Impact of the COVID-19 pandemic on antipsychotic prescribing in individuals with autism, dementia, learning disability, serious mental illness or living in a care home: a federated analysis of 59 million patients' primary care records in situ using OpenSAFELY.

BACKGROUND: The COVID-19 pandemic affected how care was delivered to vulnerable patients, such as those with dementia or learning disability. OBJECTIVE: To explore whether this affected antipsychotic prescribing in at-risk populations. METHODS: With the approval of NHS England, we completed a retrospective cohort study, using the OpenSAFELY platform to explore primary care data of 59 million patients. We identified patients in five at-risk groups: autism, dementia, learning disability, serious mental illness and care home residents. We calculated the monthly prevalence of antipsychotic prescribing in these groups, as well as the incidence of new prescriptions in each month. FINDINGS: The average monthly rate of antipsychotic prescribing increased in dementia from 82.75 patients prescribed an antipsychotic per 1000 patients (95% CI 82.30 to 83.19) in January-March 2019 to 90.1 (95% CI 89.68 to 90.60) in October-December 2021 and from 154.61 (95% CI 153.79 to 155.43) to 166.95 (95% CI 166.23 to 167.67) in care homes. There were notable spikes in the rate of new prescriptions issued to patients with dementia and in care homes. In learning disability and autism groups, the rate of prescribing per 1000 decreased from 122.97 (95% CI 122.29 to 123.66) to 119.29 (95% CI 118.68 to 119.91) and from 54.91 (95% CI 54.52 to 55.29) to 51.04 (95% CI 50.74 to 51.35), respectively. CONCLUSION AND IMPLICATIONS: We observed a spike in antipsychotic prescribing in the dementia and care home groups, which correlated with lockdowns and was likely due to prescribing of antipsychotics for palliative care. We observed gradual increases in antipsychotic use in dementia and care home patients and decreases in their use in patients with learning disability or autism.

Eleven key measures for monitoring general practice clinical activity during COVID-19: A retrospective cohort study using 48 million adults' primary care records in England through OpenSAFELY.

Background: The COVID-19 pandemic has had a significant impact on delivery of NHS care. We have developed the OpenSAFELY Service Restoration Observatory (SRO) to develop key measures of primary care activity and describe the trends in these measures throughout the COVID-19 pandemic. Methods: With the approval of NHS England, we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care electronic health record (EHR) data on 48 million adults.We developed SNOMED-CT codelists for key measures of primary care clinical activity such as blood pressure monitoring and asthma reviews, selected by an expert clinical advisory group and conducted a population cohort-based study to describe trends and variation in these measures January 2019-December 2021, and pragmatically classified their level of recovery one year into the pandemic using the percentage change in the median practice level rate. Results: We produced 11 measures reflective of clinical activity in general practice. A substantial drop in activity was observed in all measures at the outset of the COVID-19 pandemic. By April 2021, the median rate had recovered to within 15% of the median rate in April 2019 in six measures. The remaining measures showed a sustained drop, ranging from a 18.5% reduction in medication reviews to a 42.0% reduction in blood pressure monitoring. Three measures continued to show a sustained drop by December 2021. Conclusions: The COVID-19 pandemic was associated with a substantial change in primary care activity across the measures we developed, with recovery in most measures. We delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. We will continue to expand the set of key measures to be routinely monitored using our publicly available NHS OpenSAFELY SRO dashboards with near real-time data. Funding: This research used data assets made available as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058).The OpenSAFELY Platform is supported by grants from the Wellcome Trust (222097/Z/20/Z); MRC (MR/V015757/1, MC_PC-20059, MR/W016729/1); NIHR (NIHR135559, COV-LT2-0073), and Health Data Research UK (HDRUK2021.000, 2021.0157).

Changes in medication safety indicators in England throughout the covid-19 pandemic using OpenSAFELY: population based, retrospective cohort study of 57 million patients using federated analytics.

Objective: To implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing. Design: Population based, retrospective cohort study using federated analytics. Setting: Electronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England. Participants: NHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator. Main outcome measure: Between 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety. Results: The PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event. Conclusion: NHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.

Nutritional Supplement and Dietary Interventions as a Prophylaxis or Treatment of Sub-Concussive Repetitive Head Impact and Mild Traumatic Brain Injury: A Systematic Review.

