Dexamethasone for Cardiac Surgery: A Practice Preference-Randomized Consent Comparative Effectiveness Trial.

BACKGROUND: High-dose corticosteroids have been used to attenuate the inflammatory response to cardiac surgery and cardiopulmonary bypass, but patient outcome benefits remain unclear. Our primary aim was to determine whether using dexamethasone was superior to not using dexamethasone to increase the number of home days in the first 30 days after cardiac surgery. Our secondary aim was to evaluate efficiency, value and impact of the novel trial design. METHODS: This pragmatic, international trial incorporating a prerandomized consent design favoring local practice enrolled patients undergoing cardiac surgery across 7 hospitals in Australia and The Netherlands. Patients were randomly assigned to dexamethasone, 1 mg/kg, or not (control). The primary outcome was the number of days alive and at home up to 30 days after surgery ("home days"). Secondary outcomes included prolonged mechanical ventilation (>48 h), sepsis, renal failure, myocardial infarction, stroke and death. RESULTS: Of 2093 patients assessed for eligibility, 1951 were randomized (median age 63 years, 80% male). The median number of home days was 23.0 (IQR, 20.1 to 24.1) in the dexamethasone group and 23.1 (IQR, 20.1 to 24.6) in the no dexamethasone group; median difference 0.1 (95% CI, -0.3 to 0.5), P=0.66. The rates of prolonged mechanical ventilation, RR 0.72 (95% CI, 0.48 to 1.08), sepsis, RR 1.02 (95% CI, 0.57 to 1.82), renal failure, RR 0.94 (95% CI, 0.80 to 1.12), myocardial infarction, RR 1.20 (95% CI, 0.30 to 4.82), stroke, RR 1.06 (95% CI, 0.54 to 2.08), and death, RR 0.72 (95% CI, 0.22 to 2.35), were comparable between groups (all P>0.10). Dexamethasone reduced intensive care unit stay, median 29 (IQR, 22 to 50) h vs. 43 (24 to 72) h, P=0.004. Our novel trial design was highly efficient (89.3% enrolment). CONCLUSIONS: Among patients undergoing cardiac surgery, high-dose dexamethasone decreased intensive care unit stay but did not increase the number of home days after surgery.

Animal and human bites: Navigating evaluation and care.

ABSTRACT: Patients who have experienced animal or human bites may present for care in a number of settings with a variety of injuries requiring different approaches to treatment and management. Because animal and human bites range in severity and can result in a host of sequelae, their evaluation and management can be complex. In caring for patients with an animal or human bite, NPs must consider the many factors relevant to such an injury.

Epidemiology of fractures in adults of African ancestry with diabetes mellitus: A systematic review and meta-analysis.

Diabetes mellitus (DM) is associated with increased fracture risk in White adults. However, the impact of DM on fractures in Black adults is unknown. This systematic review and meta-analysis investigated the association between DM and fractures in adults of African ancestry. MEDLINE, Scopus, CINAHL and Embase databases were searched from their inception up to November 2023 for all studies in the English language investigating the epidemiology of fractures (prevalence, incidence, or risk) in Black men and women (age ≥ 18 years) with type 1 or type 2 DM. Effect sizes for prevalence of previous fractures (%) and incident fracture risk (hazard ratio [HR]) were calculated using a random-effects model on Stata (version 18.0). There were 13 eligible studies, of which 12 were conducted in Black adults from the United States, while one was conducted in adults of West African ancestry from Trinidad and Tobago. We found no fracture data in Black adults with DM living in Africa. Five studies were included in a meta-analysis of incident fracture risk, reporting data from 2926 Black and 6531 White adults with DM. There was increased risk of fractures in Black adults with DM compared to non-DM (HR = 1.65; 95 % confidence interval [CI]: 1.14, 2.39). The risk of fractures was also higher in White adults with DM compared to non-DM (HR = 1.31; 95 % CI: 1.06, 1.61) among these studies. Five studies were included in a meta-analysis of fracture prevalence, of which three also reported fracture prevalence in White adults. There were 175 previous fractures among 993 Black adults with DM and 384 previous fractures among 1467 White adults with DM, with a pooled prevalence of 17.5 % (95 % CI: 15.4, 19.6) and 25.8 % (95 % CI: 4.8, 46.8), respectively. Our results indicate a high burden of fractures in Black adults with DM.

