It is important for SARS-CoV-2 vaccine providers, vaccine recipients, and those not yet vaccinated to be well informed about vaccine side effects. We sought to estimate the risk of post-vaccination venous thromboembolism (VTE) to meet this need.

We conducted a retrospective cohort study to quantify excess VTE risk associated with SARS-CoV-2 vaccination in US veterans age 45 and older using data from the Department of Veterans Affairs (VA) National Surveillance Tool. The vaccinated cohort received at least one dose of a SARS-CoV-2 vaccine at least 60 days prior to 3/06/22 (N = 855,686). The control group was those not vaccinated (N = 321,676). All patients were COVID-19 tested at least once before vaccination with a negative test. The main outcome was VTE documented by ICD10-CM codes.

Vaccinated persons had a VTE rate of 1.3755 (CI: 1.3752–1.3758) per thousand, which was 0.1 percent over the baseline rate of 1.3741 (CI: 1.3738–1.3744) per thousand in the unvaccinated patients, or 1.4 excess cases per 1,000,000. All vaccine types showed a minimal increased rate of VTE (rate of VTE per 1000 was 1.3761 (CI: 1.3754–1.3768) for Janssen; 1.3757 (CI: 1.3754–1.3761) for Pfizer, and for Moderna, the rate was 1.3757 (CI: 1.3748–1.3877)). The tiny differences in rates comparing either Janssen or Pfizer vaccine to Moderna were statistically significant (p < 0.001). Adjusting for age, sex, BMI, 2-year Elixhauser score, and race, the vaccinated group had a minimally higher relative risk of VTE as compared to controls (1.0009927 CI: 1.007673–1.0012181; p < 0.001).

The results provide reassurance that there is only a trivial increased risk of VTE with the current US SARS-CoV-2 vaccines used in veterans older than age 45. This risk is significantly less than VTE risk among hospitalized COVID-19 patients. The risk-benefit ratio favors vaccination, given the VTE rate, mortality, and morbidity associated with COVID-19 infection.

Many clinical trials leverage real-world data. Typically, these data are manually abstracted from electronic health records (EHRs) and entered into electronic case report forms (CRFs), a time and labor-intensive process that is also error-prone and may miss information. Automated transfer of data from EHRs to eCRFs has the potential to reduce data abstraction and entry burden as well as improve data quality and safety.

We conducted a test of automated EHR-to-CRF data transfer for 40 participants in a clinical trial of hospitalized COVID-19 patients. We determined which coordinator-entered data could be automated from the EHR (coverage), and the frequency with which the values from the automated EHR feed and values entered by study personnel for the actual study matched exactly (concordance).

The automated EHR feed populated 10,081/11,952 (84%) coordinator-completed values. For fields where both the automation and study personnel provided data, the values matched exactly 89% of the time. Highest concordance was for daily lab results (94%), which also required the most personnel resources (30 minutes per participant). In a detailed analysis of 196 instances where personnel and automation entered values differed, both a study coordinator and a data analyst agreed that 152 (78%) instances were a result of data entry error.

An automated EHR feed has the potential to significantly decrease study personnel effort while improving the accuracy of CRF data.

To examine differences in surgical practices between salaried and fee-for-service (FFS) surgeons for two common degenerative spine conditions. Surgeons may offer different treatments for similar conditions on the basis of their compensation mechanism.

The study assessed the practices of 63 spine surgeons across eight Canadian provinces (39 FFS surgeons and 24 salaried) who performed surgery for two lumbar conditions: stable spinal stenosis and degenerative spondylolisthesis. The study included a multicenter, ambispective review of consecutive spine surgery patients enrolled in the Canadian Spine Outcomes and Research Network registry between October 2012 and July 2018. The primary outcome was the difference in type of procedures performed between the two groups. Secondary study variables included surgical characteristics, baseline patient factors, and patient-reported outcome.

For stable spinal stenosis (n = 2234), salaried surgeons performed statistically fewer uninstrumented fusion (p < 0.05) than FFS surgeons. For degenerative spondylolisthesis (n = 1292), salaried surgeons performed significantly more instrumentation plus interbody fusions (p < 0.05). There were no statistical differences in patient-reported outcomes between the two groups.

Surgeon compensation was associated with different approaches to stable lumbar spinal stenosis and degenerative lumbar spondylolisthesis. Salaried surgeons chose a more conservative approach to spinal stenosis and a more aggressive approach to degenerative spondylolisthesis, which highlights that remuneration is likely a minor determinant in the differences in practice of spinal surgery in Canada. Further research is needed to further elucidate which variables, other than patient demographics and financial incentives, influence surgical decision-making.

