General Clinic Population Research Articles

Mental Health and Mobile Communication Profiles of Crowdsourced Participants.

Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) are highly prevalent and burdensome. To increase mental health screening rates, the digital health research community has been exploring the ability to augment self reporting instruments with digital logs. Crowdsourced workers are being increasingly recruited for behavioral health research studies as demographically representative samples are desired for later translational applications. Overshadowed by predictive modeling, descriptive modeling has the ability to expand knowledge and understanding of the clinical generalizability of models trained on data from crowdsourced participants. In this study, we identify mobile communication profiles of a crowdsourced sample. To achieve this, we cluster features derived from time series of call and text logs. The psychiatric, behavioral, and demographic characteristics were notably different across the four identified mobile communication profiles. For example, the profile that had the lowest average depression and anxiety screening scores only shared incoming text logs. This cluster had statistically significantly different depression and anxiety screening scores in comparison to the cluster that shared the most outgoing text logs. These profiles expose important insights regarding the generalizability of crowdsourced samples to more general clinical populations and increase understanding regarding the limitations of crowdsourced samples for translational mental health research.

Sex as a predictor of clinical phenotype and determinant of immune response in IgG4-related disease: a retrospective study of patients fulfilling the American College of Rheumatology-European League Against Rheumatism classification criteria.

IgG4-related disease is a multiorgan fibroinflammatory disease considered to have an autoimmune origin. Case series describing individual organ involvement have suggested differences in phenotypic expression between males and females. We aimed to characterise differences in IgG4-related disease manifestations between male and female patients in a large single-centre cohort. In this retrospective, single-centre cohort study, patients were recruited from the Massachusetts General Hospital Rheumatology Clinic (Boston, MA, USA) and classified according to the American College of Rheumatology-European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria. Only patients satisfying the ACR-EULAR classification criteria were included in the study. Data on age at diagnosis, organ involvement at baseline, treatment status, and pre-treatment laboratory values were collected. Circulating plasmablasts and B-cell subsets were quantitated by flow cytometry. Active disease was defined by an IgG4-related disease Responder Index score of more than 0. Laboratory values were analysed for patients who were untreated at baseline and had active IgG4-related disease. The main outcomes were assessed in all participants with available data. Of the 564 participants enrolled in the Massachusetts General Hospital Rheumatology Clinic IgG4-related disease Registry, 328 fulfilled ACR-EULAR classification criteria and were included between January, 2008, and May, 2023. There was a strong male predominance (male:female ratio 2·2:1) with 226 (69%) males and 102 (31%) females, which contrasted markedly with our general rheumatology clinic population (0·4:1; p<0·001). The male predominance increased with each decade of life starting at age 40 years. On average, male patients were 5·5 years older at diagnosis than female patients (63·7 years vs 58·2 years; p=0·0031). We observed male patients to have higher ACR-EULAR classification criteria scores at baseline with a median score of 35·0 (IQR 28·0-46·0), compared with 29·5 (25·0-39·0) for females (p=0·0010). The proportion of male patients with pancreatic and renal involvement was almost double the proportion observed in female patients (50% of the male patients had pancreatic involvement, compared with about 26% of the female patients; p<0·0001). Male patients were more likely to have serological abnormalities at baseline. The distribution of IgG4 values differed significantly between male an female sexes, favouring higher values in males. We found that male patients with IgG4-related disease were more likely to have active B-cell responses in the blood as defined by plasmablast expansions. IgG4-related disease is unusual among autoimmune diseases in that it is more likely to affect males than females and to present with a striking sex-dependent organ distribution and degree of B-cell response. These findings highlight important variation between IgG4-related disease and other conditions generally believed to have an autoimmune basis. Most autoimmune diseases, by contrast to IgG4-related disease, demonstrate pronounced predilections for affecting females more frequently than males. Hypotheses surrounding the cause and pathophysiology of this condition need to consider this unusual sex distribution among patients with IgG4-related disease. National Institutes of Health, National Institute of Allergy and Infectious Diseases, Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Low HDL cholesterol and the eNOS Glu298Asp polymorphism are associated with inducible myocardial ischemia in patients with suspected stable coronary artery disease