Developmental milestones in captive Galago moholi.

Systems of the body develop in a modular manner. For example, neural development in primates is generally rapid, whereas dental development varies much more. In the present study, we examined development of the skull, teeth, and postcrania in a highly specialized leaping primate, Galago moholi. Eighteen specimens ranging from birth to adult were studied. Bones, teeth, and the cranial cavity (i.e., endocast) were reconstructed with Amira software based on microCT cross-referenced to histology. Amira was also used to compute endocast volume (as a proxy for brain size). Reconstructions of the wrist and ankle show that ossification is complete at 1 month postnatally, consistent with the onset of leaping locomotion in this species. Endocranial volume is less than 50% of adult volume at birth, ~80% by 1 month, and has reached adult volume by 2 months postnatal age. Full deciduous dentition eruption occurs by 2 weeks, and the young are known to begin capturing and consuming arthropods on their own by 4 weeks, contemporaneous with the timing of bone and ankle ossification that accompanies successful hunting. The modular pattern of development of body systems in Galago moholi provides an interesting view of a "race" to adult morphology for some joints that are critical for specialized leaping and clinging, rapid crown mineralization to begin a transitional diet, but perhaps more prolonged reliance on nursing to support brain growth.

Experiences of oral pre-exposure prophylaxis use among heterosexual men accessing sexual and reproductive health services in South Africa: a qualitative study.

INTRODUCTION: South African men face a substantial burden of HIV and are less likely to test for HIV and initiate antiretroviral therapy if tested positive and more likely to die from AIDS-related causes than women. In addition to condoms and circumcision, guidelines provide for the use of daily oral pre-exposure prophylaxis (PrEP) as an HIV prevention intervention for any men who recognize their need and request PrEP. However, heterosexual men have not been a focus of PrEP programmes, and since its introduction, there is limited literature on PrEP use among men in South Africa. This study explores the experiences, motivators and barriers to oral PrEP use among heterosexual men accessing primary healthcare services in South Africa. METHODS: This study forms part of a mixed-methods implementation science study aimed at generating evidence for oral PrEP introduction and conducted in primary healthcare clinics in South Africa since 2018. Men aged ≥15 years who initiated oral PrEP and enrolled in a parent cohort study were purposefully invited to participate in an in-depth interview (IDI). Between March 2020 and May 2022, 30 men participated in IDIs exploring their motivators for PrEP use, and experiences with accessing health services. Interviews were audio recorded, transcribed and analysed thematically. RESULTS: The final analysis included 28 heterosexual men (18-56 years old). Motivations to initiate PrEP included fear of acquiring HIV, self-perceived vulnerability to HIV and mistrust in relationships; health systems factors which motivated PrEP use included the influence of healthcare providers, educational materials and mobile services. Perceived reduction in HIV vulnerability and changing proximity to partners were reasons for PrEP discontinuation. Side effects, daily-pill burden and stigma were noted as challenges to PrEP use. Health system barriers to PrEP use included limited PrEP availability, school and work demands, and inconsistent mobile clinic schedules. CONCLUSIONS: Our study reports on the experiences of heterosexual men accessing oral PrEP in real-world settings and contributes to the limited literature among this population. We highlight multiple levels which could be strengthened to improve men's PrEP use, including individual support, education among partners and communities, and addressing health system barriers to access.

Treatment of Depression in Adolescents With Myasthenia Gravis.

Myasthenia gravis (MG) is an autoimmune disorder in which, most commonly, there is a production of autoantibodies against the nicotinic acetylcholinergic receptors at the neuromuscular junction, resulting in skeletal muscle weakness. For pediatric patients, literature addressing the psychiatric implications of MG and suitable treatment options for individuals with concurrent psychiatric illnesses is scarce. In this case report, an adolescent with MG and comorbid depression was treated following a suicide attempt via self-poisoning. The patient experienced an improvement of depressive symptoms upon initiating fluoxetine, despite concerns raised by previous studies suggesting that fluoxetine might block acetylcholine receptors at the neuromuscular junction with varying degrees of affinity, potentially worsening MG symptoms. In this case, our patient exhibited sustained control of her MG symptoms without exacerbation once she was started on fluoxetine. This case highlights the value of further investigation into the safety and efficacy of selective serotonin reuptake inhibitors (SSRIs) in the management of depression among pediatric patients with MG.

