Cancer Incidence and Survival Among Patients Following an Acute Coronary Syndrome.

To examine the role of acute coronary syndrome (ACS) in subsequent cancer incidence and survival, 2 cohorts of patients hospitalized with ACS were matched 1:1 by gender and age (±3 years) to cardiovascular disease (CVD)-free patients from 2 cycles of the Israeli National Health and Nutrition Surveys. Data on all-cause mortality were retrieved from national registries. Cancer incidence with death treated as a competing event, overall survival, and mortality risk associated with incident cancer as a time-dependent variable were compared between the groups. Our cohort included 2,040 cancer-free matched pairs (mean age of 60±14 years, 42.5% women). Despite higher rates of smokers and patients with hypertension and diabetes mellitus, 10-year cumulative cancer incidence was significantly lower in the ACS group compared with CVD-free group (8.0% vs 11.4%, p = 0.02). This decreased risk was more pronounced in women than men (pinteraction = 0.05). Although being free of CVD meant a significant (p <0.001) survival advantage in the general cohort, this advantage faded once a cancer diagnosis was made (p = 0.80). After adjustment for sociodemographic and clinical covariates, the hazard ratios for mortality associated with a cancer diagnosis were 2.96 (95% confidence interval: 2.36 to 3.71) in the ACS group versus 6.41 (95% confidence interval: 4.96 to 8.28) in the CVD-free group (Pinteraction<0.001). In conclusion, in this matched cohort, ACS was associated with a lower risk of cancer and mitigated the excess risk of mortality associated with cancer incidence.

Burnout and Wellness Strategies Used by Academic Physiatry Programs: An Analysis and Perspective From the AAP Chairs Council.

ABSTRACT: Physiatrists are at elevated risk of burnout, a work-related exhaustion syndrome resulting from chronic stress associated with emotionally draining work demands. The high reported rate of burnout in physical medicine and rehabilitation led the Association of Academic Physiatrists Chair Council to convene a workgroup to address burnout among academic physical medicine and rehabilitation physicians. The council recognizes that leaders of departments are accountable for all organizational stakeholders, including faculty, trainees, and staff. Department leaders are expected to understand and effectively manage the drivers of burnout among stakeholders. The workgroup identified several opportunities, including identifying and disseminating effective burnout mitigation across US academic medical center physical medicine and rehabilitation programs. As a result, in 2019, a work group conducted a survey of US academic physical medicine and rehabilitation program leaders to ascertain the use of strategies for reducing physician burnout. With the aim of identifying, educating, and advancing the development of effective interventions to address burnout among academic physical medicine and rehabilitation departments, the Association of Academic Physiatrists Chair Council advocates for increased education and utilization of effective strategies aimed at promoting physician well-being across organizational levels (national, organizational, work unit, and individual).

Public responses to foreign protectionism: Evidence from the US-China trade war.

America's recent turn towards protectionism has raised concerns over the future viability of the liberal international trading system. This study examines how and why public attitudes towards international trade change when one's country is targeted by protectionist measures from abroad. To address this question, we fielded three original survey experiments in the country most affected by US protectionism: China. First, we find consistent evidence that US protectionism reduces support for trade among Chinese citizens. We replicate this finding in parallel experiments on technology cooperation, and provide further external validation with a survey experiment in Argentina. Second, we show that responses to US protectionism reflect both a "direct reciprocity" logic, whereby citizens want to retaliate against the US specifically, as well as a "generalized reciprocity" logic that reduces support for trade on a broader, systemic, basis. Supplementary Information: The online version contains supplementary material available at 10.1007/s11558-022-09468-y.

The role of models in the covid-19 pandemic.

Mathematical and statistical models have played an important role in the analysis of data from COVID-19. They are important for tracking the progress of the pandemic, for understanding its spread in the population, and perhaps most significantly for forecasting the future course of the pandemic and evaluating potential policy options. This article describes the types of models that were used by research teams in Israel, presents their assumptions and basic elements, and illustrates how they were used, and how they influenced decisions. The article grew out of a "modelists' dialog" organized by the Israel National Institute for Health Policy Research with participation from some of the leaders in the local modeling effort.

Association between objective measures and parent-reported measures of child tobacco smoke exposure: A secondary data analysis of four trials.

