Absolute Risk Research Articles

How much protection does clopidogrel provide to cats with hypertrophic cardiomyopathy?

Cats with hypertrophic cardiomyopathy (HCM) have a risk of developing aortic thromboembolism (ATE). Clopidogrel reduces the risk of redeveloping ATE and delays recurrence of ATE in cats that have experienced an ATE episode. Consequently, cardiologists have recommended administering clopidogrel to cats as a primary preventative, suggesting that all cats with severe HCM be administered clopidogrel. However, clopidogrel is unpalatable in its manufactured format, making such administration problematic for many clients. Therefore, estimating the potential benefit of administration might help clinicians determine on a case-by-case basis the need to treat cats with clopidogrel. Relatively simple statistical analyses of currently available data, along with certain assumptions and extrapolations, allow such an estimation of benefit in terms of relative and absolute risk reduction conferred by clopidogrel. Using this approach, and provided certain assumptions are true, clopidogrel likely confers a reduction in risk of ATE in cats with moderate to severe HCM of approximately 3% to 4%. Given the difficulty of administering clopidogrel to cats, clinicians should weigh these relatively small potential benefits against the potential harms (difficulty of administration) and not necessarily insist that clients administer clopidogrel.

Adverse outcomes and mortality in individuals with eating disorder-related electrolyte abnormalities in Ontario, Canada: a population-based cohort study

Individuals with eating disorders are at a higher risk of electrolyte abnormalities than the general population. We conducted the first representative cohort study assessing whether electrolyte abnormalities in people with eating disorders were associated with mortality and physical health outcomes. This was a retrospective population-based cohort study in Ontario including people aged 13 years or older with an eating disorder and an outpatient electrolyte measure within 1 year (between Jan 1, 2008 and June 30, 2019). An electrolyte abnormality was any of hypokalaemia, hyperkalaemia, hyponatraemia, hypernatraemia, hypomagnesaemia, hypophosphataemia, metabolic acidosis, or metabolic alkalosis. The primary outcome was all-cause mortality. Secondary outcomes were hospitalisation, a cardiac event, infection, acute or chronic kidney disease, fracture, and bowel obstruction. In additional analyses, we examined a younger cohort (<25 years old) and individuals with no previously diagnosed secondary outcome. We involved people with related lived or family experience in the study. 6163 patients with an eating disorder and an electrolyte measure within 1 year since diagnosis (mean age 26·8 years [SD 17·5]; 5456 [88·5%] female, 707 [11·5%] male; median follow-up 6·4 years [IQR 4-9]) were included. Ethnicity data were not available. The most common electrolyte abnormalities were hypokalaemia (994/1987 [50·0%]), hyponatraemia (752/1987 [37·8%]), and hypernatraemia (420/1987 [21·1%]). Overall, mortality occurred in 311/1987 (15·7%) of those with an electrolyte abnormality versus 234/4176 (5·6%) in those without (absolute risk difference 10·1%; adjusted hazard ratio 1·23 [95% CI 1·03-1·48]). Hospitalisation (1202/1987 [60·5%] vs 1979/4176 [47·4%]; 1·35 [1·25-1·46]), acute kidney injury (206/1987 [10·4%] vs 124/4176 [3%]; 1·91 [1·50-2·43]), chronic kidney disease (245/1987 [12·3%] vs 181/4176 [4·3%]; 1·44 [1·17-1·77]), bone fracture (140/1987 [7·0%] vs 167/4176 [4·0%]; 1·40 [1·10-1·78]), and bowel obstruction (72/1987 [3·6%] vs 57/4176 [1·4%]; 1·62 [1·12-2·35]) were associated with an electrolyte abnormality, but not infection or a cardiovascular event. Findings were consistent in young individuals (<25 years old) and those without secondary outcomes at baseline, by eating disorder type, and by sex. Electrolyte abnormalities are associated with death and poor physical health outcomes, supporting the importance of monitoring and possible interventions to prevent adverse outcomes. Findings also call for a refinement of the definition of severity of eating disorder and replication of these findings in other jurisdictions. None.

