The association between living alone, loneliness and suicide mortality and effect modification by age: A case:control study.

BACKGROUND: Social isolation is a potentially reversible risk factor for suicide. METHODS: A matched case control study design was used. The study population was from England and identified from an electronic primary case database with linkage to a secondary care database and Office for National Statistics mortality data. Cases were individuals who had been recorded as dying by suicide. Controls were randomly selected, matched by primary care centre and date of suicide mortality. RESULTS: Data were available from 14,515 cases who died from suicide and 580,159 controls. After adjustment for age and sex, the risk of suicide in individuals who had previously been reported to be either living alone or suffering loneliness was increased (Odds ratio OR 4.9; 95 % confidence intervals CI: 4.4 to 5.5). Age affected the level of this risk, with individuals aged 15 to 34 years who were lonely or lived alone having a much higher risk of suicide (OR 16.4; 95 % CI: 8.7 to 31.1). LIMITATIONS: We can demonstrate an association between loneliness and living alone, but this may not be a causal effect. The conclusions may not be generalisable to societies outside the UK. CONCLUSIONS: Loneliness and social isolation are associated with an approximately five-fold increase in risk of mortality from suicide, which was substantially higher in younger adults. These represent potentially reversible risk factors for suicide mortality and may also help identify individuals who are at a higher risk of suicide.

Smoking is a Risk Factor for Autoimmune Hepatitis: An English Registry-Based Case-Control Study.

Purpose: Smoking is a risk factor for some autoimmune diseases, but its association with autoimmune hepatitis remains unknown. We conducted a population-based matched case-control study to examine the association between tobacco smoking and the risk of autoimmune hepatitis in England. Patients and Methods: From the Clinical Practice Research Datalink and linked Hospital Episode Statistics, 2005-2017, we included 987 cases diagnosed with autoimmune hepatitis after age 18 years and up to 10 frequency-matched population controls per case. We used multiple logistic regression to estimate the odds ratio of autoimmune hepatitis in ever-smokers vs never-smokers, adjusting for sex, age, general practice, calendar time of registration with the general practice, and socioeconomic status. Results: The autoimmune hepatitis cases were more likely to be ever-smokers than the controls (44% vs 37%). The ever-smokers had an increased risk of autoimmune hepatitis compared with the never-smokers (adjusted odds ratio = 1.20, 95% confidence interval 1.03-1.39). Conclusion: Smoking was associated with an increased risk of autoimmune hepatitis.

Primary care consultation patterns prior to suicide: a nationally representative case-control study.

BACKGROUND: Consultation with primary health care may provide an opportunity to identify patients at higher suicide risk. AIMS: To explore primary care consultation patterns in the 5 years before suicide to identify suicide high-risk groups and common reasons for consulting. DESIGN: A case-control study in England from 2001 to 2019 using electronic health records. METHOD: Analysis of 14515 patients aged ≥15 who died by suicide and up to 40 matched live controls per case (N=594674). RESULTS: Frequent consultations (>once per month in the final year) were associated with increased suicide risk (age and sex adjusted odds ratio (OR) 5.88; 95% CI: 5.47-6.32). The associated rise in suicide risk was seen across all sociodemographic groups as well as in those with and without psychiatric comorbidities. However, specific groups were more influenced by the effect of high-frequency consultation (>once per month in the final year) demonstrating higher suicide risk compared to their counterparts who consulted once: females (adjusted OR 9.50; 95% CI: 7.82-11.54); patients aged 15 to 45 (adjusted OR 8.08; 95% CI: 7.29-8.96); patients experiencing less socioeconomic deprivation (adjusted OR 6.56; 95% CI: 5.77-7.46); and those with psychiatric conditions (adjusted OR 4.57;95% CI: 4.12 to 5.06). Medication review, depression and pain were the commonest reasons for which suicide decedents consulted in the year before death. CONCLUSION: Escalating, or more than monthly consultations are associated with increased suicide risk regardless of patients' sociodemographic characteristics and regardless of the presence (or absence) of known psychiatric illnesses.

Ethnicity and socio-economic status affects the incidence and survival of hepatosplenic T-cell lymphoma.