INTRODUCTION: Tobacco smoke exposure (TSE) harms children and adults. Studies of childhood TSE exposure often relies on parental reports, but may benefit from objective measures. The objective of our study was to study the relationship between reported and objective measures of TSE. METHODS: We analyzed data from four intervention trials, conducted in clinical or community settings, to identify objective measures most closely associated with parent-reported measures and the optimal set of parent-reported measures for predicting objective measures. We also assessed whether there was a learning curve in reported exposure over time, and the importance of replicate biomarker measures. RESULTS: Correlations between objective and parent-reported measures of child TSE were modest at best, ranging from zero to 0.41. Serum cotinine and urinary cotinine were most strongly associated with parental reports. Parental questions most closely related to biomarkers were number of cigarettes and home smoking rules; together these formed the best set of predictive questions. No trial included all objective measures and all questions, precluding definitive statements about relative advantages. Within-subject repeatability of biomarker measures varied across studies, suggesting that direct pilot data are needed to assess the benefit of replicate measurements. CONCLUSIONS: Improvements in objective and parent-reported child exposure measurements are needed to accurately monitor child TSE, evaluate efforts to reduce such exposure, and better protect child health.

Gravity-based patterning of osteogenic factors to preserve bone structure after osteochondral injury in a large animal model.

Chondral and osteochondral repair strategies are limited by adverse bony changes that occur after injury. Bone resorption can cause entire scaffolds, engineered tissues, or even endogenous repair tissues to subside below the cartilage surface. To address this translational issue, we fabricated thick-shelled poly(D,L-lactide-co-glycolide) microcapsules containing the pro-osteogenic agents triiodothyronine andß-glycerophosphate, and delivered these microcapsules in a large animal model of osteochondral injury to preserve bone structure. We demonstrate that the developed microcapsules rupturedin vitrounder increasing mechanical loads, and readily sink within a liquid solution, enabling gravity-based patterning along the osteochondral surface. In a large animal, these mechanically-activated microcapsules (MAMCs) were assessed through two different delivery strategies. Intra-articular injection of control MAMCs enabled fluorescent quantification of MAMC rupture and cargo release in a synovial joint setting over timein vivo. This joint-wide injection also confirmed that the MAMCs do not elicit an inflammatory response. In the contralateral hindlimbs, chondral defects were created, MAMCs were patternedin situ, and nanofracture (Nfx), a clinically utilized method to promote cartilage repair, was performed. The Nfx holes enabled marrow-derived stromal cells to enter the defect area and served as repeatable bone injury sites to monitor over time. Animals were evaluated one and two weeks after injection and surgery. Analysis of injected MAMCs showed that bioactive cargo was released in a controlled fashion over two weeks. A bone fluorochrome label injected at the time of surgery displayed maintenance of mineral labeling in the therapeutic group, but resorption in both control groups. Alkaline phosphatase (AP) staining at the osteochondral interface revealed higher AP activity in defects treated with therapeutic MAMCs. Overall, this study develops a gravity-based approach to pattern bioactive factors along the osteochondral interface, and applies this novel biofabrication strategy to preserve bone structure after osteochondral injury.

Investigating Patient-Level Radiation Exposure in Hand and Wrist Fracture Surgery.