Mild traumatic brain injury (mTBI) affects 42 to 56 million individuals worldwide annually. Even more individuals are affected by sub-concussive repetitive head impacts (SRHIs). Such injuries may result in significant acute and chronic symptoms. A study of how individuals may adjust or augment their nutritional and dietary habits to prevent cumulative neurotrauma and promote post-injury recovery is necessary. The objective of the current study is to systematically review nutritional and dietary interventions for neurotrauma prevention and mTBI recovery to direct clinical decision-making and identify future areas of research. This systematic review, without a specified time-period, was performed in PubMed, Scopus, Cochrane, CINAHL, and Web of Science followed by a manual search of references. Search strings were generated by a research librarian. Studies were included if they: 1) investigate human subjects with mTBI or SRHI; 2) investigate a supplement/ingredient of dietary supplement sold in the U.S. or dietary intervention without classification as a drug or prohibitive statement against use by the U.S. Food and Drug Administration (FDA); 3) assess a quantifiable outcome; and 4) are published in English in a peer-reviewed journal with an accessible full-length article. Studies were excluded if: 1) the study included non-mTBI or SRHI subjects (e.g., moderate/severe TBI, stroke); 2) mTBI is not assessed separately from moderate/severe mTBI; or 3) the studies that required intracranial hemorrhage. Fifteen studies from 12 unique subject populations met inclusion and exclusion criteria. A total of 1139 mTBI or SRHI subjects were enrolled across intervention arms in the study populations. A total of eight intervention were studied. Omega-3 fatty acid (n-3FA), melatonin, and Pinus radiata were the only interventions examined in multiple studies. Studies included 10 randomized-control trials, three prospective observational studies, and two retrospective observational studies. Seven of the 15 studies had a low risk of bias. Eleven studies reported benefit of the intervention. Strongest evidence supports n-3FA utility for neurotrauma prevention in athletes exposed to SRHI. Both Pinus radiata and melatonin may have benefit for persistent post-concussion symptoms; however, additional multi-center studies are necessary prior to making a definitive conclusion on these supplements' efficacy. Future studies should continue to assess both novel interventions and additional interventions examined in this review to bring additional evidence to the burgeoning field of nutritional and dietary interventions for SRHI and mTBI.

Recording of 'COVID-19 vaccine declined': a cohort study on 57.9 million National Health Service patients' records in situ using OpenSAFELY, England, 8 December 2020 to 25 May 2021.

BackgroundPriority patients in England were offered COVID-19 vaccination by mid-April 2021. Codes in clinical record systems can denote the vaccine being declined.AimWe describe records of COVID-19 vaccines being declined, according to clinical and demographic factors.MethodsWith the approval of NHS England, we conducted a retrospective cohort study between 8 December 2020 and 25 May 2021 with primary care records for 57.9 million patients using OpenSAFELY, a secure health analytics platform. COVID-19 vaccination priority patients were those aged ≥ 50 years or ≥ 16 years clinically extremely vulnerable (CEV) or 'at risk'. We describe the proportion recorded as declining vaccination for each group and stratified by clinical and demographic subgroups, subsequent vaccination and distribution of clinical code usage across general practices.ResultsOf 24.5 million priority patients, 663,033 (2.7%) had a decline recorded, while 2,155,076 (8.8%) had neither a vaccine nor decline recorded. Those recorded as declining, who were subsequently vaccinated (n = 125,587; 18.9%) were overrepresented in the South Asian population (32.3% vs 22.8% for other ethnicities aged ≥ 65 years). The proportion of declining unvaccinated patients was highest in CEV (3.3%), varied strongly with ethnicity (black 15.3%, South Asian 5.6%, white 1.5% for ≥ 80 years) and correlated positively with increasing deprivation.ConclusionsClinical codes indicative of COVID-19 vaccinations being declined are commonly used in England, but substantially more common among black and South Asian people, and in more deprived areas. Qualitative research is needed to determine typical reasons for recorded declines, including to what extent they reflect patients actively declining.

Trends and clinical characteristics of COVID-19 vaccine recipients: a federated analysis of 57.9 million patients' primary care records in situ using OpenSAFELY.