On the Need for Better Information from Randomized Clinical Trials in Oncology

Cancer patients frequently seek information from their oncologists regarding the anticipated outcomes of their treatment. They commonly inquire about the potential for a cure and the likelihood of achieving it, as well as whether the treatment will prolong their life and, if so, by how much. In oncology, randomized controlled trials play a pivotal role in informing treatment decisions. It is essential that published randomized controlled trials provide comprehensive data to enable clinicians to deliver precise and reliable information to patients. The concept of the Hazard Ratio (HR) can be challenging for many oncologists and is often misunderstood in terms of its implications for risk. Thus, incorporating both relative and absolute risk metrics in addition to hazard ratios could substantially enhance patient care. This consideration is crucial not only for patients and oncologists but also for policymakers within public health systems.

Chronic low-grade inflammation associated with higher risk and earlier onset of cardiometabolic multimorbidity in middle-aged and older adults: a population-based cohort study.

Evidence regarding the role of chronic low-grade inflammation in the progression of cardiometabolic diseases (CMDs) and cardiometabolic multimorbidity (CMM) is currently limited. This prospective cohort study, utilising data from the UK Biobank, included 273,804 adults aged 40-69years initially free of CMD at baseline. CMM was defined as the coexistence of two or more CMDs, such as coronary artery disease, type 2 diabetes mellitus, hypertension and stroke. The aggregated inflammation score (INFLA-score), incorporating C-reactive protein, white blood cell count, platelet count and granulocyte-to-lymphocyte ratio, quantified chronic low-grade inflammation. Absolute risks (ARs), hazard ratios (HRs) and 95% confidence intervals (CIs) assessed the association of increased INFLA-score with the risk of CMMs and CMDs. The accelerated failure time model explored the effect of INFLA-score on the time to CMM onset, and a restricted cubic spline characterised the dose-dependent relationship between INFLA-score and CMM risk. After a median follow-up of 166.37months, 13,755 cases of CMM were identified. In quartiles with increasing INFLA-score levels, CMM ARs were 4.41%, 4.49%, 5.04% and 6.01%, respectively; HR increased by 2%, 15% and 36%, respectively, compared to the lowest quartile. The INFLA-score and CMM risk relationship was nonlinear (P for nonlinear < 0.001), exhibiting a significant risk trend change at a score of 9. For INFLA-score < 9, CMM risk increased by 1.9% for each 1-point increase; for INFLA-score ≥ 9, the risk increased by 5.9% for each 1-point increase. Additionally, a higher INFLA-score was associated with an earlier onset of CMM (P < 0.001). Compared to the first INFLA-score quartile, the AFT model revealed adjusted median times to CMM occurrence were 2.92, 6.10 and 13.19months earlier in the second, third and fourth quartile groups, respectively. Chronic low-grade inflammation is associated with a higher risk of cardiometabolic multimorbidity and earlier onset among middle-aged and older adults. Monitoring and screening the INFLA-score in adults without CMDs may improve early prevention of CMM.

Predicting Individual Treatment Effects to Determine Duration of Dual Antiplatelet Therapy After Stent Implantation.

After coronary stent implantation, prolonged dual antiplatelet therapy (DAPT) increases bleeding risk, requiring personalization of DAPT duration. The aim of this study was to develop and validate a machine learning model to predict optimal DAPT duration after contemporary drug-eluting stent implantation in patients with coronary artery disease. The One-Month DAPT, RESET (Real Safety and Efficacy of 3-Month Dual Antiplatelet Therapy Following Endeavor Zotarolimus-Eluting Stent Implantation), and IVUS-XPL (Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesion) trials provided a derivation cohort (n=6568). Using the X-learner approach, an individualized DAPT score was developed to determine the therapeutic benefit of abbreviated (1-6 months) versus standard (12-month) DAPT using various predictors. The primary outcome was major bleeding; the secondary outcomes included 1-year major adverse cardiac and cerebrovascular events and 1-year net adverse clinical events. The risk reduction with abbreviated DAPT (3 months) in the individualized DAPT-determined higher predicted benefit group was validated in the TICO (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus-Eluting Stent for Acute Coronary Syndrome) trial (n=3056), which enrolled patients with acute coronary syndrome treated with ticagrelor. The validation cohort comprised 1527 abbreviated and 1529 standard DAPT cases. Major bleeding occurred in 25 (1.7%) and 45 (3.0%) patients in the abbreviated and standard DAPT groups, respectively. The individualized DAPT score identified 2582 (84.5%) participants who would benefit from abbreviated DAPT, which was significantly associated with a lower major bleeding risk (absolute risk difference [ARD], 1.26 [95% CI, 0.15-2.36]) and net adverse clinical events (ARD, 1.59 [95% CI, 0.07-3.10]) but not major adverse cardiac and cerebrovascular events (ARD, 0.63 [95% CI, -0.34 to 1.61]), compared with standard DAPT in the higher predicted benefit group. Abbreviated DAPT had no significant difference in clinical outcomes of major bleeding (ARD, 1.49 [95% CI, -1.74 to 4.72]), net adverse clinical events (ARD, 2.57 [95% CI, -1.85 to 6.99]), or major adverse cardiac and cerebrovascular events (ARD, 1.54 [95% CI, -1.26 to 4.34]), compared with standard DAPT in the individualized DAPT-determined lower predicted benefit group. Machine learning using the X-learner approach identifies patients with acute coronary syndrome who may benefit from abbreviated DAPT after drug-eluting stent implantation, laying the groundwork for personalized antiplatelet therapy.

