Effects of saline submersion at body temperature on airway supportive devices including a novel nasopharyngeal device produced using 3D-printing.

PURPOSE: This study investigated dimension changes of various nasopharyngeal airways, including a novel self-supporting device, after saline submersion at body temperature to simulate in-vivo use. Dimension changes over time may reduce efficacy during long-term use and require sizing adjustments or limits on duration of use. MATERIALS AND METHODS: Cuffless Covidien endotracheal tubes, pediatric Rusch fixed flange polyvinyl chloride nasal airway tubes, pediatric Rusch Robertazzi style Mediprene nasal airway tubes, and novel silicone elastomer self-supporting nasopharyngeal airways were fully submerged in 0.9 % normal saline solution incubated at 37 degrees Celsius for 15 days. All devices had tube length and wall thickness measured after 0, 1, 2, 3, 4, 5, 10, and 15 days. The 95 % confidence intervals of tube dimensions at each date were compared with the 95 % confidence intervals at day 0. RESULTS: The Covidien ET tube, Rusch PVC NPA, and ssNPA tube lengths and wall thicknesses did not change significantly over 15 days. The Rusch Mediprene NPAs had a statistically significant increase in length starting at day 1 and wall thickness at day 2. CONCLUSIONS: The novel ssNPA did not expand in the in-vitro environment, supporting its safety for extended use. The PVC NPA and ET tube dimensions also remained stable. However, the Rusch Mediprene NPAs had significant length expansion after 1 day of submersion, indicating a considerable risk of expansion during extended use with potential implications for patient care. Silicone and PVC NPA dimensions remained stable when saturated, indicating these materials may be more appropriate for extended use.

An update on clinical presentation and responses to therapy of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH).

Pathogenic variants in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Here, we report a pooled analysis of clinical and laboratory records of 304 individuals from 145 kindreds, including 20 previously unreported HHRH kindreds, in which two novel SLC34A3 pathogenic variants were identified. Compound heterozygous/homozygous carriers show above 90% penetrance for kidney and bone phenotypes. The biochemical phenotype for heterozygous carriers is intermediate with decreased serum phosphate, tubular reabsorption of phosphate (TRP (%)), fibroblast growth factor 23, and intact parathyroid hormone, but increased serum 1,25-dihydroxy vitamin D, and urine calcium excretion causing idiopathic hypercalciuria in 38%, with bone phenotypes still observed in 23% of patients. Oral phosphate supplementation is the current standard of care, which typically normalizes serum phosphate. However, although in more than half of individuals this therapy achieves correction of hypophosphatemia it fails to resolve the other outcomes. The American College of Medical Genetics and Genomics score correlated with functional analysis of frequent SLC34A3 pathogenic variants in vitro and baseline disease severity. The number of mutant alleles and baseline TRP (%) were identified as predictors for kidney and bone phenotypes, baseline TRP (%) furthermore predicted response to therapy. Certain SLC34A3/NPT2c pathogenic variants can be identified with partial responses to therapy, whereas with some overlap, others present only with kidney phenotypes and a third group present only with bone phenotypes. Thus, our report highlights important novel clinical aspects of HHRH and heterozygous carriers, raises awareness to this rare group of disorders and can be a foundation for future studies urgently needed to guide therapy of HHRH.

A contemporary analysis of 20,086 deceased donor liver biopsies.