BackgroundThe endothelial nitric oxide synthase (eNOS) gene deficiency is known to cause impaired coronary vasodilating capability in animal models. In the general clinical population, the eNOS gene polymorphisms, able to affect eNOS activity, were associated with cardiometabolic risk features and prevalence of coronary artery disease (CAD).AimTo investigate the association of eNOS Glu298Asp gene polymorphism, cardiometabolic profile, obstructive CAD and inducible myocardial ischemia in patients with suspected stable CAD.MethodsA total of 506 patients (314 males; mean age 62 ± 9 years) referred for suspected CAD was enrolled. Among these, 325 patients underwent stress ECG or cardiac imaging to assess the presence of inducible myocardial ischemia and 436 patients underwent non-invasive computerized tomography or invasive coronary angiography to assess the presence of obstructive CAD. Clinical characteristics and blood samples were collected for each patient.ResultsIn the whole population, 49.6% of patients were homozygous for the Glu298 genotype (Glu/Glu), 40.9% heterozygotes (Glu/Asp) and 9.5% homozygous for the 298Asp genotype (Asp/Asp). Obstructive CAD was documented in 178/436 (40.8%) patients undergoing coronary angiography while myocardial ischemia in 160/325 (49.2%) patients undergoing stress testing. Patients with eNOS Asp genotype (Glu/Asp + Asp/Asp) had no significant differences in clinical risk factors and in circulating markers. Independent predictors of obstructive CAD were age, gender, obesity, and low HDL-C. Independent predictors of myocardial ischemia were gender, obesity, low HDL-C and Asp genotype. In the subpopulation in which both stress tests and coronary angiography were performed, the Asp genotype remained associated with increased myocardial ischemia risk after adjustment for obstructive CAD.ConclusionIn this population, low-HDL cholesterol was the only cardiometabolic risk determinant of obstructive CAD. The eNOS Glu298Asp gene polymorphism was significantly associated with inducible myocardial ischemia independently of other risk factors and presence of obstructive CAD.

Outcomes of collagenase Clostridium histolyticum in men with ventral curvatures: an updated series.

The efficacy and safety of collagenase Clostridium histolyticum (CCH) have been demonstrated in the treatment of men with Peyronie's disease (PD); however, the pivotal clinical trials excluded men with ventral penile curvature. The study sought to evaluate outcomes of CCH treatment in men with ventral curvatures secondary to PD. Men with PD treated with CCH were identified from a prospective database. Patients received up to 4 series of CCH injections using a progressively modified protocol over time. Results were compared between those with baseline ventral vs nonventral penile curvatures. Changes in penile curvature, Peyronie's Disease Questionnaire scores, International Index of Erectile Function scores, nonstandardized assessments, and adverse events. A total of 560 men with PD (85 ventral curvature, 475 nonventral curvature) were included in the analysis. Baseline median curvature was 60.0° (interquartile range, 48.8°-75.0°) in the ventral cohort and 65.0° (interquartile range, 45.0°-80.0°) in the nonventral cohort. Median change from baseline penile curvature was -25.0° in the ventral cohort vs -24.0° in the nonventral cohort (P = .08, between-group comparison), which corresponded to curvature reductions of 44.7% and 33.6%, respectively (P = .03). In the subset of patients who completed CCH treatment (ie, received 8 injections or discontinued early because of patient satisfaction with curvature reduction), median change from baseline was -35.0° in the ventral cohort vs -25.0° in the nonventral cohort (P < .05); median percent improvement was 48.3% and 37.5%, respectively (P = .11). Median change from baseline in Peyronie's Disease Questionnaire and International Index of Erectile Function domain scores and adverse events were similar between cohorts, with the exception of possibly higher hematoma rates in the nonventral group (50% vs 37%; P = .05). No urethral injuries were sustained in either cohort. Data support the use of CCH for the treatment of ventral as well as nonventral penile curvatures in men with PD. Study strengths are the inclusion of a general clinical population of men with PD, the prospective design, and the relatively large series of men with ventral curvature. Limitations include the single-center and observational nature of the study. CCH was safe and effective in the treatment of both ventral and nonventral penile curvatures in men with PD.

The incidence of transfusion-related acute lung injury using active surveillance: A systematic review and meta-analysis.