Association Between Mycobacterium tuberculosis Sensitization and Insulin Resistance Among US Adults Screened for Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) may be a long-term sequela of infection with Mycobacterium tuberculosis (Mtb) by mechanisms that remain to be fully explained. We evaluated the association between Mtb sensitization and T2DM and, via mediation analysis, the extent to which it is mediated by insulin resistance and/or β-cell failure. Adults were assessed for T2DM by fasting plasma glucose, 2-hour oral glucose tolerance testing, and hemoglobin A1c; β-cell dysfunction and insulin resistance by homoeostasis model assessment 2; and Mtb sensitization by tuberculin skin testing. Associations between Mtb sensitization and T2DM were modeled with probit regression and decomposed into indirect effects of β-cell dysfunction and insulin resistance. Analyses were adjusted for sociodemographic, behavioral, and clinical characteristics. We included 1843 adults. Individuals with Mtb sensitization were older than those without Mtb (median [IQR], 54 [39-64] vs 47 [33-62] years). As compared with being uninfected, Mtb sensitization was associated with T2DM (adjusted absolute risk difference, 9.34% [95% CI, 2.38%-15.0%]; P < .001) and increased insulin resistance (adjusted median difference, 0.16 [95% CI, .03-.29]; P = .014) but not β-cell dysfunction (adjusted median difference, -3.1 [95% CI, -10.4 to 4.3]; P = .42). In mediation analyses, insulin resistance mediated 18.3% (95% CI, 3.29%-36.0%; P = .020) of the total effect of the association between Mtb sensitization and T2DM. Definitive prospective studies examining incident T2DM following tuberculosis are warranted. Notwithstanding, our findings suggest that exposure to Mtb may be a novel risk factor for T2DM, likely driven by an increase in insulin resistance.

Congenital heart defects in children born after assisted reproductive technology: a CoNARTaS study.

Children born after assisted reproductive technology (ART) have worse perinatal outcomes compared with spontaneously conceived children. This study investigates whether children conceived after ART have a higher risk of congenital heart defects (CHDs) compared with children born after spontaneous conception (SC). All 7 747 637 liveborn children in Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015), and Sweden (1987-2015), where 171 735 children were conceived after ART, were included. National ART and medical birth registry data were cross-linked with data from other health and population registries. Outcomes were major CHDs, severe CHDs, 6 hierarchical CHD lesion groups, and 10 selected major CHDs, diagnosed prenatally or up to 1 year of age (Denmark, Finland, and Sweden) and prenatally or at birth (Norway). The association between ART and CHDs was assessed with multivariable logistic regression analysis, with adjustment for available confounders. Major CHDs were detected in 3159 children born after ART (1.84%) and in 86 824 children born after SC [1.15%; adjusted odds ratio (AOR) 1.36; 95% confidence interval (CI) 1.31-1.41]. Risk was highest in multiples, regardless of conception method. Severe CHDs were detected in 594 children born after ART (0.35%) and in 19 375 children born after SC (0.26%; AOR 1.30; 95% CI 1.20-1.42). Risk was similar between ICSI and IVF and between frozen and fresh embryo transfer. Assisted reproductive technology-conceived children have a higher prevalence of major CHDs, being rare, but severe conditions. The absolute risks are, however, modest and partly associated with multiple pregnancies, more prevalent in ART.