BACKGROUND: Pre-transplant deceased donor liver biopsy may impact decision making; however, interpretation of the results remains variable and depends on accepting center practice patterns. METHODS: In this cohort study, adult recipients from 04/01/2015-12/31/2020 were identified using the UNOS STARfile data. The deceased donor liver biopsies were stratified by risk based on degree of fibrosis, macrovesicular fat content, and level of portal infiltration (low-risk: no fibrosis, no portal infiltrates, and <30% macrosteatosis; moderate-risk: some fibrosis or mild infiltrates and <30% macrosteatosis; high-risk: most fibrosis, moderate/marked infiltrates, or ≥30% macrosteatosis). Graft utilization, donor risk profile, and recipient outcomes were compared across groups. RESULTS: Of the 51,094 donor livers available, 20,086 (39.3%) were biopsied, and 34,606 (67.7%) were transplanted. Of the transplanted livers, 14,908 (43.1%) were biopsied. The transplanted grafts had lower mean macrovesicular fat content (9.3% transplanted vs. 26.9% non-transplanted, P < 0.001) and less often had any degree of fibrosis (20.9% vs. 39.9%, P < 0.001) or portal infiltration (51.3% vs. 58.2%, P < 0.001) versus non-transplanted grafts. Post-transplant recipient LOS (14.2 days high-risk vs. 15.2 days low-risk, P = 0.170) and 1-year graft survival (90.5% vs. 91.7%, P = 0.137) did not differ significantly between high- versus low-risk groups. Kaplan-Meier survival estimates further revealed no differences in the 5-year graft survival across risk strata (P = 0.833). Of the 5178 grafts biopsied and turned down, PSM revealed 1338 (26.0%) were potentially useable based on biopsy results and donor characteristics. CONCLUSION: Carefully matched deceased donor livers with some fibrosis, inflammation, or steatosis ≥30% may be suitable for transplantation. Further study of this group of grafts may decrease turndowns of potentially useable organs.

Peripheral Administration of Norepinephrine: A Prospective Observational Study.

BACKGROUND: Historically, norepinephrine has been administered through a central venous catheter (CVC) because of concerns about the risk of ischemic tissue injury if extravasation from a peripheral IV catheter (PIVC) occurs. Recently, several reports have suggested that peripheral administration of norepinephrine may be safe. RESEARCH QUESTION: Can a protocol for peripheral norepinephrine administration safely reduce the number of days a CVC is in use and frequency of CVC placement? STUDY DESIGN AND METHODS: This was a prospective observational cohort study conducted in the medical ICU at a quaternary care academic medical center. A protocol for peripheral norepinephrine administration was developed and implemented in the medical ICU at the study site. The protocol was recommended for use in patients who met prespecified criteria, but was used at the treating clinician's discretion. All adult patients admitted to the medical ICU receiving norepinephrine through a PIVC from February 2019 through June 2021 were included. RESULTS: The primary outcome was the number of days of CVC use that were avoided per patient, and the secondary safety outcomes included the incidence of extravasation events. Six hundred thirty-five patients received peripherally administered norepinephrine. The median number of CVC days avoided per patient was 1 (interquartile range, 0-2 days per patient). Of the 603 patients who received norepinephrine peripherally as the first norepinephrine exposure, 311 patients (51.6%) never required CVC insertion. Extravasation of norepinephrine occurred in 35 patients (75.8 events/1,000 d of PIVC infusion [95% CI, 52.8-105.4 events/1,000 d of PIVC infusion]). Most extravasations caused no or minimal tissue injury. No patient required surgical intervention. INTERPRETATION: This study suggests that implementing a protocol for peripheral administration of norepinephrine safely can avoid 1 CVC day in the average patient, with 51.6% of patients not requiring CVC insertion. No patient experienced significant ischemic tissue injury with the protocol used. These data support performance of a randomized, prospective, multicenter study to characterize the net benefits of peripheral norepinephrine administration compared with norepinephrine administration through a CVC.

Antipsychotic Use for ICU Delirium and Associated Inflammatory Markers.

Purpose: We sought to evaluate critically ill patients with delirium to evaluate inflammatory cytokine production and delirium progression and the role of antipsychotics. Materials and Methods: Adult critically ill patients with confirmed delirium according to a positive CAM-ICU score were included and IL-6 and IL-8 levels were trended for 24 h in this single-center, prospective, observational cohort study. Results: A total of 23 patients were consented and had blood samples drawn for inclusion. There was no difference in IL-6 and IL-8 levels at baseline, 4 to 8 h, and 22 to 28 h after enrollment when comparing patients based on antipsychotic exposure. We identified 2 patient clusters based on age, APACHE III, need for mechanical ventilation, and concomitant infection. In cluster 1, 5 (33.3%) patients received antipsychotics versus 5 (62.5%) patients in cluster 2 (P = .18). Patients in cluster 1 had more co-inflammatory conditions (P < .0001), yet numerically lower baseline IL-6 (P = .18) and IL-8 levels (P = .80) compared to cluster 2. Patients in cluster 1 had a greater median number of delirium-free days compared to cluster 2 (17.0 vs 6.0 days; P = .05). Conclusions: In critically ill patients with delirium, IL-6 and IL-8 levels were variable and antipsychotics were not associated with improvements in delirium or inflammatory markers.