Transfusion-related acute lung injury (TRALI) is a leading cause of transfusion-related mortality. A concern with passive surveillance to detect transfusion reactions is underreporting. Our aim was to obtain evidence-based estimates of TRALI incidence using meta-analysis of active surveillance studies and to compare these estimates with passive surveillance. We performed a systematic review and meta-analysis of studies reporting TRALI rates. A search of Medline and Embase by a research librarian identified studies published between January 1, 1991 and January 20, 2023. Prospective and retrospective observational studies reporting TRALI by blood component (red blood cells [RBCs], platelets, or plasma) were identified and all inpatient and outpatient settings were eligible. Adult and pediatric, as well as general and specific clinical populations, were included. Platelets and plasma must have used at least one modern TRALI donor risk mitigation strategy. A random effects model estimated TRALI incidence by blood component for active and passive surveillance studies and heterogeneity was examined using meta-regression. Eighty studies were included with approximately 176-million blood components transfused. RBCs had the highest number of studies (n = 66) included, followed by platelets (n = 35) and plasma (n = 34). Pooled TRALI estimates for active surveillance studies were 0.17/10,000 (95% confidence intervals [CI]: 0.03-0.43; I2 = 79%) for RBCs, 0.31/10,000 (95% CI: 0.22-0.42; I2 = <1%) for platelets, and 3.19/10,000 (95% CI: 0.09-10.66; I2 = 86%) for plasma. Studies using passive surveillance ranged from 0.02 to 0.10/10,000 among the various blood components. In summary, these estimates may improve a quantitative understanding of TRALI risk, which is important for clinical decision-making weighing the risks and benefits of transfusion.

Self-Perception of HIV Risk and Interest in Pre-Exposure Prophylaxis in a General Obstetrics and Gynecology Clinic Population.

Background: Pre-exposure prophylaxis (PrEP) for HIV is underutilized, particularly among attendees of obstetrics and gynecology (Ob/Gyn) clinics. Lack of self-perception of HIV risk is a barrier to PrEP utilization, and a lack of understanding of community risk factors for HIV may contribute to that lack of self-perception of risk. Methods: Attendees of general Ob/Gyn clinics in New Orleans completed a survey assessing HIV knowledge, self-perception of HIV risk, and interest in PrEP. They reviewed a brief written educational intervention on demographic and behavioral risk factors for HIV and availability of PrEP. HIV knowledge, self-perception of HIV risk, and interest in PrEP were reassessed after the intervention. Results: One-hundred seventy individuals completed the survey. Eighty-five participants (50%) expressed initial interest in PrEP. Self-perception of risk of HIV acquisition was associated with interest in PrEP. Ten of 11 (90.9%) respondents who had high self-perceived risk of HIV were interested in PrEP, compared with 75 of 159 (47.2%) of those who had low self-perceived risk (p = 0.01). The association remained significant in a multivariate analysis. After the intervention, the number of those who perceived themselves to be at risk of HIV increased from 11 to 25 individuals (p < 0.01) and 20 of these (80%) were interested in PrEP. Knowledge of HIV risk factors increased (p < 0.01). The intervention did not significantly alter interest in PrEP. Conclusions: Self-perception of HIV risk was associated with interest in PrEP. A brief written educational intervention increased knowledge of HIV risk factors and increased self-perception of risk of HIV. The intervention did not translate to increased interest in PrEP.

Predictors of pelvic pain in a general urology clinic population.

To assess the prevalence and predictors of chronic pelvic pain in a general urology population presenting for evaluation of unrelated non-painful complaints.Generalized pelvic pain is estimated to afflict between 6% and 26% of women and is often multifactorial in aetiology. A paucity of prospective research exists to characterize chronic pelvic pain patterns and to understand related predictors. This is a prospective, cross-sectional survey-based study of female patients presenting to a general urology clinic over a 10-month period (7/2018-5/2019). Patients completed a 32-item survey with questions pertaining to demographics, comorbidities and chronic pelvic pain characteristics. Comparison tests (chi-squared, Fisher's exact) and stepwise multivariable logistic modelling were performed to assess for predictors of chronic pelvic pain. A total of 181 women completed the survey, with a mean age of 56 years. Overall, 75 (41%) women reported chronic pelvic pain. Those with chronic pelvic pain were younger compared to those without (52 vs 59 years, p= 0.001). Univariable logistic regression analysis identified BMI, depression, fibromyalgia, overactive bladder and any bowel symptoms as possible positive predictors of chronic pelvic pain. Final best-fit multivariable model found overactive bladder, fibromyalgia and presence of bowel symptoms as independent positive predictors of chronic pelvic pain. Our study is one of the few studies that has prospectively analysed chronic pelvic pain and its predictors. The present study identified significant associations with overactive bladder, fibromyalgia and bowel symptoms. Further research is needed to better understand the aetiologies of chronic pelvic pain and the possible relationship with identified clinical predictors.

