Prescription Of Therapy Research Articles

Association of testosterone replacement therapy with atrial fibrillation and acute kidney injury.

Secondary analyses of the Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) trial revealed significantly higher rates of new-onset atrial fibrillation (AF) and acute kidney injury (AKI) in the testosterone replacement therapy (TRT) cohort. To validate the secondary findings of the TRAVERSE trial. We utilized the TriNetX Research Network to identify a cohort of men ages 45-80years old who met similar inclusion criteria to the TRAVERSE trial. We compared hypogonadal men (testosterone 100-300ng/dL) who had a prescription for topical testosterone therapy and men who did not. Propensity score matching was used to match patient populations. Kaplan Meier survival analysis was used to determine the relative risk of new-onset AF and AKI within 3years. New-onset AF and AKI within 3years. There were 2134 men included in each cohort after propensity score matching. Men on TRT had significantly lower testosterone (T) at the time of diagnosis compared to men not prescribed TRT (207 ± 66ng/dL vs 246 ± 140ng/dL, P< 0.001). Kaplan-Meier survival analysis showed a significantly increased risk of AKI among men on TRT (RR 1.53, 95% CI 1.07-2.18). However, TRT was not associated with a significantly increased risk of new-onset AF (RR 1.48, 95% CI 0.93-2.37). Hypogonadal men with underlying cardiovascular risk factors or pre-existing cardiovascular disease who receive TRT may be at increased risk of AKI after starting therapy. We evaluated a large global research database and utilized similar inclusion and exclusion to the TRAVERSE trial. However, our results are limited by the retrospective study design and reliance on documented claims data. Similar to the TRAVERSE trial, our study demonstrated an increased risk of AKI among men on TRT, but did not find increased risk of AF. However, further studies are required to validate these results.

Feasibility of a multifaceted nutrition-risk screening tool for mental health settings: the NutriMental screener.

People living with mental illness report a broad spectrum of nutrition risks, beyond malnutrition, but appropriate and adequately validated nutrition risk screening tools for mental health settings are lacking. This study aimed to develop a nutrition-risk screening tool, the NutriMental Screener, and to perform preliminary feasibility and validity testing. In an international, stakeholder engaging approach, a multifaceted nutrition-risk screening tool for mental health services was developed by means of workshops with international stakeholders and two online surveys. Feasibility of the NutriMental screener was tested as part of a research study in Switzerland with 196 participants, evenly distributed across the three study groups (sixty-seven outpatients and sixty-five inpatients with psychotic or depressive disorders as well as sixty-four controls without mental illness). The NutriMental screener consists of ten items covering different nutritional issues that indicate the need for referral to a dietitian or clinical nutritionist. Almost all patients (94·7 %) reported at least one nutrition risk by means of the NutriMental screener. Prevalence for nutrition risks via NutriMental screener was higher in patients than in controls. Almost every second patient expressed a desire for nutritional support (44·7 %). After further validity testing is completed, there is the potential for the NutriMental Screener to replace malnutrition screening tools as routine screening in various mental health settings aiming to organise nutritional therapy prescriptions in a more targeted and efficient manner.

Temporal trends in clinical outcomes in heart failure patients with and without atrial fibrillation: a nationwide study from 1997-2018

Abstract Background Given the many advances in treating heart failure (HF) and atrial fibrillation (AF) separately over the past decades, it remains unclear how the prognosis of patients diagnosed with both conditions has changed over time. Purpose We aimed to investigate the temporal trends in all-cause mortality, HF hospitalisation, and stroke from 1997 to 2018 in patients diagnosed with both HF and AF. Methods From Danish nationwide registries, we identified 152,059 patients with a first-time HF-diagnosis from 1997 to 2018. Patients were categorised into groups based on their AF status: prevalent AF (n=34,734), new-onset AF (n=12,691), and absence of AF (n=104,634). Patients were further subdivided into four year groups (1997-2001, 2002-2006, 2007-2012, 2013-2018), based on the year of HF onset. The primary outcome of interest was the absolute five-year risk of all-cause mortality, and key secondary outcomes were HF hospitalisation and stroke, investigated using the Aalen-Johansen estimator, accounting for competing risk of death. Results Between 1997 and 2018 the proportion of patients with new-onset HF and prevalent AF increased from 17.0% (n = 6,372) to 27.7% (n = 11,569), while those with concurrent new-onset AF increased from 7.7% (n = 2,884) to 8.1% (n = 3401). Contrary, the proportion of patients decreased among those with no AF from 75.3% (n = 28,235) to 64.2% (n = 26,850). The five-year risk of all-cause mortality decreased from 69.1% (95% CI): 67.9%-70.2%) to 51.3% (49.9%-52.7%), 62.3% (60.5%-64.4%) to 43.0% (40.5%-45.5%), and 61.9% (61.3%-62.4%) to 36.7% (35.9%-37.6%) for the prevalent AF, new-onset AF, and no AF group, respectively (Figure 1). The five-year risk of HF hospitalisation went from 33.3% (32.1%-34.4%) to 30.3% (29.2%-31.4%) in the prevalent AF group, from 25.8% (24.2%-27.4%) to 29.6% (27.7%-31.5%) in the new-onset AF group, and from 28.4% (27.8%-28.9%) to 28.0% (27.2%-28.6%) in the no AF group. The five-year risk of stroke decreased from 8.5% (7.8%-9.1%) to 5.0% (4.4%-5.5%) in the prevalent AF group, 8.2% (7.2%-9.2%) to 4.6% (3.7%-5.5%) in the new-onset AF group, and 6.3% (6.1%-6.6%) to 4.9% (4.6%-5.3%) in the no AF group (Figure 2). Simultaneously, the proportion of patients prescribed anticoagulant therapy within 90 days after HF onset increased from 42.7% to 93.1% in patients with prevalent AF and 41.9% to 92.5% in patients with new-onset AF. Conclusion From 1997 to 2018, we observed an increase in patients with HF and coexisting AF. The five-year risk of mortality and stroke decreased across all patient groups regardless of AF-status. Additionally, prescriptions of anticoagulation therapy increased, and stroke risk in patients with HF and AF was reduced to similar levels as patients with HF without AF at the end of the study period.Figure 1 - Mortality in HF patientsFigure 2 - Stroke risk in HF patients