Budesonide, an anti-inflammatory drug, exacerbate clostridioides difficile colitis in mice.

BACKGROUND AND AIMS: Clostridioides difficile infection (CDI) induces intense acute inflammatory responses through toxin release. A combination of antibiotic and anti-inflammatory agents is sometimes recommended in severe, non-responsive cases, although clinical trials have been inconclusive, raising concerns about potential complications. This study aims to investigate the effect of budesonide and mesalamine in the treatment of CDI in a murine model, by evaluating the combination of fidaxomicin and these anti-inflammatory drugs. METHOD: C57BL/6 J female mice pretreated with an antimicrobial mixture were challenged with C. difficile VPI 10463 or culture media by gavage. After the challenge, mice received placebo, fidaxomicin alone (20 mg/kg), or fidaxomicin combined with mesalamine (200, 400 mg/kg) or budesonide (0.2, 1, 10 mg/kg) for 5 days. The mice were monitored for 7 days with weight and survival. Colon and cecum tissues were harvested for histological assessment. RESULTS: CDI of mice caused 80% mortality. Fidaxomicin completely protected against CDI in all parameters (weight, survival and pathscores). Mortality rates were up to 90%, 70% in budesonide(10 mg/kg) and mesalamine (400 mg/kg) treatment group, respectively. Budesonide (0.02,0.1 and 1 mg/kg) adjunction to fidaxomicin worsened the disease outcome according to all tested parameters. While mesalamine in combination with fidaxomicin (200, 400 mg/kg) did not lead to any deaths during CDI treatment, it did not provide additional benefits. CONCLUSIONS: Anti-inflammatory drugs including corticosteroid therapy may worsen the incidence and severity of CDI in this mouse model. These studies may have important clinical implications for understanding the role of anti-inflammatory/ corticosteroid therapy in CDI and inflammatory bowel disease management.

A Large-Scale Multicenter Retrospective Study on Nephrotoxicity Associated With Empiric Broad-Spectrum Antibiotics in Critically Ill Patients.

BACKGROUND: Evidence regarding acute kidney injury associated with concomitant administration of vancomycin and piperacillin-tazobactam is conflicting, particularly in patients in the ICU. RESEARCH QUESTION: Does a difference exist in the association between commonly prescribed empiric antibiotics on ICU admission (vancomycin and piperacillin-tazobactam, vancomycin and cefepime, and vancomycin and meropenem) and acute kidney injury? STUDY DESIGN AND METHODS: This was a retrospective cohort study using data from the eICU Research Institute, which contains records for ICU stays between 2010 and 2015 across 335 hospitals. Patients were enrolled if they received vancomycin and piperacillin-tazobactam, vancomycin and cefepime, or vancomycin and meropenem exclusively. Patients initially admitted to the ED were included. Patients with hospital stay duration of < 1 h, receiving dialysis, or with missing data were excluded. Acute kidney injury was defined as Kidney Disease: Improving Global Outcomes stage 2 or 3 based on serum creatinine component. Propensity score matching was used to match patients in the control (vancomycin and meropenem or vancomycin and cefepime) and treatment (vancomycin and piperacillin-tazobactam) groups, and ORs were calculated. Sensitivity analyses were performed to study the effect of longer courses of combination therapy and patients with renal insufficiency on admission. RESULTS: Thirty-five thousand six hundred fifty-four patients met inclusion criteria (vancomycin and piperacillin-tazobactam, n = 27,459; vancomycin and cefepime, n = 6,371; vancomycin and meropenem, n = 1,824). Vancomycin and piperacillin-tazobactam was associated with a higher risk of acute kidney injury and initiation of dialysis when compared with that of both vancomycin and cefepime (Acute kidney injury: OR, 1.37 [95% CI, 1.25-1.49]; dialysis: OR, 1.28 [95% CI, 1.14-1.45]) and vancomycin and meropenem (Acute kidney injury: OR, 1.27 [95%, 1.06-1.52]; dialysis: OR, 1.56 [95% CI, 1.23-2.00]). The odds of acute kidney injury developing was especially pronounced in patients without renal insufficiency receiving a longer duration of vancomycin and piperacillin-tazobactam therapy compared with vancomycin and meropenem therapy. INTERPRETATION: VPT is associated with a higher risk of acute kidney injury than both vancomycin and cefepime and vancomycin and meropenem in patients in the ICU, especially for patients with normal initial kidney function requiring longer durations of therapy. Clinicians should consider vancomycin and meropenem or vancomycin and cefepime to reduce the risk of nephrotoxicity for patients in the ICU.