#4727 FLOZINATION: A ROLLING QUALITY IMPROVEMENT PROGRAMME

Abstract Background and Aims Sodium glucose linked transporter-2 inhibitors (SGLT2i) reduce renal and cardiovascular end points in people with chronic kidney disease (CKD), both with and without diabetes. Despite exciting data from the CREDENCE and DAPA-CKD trials, implementation of new evidence to every day clinical practice can be challenging. We present the results of a rolling quality improvement project regarding SGLT2i prescription. The aim of the project was to support clinicians in the evidence based prescribing of SGLT2i for CKD. Method Three renal units who share a single electronic clinical database agreed a joint protocol and staged implementation programme. These tertiary referral renal units cover a population of around 2.3 million people. The important timeline regarding SGLT2i licensing and interventions is shown in Figure 1. Interventions were as follows: 1. Identification of patients meeting the licensing criteria for prescription of canagliflozin for CKD with diabetes. 2. Addition of an alert to the electronic patient record. 3. SGLT2i protocol developed and advertised via poster in outpatient clinic sites. 4. Evaluation of clinician attitude to prescribing. 5. Measurement of number of patients meeting the licensing criteria for prescription of dapagliflozin for CKD with and without diabetes. Measurement of SGLT2i prescription was audited from the electronic record. Results In the first wave of the programme, 326 patients were identified as suitable under the initial licensing criteria for canagliflozin, and electronic alerts were added to the records of these patients. When measuring number of patients who may be suitable under the dapagliflozin licensing, there were 562 patients with diabetes and 5262 without diabetes. In a survey of clinician attitudes, 94% suggested they felt well equipped to prescribe SGLT2i. Prescribing of SGLT2i across time is shown in Figure 2. 1146 patients have been prescribed SGLT2i. Age was 64±13 years, and the majority were male (68%) with type 2 diabetes mellitus (61%). Most (73.6%) were treated with angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB). More than half (54%) of patients live in areas with high levels of socio-economic deprivation (Scottish Index of Multiple Deprivation quintiles 1 or 2). Estimated glomerular filtration rate was 40.9±23.5ml/min/1.73 m2 and Kidney Failure Risk Equation (KFRE) 5 year risk of end stage kidney disease (ESKD) was 23.2±28.2%. In comparison with the general outpatient clinic population, the distribution of socioeconomic deprivation was similar, but a higher proportion were female (46%). Conclusion An iterative quality improvement project was designed around the evolving drug licensing of SGLT2i and capitalised on local strengths, including an effective and well used clinical electronic database shared across renal units. Clinicians have been supported in SGLT2i prescribing with highly visible clinical protocols, and electronic alerts to highlight candidate patients. A high level of SGLT2i prescribing has been achieved in a population at high risk of ESKD. Further interventions should focus on prescribing in groups where gaps have been identified – such as women and those without diabetes. Other units would be recommended to capitalise on existing strengths, exploit the use of clinical databases, and ensure protocols are inclusive and well-advertised in order to optimise evidence based treatment of CKD.

Are student cohorts with psychopathology representative of general clinical populations? The case for OCD

A longstanding assumption suggests that college student cohorts are not representative of clinical cohorts as students are perceived as ‘high functioning’ which may limit generalizability. Yet little research has compared the profile of DSM disorders among students to those reported in community or treatment-seeking samples, particularly in the context of obsessive-compulsive disorder (OCD). To address this gap in the literature, we compared the profile of DSM OCD in college students, to treatment-seeking and community OCD samples, and student subsamples with other DSM disorders, or with no diagnosis. 529 students from two US and one Belgian university were screened using semi-structured interviews and completed self-report questionnaires. 36 students met DSM criteria for OCD. Comparison with non-OCD diagnoses (n = 183), and non-clinical student controls (n = 311) yielded expected differences on symptomatic OCD measures and comorbidity profiles. Comparisons with published OCD samples yielded a similar profile. Therefore, OCD in students is similar to OCD in clinical samples, with minor differences. We conclude that when appropriately screened, students are a viable population for the study of OCD. This may enhance research into OCD, allowing researchers without access to clinical cohorts to contribute to the field.

Demographics and clinical presentations of 844 patients with light and dark skin types with polymorphous light eruption and chronic actinic dermatitis evaluated over 23 years.