The effect of an extended-hours ED clinical pharmacy service on admission medication prescribing errors.

OBJECTIVE: The aim of this study was to determine the effect of a 7-day extended-hours clinical pharmacy service in the ED on medication prescribing errors upon hospital admission and time to medication reconciliation. METHODS: In this retrospective observational study, high-needs patients reviewed by ED pharmacists were compared against those not reviewed, to determine if the service was associated with reduction in admission medication errors. The primary outcome was the rate of medication errors. Errors were independently rated by two senior clinicians using a risk-probability matrix. Secondary outcomes included service's impact on time to best possible medication history (BPMH) and medication reconciliation. RESULTS: There were 242 patients who met the inclusion criteria: 105 intervention vs 137 control. In the intervention arm, 74 patients had at least 1 medication error compared with 113 in the control arm (total errors 206 vs 407). The error rate per 10 medications (interquartile range) was 1.4 (0, 2.9) in the intervention arm compared with 2.7 (1.2, 4.3) in the control arm (risk ratio 0.66 [95% confidence interval: 0.56-0.78]; P < 0.001). There were 33 moderate-risk and no high-risk errors (intervention), compared with 84 moderate-risk and 3 high-risk errors (control). Percent agreement was 98.98% (weighted kappa: 0.62). Time to BPMH and medication reconciliation were reduced from 40.5 and 45.0 h to 7.8 and 40.0 h, respectively. CONCLUSIONS: The 7-day extended-hours ED clinical pharmacy service was associated with a reduction in medication prescribing errors in high-needs patients and improved time to BPMH and medication reconciliation.

Key programmatic and policy considerations for introducing multipurpose prevention (MPT) methods: reflections from healthcare providers and key stakeholders in South Africa.

Introduction: Multipurpose prevention technologies (MPTs) simultaneously prevent HIV, other sexually transmitted infections, and/or unintended pregnancy. Key gatekeepers, [healthcare providers (HCPs) and key stakeholders] require proactive engagement before product implementation. This manuscript identifies HCP demand creation strategies, key stakeholder considerations for the adoption of MPTs in South Africa. Methods: Formative research was conducted in three districts in three South African provinces (July to November 2022). Nurses initiating oral PrEP at facility and mobile study sites participated in 4-hour participatory workshops, exploring HIV prevention, including MPTs, demand creation strategies, and preferred MPTs training packages. Activities were observed, transcribed, and thematically analysed. Five online in-depth interviews (IDIs) with Key informants (KIs) (National/district programme implementers and technical leads) and one in person, exploring key programmatic and policy considerations for MPT adoption. IDIs were approximately 40 min long, audio recorded, transcribed, and thematically analysed. Results: Twenty-one Professional Nurses completed workshops: 19 female. Six IDIs were conducted with 4 Facility Managers, 1 NDoH representative and 1 DoH Provincial Deputy Director. All participants were females, aged 30-60+ years with >10 years' in SRH/HIV policy/advocacy/research. Community conversations and information at the clinic were the best MPT demand creation methods among HCPs. KIs identified five considerations for future MPT implementation: HCP training; demand creation and messaging; existing PrEP policy amendments; preparing users for additional choice; and sustaining MPT provision. Conclusion: Contraceptive implant and oral PrEP implementation lessons learned should be proactively considered when preparing for MPT introduction. HCP training and demand creation are of particular importance before MPT introduction.

Assessment of weight gain in adult patients living with HIV receiving first-line dolutegravir-based or efavirenz-based ART regimens in routine care clinics in Tshwane district, South Africa: An observational study.