To address the lack of contemporary population-based epidemiological studies of hepatosplenic T-cell lymphoma (HSTCL), we undertook a population-based study of ICD-O-3-coded HSTCL in England. We used the National Cancer Registration Dataset and linked datasets on hospital admissions, Systemic Anti-Cancer Therapy, socio-demographics, comorbidities and death, identifying cases from 1 January 2013 to 31 December 2019 with survival data up to 5 January 2021. Crude and directly age-standardised incidence rates per million persons per year were calculated. Crude and adjusted incidence rate ratios compared incidence between groups using Poisson regression. A Cox proportional hazards model estimated mortality risks adjusted for age, sex, ethnicity, deprivation and allogenic stem cell transplant (allo-SCT; time varying). We identified 44 patients, mean age 42 years. Median survival was 11 months, and 1 and 5 year survivals were 48% (95% CI 29%-43%) and 22% (95% CI 12%-42%) respectively. The age-standardised incidence was 0.1 per million/year. Incidence was higher in areas with greater deprivation (0.15 per million/year), and more cases than expected were in non-White patients (39%). Non-Whites had a twofold increased risk of death (adjusted hazard ratio 2.21 [95% CI 1.03-4.78]) even after adjusting for deprivation, younger age and allo-SCT. In conclusion, ethnicity and socio-economic status affect both the incidence and survival of HSTCL.

Evaluation of common prescription analgesics and adjuvant analgesics as markers of suicide risk: a longitudinal population-based study in England.

Background: Analgesics prescriptions may provide a marker for identifying individuals at higher risk of suicide. In particular, awareness of which analgesics are implicated may help clinicians assess and modify risk. Method: A case-control study in England using the Clinical Practice Research Datalink (for primary care records) linked with hospital and national mortality electronic registries. We included patients aged ≥15 who died by suicide between 2001 and 2019 (N = 14,515), to whom we individually matched 580,159 controls by suicide date and general practice (N = 594,674). Odds ratios (ORs) for suicide, controlled for age and sex, were assessed using conditional logistic regression. Findings: Suicide risks were highest in those prescribed adjuvant analgesics (pregabalin, gabapentin and carbamazepine) (adjusted OR 4.07; 95% confidence intervals CI: 3.62-4.57), followed by those prescribed opioids (adjusted OR 2.01; 95% CI: 1.88-2.15) and those prescribed non-opioid analgesics (adjusted OR 1.48; 95% CI: 1.39-1.58) compared to those not prescribed these medications. By individual analgesic, the highest suicide risks were seen in patients prescribed oxycodone (adjusted OR 6.70; 95% CI: 4.49-9.37); pregabalin (adjusted OR 6.50; 95% CI: 5.41-7.81); morphine (adjusted OR 4.54; 95% CI: 3.73-5.52); and gabapentin (adjusted OR 3.12; 95% CI: 2.59-3.75). Suicide risk increased linearly with the number of analgesic prescriptions in the final year (p < 0.01 based on the likelihood ratio test), and the more different analgesics categories were prescribed in the final year (p < 0.01 based on the likelihood ratio test). Interpretation: Analgesic prescribing was associated with higher suicide risk. This is a particular issue with regard to adjuvant non-opiate analgesics. Funding: There was no funding for this study.

Respiratory rate responses to both hypercapnia and acidaemia are modified by age in patients with acidosis.

OBJECTIVE: To explore the associations between arterial pO2, pCO2 and pH and how these are modified by age. METHODS: An analysis of 2598 patients admitted with a diagnosis of Covid-19 infection to a large UK teaching hospital. RESULTS: There were inverse associations for arterial pO2, pCO2 and pH with respiratory rate. The effects of pCO2 and pH on respiratory rate were modified by age; older patients had higher respiratory rates at higher pCO2 (p = 0.004) and lower pH (p = 0.007) values. CONCLUSIONS: This suggests that ageing is associated with complex changes in the physiological feedback loops that control respiratory rate. As well as having clinical relevance, this may also impact on the use of respiratory rate in early warning scores across the age range.

Anaemia of acute inflammation: a higher acute systemic inflammatory response is associated with a larger decrease in blood haemoglobin levels in patients with COVID-19 infection.