BACKGROUND: Although occupational exposure to radiation has been previously studied in the hand surgery literature, there is a paucity of studies looking at radiation exposure to the patient during fluoroscopy-guided hand surgery. We aimed to describe the level of radiation experienced by patients undergoing common hand and wrist fracture fixation and to identify risk factors for increased radiation exposure. METHODS: We performed a retrospective review of patients at a single institution who underwent fracture fixation of the hand, wrist, or forearm requiring mini c-arm fluoroscopic guidance from 2016 to 2020. Data points collected included patient demographics, procedural details, and indicators of radiation exposure including dose-area product (DAP), total intraoperative images, and total fluoroscopy time. Effective dose (ED) was calculated using DAP, field size, and a previously established conversion factor. RESULTS: The final sample included 361 patients with an average age of 46 years. Procedures included fixation of forearm fractures (3.3%), distal radius fractures (35.7%), metacarpal fractures (30.8%), and phalangeal fractures (30.2%). The median number of intraoperative images acquired was 36, median total fluoroscopy time was 43 seconds, median DAP was 4.8 cGycm2, and median ED was 0.13 µSv. Distal (metacarpal and phalangeal) fractures required more intraoperative images and longer total fluoroscopy time (49 images, 61 seconds) compared with proximal (forearm and distal radius) fractures (39 images, 47 seconds) (images, P = 0.004; exposure time, P = 0.004). However, distal fractures had a lower average ED compared with proximal fractures (0.15 vs 0.19 µSv, P = 0.020). When compared with open procedures, percutaneous procedures had higher DAPs (8.8 vs 4.9 cGycm2, P < 0.001), higher ED (0.22 vs 0.15 µSv, P < 0.001), more intraoperative images (65 vs 36 images, P < 0.001), and longer total fluoroscopy time (81.9 vs 44.4 seconds, P < 0.001). CONCLUSIONS: Patient-level radiation exposure during fluoroscopy-guided hand and wrist procedures is low relative to other common imaging modalities, such as dental radiographs, chest x-rays, and computed tomography scans, and is comparable with less than a few hours of natural background radiation exposure, highlighting the overall safety of this important technology. Further study should be performed to establish reference ranges, which could lead to improved patient counseling and evidence-based guidelines on patient shielding.

Incisional Hernia Repair During Cesarean Section.

This case report follows the treatment of a 32-year-old Hispanic female who developed an incisional hernia after her first cesarean delivery. During her second cesarean section, the ventral hernia needed to be repaired due to the inability to approximate the fascial ring and close the abdominal wall. Hernias, in general, are uncommon during pregnancy and given that ventral hernias are virtually nonexistent in this patient population, we are left to deal with a host of different obstacles in their diagnosis and treatment.

Statistical Emulation of Neural Simulators: Application to Neocortical L2/3 Large Basket Cells.

Many scientific systems are studied using computer codes that simulate the phenomena of interest. Computer simulation enables scientists to study a broad range of possible conditions, generating large quantities of data at a faster rate than the laboratory. Computer models are widespread in neuroscience, where they are used to mimic brain function at different levels. These models offer a variety of new possibilities for the neuroscientist, but also numerous challenges, such as: where to sample the input space for the simulator, how to make sense of the data that is generated, and how to estimate unknown parameters in the model. Statistical emulation can be a valuable complement to simulator-based research. Emulators are able to mimic the simulator, often with a much smaller computational burden and they are especially valuable for parameter estimation, which may require many simulator evaluations. This work compares different statistical models that address these challenges, and applies them to simulations of neocortical L2/3 large basket cells, created and run with the NEURON simulator in the context of the European Human Brain Project. The novelty of our approach is the use of fast empirical emulators, which have the ability to accelerate the optimization process for the simulator and to identify which inputs (in this case, different membrane ion channels) are most influential in affecting simulated features. These contributions are complementary, as knowledge of the important features can further improve the optimization process. Subsequent research, conducted after the process is completed, will gain efficiency by focusing on these inputs.

The role of statisticians in the response to COVID-19 in Israel: a holistic point of view.

The COVID-19 pandemic cast a dramatic spotlight on the use of data as a fundamental component of good decision-making. Evaluating and comparing alternative policies required information on concurrent infection rates and insightful analysis to project them into the future. Statisticians in Israel were involved in these processes early in the pandemic in some silos as an ad-hoc unorganized effort. Informal discussions within the statistical community culminated in a roundtable, organized by three past presidents of the Israel Statistical Association, and hosted by the Samuel Neaman Institute in April 2021. The meeting was designed to provide a forum for exchange of views on the profession's role during the COVID-19 pandemic, and more generally, on its influence in promoting evidence-based public policy. This paper builds on the insights and discussions that emerged during the roundtable meeting and presents a general framework, with recommendations, for involving statisticians and statistics in decision-making.

Excess mortality in Israel associated with COVID-19 in 2020-2021 by age group and with estimates based on daily mortality patterns in 2000-2019.