BACKGROUND: On 8 December 2020 NHS England administered the first COVID-19 vaccination. AIM: To describe trends and variation in vaccine coverage in different clinical and demographic groups in the first 100 days of the vaccine rollout. DESIGN AND SETTING: With the approval of NHS England, a cohort study was conducted of 57.9 million patient records in general practice in England, in situ and within the infrastructure of the electronic health record software vendors EMIS and TPP using OpenSAFELY. METHOD: Vaccine coverage across various subgroups of Joint Committee on Vaccination and Immunisation (JCVI) priority cohorts is described. RESULTS: A total of 20 852 692 patients (36.0%) received a vaccine between 8 December 2020 and 17 March 2021. Of patients aged ≥80 years not in a care home (JCVI group 2) 94.7% received a vaccine, but with substantial variation by ethnicity (White 96.2%, Black 68.3%) and deprivation (least deprived 96.6%, most deprived 90.7%). Patients with pre-existing medical conditions were more likely to be vaccinated with two exceptions: severe mental illness (89.5%) and learning disability (91.4%). There were 275 205 vaccine recipients who were identified as care home residents (JCVI group 1; 91.2% coverage). By 17 March, 1 257 914 (6.0%) recipients had a second dose. CONCLUSION: The NHS rapidly delivered mass vaccination. In this study a data-monitoring framework was deployed using publicly auditable methods and a secure in situ processing model, using linked but pseudonymised patient-level NHS data for 57.9 million patients. Targeted activity may be needed to address lower vaccination coverage observed among certain key groups.

Clinical coding of long COVID in English primary care: a federated analysis of 58 million patient records in situ using OpenSAFELY.

BACKGROUND: Long COVID describes new or persistent symptoms at least 4 weeks after onset of acute COVID-19. Clinical codes to describe this phenomenon were recently created. AIM: To describe the use of long-COVID codes, and variation of use by general practice, demographic variables, and over time. DESIGN AND SETTING: Population-based cohort study in English primary care. METHOD: Working on behalf of NHS England, OpenSAFELY data were used encompassing 96% of the English population between 1 February 2020 and 25 May 2021. The proportion of people with a recorded code for long COVID was measured overall and by demographic factors, electronic health record software system (EMIS or TPP), and week. RESULTS: Long COVID was recorded for 23 273 people. Coding was unevenly distributed among practices, with 26.7% of practices having never used the codes. Regional variation ranged between 20.3 per 100 000 people for East of England (95% confidence interval [CI] = 19.3 to 21.4) and 55.6 per 100 000 people in London (95% CI = 54.1 to 57.1). Coding was higher among females (52.1, 95% CI = 51.3 to 52.9) than males (28.1, 95% CI = 27.5 to 28.7), and higher among practices using EMIS (53.7, 95% CI = 52.9 to 54.4) than those using TPP (20.9, 95% CI = 20.3 to 21.4). CONCLUSION: Current recording of long COVID in primary care is very low, and variable between practices. This may reflect patients not presenting; clinicians and patients holding different diagnostic thresholds; or challenges with the design and communication of diagnostic codes. Increased awareness of diagnostic codes is recommended to facilitate research and planning of services, and also surveys with qualitative work to better evaluate clinicians' understanding of the diagnosis.

From Blocking Shots to Blocking GI Transit, This Professional Basketball Player Does It All: A Case Report on Small Bowel Obstruction.

Small bowel obstructions (SBO) are a commonly encountered diagnosis within emergency departments. Typically, these patients have evident risk factors including, but not limited to, prior abdominal surgery, personal or family history of gastrointestinal disorders, femoral and inguinal hernias, or neoplasm. In this case, we describe an SBO in a female, professional athlete whose swift, severe symptom onset, rapid resolution with conservative treatment, lack of identifiable risk factors, and prompt return to high level competition without recurrence are certainly unique. A female professional basketball player in her mid-20's with no past medical history presented with a seven-hour history of worsening abdominal pain beginning in the epigastric region and migrating to the right lower quadrant. Physical exam did not reveal abdominal distension, tympany to percussion, or high-pitched bowel sounds. Initial differential diagnosis included appendicitis, ruptured ectopic pregnancy, and other genitourinary pathology. Computed tomography with contrast revealed distended loops of small bowel with wall thickening, enhancement, and decompressed loops of bowel distally, consistent with an SBO. Symptoms resolved after 24 hours with conservative treatment, including decompression with a nasogastric tube. The athlete returned to full participation five days after initial presentation without recurrence of symptoms. Outpatient gastroenterology workup was negative for predisposing conditions. This presentation is rare in the absence of bowel pathology, family history, or prior abdominal surgery. Perhaps, her profession as an athlete, with frequent air travel and extensive exercise, may have contributed to this unique presentation. This case report should serve as a reminder to all providers that SBOs can occur in young, active patients devoid of risk factors. Even in the absence of typical signs on physical examination, providers should use imaging as adjuncts based on their clinical gestalt and utilize conservative management, when appropriate, to maximize chances of recovery with minimal morbidity.