Safety of In-hospital Parenteral Antiosteoporosis Therapy Following a Hip Fracture: A Retrospective Cohort

Abstract Purpose To assess the safety of zoledronic acid (ZOL) and denosumab (Dmab) administered following hip fracture in a hospital setting. Methods Patients older than 65 years were treated by a fracture liaison service following hip fracture. Generally, patients who had a glomerular filtration rate (eGFR) &amp;gt; 35 mL/min were treated with ZOL, whereas patients who had previously received bisphosphonates or had a eGFR between 20 and 35 mL/min were treated with Dmab. Adverse events included hypocalcemia (calcium corrected for albumin less than 8.5 mg/day), renal functional impairment (0.5 mg/dL or more increase in serum creatinine) within 30 days of treatment, or a fever (&amp;gt;38 °C) within 48 hours of drug administration. Results Two hundred twenty-eight and 134 patients were treated with ZOL and Dmab, respectively. Mean body temperature was elevated following ZOL administration (0.18 °C P &amp;lt; .001) but remained below 38 °C. Hypocalcemia occurred in 18% and 29% of the ZOL and Dmab groups, respectively (P = .009). Renal functional impairment was observed in 9 and 6 patients (4% and 5%) in the ZOL and Dmab groups, respectively (P = .8). Pretreatment calcium above 9.3 mg/dL was associated with a lower risk of posttreatment hypocalcemia (odds ratio 0.30, 95% confidence interval 0.13-0.68, P = .004). While the absolute risk of hypocalcemia was higher in the Dmab group, multivariate analysis did not find that the choice of drug was predictive of hypocalcemia. Conclusion In-hospital parenteral osteoporosis treatment was rarely associated with fever or renal function impairment but was associated with hypocalcemia. Posttreatment hypocalcemia risk did not vary significantly between patients receiving ZOL or Dmab.

Simultaneous evaluation of the imprecision and inconsistency domains of GRADE can be performed using prediction intervals

ObjectivesTo explore the use of prediction interval (PI) for the simultaneous evaluation of the imprecision and inconsistency domains of Grading of Recommendations, Assessment, and Evaluation using stakeholder-provided decision thresholds. Study Design and SettingWe propose transforming the PI of a meta-analysis from a relative risk scale to an absolute risk difference using an appropriate baseline risk. The transformed PI is compared to stakeholder-provided thresholds on an absolute scale. We applied this approach to a large convenience sample of meta-analyses extracted from the Cochrane Database of Systematic Reviews and compared it against the traditional approach of rating imprecision and inconsistency separately using confidence intervals and statistical measures of heterogeneity, respectively. We used empirically derived thresholds following Grading of Recommendations, Assessment, and Evaluation guidance. ResultsThe convenience sample consisted of 2516 meta-analyses (median of 7 studies per meta-analysis; interquartile range: 5–11). The main analysis showed the percentage of meta-analyses in which both approaches had the same number of certainty levels rated down was 59%. The PI approach led to more levels of rating down (lower certainty) in 27% and to fewer levels of rating down (higher certainty) in 14%. Multiple sensitivity analyses using different thresholds showed similar results, but the PI approach had particularly increased width with a larger number of included studies and higher I2 values. ConclusionUsing the PI for simultaneous evaluation of imprecision and inconsistency seems feasible and logical but can lead to lower certainty ratings. The PI-based approach requires further testing in future systematic reviews and guidelines using context-specific thresholds and evidence-to-decision criteria. Plain Language SummaryThe prediction interval (PI) addresses both the imprecision and inconsistency domains of certainty. In this study, we applied this PI approach to simultaneously judge both domains and compared this to the traditional approach of making these separate judgments. The 2 approaches had moderate agreement. The PI-based approach requires further testing in future systematic reviews and guidelines using context-specific thresholds and evidence-to-decision criteria.

A Rare Coexistence of Turner Syndrome and Mycosis Fungoides: A Case Report.

Turner syndrome (TS) is the most common sex chromosome abnormality among females, characterised by short stature, hypergonadotropic hypogonadism, congenital heart anomalies, and an increased risk of autoimmune diseases. Although TS does not typically increase the absolute risk of malignancy, specific cancers, such as those affecting the nervous system and gastrointestinal tract and malignant melanoma, may occur more frequently. Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma, typically affecting adults but also seen in children and adolescents. We report an 11.2-year-old girl with TS presenting with substantial weight gain and short stature. Clinical examination revealed characteristic TS features and karyotype analysis confirmed mosaic TS. Following growth hormone (GH) therapy, the patient developed persistent, erythematous, itchy skin lesions diagnosed as CD4+ MF. GH therapy was discontinued, and topical steroids controlled the skin lesions effectively. MF in TS is rare and unexpected, especially in a child. The coexistence of these conditions suggests a potential link between TS and an increased risk of MF, possibly due to T-cell dysregulation or autoimmune processes. While the clinical course of MF is typically indolent, careful monitoring and annual dermatologic evaluations are recommended for TS patients, particularly when skin lesions are present. This is the first reported case of MF in a child with TS. This case emphasises the importance of carefully evaluating skin lesions in patients with TS and suggests considering MF as a differential diagnosis.