Polymorphous light eruption (PMLE) and chronic actinic dermatitis (CAD) have been classically described in White individuals, although recent studies have reported higher prevalence in patients with dark skin types, particularly African Americans. To evaluate for differences in demographic, and clinical features between persons with light and dark skin types who have PMLE and CAD. Retrospective review of patients with PMLE and CAD who were diagnosed from January 1, 1998, through November 31, 2021, at a single academic dermatology center. A total of 844 patients (725 [85.9%] female; mean [SD] age of onset: 41.7 [16.9] years) were diagnosed with PMLE, and 60 patients (22 [36.6%] female; mean age, [SD]: 60.6 [10.6] years) of age at presentation, disease duration of 8.2 [7.3] years were diagnosed with CAD. Although just over 50% of the general clinic population was White, the prevalence of PMLE and CAD was significantly higher in dark-skinned individuals compared to light-skinned individuals (PMLE: 625 [74.0%] vs. 219 [25.9%], p value < .001; CAD: 43 [71.6%] vs. 17 [28.3%], p value=.003) respectively. The pinpoint papular variant of PMLE (PP-PMLE) was predominantly seen in dark-skinned individuals. A substantial proportion of PMLE and CAD cases are present in dark-skinned individuals. PP-PMLE can be mistaken for lichen nitidus. As such, recognition of this entity is important for adequate evaluation and management of patients with PMLE.

1768. Characteristics and Impact of Penicillin Allergy Mislabeling Among People with HIV

Abstract Background Rates of penicillin allergy mislabeling (PAM) are prevalent and lead to suboptimal antibiotic selection. However, data regarding PAM are lacking for people with HIV (PWH). We aimed to characterize the penicillin allergy labels for PWH at the University of California, San Diego’s (UCSD) HIV primary care clinic, evaluate the impact of penicillin allergy labels on treatment choice for syphilis and gonorrhea, and implement a quality improvement project to address PAM. Methods We conducted a cross-sectional study of PWH with a penicillin allergy label in their medical record who were seen in our clinic between 2018 and 2022. We collected demographic information, type of allergic reaction listed, whether patients tolerated other beta-lactam antibiotics, whether patients were referred for formal Allergy consultation, and, where relevant, what treatment they received for syphilis and/or gonorrhea. Results Among the 4,702 people with HIV receiving care in our clinic between 2018 and 2022, 427 (9.1%) had a penicillin allergy label in the medical record. This cohort reflected the demographics of the general clinic population (Table 1). Even though the majority of allergic reactions (327, 77%) were labeled as IgE-mediated, 282 (66%) patients tolerated another beta-lactam antibiotic (Table 2). Referrals to Allergy Clinic were rare (52, 12%). The majority of patients with syphilis (91/140, 65%) received 2nd line therapy with doxycycline. However, most patients with gonorrhea (65/88, 74%) were treated with a preferred ceftriaxone-based regimen. When relevant, we updated penicillin labels for 209/268 (77.9%) patients to indicate that they had tolerated other beta-lactam antibiotics and created a tiered referral process to prioritize the highest-risk patients for Allergy Clinic referral (Figure 1). Conclusion Penicillin allergy labels were prevalent in our cohort of PWH and often resulted in receiving 2nd line therapy for treatment of syphilis. We updated allergy labels for a substantial number of patients and created a triage system to refer patients to Allergy clinic for further testing based on risk in order to decrease PAM. Disclosures All Authors: No reported disclosures.

Association of eNOS Glu298Asp polymorphism with cardiometabolic risk and inducible myocardial ischemia in patients with stable coronary artery disease