Improving the Hospital Transfer Process for Acute Type A Aortic Dissections.

Patients with acute type A aortic dissection who arrive at hospitals that lack the facilities to treat them must be transferred to a tertiary care facility to receive treatment. The transfer process involves a checkpoint at which the transfer is accepted or denied. Delays in making this decision may lead to suboptimal health outcomes. In light of this, the goal of this project was to devise a way to reduce the time to decision of transfer requests for patients with an acute type A aortic dissection. The project followed the Define-Measure-Analyze-Improve-Control (DMAIC) approach. To better understand the process, data were obtained from the University of Texas Southwestern Medical Center regarding reasons for patient transfer cancellation and the average time until a transfer was denied or accepted. After data analysis, a fishbone diagram was used to display 23 root causes of the delays in time to decision of the transfer request. These were narrowed down to the following four significant causes using a nominal voting technique: (1) no standard on disease-specific information for the handoff, (2) lack of a real-time database, (3) incompatible electronic health record system between facilities, and (4) multiple communication handoffs causing confusion. Solutions to each root cause were evaluated using a solution selection matrix. The final two solutions proposed for implementation were as follows: (1) to establish checklists of required documents and patient transfer criteria and (2) to create a regional database to provide real-time information on hospital capacity.

Association of 48-h net fluid status with change in renal function and dyspnea among patients with decompensated heart failure: A pooled cohort analysis of three acute heart failure trials.

BACKGROUND: Acute heart failure (AHF) exacerbations are a leading cause of hospitalization in the United States. Despite the frequency of AHF hospitalizations, there are inadequate data or practice guidelines on how quickly diuresis should be achieved. OBJECTIVE: To study the association of 48-h net fluid change and (A) 72-h change in creatinine and (B) 72-h change in dyspnea among patients with acute heart failure. DESIGNS, SETTINGS, AND PARTICIPANTS: This is a retrospective, pooled cohort analysis of patients from the DOSE, ROSE, and ATHENA-HF trials. INTERVENTIONS: The primary exposure was 48-h net fluid status. MAIN OUTCOMES AND MEASURES: The co-primary outcomes were 72-h change in creatinine and 72-h change in dyspnea. The secondary outcome was risk of 60-day mortality or rehospitalization. RESULTS: Eight hundred and seven patients were included. The mean 48-h net fluid status was -2.9 L. A nonlinear association was observed with net fluid status and creatinine change, such that creatinine improved with each liter net negative up to 3.5 L (-0.03 mg/dL per liter negative [95% confidence interval [CI]: -0.06 to -0.01) and remained stable beyond 3.5 L (-0.01 [95% CI: -0.02 to 0.001], p = .17). Net fluid loss was associated with a monotonic improvement of dyspnea (1.4-point improvement per liter negative [95% CI: 0.7-2.2], p = .0002). Each liter net negative by 48 h was also associated with 12% decreased odds of 60-day rehospitalization or death (odds ratio: 0.88; 95% CI: 0.82-0.95; p = .002). CONCLUSION: Aggressive net fluid targets within the first 48 h are associated with effective relief of patient self-reported dyspnea and improved long-term outcomes without adversely affecting renal function.