Statins in the Cause and Prevention of Cancer: Confounding by Indication and Mediation by Rhabdomyolysis and Phosphate Toxicity.

Statins are drugs used in cardiovascular pharmacotherapy to decrease hypercholesterolemia and lower the risk of atherosclerosis. Statins also increase the risk of rhabdomyolysis, which is often minimized in comparison with large relative risk reductions of cardiovascular disease reported in clinical trials. By contrast, absolute risk reductions of cardiovascular disease are often clinically insignificant and unreported in statin clinical trials. Additionally, cytotoxic effects of statins inhibit cancer cell proliferation and reduce cancer risk, but other studies found that statins are carcinogenic. Due to an inverse association between incidence of cancer and atherosclerosis, the indication to prescribe statins likely biases the association of statins with cancer prevention. Dietary patterns associated with atherosclerosis and cancer contain inverse amounts of cholesterol and phosphate, an essential mineral that stimulates tumorigenesis. Accordingly, lower cancer risk is associated with high dietary cholesterol intake and increased risk of atherosclerosis. Furthermore, serum is exposed to excessive inorganic phosphate that could increase cancer risk as rhabdomyolysis induced by statins releases phosphate from skeletal muscle breakdown. Increased risk of comorbid conditions associated with statins may share the mediating factor of phosphate toxicity. More research is warranted on statins in the cause and prevention of cancer.

On the Need for Better Information from Randomized Clinical Trials in Oncology

Cancer patients frequently seek information from their oncologists regarding the anticipated outcomes of their treatment. They commonly inquire about the potential for a cure and the likelihood of achieving it, as well as whether the treatment will prolong their life and, if so, by how much. In oncology, randomized controlled trials play a pivotal role in informing treatment decisions. It is essential that published randomized controlled trials provide comprehensive data to enable clinicians to deliver precise and reliable information to patients. The concept of the Hazard Ratio (HR) can be challenging for many oncologists and is often misunderstood in terms of its implications for risk. Thus, incorporating both relative and absolute risk metrics in addition to hazard ratios could substantially enhance patient care. This consideration is crucial not only for patients and oncologists but also for policymakers within public health systems.

Effectiveness of the First and Second Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Dose: A Nationwide Cohort Study From Austria on Hybrid Versus Natural Immunity.

We aimed to evaluate the effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations in previously SARS-CoV-2-infected adults in the general population of Austria during the Delta wave and with extended follow-up. In a nationwide retrospective cohort study, we calculated age-, sex-, and nursing home residency-adjusted Cox proportional hazard ratios (HRs) of coronavirus disease 2019 (COVID-19) deaths, SARS-CoV-2 infections, and non-COVID-19 deaths from 1 October to 31 December 2021, and secondarily with extended follow-up to 30 June 2022. Relative vaccine effectiveness (rVE) is rVE = (1 - HR) × 100. Among 494 646 previously infected adults, 169 543 had received 2 vaccine doses, 133 567 had received 1 dose, and 190 275 were unvaccinated at baseline. We recorded 17 COVID-19 deaths (6 vaccinated, 11 unvaccinated) and 8209 SARS-CoV-2 infections. Absolute risk of COVID-19 deaths was 0.003%. rVE estimates for COVID-19 deaths and reinfections exceeded 75% until the end of 2021 but decreased substantially with extended follow-up. The risk of non-COVID-19 death was lower in those vaccinated versus unvaccinated. First and second SARS-CoV-2 vaccine doses appear effective in the short-term, but with diminishing effectiveness over time. The extremely low COVID-19 mortality, regardless of vaccination, indicates strong protection of previous infection against COVID-19 death. Lower non-COVID-19 mortality in the vaccinated population might suggest a healthy vaccinee bias.

Effects of Mediterranean diet during pregnancy on the onset of overweight or obesity in the offspring: a randomized trial.