INTRODUCTION: Although dolutegravir (DTG) is deemed stable, safe, cost-effective, and clinically beneficial, it also carries the risk of side effects, including observed weight gain among patients on DTG-based antiretroviral therapy (ART) regimens. We compared weight changes among adults (≥18 years) initiating tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) or tenofovir disoproxil fumarate, emtricitabine, and efavirenz (TEE) regimens and those switching from TEE to TLD (TEE-to-TLD switchers) in three large primary care facilities in South Africa METHODS: We conducted a retrospective longitudinal record review using patient medical records, extracting relevant demographic and clinical data from October 2018 to June 2021 from randomly selected adults who initiated TLD or TEE (initiators) and adult TEE-to-TLD switchers. We assessed weight, body mass index (BMI), and percentage weight changes for both groups and fitted linear regression and generalized linear models to determine factors associated with weight and BMI change and percentage weight change ≥10%, respectively, among treatment initiators. We fitted linear mixed-effect models among TEE-to-TLD switchers to consider repeated measures. RESULTS: Of 860 initiators, 450 (52.3%) initiated on TEE and 410 (47.7%) on TLD, with median follow-up of 1.4 years and 1.0 year, respectively. At initiation, 43.3% on TEE and 40.8% on TLD were overweight or obese. TLD initiators had an adjusted higher mean weight gain of 1.6 kg (p < 0.001) and mean BMI gain of 0.51 kg/m2 (p < 0.001) than TEE initiators. Independent risk factors for higher mean weight and BMI included age ≥50 years, male, on ART for >12 months, initial BMI of <18.5 kg/m2, and CD4 counts <200 cells/µL. Of 298 TEE-to-TLD switchers, 36.6% were overweight or obese at TEE initiation. Comparing before and after TLD switch, TEE-to-TLD switchers had an adjusted mean weight of 1.2 kg less while on TLD (p = 0.026). Being overweight and CD4 counts >350 cells/µL were independent risk factors for lower weight gain after TLD switch. CONCLUSIONS: We report more weight gain among TLD than among TEE initiators, although to a lesser extent than previously reported. TEE-to-TLD switchers experienced less weight gain after TLD switch; return to health before receiving TLD may be a contributory factor. The current findings are reassuring for those switching to a DTG-based regimen.

Transcriptional landscape of human keratinocyte models exposed to 60-GHz millimeter-waves.

The use of millimeter waves (MMW) will exponentially grow in the coming years due to their future utilization in 5G/6G networks. The question of possible biological effects at these frequencies has been raised. In this present study, we aimed to investigate gene expression changes under exposure to MMW using the Bulk RNA Barcoding and sequencing (BRB-seq) technology. To address this issue, three exposure scenarios were performed aiming at: i) comparing the cellular response of two primary culture of keratinocytes (HEK and NHEK) and one keratinocyte derivate cell line (HaCaT) exposed to MMW; ii) exploring the incident power density dose-effect on gene expression in HaCaT cell line; and, iii) studying the exposure duration at the new ICNIRP exposure limit for the general population. With the exception of heat effect induced by high power MMW (over 10 mW/cm2), those exposure scenarios have not enabled us to demonstrate important gene expression changes in the different cell populations studied. Very few differentially genes were observed between MMW exposed samples and heat shock control, and most of them were significantly associated with heat shock response that may reflect small differences in the heat generation. Together these results show that acute exposure to MMW has no effects on the transcriptional landscape of human keratinocyte models under athermal conditions.

Neuropathic Pain With and Without Diabetic Peripheral Neuropathy in Type 1 Diabetes.

OBJECTIVE: Diabetic peripheral neuropathy (DPN) is common; however, the features and burden of neuropathic pain (NP) in type 1 diabetes (T1D) are poorly understood. We evaluated the incidence of first occurrence, annual prevalence, remission, and risk factors for NP during long-term follow-up of participants with T1D. RESEARCH DESIGN AND METHODS: The Michigan Neuropathy Screening Instrument (MNSI) was administered annually (1994-2020) for 1,324 participants in the Epidemiology of Diabetes Interventions and Complications (EDIC) study. NP with clinical signs of DPN (NP DPN+) was defined according to self-reported NP plus an examination score >2, while NP without clinical signs of DPN (NP DPN-) was defined according to self-reported NP and an examination score ≤2. RESULTS: At EDIC year 1, median age for participants was 36 years (interquartile range 30, 41), diabetes duration 13 years (10, 18), and HbA1c 7.9% (7.2, 8.9). At year 26 (median diabetes duration 39 years), cumulative incidence of NP was 57%, regardless of concomitant clinical signs of DPN (36% NP DPN+ vs. 46% NP DPN-). NP prevalence was 20% at 26 years (11% NP DPN+ and 9% NP DPN-), suggesting frequent remission. Annualized remission rates were similar regardless of pain medication use. In addition to HbA1c, female sex was associated with NP DPN-. CONCLUSIONS: NP incidence in T1D was high and frequently occurred in the absence of clinical signs of neuropathy, as assessed with the MNSI. Pain remission was not explained by pain medication use. Effective clinical strategies for identification and management are needed.