Clinical Utilization of Stress Dose Hydrocortisone in Adult Patients With Septic Shock: A Retrospective Observational Study at a Large Academic Medical Center.

Background: The use of stress dose corticosteroids, specifically, hydrocortisone, in septic shock is heterogeneous, and current clinical trials yield conflicting results. Regardless, they are still recommended by guidelines for vasopressor-dependent septic shock. Objectives: This study sought to characterize current practice of hydrocortisone use in patients with septic shock and secondarily to compare clinical outcomes of those who received hydrocortisone to those who did not. Methods: This single center, retrospective cohort study evaluated patients with septic shock admitted to a tertiary care center between 2012 and 2017. Patients receiving hydrocortisone for at least two doses were compared to those without. Results: 3411 septic shock patients were included; 1593 (47%) received hydrocortisone and 1818 (53%) did not. Patients who received hydrocortisone had higher lactate (4.0 vs 3.4 mmol/L; P < .01) and Acute Physiology and Chronic Health Evaluation (APACHE) III scores (104.1 vs 91.0; P < .01). Vasopressor duration was 1.7 days longer in the hydrocortisone group (P < .01), and the hydrocortisone group had higher hospital mortality (52% vs 38%; P < .01). A propensity score-matched population was conducted in patients with APACHE scores >100: vasopressor duration was longer in those who received hydrocortisone (3.9 vs 2.0 days; P < .01), and hospital mortality was higher (59.3% vs 53.1%; P = .036); however, after multivariable adjustment, no association between receipt of hydrocortisone and hospital mortality was detected (OR 1.2 [95% CI .9-1.6]). Conclusions: Patients who received hydrocortisone were more severely ill than those that did not, making retrospective evaluation of this question challenging. These results highlight the wide variability and heterogeneity in hydrocortisone use in clinical practice.

Hearing Outcomes of a New Cartilage Conduction Device vs Bone Conduction Devices.

OBJECTIVE: To compare audiometric outcomes of a new cartilage conduction hearing device (CCD) with traditional bone conduction hearing devices (BCDs). STUDY DESIGN: Clinical trial and crossover study design. SETTING: Tertiary academic center. METHODS: Sixteen adults (19 ears) with congenital aural atresia or overclosed ear canals who previously underwent BCD implantation were fitted with a CCD. Audiometric data were collected with use of the BCD and the CCD. RESULTS: The mean pretreatment 4-frequency pure tone average was 81 dB. The mean aided pure tone averages with the BCD and CCD were 27 and 32 dB (P = .002), and the mean functional gains were 54 and 49 dB (P = .002), respectively. The mean consonant-nucleus-consonant scores with the BCD were 90% (best aided) and 80% (aided ear isolated), and those with the CCD were 86% and 76%. Mean AzBio scores were 90% (quiet), 77% (+10 dB SNR [signal to noise ratio]), and 52% (+5 dB SNR) when isolating the BCD ear and 90%, 73%, and 41% when isolating the CCD ear. No difference in speech scores achieved statistical significance except the AzBio isolated to the aided ear in the +5-dB SNR condition, which favored the BCD (P = .01). CONCLUSION: Pure tone audiometric outcomes with the BCD show a small advantage over the CCD, with the difference driven mainly by high-frequency responses. Speech outcomes were equivalent apart from the +5-db SNR condition, which favored the BCD.

Glaucoma Diagnosis Through the Integration of Optical Coherence Tomography/Angiography and Machine Learning Diagnostic Models.