The PREMEDI study was designed to assess the efficacy of nutritional counseling aimed at promoting Mediterranean Diet (MD) during pregnancy on the incidence of overweight or obesity at 24 months in the offspring. PREMEDI was a parallel-arm randomized-controlled trial. 104 women in their first trimester of pregnancy were randomly assigned in a 1:1 ratio to standard obstetrical and gynecological care alone (CT) or with nutritional counseling promoting MD. Women enrolled in the MD arm were provided with 3 sessions of nutritional counseling (one session per trimester). The main outcome was the proportion of overweight or obesity among the offspring at the age of 24 months. Maternal MD-adherence and weight gain during pregnancy were also evaluated. Lastly, the evaluation of epigenetic modulation of metabolic pathways in the offspring was analyzed in cord blood. Five women in the MD arm and 2 in the CT arm were lost to follow-up, so a total of 97 completed the study. At 24 months, children of MD mothers were less likely to have overweight or obesity than those of the CT mothers (6% vs. 33%, absolute risk difference = -27%, 95% CI -41% to -12%, p < 0.001; number needed to treat 3, 95% CI 2 to 8, intention to treat analysis). A significantly higher increase of MD-adherence during the trial was observed in the MD arm compared to the CT arm. A similar body weight gain at the end of pregnancy was observed in the two arms. The mean (SD) methylation rate of the leptin gene in cord blood was 30.4 (1.02) % and 16.9 (2.99) % in the CT and MD mothers, respectively (p < 0.0001). MD during pregnancy could be an effective strategy for preventing pediatric overweight or obesity at 24 months. This effect involves, at least in part, an epigenetic modification of leptin expression.

Relationship between cumulative silica exposure and silicosis: a systematic review and dose-response meta-analysis

BackgroundSilicosis, a chronic respiratory disease caused by crystalline silica exposure, is a persistent global lung health issue. No systematic review of the relationship between cumulative respirable crystalline silica (RCS) exposure...

Impact of Biologics on Surgery in Chronic Rhinosinusitis with Polyps and Allergic Fungal Sinusitis.

To compare the efficacy of th2-targeted biologic medications (dupilumab, omalizumab, and mepolizumab) on absolute risk reduction (ARR) of functional endoscopic sinus surgery (FESS) in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) and allergic fungal rhinosinusitis (AFRS). The TriNetX Research Network database was queried for each mAb's market lifespan through March 2024. Adults with CRSwNP were propensity score matched against non-mAb controls based on age, sex, race, and asthma diagnosis. The primary outcome was rate of FESS, with secondary outcomes including inpatient admission, emergency department (ED) visit, and incidence of acute sinusitis. Subgroup analysis was performed for patients with AFRS. All mAbs decreased FESS risk (dupilumab, ARR 11.48%, 95% CI 9.82%-13.15%, p < 0.001; omalizumab, ARR 12.02%, 95% CI 4.36%-19.68%, p = 0.002; mepolizumab, ARR 10.32%, 95% CI 5.24%-15.40%, p < 0.001) in CRSwNP patients. Only dupilumab also reduced risk of inpatient admission (ARR 8.59%, 95% CI 7.04%-10.15%, p < 0.001), ED visit (ARR 5.94%, 95% CI 4.28%-7.61%, p < 0.001), and acute sinusitis (ARR 2.60%, 95% CI 1.09%-4.12%, p = 0.001). In AFRS patients, only dupilumab reduced the risk of all outcomes: FESS (ARR 6.97%, 95 CI 2.86%-11.09%, p = 0.001), inpatient admission (ARR 16.93%, 95% CI 11.30%-22.57%, p < 0.001), ED visit (ARR 13.15%, 95% CI 7.15%-19.14%, p < 0.001), and acute sinusitis (ARR 7.17%, 95% CI 2.18%-12.17%, p = 0.005). Although all mAbs reduced FESS risk in CRSwNP, only dupilumab reduced secondary outcomes as well. Similarly, only dupilumab improved all outcomes in AFRS patients. These data demonstrate the potential of mAbs in reducing disease burden and enhancing patient outcomes in CRSwNP and AFRS. NA Laryngoscope, 2024.

Sensitivity of the familial high-risk approach for the prediction of future psychosis: a total population study.