Treatment and prognostic implications of strong PD-L1 expression in primary hepatic sarcomatoid carcinoma.

Primary hepatic sarcomatoid carcinoma (HSC) is an extremely rare and aggressive subtype of primary liver cancer. HSC has uncertain pathogenesis and dismal prognosis with overall survival of only 8.3 months. The molecular alterations of HSC are also not well understood. In this study, the authors describe a patient who presented with a large liver mass. The patient underwent complete surgical resection and histological examination demonstrated HSC, infiltrating the stomach. PD-L1 was strongly positive in the tumor cells. The patient was started on anti-PD-L1 immunotherapy postsurgery and is doing well 15 months after surgical resection. Tumor whole exome sequencing revealed genetic alterations in TP53, NF2 and MAGEC3 genes, indicating their potential role in tumor development.

Primary sarcomatoid cancer of the liver is a rare type of severe cancer that generally has a very poor prognosis. People diagnosed with primary sarcomatoid of the liver normally survive for only a few months. Surgery is not very effective in treating this type of cancer and recurrence is common even after complete removal. In this paper, the authors report a patient who presented to them with a large liver tumor. The patient underwent operation and the tumor was completely removed from the liver. Pathological testing of the tumor revealed it was severe primary sarcomatoid liver cancer. The patient was started on an immunotherapy treatment. The treatment enhanced the ability of the body's immune system to fight cancer. The patient is doing well 15 months after the operation, which might mean that this type of immunotherapy treatment after surgery helps prolong the life of people diagnosed with primary sarcomatoid cancer of the liver.

Infectious and sepsis presentations to, and hospital admissions from emergency departments in Victoria, Australia.

OBJECTIVE: To investigate the frequency and outcomes of adult infectious and sepsis presentations to, and hospital admissions from, Emergency Departments (EDs) in Victoria, Australia. METHODS: Retrospective cohort study using the Victorian Emergency Minimum Dataset and Victorian Admitted Episodes Dataset. We included adults (age ≥ 18 years) presenting to an ED, or admitted to hospital from ED in Victoria between July 2017 and June 2018. One-year mortality was analysed until June 2019 using the Victorian Death Index, and ICD-10 coding was used to identify cases. RESULTS: Among 1.28 million ED presentations over 1 year, 12.00% and 0.45% were coded with infectious and sepsis diagnoses, respectively. Despite having lower triage categories, patients with infections were more likely to be admitted to hospital (50.4% vs 44.9%), but not directly to ICU (0.8%). Patients coded with sepsis were assigned higher triage categories and required hospital admission much more frequently (96.4% vs 44.9%), including to ICU (15.9% vs 0.8%). Patients presenting with infections and sepsis had increased risk of 1-year mortality (adjusted hazard ratio 1.44 and 4.13, respectively). Of the 648 280 hospital admissions from the ED, infection and sepsis were coded in 23.69% and 2.66%, respectively, and the adjusted odds ratio for 1-year mortality were 1.64 and 4.79, respectively. CONCLUSIONS: Infections and sepsis are common causes of presentation to, and admission from the ED in Victoria. Such patients experience higher mortality than non-infectious patients, even after adjusting for age. There is a need to identify modifiable factors contributing to these outcomes.

Factors influencing the uptake of a mono-PrEP implant for the prevention of HIV: Males' perspectives from three South African provinces.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) is an effective HIV prevention method; however, males over 15 years face challenges with its effective use. Long-acting prevention products could address barriers to effective PrEP use. This study aimed to estimate the potential uptake of a mono-PrEP implant and the factors influencing uptake among males in South Africa. The study also examined messaging and demand creation tactics that males perceive will improve HIV prevention uptake. METHODS: We conducted a mixed methods study comprising participatory workshops and a self-administered survey among 142 PrEP-eligible males (18-40 years) in three provinces (Gauteng, Eastern Cape, and Kwa-Zulu Natal) in South Africa from July to November 2022. Logistic regression was used to assess the relationship between the potential uptake of a hypothetical, non-biodegradable mono-PrEP implant and socioeconomic and behavioural factors. Workshop data were analysed using content analysis. RESULTS: The top three HIV prevention products that males would consider using were the monthly pill (74.6%), the mono-PrEP implant (62.7%), and event-driven oral PrEP (59.2%). If one prevention option was available, 31.7% of participants stated that they would use the monthly oral pill, 28.2% would use the six-monthly injection, and 19.7% the mono-PrEP implant. Four key themes were noted as influential to potential mono-PrEP uptake: "Health Over Everything", "Mono-PrEP Implant Concerns", "Potential Disclosure of Mono-PrEP Use", and "Information Distribution Channels". Participants preferred social and mainstream media as information distribution channels to receive information on HIV prevention services, including the mono-PrEP implant. CONCLUSION: In this study among predominantly heterosexual men in South Africa, there was interest in long-acting HIV prevention methods but concerns about the mono-PrEP implant. A comprehensive and participatory introduction will be needed for the implant, to improve acceptability and address potential concerns. Demand-creation strategies utilising social media and health campaigns should be considered to engage and reach males.