The coronavirus disease 2019 (COVID-19) pandemic has required healthcare systems to meet new demands for rapid information dissemination, resource allocation, and data reporting. To help address these challenges, our institution leveraged electronic health record (EHR)–integrated clinical pathways (E-ICPs), which are easily understood care algorithms accessible at the point of care.

To describe our institution’s creation of E-ICPs to address the COVID-19 pandemic, and to assess the use and impact of these tools.

Urban academic medical center with adult and pediatric hospitals, emergency departments, and ambulatory practices.

Using the E-ICP processes and infrastructure established at our institution as a foundation, we developed a suite of COVID-19–specific E-ICPs along with a process for frequent reassessment and updating. We examined the development and use of our COVID-19–specific pathways for a 6-month period (March 1–September 1, 2020), and we have described their impact using case studies.

In total, 45 COVID-19–specific pathways were developed, pertaining to triage, diagnosis, and management of COVID-19 in diverse patient settings. Orders available in E-ICPs included those for isolation precautions, testing, treatments, admissions, and transfers. Pathways were accessed 86,400 times, with 99,081 individual orders were placed. Case studies demonstrate the impact of COVID-19 E-ICPs on stewardship of resources, testing optimization, and data reporting.

E-ICPs provide a flexible and unified mechanism to meet the evolving demands of the COVID-19 pandemic, and they continue to be a critical tool leveraged by clinicians and hospital administrators alike for the management of COVID-19. Lessons learned may be generalizable to other urgent and nonurgent clinical conditions.

Hypersomnolence has been considered a prominent feature of seasonal affective disorder (SAD) despite mixed research findings. In the largest multi-season study conducted to date, we aimed to clarify the nature and extent of hypersomnolence in SAD using multiple measurements during winter depressive episodes and summer remission.

Sleep measurements assessed in individuals with SAD and nonseasonal, never-depressed controls included actigraphy, daily sleep diaries, retrospective self-report questionnaires, and self-reported hypersomnia assessed via clinical interviews. To characterize hypersomnolence in SAD we (1) compared sleep between diagnostic groups and seasons, (2) examined correlates of self-reported hypersomnia in SAD, and (3) assessed agreement between commonly used measurement modalities.

In winter compared to summer, individuals with SAD (n = 64) reported sleeping 72 min longer based on clinical interviews (p < 0.001) and 23 min longer based on actigraphy (p = 0.011). Controls (n = 80) did not differ across seasons. There were no seasonal or group differences on total sleep time when assessed by sleep diaries or retrospective self-reports (p's > 0.05). Endorsement of winter hypersomnia in SAD participants was predicted by greater fatigue, total sleep time, time in bed, naps, and later sleep midpoints (p's < 0.05).

Despite a winter increase in total sleep time and year-round elevated daytime sleepiness, the average total sleep time (7 h) suggest hypersomnolence is a poor characterization of SAD. Importantly, self-reported hypersomnia captures multiple sleep disruptions, not solely lengthened sleep duration. We recommend using a multimodal assessment of hypersomnolence in mood disorders prior to sleep intervention.

Data from randomized controlled trials (RCTs) are the primary source for health technology assessment (HTA) however these are limited by strict patient inclusion criteria, leading to concerns about whether treatment benefit estimates are accurate for all patients (generalizability). Real-World Data (RWD) have been proposed as a solution however as these are observational data there is additional potential for bias when estimating treatment effectiveness. To maximize the utility of RWD it is useful to consider the whole process of evidence generation and robustly address issues of feasibility and validity.

A series of complementary studies investigated whether population-based routinely collected health data from Scotland are suitable for estimating the effectiveness of chemotherapy for early breast cancer. Firstly, a prognostic score was validated in this population. Secondly, a comparison of RWD and randomized trial effectiveness estimates was made to investigate feasibility and validity of several methods – Propensity Score Matching (PSM), Instrumental variables (IV) and Regression Discontinuity. Finally, effectiveness estimates in trial underrepresented groups were produced.

PSM and IV were feasible and produced results in relatively close agreement with randomized data. Effectiveness estimates in trial underrepresented groups (women over 70 years and women with high comorbidity) were consistent with an approximate one-third reduction in the risk of death from breast cancer. This is equivalent to approximately a 3–4 percentage point difference in all cause mortality over 10 years in these groups.