AIMS: The study tests the hypothesis that a higher acute systemic inflammatory response was associated with a larger decrease in blood hemoglobin levels in patients with Coronavirus 2019 (COVID-19) infection. METHODS: All patients with either suspected or confirmed COVID-19 infection admitted to a busy UK hospital from February 2020 to December 2021 provided data for analysis. The exposure of interest was maximal serum C-reactive protein (CRP) level after COVID-19 during the same admission. RESULTS: A maximal serum CRP >175mg/L was associated with a decrease in blood haemoglobin (-5.0 g/L, 95% confidence interval: -5.9 to -4.2) after adjustment for covariates, including the number of times blood was drawn for analysis.Clinically, for a 55-year-old male patient with a maximum haemoglobin of 150 g/L who was admitted for a 28-day admission, a peak CRP >175 mg/L would be associated with an 11 g/L decrease in blood haemoglobin, compared with only 6 g/L if the maximal CRP was <4 mg/L. CONCLUSIONS: A higher acute systemic inflammatory response is associated with larger decreases in blood haemoglobin levels in patients with COVID-19. This represents an example of anaemia of acute inflammation, and a potential mechanism by which severe disease can increase morbidity and mortality.

Is Vaccination Against COVID-19 Associated With Inflammatory Bowel Disease Flare? Self-Controlled Case Series Analysis Using the UK CPRD.

INTRODUCTION: To investigate the association between vaccination against coronavirus disease 2019 (COVID-19) and inflammatory bowel disease (IBD) flare. METHODS: Patients with IBD vaccinated against COVID-19 who consulted for disease flare between December 1, 2020, and December 31, 2021, were ascertained from the Clinical Practice Research Datalink. IBD flares were identified using consultation and corticosteroid prescription records. Vaccinations were identified using product codes and vaccination dates. The study period was partitioned into vaccine-exposed (vaccination date and 21 days immediately after), prevaccination (7 days immediately before vaccination), and the remaining vaccine-unexposed periods. Participants contributed data with multiple vaccinations and IBD flares. Season-adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) were calculated using self-controlled case series analysis. RESULTS: Data for 1911 cases with IBD were included; 52% of them were female, and their mean age was 49 years. Approximately 63% of participants had ulcerative colitis (UC). COVID-19 vaccination was not associated with increased IBD flares in the vaccine-exposed period when all vaccinations were considered (aIRR [95% CI] 0.89 [0.77-1.02], 0.79 [0.66-0.95], and 1.00 [0.79-1.27] in IBD overall, UC, and Crohn's disease, respectively). Analyses stratified to include only first, second, or third COVID-19 vaccinations found no significant association between vaccination and IBD flares in the vaccine-exposed period (aIRR [95% CI] 0.87 [0.71-1.06], 0.93 [0.75-1.15], and 0.86 [0.63-1.17], respectively). Similarly, stratification by COVID-19 before vaccination and by vaccination with vectored DNA or messenger RNA vaccine did not reveal an increased risk of flare in any of these subgroups. DISCUSSION: Vaccination against COVID-19 was not associated with IBD flares regardless of prior COVID-19 infection and whether messenger RNA or DNA vaccines were used.

Risk of Suicide After Dementia Diagnosis.

