient SICs. Design, Setting, and Participants This stepped-wedge cluster randomized clinical trial was conducted across 20 weeks (from June 17 to November 1, 2019) at 9 medical oncology clinics (8 subspecialty oncology and 1 general oncology clinics) within a large academic health system in Pennsylvania. Clinicians at the 2 smallest subspecialty clinics were grouped together, resulting in 8 clinic groups randomly assigned to the 4 intervention wedge periods. Included participants in the intention-to-treat analyses were 78 oncology clinicians who received SIC training and their patients (N = 14 607) who had an outpatient oncology encounter during the study period. Interventions (1) Weekly emails to oncology clinicians with SIC performance feedback and peer comparisons; (2) a list of up to 6 high-risk patients (≥10% predicted risk of 180-day mortality) scheduled for the next week, estimated using a validated machine learning algorithm; and (3) opt-out text message prompts to clinicians on the patient's appointment day to consider an SIC. Clinicians in the control group received usual care consisting of weekly emails with cumulative SIC performance. Main Outcomes and Measures Percentage of patient encounters with an SIC in the intervention group vs the usual care (control) group. Results The sample consisted of 78 clinicians and 14 607 patients. The mean (SD) age of patients was 61.9 (14.2) years, 53.7% were female, and 70.4% were White. For all encounters, SICs were conducted among 1.3% in the control group and 4.6% in the intervention group, a significant difference (adjusted difference in percentage points, 3.3; 95% CI, 2.3-4.5; P

Importance Machine learning (ML) algorithms can identify patients with cancer at risk of short-term mortality to inform treatment and advance care planning. However, no ML mortality risk prediction algorithm has been prospectively validated in oncology or compared with routinely used prognostic indices. Objective To validate an electronic health record–embedded ML algorithm that generated real-time predictions of 180-day mortality risk in a general oncology cohort. Design, Setting, and Participants This prognostic study comprised a prospective cohort of patients with outpatient oncology encounters between March 1, 2019, and April 30, 2019. An ML algorithm, trained on retrospective data from a subset of practices, predicted 180-day mortality risk between 4 and 8 days before a patient’s encounter. Patient encounters took place in 18 medical or gynecologic oncology practices, including 1 tertiary practice and 17 general oncology practices, within a large US academic health care system. Patients aged 18 years or older with outpatient oncology or hematology and oncology encounters were included in the analysis. Patients were excluded if their appointment was scheduled after weekly predictions were generated and if they were only evaluated in benign hematology, palliative care, or rehabilitation practices. Exposures Gradient-boosting ML binary classifier. Main Outcomes and Measures The primary outcome was the patients’ 180-day mortality from the index encounter. The primary performance metric was the area under the receiver operating characteristic curve (AUC). Results Among 24 582 patients, 1022 (4.2%) died within 180 days of their index encounter. Their median (interquartile range) age was 64.6 (53.6-73.2) years, 15 319 (62.3%) were women, 18 015 (76.0%) were White, and 10 658 (43.4%) were seen in the tertiary practice. The AUC was 0.89 (95% CI, 0.88-0.90) for the full cohort. The AUC varied across disease-specific groups within the tertiary practice (AUC ranging from 0.74 to 0.96) but was similar between the tertiary and general oncology practices. At a prespecified 40% mortality risk threshold used to differentiate high- vs low-risk patients, observed 180-day mortality was 45.2% (95% CI, 41.3%-49.1%) in the high-risk group vs 3.1% (95% CI, 2.9%-3.3%) in the low-risk group. Integrating the algorithm into the Eastern Cooperative Oncology Group and Elixhauser comorbidity index–based classifiers resulted in favorable reclassification (net reclassification index, 0.09 [95% CI, 0.04-0.14] and 0.23 [95% CI, 0.20-0.27], respectively). Conclusions and Relevance In this prognostic study, an ML algorithm was feasibly integrated into the electronic health record to generate real-time, accurate predictions of short-term mortality for patients with cancer and outperformed routinely used prognostic indices. This algorithm may be used to inform behavioral interventions and prompt earlier conversations about goals of care and end-of-life preferences among patients with cancer.