Association of Baseline Factors With Glycemic Outcomes in GRADE: A Comparative Effectiveness Randomized Clinical Trial.

OBJECTIVE: To describe the individual and joint associations of baseline factors with glycemia, and also with differential effectiveness of medications added to metformin. RESEARCH DESIGN AND METHODS: Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) participants (with type 2 diabetes diagnosed for <10 years, on metformin, and with HbA1c 6.8-8.5%; N = 5,047) were randomly assigned to a basal insulin (glargine), sulfonylurea (glimepiride), glucagon-like peptide 1 agonist (liraglutide), or dipeptidyl peptidase 4 inhibitor (sitagliptin). The glycemic outcome was HbA1c ≥7.0%, subsequently confirmed. Univariate and multivariate regression and classification and regression tree (CART) analyses were used to assess the association of baseline factors with the glycemic outcome at years 1 and 4. RESULTS: In univariate analyses at baseline, younger age (<58 years), Hispanic ethnicity, higher HbA1c, fasting glucose, and triglyceride levels, lower insulin secretion, and relatively greater insulin resistance were associated with the glycemic outcome at years 1 and/or 4. No factors were associated with differential effectiveness of the medications by year 4. In multivariate analyses, treatment group, younger age, and higher baseline HbA1c and fasting glucose were jointly associated with the glycemic outcome by year 4. The superiority of glargine and liraglutide at year 4 persisted after multiple baseline factors were controlled for. CART analyses indicated that failure to maintain HbA1c <7% by year 4 was more likely for younger participants and those with baseline HbA1c ≥7.4%. CONCLUSIONS: Several baseline factors were associated with the glycemic outcome but not with differential effectiveness of the four medications. Failure to maintain HbA1c <7% was largely driven by younger age and higher HbA1c at baseline. Factors that predict earlier glycemic deterioration could help in targeting patients for more aggressive management.

Nirmatrelvir/Ritonavir Utilization for the Treatment of Non-hospitalized Adults with COVID-19 in the National Veterans Affairs (VA) Healthcare System.

INTRODUCTION: Limited data exist regarding real-world utilization of nirmatrelvir/ritonavir. We identified predictors of nirmatrelvir/ritonavir use among Veterans Affairs (VA) outpatients nationally. METHODS: We conducted a retrospective cohort study among outpatients with coronavirus disease 2019 (COVID-19) who were eligible to receive nirmatrelvir/ritonavir between January and December of 2022, to identify factors associated with nirmatrelvir/ritonavir use (i.e., demographics, medical history, prior medication and healthcare exposures, frailty, and other clinical characteristics) using multivariable logistic regression. RESULTS: We included 309,755 outpatients with COVID-19 who were eligible for nirmatrelvir/ritonavir, of whom 12.2% received nirmatrelvir/ritonavir. Nirmatrelvir/ritonavir uptake increased from 1.1% to 23.2% over the study period. Factors associated with nirmatrelvir/ritonavir receipt included receiving a COVID-19 booster vs. none (adjusted odds ratio [aOR] 2.19 [95% confidence interval [CI] 2.12-2.26]), age ≥ 50 vs. 18-49 years (aORs > 1.5 for all age groups ≥ 50 years), having HIV (aOR 1.36 [1.22-1.51]), being non-frail vs. severely frail (aOR 1.22 [1.13-1.33]), and having rheumatoid arthritis (aOR 1.12 [1.04-1.21). Those with concomitant use of potentially interacting antiarrhythmics (aOR 0.35 [0.28-0.45]), anticoagulants/antiplatelets (aOR 0.42 [0.40-0.45]), and/or psychiatric/sedatives (aOR 0.84 [0.81-0.87]) were less likely to receive nirmatrelvir/ritonavir. CONCLUSIONS: Despite increases over time, overall utilization of nirmatrelvir/ritonavir was low. Predictors of nirmatrelvir/ritonavir utilization were consistent with known risk factors for progression to severe COVID-19, including older age and underlying medical conditions. Unvaccinated and undervaccinated patients and those receiving potentially interacting medications for cardiovascular or mental health conditions (antiarrhythmic, alpha-1 antagonist, anticoagulant/antiplatelet, sedative/hypnotic/psychiatric) were less likely to receive nirmatrelvir/ritonavir. Further education of prescribers and patients about nirmatrelvir/ritonavir treatment guidelines is needed to improve overall uptake and utilization in certain high-risk subpopulations.