Purpose: To establish optical coherence tomography (OCT)/angiography (OCTA) parameter ranges for healthy eyes (HE) and glaucomatous eyes (GE) for a North Texas based population; to develop a machine learning (ML) tool and to identify the most accurate diagnostic parameters for clinical glaucoma diagnosis. Patients and Methods: In this retrospective cross-sectional study, we included 1371 eligible eyes, 462 HE and 909 GE (377 ocular hypertension, 160 mild, 156 moderate, 216 severe), from 735 subjects. Demographic data and full OCTA parameters were collected. A Kruskal-Wallis test was used to produce the normative database. Models were trained to solve a two-class problem (HE vs GE) and four-class problem (HE vs mild vs moderate vs severe GE). A rigorous nested, stratified, group, 5×10 fold cross-validation strategy was applied to partition the data. Six ML algorithms were compared using classical and deep learning approaches. Over 2500 ML models were optimized using random search, with performance compared using mean validation accuracy. Final performance was reported on held-out test data using accuracy and F1 score. Decision trees and feature importance were produced for the final model. Results: We found differences across glaucoma severities for age, gender, hypertension, Black and Asian race, and all OCTA parameters, except foveal avascular zone area and perimeter (p<0.05). The XGBoost algorithm achieved the highest test performance for both the two-class (F1 score 83.8%; accuracy 83.9%; standard deviation 0.03%) and four-class (F1 score 62.4%; accuracy 71.3%; standard deviation 0.013%) problem. A set of interpretable decision trees provided the most important predictors of the final model; inferior temporal and inferior hemisphere vessel density and peripapillary retinal nerve fiber layer thickness were identified as key diagnostic parameters. Conclusion: This study established a normative database for our North Texas based population and created ML tools utilizing OCT/A that may aid clinicians in glaucoma management.

Retrospective evaluation of a delirium order set utilizing nonpharmacologic and pharmacologic interventions for the treatment of delirium in medical intensive care unit patients.

PURPOSE: To describe the use of a medical intensive care unit (MICU) delirium order set pilot and its associated impact on utilization of nonpharmacologic and pharmacologic interventions, pharmacologic continuation at transitions of care, and resolution of ICU delirium. METHODS: This was a retrospective cohort analysis of MICU patients who received delirium management using an order set pilot compared to standard care. Patients 18 years of age or older admitted to the MICU between May 2019 and January 2020 who received an antipsychotic or valproic acid for the treatment of delirium were included. RESULTS: Pharmacologic treatment continuation past ICU discharge occurred in 30% of patients in the pilot cohort (n = 50) compared to 54% of patients receiving standard care (n = 50; P = 0.027). On treatment days 1 through 7, utilization of deliriogenic medications was significantly lower in the pilot cohort (78% vs 96%, P = 0.007). No differences were observed between the groups in delirium resolution, delirium recurrence, hospital and ICU length of stay, or mortality. CONCLUSION: A MICU order set prioritizing nonpharmacologic management and limiting the duration of pharmacologic agents for delirium may aid providers in the management of ICU delirium and reduce exposure to pharmacologic interventions.

Bibliometric study of 'overviews of systematic reviews' of health interventions: Evaluation of prevalence, citation and journal impact factor.

Overviews synthesising the results of multiple systematic reviews help inform evidence-based clinical practice. In this first of two companion papers, we evaluate the bibliometrics of overviews, including their prevalence and factors affecting citation rates and journal impact factor (JIF). We searched MEDLINE, Epistemonikos and Cochrane Database of Systematic Reviews (CDSR). We included overviews that: (a) synthesised reviews, (b) conducted a systematic search, (c) had a methods section and (d) examined a healthcare intervention. Multivariable regression was conducted to determine the association between citation density, JIF and six predictor variables. We found 1218 overviews published from 2000 to 2020; the majority (73%) were published in the most recent 5-year period. We extracted a selection of these overviews (n = 541; 44%) dated from 2000 to 2018. The 541 overviews were published in 307 journals; CDSR (8%), PLOS ONE (3%) and Sao Paulo Medical Journal (2%) were the most prevalent. The majority (70%) were published in journals with impact factors between 0.05 and 3.97. We found a mean citation count of 10 overviews per year, published in journals with a mean JIF of 4.4. In multivariable analysis, overviews with a high number of citations and JIFs had more authors, larger sample sizes, were open access and reported the funding source. An eightfold increase in the number of overviews was found between 2009 and 2020. We identified 332 overviews published in 2020, which is equivalent to one overview published per day. Overviews perform above average for the journals in which they publish.