BACKGROUND: We aimed to build a basic daily mortality curve in Israel based on 20-year data accounting for long-term and annual trends, influenza-like illness (ILI) and climate factors among others, and to use the basic curve to estimate excess mortality during 65 weeks of the COVID-19 pandemic in 2020-2021 stratified by age groups. METHODS: Using daily mortality counts for the period 1 January 2000 to 31 December 2019, weekly ILI counts, daily climate and yearly population sizes, we fitted a quasi-Poisson model that included other temporal covariates (a smooth yearly trend, season, day of week) to define a basic mortality curve. Excess mortality was calculated as the difference between the observed and expected deaths on a weekly and periodic level. Analyses were stratified by age group. RESULTS: Between 23 March 2020 and 28 March 2021, a total of 51 361 deaths were reported in Israel, which was 12% higher than the expected number for the same period (expected 45 756 deaths; 95% prediction interval, 45 325-46 188; excess deaths, 5605). In the same period, the number of COVID-19 deaths was 6135 (12% of all observed deaths), 9.5% larger than the estimated excess mortality. Stratification by age group yielded a heterogeneous age-dependent pattern. Whereas in ages 90+ years (11% excess), 100% of excess mortality was attributed to COVID-19, in ages 70-79 years there was a greater excess (21%) with only 82% attributed to COVID-19. In ages 60-69 and 20-59 years, excess mortality was 14% and 10%, respectively, and the number of COVID-19 deaths was higher than the excess mortality. In ages 0-19 years, we found 19% fewer deaths than expected. CONCLUSION: The findings of an age-dependent pattern of excess mortality may be related to indirect pathways in mortality risk, specifically in ages <80 years, and to the implementation of the lockdown policies, specifically in ages 0-19 years with lower deaths than expected.

JAK2V617F Is a Risk Factor for TIA/Stroke in Young Patients.

The objective of this study was to assess the risk of arterial thrombosis in patients who harbor the JAK2V617F allele burden ≥1% detected during workup for myeloproliferative neoplasms (MPNs). We conducted a large cross-sectional analysis consisted of 5,220 patients who were tested for JAK2V617F and 1,047,258 people matched in age from health care insurance provider, taking into account age, sex, hypertension, diabetes, atrial fibrillation. Compared with noncarriers, mutation carriers were older, less likely to be current or past smokers and had lower body mass index. There was no significant difference between the groups regarding myocardial infarction and peripheral vascular disease. However, JAK2V617F ≥1% at age 34 to 54 years was associated with eightfold more likely to have transient ischemic attack (TIA)/stroke history unrelated to hypertension, diabetes, or atrial fibrillation. Association of JAK2V617F with TIA/stroke was also observed in the older age group, albeit a weaker association and not statistically significant. Prevalence of TIA/stroke was higher in patients with JAK2V617F negative, with odds ratio of 3.93 when compared with the general population after confounder adjustments. Further research is warranted to verify the relation between allele burden of JAK2V617F mutation and TIA/stroke and the role of JAK2V617F per se as a risk factor for arterial thrombosis in the absence of overt MPN. Also, consideration should be paid to the screened group with JAK2V617F negative due to the high incidence of TIA/stroke among them in comparison to the general population.

Association of BNT162b2 COVID-19 Vaccination During Pregnancy With Neonatal and Early Infant Outcomes.

Importance: Pregnant women were excluded from the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine (Pfizer-BioNTech) preauthorization trial. Therefore, observational data on vaccine safety for prenatally exposed newborns are critical to inform recommendations on maternal immunization. Objective: To examine whether BNT162b2 mRNA vaccination during pregnancy is associated with adverse neonatal and early infant outcomes among the newborns. Design, Setting, and Participants: Population-based cohort study comprising all singleton live births in March through September 2021, within a large state-mandated health care organization in Israel, followed up until October 31, 2021. Exposure: Maternal BNT162b2 mRNA vaccination during pregnancy. Main Outcomes and Measures: Risk ratios (RR) of preterm birth, small birth weight for gestational age (SGA), congenital malformations, all-cause hospitalizations, and infant death. Stabilized inverse probability weighting was used to adjust for maternal age, timing of conception, parity, socioeconomic status, population subgroup, and maternal influenza immunization status. Results: The cohort included 24 288 eligible newborns (49% female, 96% born at ≥37 weeks' gestation), of whom 16 697 were exposed (n = 2134 and n = 9364 in the first and second trimesters, respectively) to maternal vaccination in utero. Median (IQR) follow-up after birth was 126 days (76-179) among exposed and 152 days (88-209) among unexposed newborns. No substantial differences were observed in preterm birth rates between exposed and unexposed newborns (RR = 0.95; 95% CI, 0.83-1.10) or SGA (RR = 0.97; 95% CI, 0.87-1.08). No significant differences were observed in the incidence of all-cause neonatal hospitalizations (RR = 0.99; 95% CI, 0.88-1.12), postneonatal hospitalizations after birth (RR = 0.95; 95% CI, 0.84-1.07), congenital anomalies (RR = 0.69; 95% CI, 0.44-1.04), or infant mortality over the study period (RR = 0.84; 95% CI, 0.43-1.72). Conclusions and Relevance: This large population-based study found no evident differences between newborns of women who received BNT162b2 mRNA vaccination during pregnancy, vs those of women who were not vaccinated, and contributes to current evidence in establishing the safety of prenatal vaccine exposure to the newborns. Interpretation of study findings is limited by the observational design.