Importance: Patients with dementia may be at an increased suicide risk. Identifying groups at greatest risk of suicide would support targeted risk reduction efforts by clinical dementia services. Objectives: To examine the association between a dementia diagnosis and suicide risk in the general population and to identify high-risk subgroups. Design, Setting, and Participants: This was a population-based case-control study in England conducted from January 1, 2001, through December 31, 2019. Data were obtained from multiple linked electronic records from primary care, secondary care, and the Office for National Statistics. Included participants were all patients 15 years or older and registered in the Office for National Statistics in England with a death coded as suicide or open verdict from 2001 to 2019. Up to 40 live control participants per suicide case were randomly matched on primary care practice and suicide date. Exposures: Patients with codes referring to a dementia diagnosis were identified in primary care and secondary care databases. Main Outcomes and Measures: Odds ratios (ORs) were estimated using conditional logistic regression and adjusted for sex and age at suicide/index date. Results: From the total sample of 594 674 patients, 580 159 (97.6%) were controls (median [IQR] age at death, 81.6[72.0-88.4] years; 289 769 male patients [50.0%]), and 14 515 (2.4%) died by suicide (median [IQR] age at death, 47.4 [36.0-59.7] years; 10 850 male patients [74.8%]). Among those who died by suicide, 95 patients (1.9%) had a recorded dementia diagnosis (median [IQR] age at death, 79.5 [67.1-85.5] years; median [IQR] duration of follow-up, 2.3 [1.0-4.4] years). There was no overall significant association between a dementia diagnosis and suicide risk (adjusted OR, 1.05; 95% CI, 0.85-1.29). However, suicide risk was significantly increased in patients diagnosed with dementia before age 65 years (adjusted OR, 2.82; 95% CI, 1.84-4.33), in the first 3 months after diagnosis (adjusted OR, 2.47; 95% CI, 1.49-4.09), and in patients with dementia and psychiatric comorbidity (adjusted OR, 1.52; 95% CI, 1.21-1.93). In patients younger than 65 years and within 3 months of diagnosis, suicide risk was 6.69 times (95% CI, 1.49-30.12) higher than in patients without dementia. Conclusions and Relevance: Diagnostic and management services for dementia, in both primary and secondary care settings, should target suicide risk assessment to the identified high-risk groups.

Predicting Need for Escalation of Care or Death From Repeated Daily Clinical Observations and Laboratory Results in Patients With Severe Acute Respiratory Syndrome Coronavirus 2.

We compared the performance of prognostic tools for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using parameters fitted either at the time of hospital admission or across all time points of an admission. This cohort study used clinical data to model the dynamic change in prognosis of SARS-CoV-2 at a single hospital center in the United Kingdom, including all patients admitted from February 1, 2020, to December 31, 2020, and then followed up for 60 days for intensive care unit (ICU) admission, death, or discharge from the hospital. We incorporated clinical observations and blood tests into 2 time-varying Cox proportional hazards models predicting daily 24- to 48-hour risk of admission to the ICU for those eligible for escalation of care or death for those ineligible for escalation. In developing the model, 491 patients were eligible for ICU escalation and 769 were ineligible for escalation. Our model had good discrimination of daily risk of ICU admission in the validation cohort (n = 1,141; C statistic: C = 0.91, 95% confidence interval: 0.89, 0.94) and our score performed better than other scores (National Early Warning Score 2, International Severe Acute Respiratory and Emerging Infection Comprehensive Clinical Characterisation Collaboration score) calculated using only parameters measured on admission, but it overestimated the risk of escalation (calibration slope = 0.7). A bespoke daily SARS-CoV-2 escalation risk prediction score can predict the need for clinical escalation better than a generic early warning score or a single estimation of risk calculated at admission.

Silent hypoxia is not an identifiable characteristic in patients with COVID-19 infection.

BACKGROUND: We aimed to assess whether asymptomatic ("happy") hypoxia was an identifiable physiological phenotype of COVID-19 acute respiratory distress syndrome (ARDS), and associated with need for ICU admission. METHODS: We performed an observational cohort study of all adult patients admitted with hypoxaemic respiratory failure to a large acute hospital Trust serving the East Midlands, UK. Patients with confirmed COVID-19 were compared to those without. Physiological response to hypoxaemia was modelled using a linear mixed effects model. RESULTS: Of 1,586 patients included, 75% tested positive for SARS-CoV-2. The ROX index was 2.08 min-1 lower (1.56-2.61, p < 0.001) in the COVID-19 cohort when adjusted for age and ethnicity, suggesting an enhanced respiratory response to hypoxia compared to the non-Covid-19 patients. There was substantial residual inter- and intra-patient variability in the respiratory response to hypoxaemia. 33% of the infected cohort required ICU, and of these 31% died within 60 days. ICU admission and mortality were both associated with an enhanced respiratory response for all degrees of hypoxaemia. CONCLUSIONS: Patients with COVID-19 display a more symptomatic phenotype in response to hypoxaemia than those with other causes of hypoxaemic respiratory failure, however individual patients exhibit a wide range of responses. As such although asymptomatic hypoxaemia may be a phenomenon in any individual patient with hypoxaemic respiratory failure, it is no more frequently observed in those with SARS-CoV-2 infection than without.