A new taxonomy was developed for overlap across 'overviews of systematic reviews': A meta-research study of research waste.

Multiple 'overviews of reviews' conducted on the same topic ("overlapping overviews") represent a waste of research resources and can confuse clinicians making decisions amongst competing treatments. We aimed to assess the frequency and characteristics of overlapping overviews. MEDLINE, Epistemonikos and Cochrane Database of Systematic Reviews were searched for overviews that: synthesized reviews of health interventions and conducted systematic searches. Overlap was defined as: duplication of PICO eligibility criteria, and not reported as an update nor a replication. We categorized overview topics according to 22 WHO ICD-10 medical classifications, overviews as broad or narrow in scope, and overlap as identical, nearly identical, partial, or subsumed. Subsummation was defined as when broad overviews subsumed the populations, interventions and at least one outcome of another overview. Of 541 overviews included, 169 (31%) overlapped across similar PICO, fell within 13 WHO ICD-10 medical classifications, and 62 topics. 148/169 (88%) overlapping overviews were broad in scope. Fifteen overviews were classified as having nearly identical overlap (9%); 123 partial overlap (73%), and 31 subsumed (18%) others. One third of overviews overlapped in content and a majority covered broad topic areas. A multiplicity of overviews on the same topic adds to the ongoing waste of research resources, time, and effort across medical disciplines. Authors of overviews can use this study and the sample of overviews to identify gaps in the evidence for future analysis, and topics that are already studied, which do not need to be duplicated.

A Large-Scale Retrospective Study on Thrombocytopenia Associated with Beta-Lactam Antibiotics.

While the ability for beta-lactams (BL) to induce thrombocytopenia (TCP) is well understood, their association is not well quantified in the general population. Despite this, when platelets drop in the clinical setting, BL are frequently substituted for alternative antibiotics, leading to suboptimal outcomes. Here, we present a large-scale, retrospective study on the association of TCP and BL when compared to alternative non beta-lactam (nBL) therapy. All adult inpatients who received at least one antibiotic between 2008 and 2021 were included. Incidence of TCP in the 30 days following antibiotic administration was compared across patients receiving exclusively BLs vs nBLs as well as with each antibiotic subclass permutation following propensity score matching. There is a mild, though statistically significant increase in TCP risk for BL when compared to alternative nBL therapy. Risks and benefits should be considered prior to switching off BL therapy if clinically indicated.

The Impact of Surgeon Adherence to Preoperative Optimization of Hernia Repairs.

BACKGROUND: At the patient level, optimizing risk factors before surgery is a proven approach to improve patient outcomes after hernia repair. However, nearly 25% of patients are not adequately optimized before surgery. It is currently unknown how surgeon-level adherence to preoperative optimization impacts postoperative outcomes. In this context, we evaluated the association between surgeon adherence to optimization practices and surgeon-level postoperative outcomes. MATERIALS AND METHODS: Michigan Surgical Quality Collaborative data from 2014 to 2018 was analyzed to examine rates of surgeon adherence to preoperative optimization when performing elective ventral and incisional hernia repair. Adherence was defined as operating on patients who were nontobacco users with a body mass index >18.5 kg/m2 and <40 kg/m2. Surgeons were assigned a risk- and reliability-adjusted adherence rate which was used to divide surgeons into tertiles. Outcomes were compared between adherence tertiles. RESULTS: Across 70 hospitals in Michigan, 15,016 patients underwent ventral and incisional hernia repair, cared for by 454 surgeons. Surgeon adherence to preoperative optimization ranged from 51% to 76%. Surgeons in the lowest optimization tertile had higher rates of emergency department visits (8.78% versus 7.05% versus 7.03%, P < 0.001), serious complications (2.12% versus 1.56% versus 1.84%, P = 0.041), and any complication (4.08% versus 3.37% versus 4.04%, P = 0.043), than middle and high optimization tertiles. CONCLUSIONS: Surgeons' clinical outcomes, including complication rates, are affected by the proportion of their patients who are preoperatively optimized with regard to obesity and tobacco use. These results suggest that surgeons can improve their postoperative outcomes by addressing these issues before surgery.