Effective bubble-based testing for SARS-CoV-2 using swab-pooling.

OBJECTIVES: Despite the success in developing COVID-19 vaccines, containment of the disease is obstructed worldwide by vaccine production bottlenecks, logistics hurdles, vaccine refusal, transmission through unvaccinated children, and the appearance of new viral variants. This underscores the need for effective strategies for identifying carriers/patients, which was the main aim of this study. METHODS: We present a bubble-based PCR testing approach using swab-pooling into lysis buffer. A bubble is a cluster of people who can be periodically tested for SARS-CoV-2 by swab-pooling. A positive test of a pool mandates quarantining each of its members, who are then individually tested while in isolation to identify the carrier(s) for further epidemiological contact tracing. RESULTS: We tested an overall sample of 25 831 individuals, divided into 1273 bubbles, with an average size of 20.3 ± 7.7 swabs/test tube, obtaining for all pools (≤37 swabs/pool) a specificity of 97.5% (lower bound 96.6%) and a sensitivity of 86.3% (lower bound 78.2%) and a post hoc analyzed sensitivity of 94.6% (lower bound 86.7%) and a specificity of 97.2% (lower bound 96.2%) in pools with ≤25 swabs, relative to individual testing. DISCUSSION: This approach offers a significant scale-up in sampling and testing throughput and savings in testing cost, without reducing sensitivity or affecting the standard PCR testing laboratory routine. It can be used in school classes, airplanes, hospitals, military units, and workplaces, and may be applicable to future pandemics.

Atraumatic Index Finger Flexor Tendon Rupture as a Presenting Sign of Capitate Osteonecrosis: A Report of 2 Cases.

CASE: We present 2 cases of spontaneous index finger (IF) flexor tendon ruptures because of previously undiagnosed osteonecrosis (OA) of the capitate. Imaging revealed fragmentation of the capitate, and patients were treated with excision or fixation of the bony fragments with tendon repair. At the final follow-up, both patients had functional digital range of motion. CONCLUSIONS: OA of the capitate is relatively rare and may present as atraumatic (IF) flexor tendon ruptures because of attritional wear when associated with bony fragmentation.

An impact of lipid profile and lipid lowering drugs on ≥70 year olds of an upper socioeconomic class: a retrospective cohort study.

BACKGROUND: Life expectancy has greatly increased, generating an improvement in screening programs for disease prevention, lifesaving drugs and medical devices. The impact of lowering low-density lipoprotein cholesterol (LDL-C) in the very elderly is not well-established. Our aim was to explore the association of LDL-C, high density lipoprotein cholesterol (HDL-C) and lipid lowering drugs (LLDs) on cognitive decline, malignancies and overall survival. METHODS: This was a retrospective cohort study. Our study comprised 1498 (72.7%) males and 561 (27.3%) females, aged ≥70 who had attended the Institute for Medical Screening (IMS), Sheba Medical Center, Israel at least twice during 2013-2019. Data were obtained from the computerized database of the IMS. A manual quality control to identify potential discrepancies was performed. RESULTS: Overall, 6.3% of the subjects treated with LLDs (95/1421) versus 4.2% not treated (28/638), cognitively declined during the study years. No statistically significant effects of LDL-C, HDL-C and LLDs on cognitive decline were observed after correcting for age, prior stroke and other vascular risk factors. With regard to cancer, after adjusting for confounders and multiple inferences, no definite relationships were found. CONCLUSIONS: This analysis of an elderly, high socioeconomic status cohort suggests several relationships between the use of LLDs and health outcomes, some beneficial, especially, with regard to certain types of cancer, but with a higher risk of cognitive decline. Further studies are warranted to clarify the health effects of these medications in the elderly.