Children who have a parent with a psychotic disorder present an increased risk of developing psychosis. It is unclear to date, however, what proportion of all psychosis cases in the population are captured by a familial high-risk for psychosis (FHR-P) approach. This is essential information for prevention research and health service planning, as it tells us the total proportion of psychosis cases that this high-risk approach would prevent if an effective intervention were developed. Through a prospective cohort study including all individuals born in Finland between January 1, 1987 and December 31, 1992, we examined the absolute risk and total proportion of psychosis cases captured by FHR-P and by a transdiagnostic familial risk approach (TDFR-P) based on parental inpatient hospitalization for any mental disorder. Outcomes of non-affective psychosis (ICD-10: F20-F29) and schizophrenia (ICD-10: F20) were identified in the index children up to December 31, 2016. Of the index children (N=368,937), 1.5% (N=5,544) met FHR-P criteria and 10.3% (N=38,040) met TDFR-P criteria. By the study endpoint, 1.9% (N=6,966) of the index children had been diagnosed with non-affective psychosis and 0.5% (N=1,846) with schizophrenia. In terms of sensitivity, of all non-affective psychosis cases in the index children, 5.2% (N=355) were captured by FHR-P and 20.6% (N=1,413) by TDFR-P approaches. The absolute risk of non-affective psychosis was 6.4% in those with FHR-P, and 3.7% in those with TDFR-P. There was notable variation in the sensitivity and total proportion of FHR-P and TDFR-P cases captured based on the age at which FHR-P/TDFR-P were determined. The absolute risk for psychosis, however, was relatively time invariant. These metrics are essential to inform intervention strategies for psychosis risk requiring pragmatic decision-making.

Associations between physical diseases and subsequent mental disorders: a longitudinal study in a population-based cohort.

People with physical diseases are reported to be at elevated risk of subsequent mental disorders. However, previous studies have considered only a few pairs of conditions, or have reported only relative risks. This study aimed to systematically explore the associations between physical diseases and subsequent mentaldisorders. It examined a population-based cohort of 7,673,978 people living in Denmark between 2000 and 2021, and followed them for a total of 119.3 million person-years. The study assessed nine broad categories of physical diseases (cardiovascular, endocrine, respiratory, gastrointestinal, urogenital, musculoskeletal, hematological and neurological diseases, and cancers), encompassing 31 specific diseases, and the subsequent risk of mental disorder diagnoses, encompassing the ten ICD-10 groupings (organic, including symptomatic, mental disorders; mental disorders due to psychoactive substance use; schizophrenia and related disorders; mood disorders; neurotic, stress-related and somatoform disorders; eating disorders; personality disorders; intellectual disabilities; pervasive developmental disorders; and behavioral and emotional disorders with onset usually occurring in childhood and adolescence). Using Poisson regression, the overall and time-dependent incidence rate ratios (IRRs) for pairs of physical diseases and mental disorders were calculated, adjusting for age, sex and calendar time. Absolute risks were estimated with the Aalen-Johansen estimator. In total, 646,171 people (8.4%) were identified as having any mental disorder during follow-up. All physical diseases except cancers were associated with an elevated risk of any mental disorder. For the nine broad pairs of physical diseases and mental disorders, the median point estimate of IRR was 1.51 (range: 0.99-1.84; interquartile range: 1.29-1.59). The IRRs ranged from 0.99 (95% CI: 0.98-1.01) after cancers to 1.84 (95% CI: 1.83-1.85) after musculoskeletal diseases. Risks varied over time after the diagnosis of physical diseases. The cumulative mental disorder incidence within 15 years after diagnosis of a physical disease varied from 3.73% (95% CI: 3.67-3.80) for cancers to 10.19% (95% CI: 10.13-10.25) for respiratory diseases. These data document that most physical diseases are associated with an elevated risk of subsequent mental disorders. Clinicians treating physical diseases should constantly be alert to the possible development of secondary mental disorders.

Effectiveness and risk of ARB and ACEi among different ethnic groups in England: A reference trial (ONTARGET) emulation analysis using UK Clinical Practice Research Datalink Aurum-linked data.