Abstract Background The endothelial nitric oxide synthase (eNOS) gene deficiency is known to cause insulin resistance, hypertension, hypertriglyceridemia and impaired coronary vasodilating capability in animal models. In the general clinical population, the eNOS gene polymorphism (Glu298Asp, G894T), able to reduce eNOS activity, was associated either with features of the metabolic syndrome or prevalence of coronary artery disease (CAD). Purpose To investigate the possible association of Glu298Asp polymorphism with cardiometabolic risk [insulin resistance, increased triglycerides (TG) and low HDL-cholesterol (HDL-C)], obstructive CAD and inducible myocardial ischemia in stable patients with suspected coronary disease. Methods Six cardiology units enrolled a total of 506 consecutive patients (314 males; mean age 62±9 years) referred for suspected CAD within the BIOGEN-CARE Tuscan Region Italian Study. Among these, 325 patients underwent stress ECG or cardiac imaging to assess the presence of inducible ischemia and 436 patients underwent non invasive computerized tomography or invasive coronary angiography to assess the presence of obstructive CAD (&amp;gt;50% stenosis in at least one major coronary vessel). Blood samples were collected from each patient for genotyping and measurements of lipid and glucose parameters. The TG/HDL-C ratio and the TyG-index [ln(TG × Fasting plasma glucose/2)] were used as synthetic markers of atherogenic dyslipidemia and insulin resistance, main components of the cardiometabolic risk. Results In the whole population, 49.6% of patients were homozygous for the G894allele, 40.9% heterozygotes, and 9.5% homozygous for T894. Myocardial ischemia was documented in 160/325 (49.2%) patients undergoing stress testing and obstructive CAD in 178/436 (40.8%) patients undergoing coronary angiography. Patients carrying the T allele (dominant model TT+GT vs GG) had higher TG/HDL ratio (2.7±1.8 vs 2.5±1.9, P=0.03) (Figure) without differences in other lipid and glucose markers. Independent predictors of obstructive CAD were age, gender, obesity, diabetes and TG/HDL-C ratio but not the the T allele (OR 0.80; CI 0.51–1.25; ns). Independent predictors of inducible ischemia were age, gender, obesity and the T allele (OR 1.91; CI 01.19–3.08; P=0.007). Stratifying the population for both obstructive CAD and ischemia, the T allele was associated with increased risk of ischemia (OR 1.96; CI 1.11–3.44; P=0.02) even after adjustment for the presence of obstructive CAD (OR 3.09; CI 1.85–5.78; P&amp;lt;0.001) (Figure 1). Conclusions In stable patients with suspected CAD, the eNOS Glu298Asp gene polymorphism is an independent risk factor for inducible myocardial ischemia and is significantly associated with the specific cardiometabolic risk expressed by high TG and low HDL-C which independently predicts obstructive CAD. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): “BIOhumoral and GENetic predictors of CARdiac Evolving phenotype in Ischemic Heart Disease (BIOGENCARE-IHD)”; funded by Toscan Region-Programma per la ricerca regionale in materia di Salute 2009

The prevalence of the ABCB1-1Δ variant in a clinical veterinary setting: The risk of not genotyping.

Multidrug sensitivity is an autosomal recessive disorder in dogs caused by a 4-bp deletion in the ABCB1 gene, often referred to as the ABCB1-1Δ variant. This disease has a high prevalence in some breeds and causes adverse reactions to certain drugs when given in normal doses. Though most dogs known to be at risk are of the collie lineage or were traced back to it, the variant has also been described in several seemingly unrelated breeds. It is generally advised to genotype dogs at risk before treating them. However, there seems to be a discrepancy between the advice and current veterinary practices, as a recent study in Belgium and the Netherlands showed that most veterinarians never order a DNA test. To assess the possible risk of not testing for multidrug sensitivity in a clinical setting, the ABCB1-1Δ variant allele frequency was established in a sample of 286 dogs from a veterinary clinic. This frequency was compared to the allelic frequency in 599 samples specifically sent for genetic testing. While the allelic frequency in the sample for genetic testing was high (21.6%) and in line with the general reports, the allelic frequency in the clinical setting was low (0.2%), demonstrating an enormous difference between laboratory and clinical frequencies. Because of the low frequency of the disease-causing variant in the general clinical population, the risk of encountering a dog displaying multidrug sensitivity despite not genotyping seems to be low. As the variant was only found in an at-risk breed, the current recommendation of routinely genotyping at-risk breeds before treatment seems justified.

Loss-of-Function FLNC Variants Are Associated With Arrhythmogenic Cardiomyopathy Phenotypes When Identified Through Exome Sequencing of a General Clinical Population.

The FLNC gene has recently garnered attention as a likely cause of arrhythmogenic cardiomyopathy, which is considered an actionable genetic condition. However, the association with disease in an unselected clinical population is unknown. We hypothesized that individuals with loss-of-function variants in FLNC (FLNCLOF) would have increased odds for arrhythmogenic cardiomyopathy-associated phenotypes versus variant-negative controls in the Geisinger MyCode cohort. We identified rare, putative FLNCLOF among 171 948 individuals with exome sequencing linked to health records. Associations with arrhythmogenic cardiomyopathy phenotypes from available diagnoses and cardiac evaluations were investigated. Sixty individuals (0.03%; median age 58 years [47-70 interquartile range], 43% male) harbored 27 unique FLNCLOF. These individuals had significantly increased odds ratios for dilated cardiomyopathy (odds ratio, 4.9 [95% CI, 2.6-7.6]; P<0.001), supraventricular tachycardia (odds ratio, 3.2 [95% CI, 1.1-5.6]; P=0.048), and left-dominant arrhythmogenic cardiomyopathy (odds ratio, 4.2 [95% CI, 1.4-7.9]; P=0.03). Echocardiography revealed reduced left ventricular ejection fraction (52±13% versus 57±9%; P=0.001) associated with FLNCLOF. Overall, at least 9% of FLNCLOF patients demonstrated evidence of penetrant disease. FLNCLOF variants are associated with increased odds of ventricular arrhythmia and dysfunction in an unselected clinical population. These findings support genomic screening of FLNC for actionable secondary findings.