Pre-diagnosis thyroid hormone dysfunction is associated with cancer mortality.

Research on the association between thyroid hormone levels and cancer mortality remains limited and inconclusive. We determined the relation of thyroid stimulating hormone (TSH), free T4 (FT4), and free T3 (FT3) levels with mortality in overall cancer and specific tumor types. Thyroid hormone levels 1-5 years prior to cancer diagnosis, as well as multiple clinical and demographic parameters, were retrospectively collected for 10,325 Israeli cancer patients, diagnosed between 2000 and 2016. Patients treated with thyroid altering medications were excluded. Cancer diagnosis was determined via the Israel National Cancer Registry. Multivariate-adjusted Cox proportional hazards model was used to assess the hazard ratios (HRs) based on thyroid hormone function for cancer mortality. A total of 5265 patients died during the follow-up period (median of 4.4 years). TSH, FT4, and FT3 levels in the hypothyroid range were associated with increase in overall mortality (adjusted HR 1.20, 1.74, 1.87, respectively). We further analyzed the association between TSH and mortality in 14 cancer subgroups. Specifically, TSH in both the hyperthyroid and hypothyroid range was associated with melanoma mortality (adjusted HR 2.20, 4.47, respectively). In conclusion, pre-diagnosis of thyroid dysfunction is associated with increased cancer mortality, a relation likely driven by specific cancer types. These findings suggest that thyroid hormones may potentially serve as prognostic markers in cancer.

Association Between BNT162b2 Vaccination and Incidence of SARS-CoV-2 Infection in Pregnant Women.

Importance: Data on BNT162b2 messenger RNA (mRNA) vaccine (Pfizer-BioNTech) effectiveness and safety in pregnancy are currently lacking because pregnant women were excluded from the phase 3 trial. Objective: To assess the association between receipt of BNT162b2 mRNA vaccine and risk of SARS-CoV-2 infection among pregnant women. Design, Setting, and Participants: This was a retrospective cohort study within the pregnancy registry of a large state-mandated health care organization in Israel. Pregnant women vaccinated with a first dose from December 19, 2020, through February 28, 2021, were 1:1 matched to unvaccinated women by age, gestational age, residential area, population subgroup, parity, and influenza immunization status. Follow-up ended on April 11, 2021. Exposures: Exposure was defined by receipt of the BNT162b2 mRNA vaccine. To maintain comparability, nonexposed women who were subsequently vaccinated were censored 10 days after their exposure, along with their matched pair. Main Outcomes and Measures: The primary outcome was polymerase chain reaction-validated SARS-CoV-2 infection at 28 days or more after the first vaccine dose. Results: The cohort included 7530 vaccinated and 7530 matched unvaccinated women, 46% and 33% in the second and third trimester, respectively, with a mean age of 31.1 years (SD, 4.9 years). The median follow-up for the primary outcome was 37 days (interquartile range, 21-54 days; range, 0-70). There were 118 SARS-CoV-2 infections in the vaccinated group and 202 in the unvaccinated group. Among infected women, 88 of 105 (83.8%) were symptomatic in the vaccinated group vs 149 of 179 (83.2%) in the unvaccinated group (P ≥ .99). During 28 to 70 days of follow-up, there were 10 infections in the vaccinated group and 46 in the unvaccinated group. The hazards of infection were 0.33% vs 1.64% in the vaccinated and unvaccinated groups, respectively, representing an absolute difference of 1.31% (95% CI, 0.89%-1.74%), with an adjusted hazard ratio of 0.22 (95% CI, 0.11-0.43). Vaccine-related adverse events were reported by 68 patients; none was severe. The most commonly reported symptoms were headache (n = 10, 0.1%), general weakness (n = 8, 0.1%), nonspecified pain (n = 6, <0.1%), and stomachache (n = 5, <0.1%). Conclusions and Relevance: In this retrospective cohort study of pregnant women, BNT162b2 mRNA vaccination compared with no vaccination was associated with a significantly lower risk of SARS-CoV-2 infection. Interpretation of study findings is limited by the observational design.