Guidelines by the National Institute for Health and Care Excellence recommend an angiotensin receptor blocker (ARB) rather than an angiotensin-converting enzyme inhibitor (ACEi) for the treatment of hypertension for people of African and Caribbean descent, due to an increased risk of angioedema associated with ACEi use observed in US trials. However, the effectiveness and risk of these drugs in Black populations in UK routine care is unknown. We applied a reference trial emulation approach to UK Clinical Practice Research Datalink Aurum data (linked with data from Hospital Episode Statistics and Office for National Statistics) to study the comparative effectiveness of ARB and ACEi in ethnic minority groups in England, after benchmarking results against the ONTARGET trial. Approximately 17,593 Black, 30,805 South Asian, and 524,623 White patients receiving a prescription for ARB/ACEi between 1 January 2001 and 31 July 2019 were included with a median follow-up of 5.2 years. The primary composite outcome was cardiovascular-related death, myocardial infarction, stroke, or hospitalisation for heart failure with individual components studied as secondary outcomes. Angioedema was a safety endpoint. We assessed outcomes using an inverse-probability-weighted Cox proportional hazards model for ARB versus ACEi with heterogeneity by ethnicity assessed on the relative and absolute scale. For the primary outcome, 27,327 (18.0%) events were recorded in the ARB group (event rate: 25% per 5.5 person-years) and 80,624 (19.1%) events (event rate: 26% per 5.5 person-years) in the ACEi group. We benchmarked results against ONTARGET and observed hazard ratio (HR) 0.96 (95% CI: 0.95, 0.98) for the primary outcome, with an absolute incidence rate difference (IRD)% of -1.01 (95% CI: -1.42, -0.60) per 5.5 person-years. We found no evidence of treatment effect heterogeneity by ethnicity for the primary outcome on the multiplicative (Pint = 0.422) or additive scale (Pint = 0.287). Results were consistent for most secondary outcomes. However, for cardiovascular-related death, which occurred in 37,554 (6.6%) people, there was strong evidence of heterogeneity on the multiplicative (Pint = 0.002) and additive scale (Pint < 0.001). Compared to ACEi, ARB were associated with more events in Black individuals (HR 1.20 (95% CI: 1.02, 1.40); IRD% 1.07 (95% CI: 0.10, 2.04); number-needed-to-harm (NNH): 93) and associated with fewer events in White individuals (HR 0.91 (95% CI: 0.88, 0.93); IRD% -0.87 (95% CI: -1.10, -0.63); number-needed-to-treat (NNT): 115), and no differences in South Asian individuals (HR 0.97 (95% CI: 0.86, 1.09); IRD% -0.17 (95% CI: -0.87, 0.53)). For angioedema, HR 0.56 (95% CI: 0.46, 0.67) with no heterogeneity for ARB versus ACEi on the multiplicative scale (Pint = 0.306). However, there was heterogeneity on the additive scale (Pint = 0.023). Absolute risks were higher in Black individuals (IRD% -0.49 (95% CI: -0.79, -0.18); NNT: 204) compared with White individuals (IRD% -0.06 (95% CI: -0.09, -0.03); NNT: 1667) and no difference among South Asian individuals (IRD% -0.05 (95% CI: -0.15, 0.05) for ARB versus ACEi. These results demonstrate variation in drug effects of ACEi and ARB for some outcomes by ethnicity and suggest the potential for adverse consequences from current UK guideline recommendations for ARB in preference to ACEi for Black individuals.

Women living with HIV: identifying and managing their menopause, age-related, and psychosocial health needs in a metropolitan sexual health service in Sydney, Australia.

Background Aging women living with HIV are significantly affected by menopause and comorbidities, yet international and Australian HIV guidance on the management of women is scarce. This study aimed to identify gaps in clinical management of menopause, age-related comorbidities, and psychosocial health of women living with HIV attending our metropolitan sexual health service. Methods A clinical audit of all cisgender women who attended Sydney Local Health District Department of Sexual Health Medicine for ongoing routine HIV care between 1 January 2021 and 1 January 2023 was undertaken. Results Twenty-seven patient files were examined. Half (13/27, 48.1%) of women were age 45years and older, of whom 6/13 (46.2%) were postmenopausal and 4/13 (30.8%) did not have menopause status recorded. In the prior 12months, most women had their blood pressure (19/27, 70.4%), total cholesterol (21/27, 77.8%), glycated haemoglobin (21/27, 77.8%), estimated glomerular filtration rate (27/27, 96.3%), and liver function tests (26/27, 96.3%) measured. Smoking and alcohol intake was documented for less than half of women (13/27, 48.1%; and 12/27, 44.4%; respectively). In women aged 45years and older, absolute cardiovascular disease risk was calculated in 2/13 (15.4%), and none had a Fracture Risk Assessment Tool score or cognitive screen performed in the prior 12months. One-fifth (5/27, 18.5%) had a documented history of depression or anxiety. Of those screened, half (4/8, 50.0%) disclosed past intimate partner violence. Conclusions Our service has now implemented a reference tool to guide routine monitoring of women living with HIV, with sections dedicated to reproductive health and psychological wellbeing. Australian HIV management guidelines would benefit from specific guidance for women.