Ventilatory Ratio Is a Valuable Prognostic Indicator in an Observational Cohort of Patients With ARDS.

How indices specific to respiratory compromise contribute to prognostication in patients with ARDS is not well characterized in general clinical populations. The primary objective of this study was to identify variables specific to respiratory failure that might add prognostic value to indicators of systemic illness severity in an observational cohort of subjects with ARDS. Fifty subjects with ARDS were enrolled in a single-center, prospective, observational cohort. We tested the contribution of respiratory variables (oxygenation index, ventilatory ratio [VR], and the radiographic assessment of lung edema score) to logistic regression models of 28-d mortality adjusted for indicators of systemic illness severity (the Acute Physiology and Chronic Health Evaluation [APACHE] III score or severity of shock as measured by the number of vasopressors required at baseline) using likelihood ratio testing. We also compared a model utilizing APACHE III with one including baseline number of vasopressors by comparing the area under the receiver operating curve (AUROC). VR significantly improved model performance by likelihood ratio testing when added to APACHE III (P = .036) or the number of vasopressors at baseline (P = .01). Number of vasopressors required at baseline had similar prognostic discrimination to the APACHE III. A model including the number of vasopressors and VR (AUROC 0.77 [95% CI 0.64-0.90]) was comparable to a model including APACHE III and VR (AUROC 0.81 [95% CI 0.68-0.93]; P for comparison = .58.). In this observational cohort of subjects with ARDS, the VR significantly improved discrimination for mortality when combined with indicators of severe systemic illness. The number of vasopressors required at baseline and APACHE III had similar discrimination for mortality when combined with VR. VR is easily obtained at the bedside and offers promise for clinical prognostication.

Opioids and older adults: Increasing trends in opioid usage in a dental population compared to a National Database (NHANES).

AimTo examine self‐reported opioid prevalence at a dental school clinic for patients ≥65 years old as compared to national data, comparing gender, ethnicity/race and older adult age groupings.Methods and resultsSelf‐reported prescription opioid medication use was extracted from the medical record for dental patients ≥65 years old who visited the school's general dental clinic (GDC) in 2012 or 2017. This data was compared to the National Health and Nutrition Examination Survey (NHANES) data for 2011–2012 and 2017–18. There was a significant increase in prevalence of opioid use in adults ≥65 between 2012 (4.5%) and 2017 (6.5%) and for ages 65–79 (from 4.7% to 6.3%) and ≥80 (3.4% to 7.9%), women (4.8% to 7.0%), and African Americans (4.7% to 8.4%) in the GDC. Older adults at the GDC reported less opioid use than the NHANES national average for both periods no matter the gender or the age with variable results for race/ethnicity.ConclusionThe prevalence of older adults taking opioids in our general dental school clinic population increased significantly in 2017 as compared to 2012 but was lower than the national average for the respective periods. Awareness of existing opioid usage in older adult patients and its higher adverse risk potential is critical when prescribing analgesics for dental pain for this age group.

Adenovirus-Based Vaccines and Thrombosis in Pregnancy: A Systematic Review and Meta-analysis.

BackgroundRare cases of thrombosis and thrombocytopenia (thrombosis with thrombocytopenia syndrome [TTS]) have been associated with 2 coronavirus disease 2019 adenovirus vector vaccines: the ChAdOx1 nCoV-19 Vaxzevria vaccine (Oxford/AstraZeneca) and the JNJ-7836735 Johnson & Johnson vaccine (Janssen). It is unknown if TTS is a class-mediated effect of adenovirus-based vaccines or if it could worsen known hypercoagulable states. Since most cases of TTS happen in women of childbearing age, pregnancy is a crucial risk factor to assess. Understanding these risks is important for advising vaccine recipients and future adenovirus vector vaccine development.MethodsTo explore the potential associations of adenovirus-based vaccine components with symptoms of TTS in the general clinical trial population and in pregnant women in clinical trials, we conducted a systematic review and meta-analysis of adenovirus-based vector vaccines to document cases of thrombocytopenia, coagulopathy, and or pregnancy from 1 January 1966 to 9 August 2021.ResultsWe found 167 articles from 159 studies of adenovirus vector–based vaccines, 123 of which targeted infectious diseases. In the general population, 20 studies reported an event of thrombocytopenia and 20 studies indicated some coagulopathy. Among pregnant women, of the 28 studies that reported a total of 1731 pregnant women, thrombocytopenia or coagulopathy were not reported.ConclusionsIn this systematic review and meta-analysis, there was no class-wide effect of adenovirus vector vaccines toward thrombocytopenia or coagulopathy events in the general population or in pregnant women.