Using Emergency Department Data to Inform Specialty Strategy: Analyzing the Distribution of 13,777 Consecutive Immediate Orthopaedic Consults in an Urban Community Emergency Department.

Although an estimated 20% of emergency department (ED) visits are musculoskeletal in nature, it is unclear which of these require urgent orthopaedic consultation and which orthopaedic subspecialties are best suited for these consults. When an ED's internal staff does not have necessary orthopaedic coverage, transfer to other facilities is required. However, transfers pose major inconveniences and financial burdens to patients and can lead to long ED wait times, hospital financial loss from walk outs, decreased patient safety, and decreased staff morale. Therefore, it is beneficial for a hospital to have the appropriate staff readily available for consults. Data can be used to assess the orthopaedic needs of an ED. We evaluated the nature of urgent ED consults requesting the timely presence of an orthopaedic provider. Methods: Between the years 2008 and 2017, the Orthopaedics Department of this Health System saw 13,777 patients from the ED requesting immediate consult from an orthopaedic provider. We retrospectively analyzed the distribution of anatomic areas and nature of these injuries for these visits. Results: Hand, foot, and ankle consults comprised 75% of the volume. Knee, hip, and spine accounted for 15% of consults. Most injuries were fractures. Infections and sprains were also common. Discussion: By determining and understanding this distribution, orthopaedic departments can improve their organization to better respond to urgent ED consults, allowing for the proper delivery of orthopaedic point-of-care service to patients, increased revenue for the hospital, proper availability of core competencies, and increased value to the healthcare delivery system as a whole. We also believe that the trends observed in our data are largely generalizable to EDs serving urban communities similar to ours. Thus, these results can help inform a synergistic strategy for the system comprising EDs, urgent care clinics, and orthopaedic surgeons servicing them.

Human-to-Human Transmission of Monkeypox Virus, United Kingdom, October 2018.

In September 2018, monkeypox virus was transmitted from a patient to a healthcare worker in the United Kingdom. Transmission was probably through contact with contaminated bedding. Infection control precautions for contacts (vaccination, daily monitoring, staying home from work) were implemented. Of 134 potential contacts, 4 became ill; all patients survived.

Patient-specific three-dimensional concomitant dose from cone beam computed tomography exposure in image-guided radiotherapy.

PURPOSE: The purpose of the present study was to quantify the concomitant dose received by patients undergoing cone beam computed tomography (CBCT) scanning in different clinical scenarios as a part of image-guided radiotherapy (IGRT) procedures. METHODS AND MATERIALS: We calculated the three-dimensional concomitant dose received as a result of CBCT scans in 6 patients representing different clinical scenarios: two pelvis, two head and neck, and two chest. We assessed the effect that a daily on-line IGRT strategy would have on the patient dose distribution, assuming 40 CBCT scans throughout the treatment course. The additional dose to the planning target volume margin region was also estimated. RESULTS: In the pelvis, a single CBCT scan delivered a mean dose to the femoral heads of 2-6 cGy and the rectum of 1-2 cGy. An additional dose to the planning target volume was within 1-3 cGy. In the chest, the mean dose to the planning target volume varied from 2.5 to 5 cGy. The lung and spinal cord planning organ at risk volume received ≤4 cGy and ≤5 cGy, respectively. In the head and neck, a single CBCT scan delivered a mean dose of 0.3 cGy, with bony structures receiving 0.5-0.8 cGy. The femoral heads received an additional dose of 1.5-2.5 Gy. A reduction of 20-30% in the mean dose to the organs at risk was achieved using bowtie filtration. In the head and neck, the dose to the eyes and brainstem was eliminated by decreasing the craniocaudal field size. CONCLUSIONS: The additional dose from on-line IGRT procedures can be clinically relevant. The organ dose can be significantly reduced with the use of appropriate patient-specific settings. The concomitant dose from CBCT should be accounted for and the acquisition settings optimized for optimal IGRT strategies on a patient basis.

Real or illusory? Case studies on the public perception of environmental health risks in the north west of England.

Applied research in a public health setting seeks to provide professionals with insights and knowledge into complex environmental issues to guide actions that reduce inequalities and improve health. We describe ten environmental case studies that explore the public perception of health risk. We employed logical analysis of components of each case study and comparative information to generate new evidence. The findings highlight how concerns about environmental issues measurably affect people's wellbeing and led to the development of new understanding about the benefits of taking an earlier and more inclusive approach to risk communication that can now be tested further.

Monte Carlo simulation of an x-ray volume imaging cone beam CT unit.