RWD are a feasible for generating estimates of effectiveness of adjuvant chemotherapy in early stage breast cancer. The process of using RWD for this purpose should include careful assessment of data quality and comparison of alternative strategies for causal identification in the context of available randomized data.

Schizotypy is a putative risk phenotype for psychosis liability, but the overlap of its genetic architecture with schizophrenia is poorly understood.

We tested the hypothesis that dimensions of schizotypy (assessed with the SPQ-B) are associated with a polygenic risk score (PRS) for schizophrenia in a sample of 623 psychiatrically healthy, non-clinical subjects from the FOR2107 multi-centre study and a second sample of 1133 blood donors.

We did not find correlations of schizophrenia PRS with either overall SPQ or specific dimension scores, nor with adjusted schizotypy scores derived from the SPQ (addressing inter-scale variance). Also, PRS for affective disorders (bipolar disorder and major depression) were not significantly associated with schizotypy.

This important negative finding demonstrates that despite the hypothesised continuum of schizotypy and schizophrenia, schizotypy might share less genetic risk with schizophrenia than previously assumed (and possibly less compared to psychotic-like experiences).

Depression and mortality have been studied separately in patients with coronary heart disease (CHD) and in populations healthy at study inception. This does not allow comparisons across risk-factor groups based on the cross-classification of depression and CHD status. We prospectively examined the effects of depressive symptoms, assessed in 2002-2004, on all-cause and cardiovascular -mortality in a large sample of 5936 middle-aged participants, with and without established CHD, followed over 5.6 years

We created 4-risk-factor groups based on the cross classification of depressive symptoms and CHD status. The age-and-sex-adjusted hazard ratios for all causes death were 1.67-fold (p< 0.05) higher for participants with only CHD, 2.10-fold (p< 0.001) higher for those with only depressive symptoms and 4.99-fold (p< 0.001) higher for those with both CHD and depressive symptoms when compared to participants without either condition. The two latter risk-factor groups remained at increased risk after adjustments for relevant confounders. Further comparisons indicated that the risks of all-cause death were also higher, but to a lesser extent, for participants with both depressive-symptoms and CHD when compared to those with only one of these conditions. These associations were also observed for cardiovascular mortality

This study provides evidence that depressive symptoms are associated with an increased risk of all-cause and CVD death and that this risk is particularly marked in depressive participants with co-morbid CHD. Several clinical guidelines have recommended screening, referral, and treatment of depression in primary and cardiovascular care units. These findings suggest that these recommendations need further consideration.

Altered neurocognitive function in schizophrenia could reflect both genetic and illness-specific effects.

To use functional magnetic resonance imaging to discriminate between the influences of the genetic risk for schizophrenia and environmental factors on the neural substrate of verbal fluency, a candidate schizophrenia endophenotype using a case control twin design.

We studied 23 monozygotic twin pairs: 13 pairs discordant for schizophrenia and 10 pairs of healthy volunteer twins. Groups were matched for age, gender, handedness, level of education, parental socio-economic status, and ethnicity. Behavioural performance and regional brain activation during a phonological verbal fluency task were assessed.

Relative to healthy control twins, both patients and their non-psychotic co-twins produced fewer correct responses and showed less activation in the medial temporal region and inferior frontal gyrus. Twins with schizophrenia showed greater activation than both their non-psychotic co-twins and controls in right lateral temporal cortex, reflecting reduced deactivation during word generation while their non-psychotic co-twins showed greater activation in the left temporal cortex.

Both genetic vulnerability to schizophrenia and schizophrenia were associated with impaired verbal fluency performance, reduced engagement of the medial temporal region and dorsal inferior frontal gyrus. Schizophrenia was specifically associated with an additional reduction in deactivation in the right temporal cortex.

To investigate associations between schizophrenia candidate gene polymorphisms and regional cortical thickness and volume in patients with schizophrenia and healthy control subjects.

Genotyping was performed using PCR and pyrosequencing techniques. Cortical morphology was analyzed by processing magnetic resonance brain images with the FreeSurfer software package. General linear model analysis was used to study associations between gene variants and cortical thickness in patients and controls, respectively. Regional cortical volumes were defined from automatic cortical parcellations. Our first studies from 96 patients with schizophrenia and 104 healthy control subjects demonstrate that polymorphisms in the brain derived neurotrophic factor (BDNF) gene may be associated with variation in frontal lobe morphology. Associations seem to be stronger in patients with schizophrenia than in healthy controls.