Comparison of joint hypermobility in general and orthopaedic clinic population in south India

Background: Generalised joint hypermobility (GJH) is associated with musculoskeletal symptoms. Beighton score is universally used to measure hypermobility and the cut off score of ≥4 is quoted in literature to define GJH. No data exists on the prevalence of GJH in patients attending orthopaedic outpatients in India. Materials and methods: The objective of this study was to compare the prevalence of GJH in the general versus orthopaedic patients. 406 patients attending a wellness clinic and 1780 patients attending orthopaedic outpatient clinic in a large private hospital in south India were scored for hypermobility using Beighton score. The mean age of the cohorts attending the wellness clinic and orthopaedic clinic was 33.47± 11.63 years and 36.37± 9.36 years respectively. There were more males than females recruited in the orthopaedic clinic. Results: The wellness group had significantly higher numbers in the 20 to 39 year age range compared to the orthopaedic group (p value &lt;0.00001). There was a significantly higher proportion of zero Beighton score in the orthopaedic group (p value &lt;0.00001). The proportion of people with Beighton score 4-9 in the wellness and orthopaedic groups were 33% and 3.3% respectively. The proportion of GJH with Beighton score 5-9 was 16% and 2% in the wellness and orthopaedic groups respectively. Conclusions: This is the only study, to the best of our knowledge, to have attempted to compare GJH prevalence in orthopaedic patients with a control group. The prevalence of GJH is significantly higher in the general population than the orthopaedic out-patients. Beighton score is simple to perform and must be included in the management of every orthopaedic patient.

Obstructive Sleep Apnea and Cardiac Arrhythmias: A Contemporary Review.

Obstructive sleep apnea (OSA) is a highly prevalent disorder with a growing incidence worldwide that closely mirrors the global obesity epidemic. OSA is associated with enormous healthcare costs in addition to significant morbidity and mortality. Much of the morbidity and mortality related to OSA can be attributed to an increased burden of cardiovascular disease, including cardiac rhythm disorders. Awareness of the relationship between OSA and rhythm disorders is variable among physicians, a fact that can influence patient care, since the presence of OSA can influence the incidence, prevalence, and successful treatment of multiple rhythm disorders. Herein, we provide a review of this topic that is intentionally broad in scope, covering the relationship between OSA and rhythm disorders from epidemiology and pathophysiology to diagnosis and management, with a particular focus on the recognition of undiagnosed OSA in the general clinical population and the intimate relationship between OSA and atrial fibrillation.

Patient Awareness of Head and Neck Cancer Risk Factors: Assessment of the General Otolaryngology Population

Objective: The general public’s knowledge of the risk factors for head and neck cancer is insufficient. The level of awareness of such risk factors amongst the otolaryngology clinic patient population has not yet been elucidated in the literature. Method: This individual cohort study took place at a tertiary academic center. A survey was designed and administered to all patients who presented to otolaryngology clinic from 2017 to 2018 to assess knowledge of head and neck cancer risk factors. The main outcome measures were percentage of correct responses for each cancer risk factor and comparison of percent correct between cancer and non-cancer patients. Results: A total of 510 patients were enrolled in the study including 69 patients (13.5%) with a history of head and neck cancer. The most well recognized risk factors by all patients were cigarettes (83.7%) and chewing tobacco (77.5%). Twenty-nine percent of patients correctly identified alcohol as a risk factor. Additional risk factors were poorly recognized. Cancer patients had a similar or better correct response rate than non-cancer patients except for chewing tobacco (68.1% vs 78.9% respectively). Conclusion: The general otolaryngology clinic population, especially patients with a history of head and neck cancer, demonstrated improved knowledge of some risk factors for head and neck cancer, but insufficient awareness of alcohol and HPV transmissible behaviors.