In this work the authors characterized the radiation field produced by a kilovolt cone beam computed tomography (CBCT) unit integrated in the Elekta Synergy linear accelerator. The x-ray volume imaging (XVI) radiation unit was modeled in detail using the BEAMNRC Monte Carlo (MC) code system. The simulations of eight collimator cassettes and the neutral filter F0 were successfully carried out. MC calculations from the EGSNRC code DOSXYZNRC were benchmarked against measurements in water. A large set of depth dose and lateral profiles was acquired with the ionization chamber in water, with the x-ray tube in a stationary position, and with the beam energy set to 120 kV. Measurements for all the available collimator cassettes were compared with calculations, showing very good agreement (< 2% in most cases). Furthermore, half value layer measurements were carried out and used to validate the MC model of the XVI unit. In this case dose calculations were performed with the EGSNRC code cavity and these showed excellent agreement. In this manuscript the authors also report on the optimization work of the relevant parameters that influenced the development of the MC model. The dosimetric part of this work was very useful in characterizing the XVI radiation output for the energy of interest. The detailed simulation part of the work is the first step toward an accurate MC based assessment of the dose delivered to patients during routine CBCT scans for image and dose guided radiotherapy.

Strategies for improving human health in contaminated situations: a review of past, present and possible future approaches.

Strategies for improving human health in contaminated situations have traditionally been based on restricting emissions, remedial reduction of exposure and, where appropriate and possible, medical reconnaissance of efficacy. We review these and the broader aspects of general public health approaches, including necessary understanding of epidemiology and the wider social context, before considering a specific local case study involving health issues associated with chromium-contaminated land and its remediation in an area of urban regeneration. The impact of remediation upon the common good, in its broadest environmental, health and socio-economic sense, including enhanced opportunities for members of the community to take personal responsibility for health-improving activities, should be taken into account in addition to conventional theoretical assessments and practical measurements of relief from environmental risk. Rapidly emerging toxicogenomic technologies may have a role to play in informing future risk assessment and remediation approaches in contaminated situations, although the ethical challenges of using personal genetic information could well be considerable.

High-throughput RNAi screening in vitro: from cell lines to primary cells.

Small interfering RNAs (siRNAs) are being used to induce sequence-specific gene silencing in cultured cells to study mammalian gene function. Libraries of siRNAs targeting entire human gene classes can be used to identify genes with specific cellular functions. Here we describe high-throughput siRNA delivery methods to facilitate siRNA library screening experiments with both immortalized and primary cells. We adapted chemical reverse transfection for immortalized adherent cell lines in a 96-well format. The method is fast, robust, and exceptionally effective for many cell types. For primary cells and immortalized cells that are recalcitrant to lipofection-based methods, we developed electropermeabilization (electroporation) conditions that facilitate siRNA delivery to a broad range of cell types, including primary human T-cells, hMSC, NHA, NDHF-Neo, HUVEC, DI TNC1, RPTEC, PC12, and K562 cells. To enable high-throughput electropermeabilization of primary cells, we developed a novel 96-well electroporation device that provides highly efficient and reproducible delivery of siRNAs. The combination of high-throughput chemical reverse transfection and electroporation makes it possible to deliver libraries of siRNAs to virtually any cell type, enabling gene function analysis and discovery on a genome scale.

c-Myc controls proliferation versus differentiation in human pancreatic endocrine cells.

Using immortalized human pancreatic endocrine cell lines, we have shown previously that differentiation into hormone-expressing cells requires cell-cell contact acting in synergy with the homeodomain transcription factor pancreatic duodenal homeobox-1 (PDX-1). Although differentiation is associated with a decrease in cell proliferation, the mechanisms behind this relationship are not known. Using TRM-6, a delta cell line, and betalox5, a beta-cell line, we show here that cell-cell contact and subsequent endocrine differentiation lead to a down-regulation of the c-myc protooncogene. Overexpression of c-Myc obtained with an inducible c-Myc-estrogen receptor fusion protein results in an increase in cell proliferation and the ablation of hormone expression. Moreover, we show that although c-Myc is expressed in a subset of cells from the human fetal and adult pancreas, it is absent in differentiated endocrine cells. The mechanism by which c-Myc interferes with hormone expression may be through effects on the homeodomain transcription factor PDX-1, as immunostaining for PDX-1 in cells with activated c-Myc revealed a redistribution of PDX-1 from the nucleus to the cytoplasm. These results suggest that c-Myc plays a central role in a cell-cell contact-mediated switch mechanism by which cell division vs. differentiation in endocrine cells is determined.