Wireless, soft electronics for rapid, multisensor measurements of hydration levels in healthy and diseased skin.

Precise, quantitative measurements of the hydration status of skin can yield important insights into dermatological health and skin structure and function, with additional relevance to essential processes of thermoregulation and other features of basic physiology. Existing tools for determining skin water content exploit surrogate electrical assessments performed with bulky, rigid, and expensive instruments that are difficult to use in a repeatable manner. Recent alternatives exploit thermal measurements using soft wireless devices that adhere gently and noninvasively to the surface of the skin, but with limited operating range (∼1 cm) and high sensitivity to subtle environmental fluctuations. This paper introduces a set of ideas and technologies that overcome these drawbacks to enable high-speed, robust, long-range automated measurements of thermal transport properties via a miniaturized, multisensor module controlled by a long-range (∼10 m) Bluetooth Low Energy system on a chip, with a graphical user interface to standard smartphones. Soft contact to the surface of the skin, with almost zero user burden, yields recordings that can be quantitatively connected to hydration levels of both the epidermis and dermis, using computational modeling techniques, with high levels of repeatability and insensitivity to ambient fluctuations in temperature. Systematic studies of polymers in layered configurations similar to those of human skin, of porcine skin with known levels of hydration, and of human subjects with benchmarks against clinical devices validate the measurement approach and associated sensor hardware. The results support capabilities in characterizing skin barrier function, assessing severity of skin diseases, and evaluating cosmetic and medication efficacy, for use in the clinic or in the home.

Evaluation of the Initiation Timing of Hydrocortisone in Adult Patients With Septic Shock.

INTRODUCTION: Clinical studies evaluating the use of hydrocortisone in patients with septic shock are heterogeneous in design with conflicting results. The appropriate time in which to initiate hydrocortisone after shock onset is unknown. This study sought to compare clinical outcomes including vasopressor duration and mortality in patients with septic shock who received hydrocortisone based on timing of initiation after shock onset. METHODS: Retrospective cohort study of patients between 2011 and 2017 admitted to 10 medical, surgical, and neurosciences intensive care units (ICUs) at a large, tertiary care academic medical center. Adult patients with vasopressor-dependent septic shock who received hydrocortisone were included. Patients were divided into five timing cohorts based on time after shock onset: 0-6, 6-12, 12-24, 24-48, or >48 h. The primary outcome was days alive and free from vasopressors. RESULTS: One thousand four hundred seventy patients were included: 567 (38.6%) received hydrocortisone between 0 and 6 h, 231 (15.7%) 6 and 12 h, 260 (17.7%) 12 and 24 h, 195 (13.3%) 24 and 48 h, and 217 (14.8%) >48 h after shock onset. Patients who received hydrocortisone earlier were sicker at baseline with higher APACHE III scores, lactate concentrations, and norepinephrine requirements. On univariate analysis, days alive and free from vasopressors did not significantly differ amongst the timing groups (median 3.3 days for 0-6 h; 1.9 for 6-12 h; 1.9 for 12-24 h; 0 for 24-48 h; 0 for >48 h; P = 0.39); similarly, ICU mortality did not differ. On multivariable linear regression, timing of hydrocortisone was independently associated with more days alive and free from vasopressors when comparing initiation within 0 to 6 h with >48 h (beta-coefficient 2.8 days [95% CI 0.8-4.7]), 6-12 h with >48 h (2.5 days [95% CI 0.2-4.7]), and 12-24 h with >48 h (2.3 days [95% CI 0.2-4.5]). On multivariable logistic regression, timing of hydrocortisone was associated with reduced ICU mortality when comparing receipt within 0 to 6 h of shock onset to >48 h after shock onset (OR 0.6, 95% CI 0.4-0.8). CONCLUSIONS: In patients in whom hydrocortisone is prescribed for vasopressor-dependent septic shock, timing is crucial and hydrocortisone should be started within the first 12 h after shock onset.