Age modifies both the maximal temperature and inflammatory response in patients with SARS-CoV-2 infection.

OBJECTIVE: To determine the maximal response of the temperature and inflammatory response to SARS-CoV-2 infection and how these are modified by age. METHODS: Participants were patients admitted to hospital with SARS-CoV-2 infection. For each participant, the maximal temperature and serum C-reactive protein (CRP) were identified and stratified by age. In a secondary analysis, these were compared in patients treated before and after dexamethasone. RESULTS: Mean maximal temperature varied by age (p<0.001; ANOVA) with the highest mean maximal temperature of 37.3°C observed in patients aged 30-49 years and decreasing maximal mean temperatures in the older age groups, with the lowest measure of 36.8°C observed in individuals aged 90-99 years. The mean maximal serum CRP also varied across age groups (p<0.001; ANOVA) and increased with age across all age categories from 34.5 mg/dL (95% confidence interval (CI) 22.0-47.0) for individuals aged 20-29 years to 77.6 mg/dL (95% CI 72.0-83.2) in those aged 80-89 years. After dexamethasone became standard treatment for COVID-19 pneumonia, mean maximal CRP decreased by 17 mg/dL (95% CI -22 to -11). CONCLUSION: Age modifies both maximal temperature and systemic inflammatory response in patients with SARS-CoV-2 infection.

The risk of unexpected hospital admissions and primary care visits after an elective day-case gastroscopy: a cohort study within England.

AIM: To determine the excess of acute medical contacts following a day-case diagnostic gastroscopy. METHODS: Cohort study using English linked primary, secondary care and death registry electronic health data. We included 277,535 diagnostic day-case gastroscopies in 225,304 people between 1998 and 2016 and followed up for 30 days. 1,383,535 30-day periods without a gastroscopy within 991,249 people frequency matched on year, gender and decade of birth. Non-cancer deaths, emergency non-cancer admissions and cardio, vascular or respiratory (CVR) primary care consultations were identified and adjusted for each other as competing risks. Outcomes related to possible indications for gastroscopy were censored. RESULTS: 5.1% of day-case diagnostic gastroscopies were followed by emergency hospital admission, 0.4% for a CVR diagnosis. Adjusted for age, sex, morbidity, time trends, indications and competing risks, there was a 0.1% excess of CVR-related hospital admissions compared to controls. This reduced to 0.05% (95% confidence interval 0.04-0.06%) in people under 40 years without morbidity and increased to 1.1% (0.6%-1.6%) in people over 90 years with high comorbidity. Similarly, by 30 days, 3.8% had a primary care consultation for a CVR problem, with an excess after adjustment ranging from 0.13% (0.11%-0.16%) to 0.31% (0.14%-0.50%). Overall numbers needed to harm ranged from 1 in 294 gastroscopies to 1 in 67 gastroscopies. CONCLUSIONS: There was an excess of vascular and respiratory events associated with a diagnostic gastroscopy. In younger patients, this risk manifested as an increase in primary care consultations while in older patients there was an increase in emergency hospital admissions.

Risk of mortality from suicide in patients with Huntington's disease is increased compared to the general population in England.

OBJECTIVE: To examine the relative risk of suicide mortality in patients with Huntington's disease (HD). METHODS: A case-control study design was used. We used linked electronic records from primary care, secondary care and Office for National Statistics from England from 2001 through 2019. Controls were matched to cases by general practice and suicide date. Odds ratios (ORs) were adjusted for gender and age at suicide/index date. RESULTS: Data were available for 594,674 individuals. Patients with HD who died from suicide were significantly younger at time of death than patients with HD who died from causes other than suicide (p < 0.001). The adjusted OR for HD was 9.2 (95% confidence intervals, CI 4.9-17.4) compared to those without HD. The increase in risk was higher amongst the younger age group who were ≤ 45.8 years at suicide/index date (OR 54.5, 95% CI 10.8-276.1). CONCLUSION: The markedly elevated suicide risk in patients with HD suggests that implementation of suicide risk assessment may improve survival in individuals with these diseases, especially in younger patients.