Tobacco use behavior among adults exposed to cumulative adverse childhood experiences: A systematic review and meta analysis.

BACKGROUND: Tobacco use remains one of the most used substances among adults globally and substantially impacts individuals and society. Adverse childhood experiences (ACEs) contribute to tobacco use. However, the association between cumulative ACEs and tobacco use behaviors (TUB) has not been established in the literature. In this review, we aimed to estimate the prevalence of ACEs among adult tobacco users and evaluated the relationship between cumulative ACEs and TUB. METHODS: We identified original articles published before October 2022 by searching PubMed, CINAHL, and Psych INFO databases. Inclusion criteria were: English language, adults and used instruments assessing for cumulative ACEs defined as four or more ACEs. RESULTS: Forty-two studies, totaling 674,087 participants; predominantly cohort and cross-sectional in study design (n = 33). Exposure to 4 ≥ ACEs was significantly associated with increasing the odds of current tobacco use (n = 35), ever or former tobacco use (n = 13), tobacco use initiation, (n = 3) nicotine dependence (n = 1), and ever using electronic cigarettes (n = 1). In the meta-analysis, as compared to those without ACEs, those with 4 ≥ ACEs were twice as likely to have ever used tobacco (OR = 2.16, 95 %CI:1.73-2.70) and approximately four times more likely to have used tobacco currently (OR = 3.73, 95 %CI:2.69-5.18). CONCLUSION: The cumulative ACEs exposure can increase the risk for TUB. However, the evidence is limited primarily to cigarette use. Ongoing research into the effects of cumulative ACEs on TUB is needed to integrate trauma-informed intervention in treating tobacco use and guide public health initiatives aimed to reduce the prevalence of ACEs and TUB among adults.

Infections in inflammatory bowel disease patients on immunomodulator and biologic therapy are not associated with high serum drug levels.

BACKGROUND: Inflammatory bowel disease (IBD) therapies now utilise higher doses of immunomodulatory and biologic therapies, predisposing patients to an increased risk of infections. AIMS: We aimed to determine whether infections were associated with high anti-tumour necrosis factor (TNF) drug levels in IBD and to quantify the risk and consequences of infections. METHODS: Two retrospective studies were performed, a descriptive cohort study and a matched case-control study. For the matched case-control study, cases of infection occurring on anti-TNF agents were matched in a 1:2 ratio to controls of anti-TNF treated patients without infections. RESULTS: In the descriptive study, 76 infections occurred in 60 patients, including 49 bacterial, 24 viral, four fungal and four parasitic. Of these, 61 (80.3%) were on biologics, 49 (64.5%) on immunomodulators and 11 (14.5%) on corticosteroids. Thirty-four (44.7%) were on combination therapy, 27 (35.5%) on biologic monotherapy and 15 (19.7%) on immunomodulator monotherapy. Median anti-TNF drug levels in infection cases were 3.9 µg/mL for infliximab and 6.0 µg/mL for adalimumab. In the case-control study, 32 cases of infection in 27 anti-TNF treated patients were matched with 64 anti-TNF treated controls without infections. Among infection cases, 59.5% were on combination therapy versus 40.6% on biologic monotherapy (P = 0.59). Median drug levels for cases and controls respectively were 3.9 µg/mL versus 5.5 µg/mL for infliximab (P = 0.72) and 6.0 µg/mL versus 9.9 µg/mL for adalimumab (P = 0.34). CONCLUSION: Infections in patients with IBD were common, and the risk was highest with combination therapy. Infections were not associated with high serum anti-TNF levels.