Sex-differences in prescription patterns of secondary prevention pharmacotherapy in patients with acute myocardial infarction: a 20-year perspective

Abstract Background Recent studies have demonstrated sex-related differences in secondary prevention pharmacotherapy in patients with acute myocardial infarction (AMI), although guidelines recommend the same preventive approach in both women and men. Purpose This study extends earlier work by examining temporal trends of prescribing practices of secondary prevention medications using contemporary data from a long-term period in Switzerland, with particular regard to sex inequalities. Methods For the purpose of this retrospective analysis of prospectively collected data in the Acute Myocardial Infarction in Switzerland (AMIS) Plus registry, optimal medical therapy (OMT) was defined as the combination of all five guideline-recommended medications in AMI at discharge: aspirin, P2Y12 inhibitors, lipid-lowering drugs, beta blockers, and angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Uni- and multivariable logistic regression analyses were performed. Results A total of 34'612 patients (men n=25’913, 75%) hospitalised with AMI between 2003 and 2022 were included in the analysis. The mean age was 66±13 years and women were on average 7 years older than men. Despite having more comorbidities, women benefited less frequently from OMT than men (51% vs. 60%) across all age groups (all p&amp;lt;0.001), with the greatest gap occurring in patients &amp;lt;50 years of age. Within the 20-year study period, significant increases over time were observed in the singular prescription of all OMT components, except for beta blockers (p=0.2). This translated into a marked increase in OMT prescription irrespective of age and sex (from 36% to 60%), mainly due to greater prescription of dual antiplatelet therapy (DAPT, from 71% to 91%) and lipid-lowering drugs (LLD, from 69% to 93%). The sex-related gap in OMT disfavoring women showed a uctuating trend over the years (getting reduced from 14% in 2003 to 0.7% in 2016 to widen again to 12% in 2022) whereas there was a continuous narrowing over time regarding the combination of DAPT plus LLD, from 18% to 10% at the beginning and the end of the observation, respectively (Figure 1). In multivariable analysis, age (OR 0.99, 95%CI 0.98-0.99, p&amp;lt;0.001) and female sex (OR 0.90, 95%CI 0.85-0.95, p&amp;lt;0.001) were independent predictors of deficient OMT prescription, while the performance of percutaneous coronary intervention was identified as the strongest positive predictor favoring it (OR 4.85, 95%CI 4.49-5.24, p&amp;lt;0.001). Conclusion Although there has been a gradual increase in the prescription of OMT over time among both women and men, concerning sex disparities disfavoring women, and particularly young women, remained. Targeted programs to reduce sex-related differences in secondary prevention care are warranted.

Association of COVID-19 and influenza vaccinations and cardiovascular drugs with hospitalisation and mortality in COVID-19 and Long COVID: 2-year follow-up of 17 million individuals in England

Abstract Introduction For COVID-19 and Long COVID, determining the highest-risk subgroups, particularly in the context of compound pressures such as influenza and cardiovascular disease (CVD), may identify effective interventions to prevent adverse health outcomes, and inform public health and policy decisions. Methods Using national, linked electronic health records for England (NHS England Secure Data Environment: via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals with COVID-19 and Long COVID from January 2020 to February 2023. We compared all-cause hospitalisation and mortality in unmatched and matched cohort analyses, by prior CVD, high CVD risk (by QRISK2), COVID-19 and influenza vaccination status, and prescription of CVD preventive therapies. We investigated potential impact of targeted vaccination and CVD prevention strategies on mortality and hospitalisations by calculating population preventable fractions. Results We identified 17,373,850 individuals with COVID-19 [54.4% female; mean age 38.8 years; COVID-19 vaccination ≥2 doses:50.0%, influenza vaccination (≥1 dose):27.8%; mean follow-up 1.28 years] and 301,115 with Long Covid [61.8% female; mean age 46.0 years; COVID-19 vaccination ≥2 doses:66.4%, influenza vaccination:33.1%; mean follow-up 1.1 years]. Hospitalisation and mortality rates were 15.3% and 2.0% in COVID-19 (Long COVID rate 1.3%) and 16.8% and 1.4% in Long COVID, respectively. Adjusted risk of mortality and hospitalisation were reduced with COVID-19 vaccination ≥2 doses (COVID-19:HR 0.36, 95% CI 0.34-0.38 and 0.69, 0.68-0.69; Long COVID:0.44, 0.42-0.47 and 0.90, 0.89-0.91). With influenza vaccination, mortality was reduced, but not hospitalisation (COVID-19: 0.86, 0.85-0.86 and HR 1.01, 1.01-1.01, and Long COVID: 0.72, 0.67-0.76, and 1.05, 1.03-1.07), with greatest effect in those with prior CVD and high CVD risk. Mortality and hospitalisation were also reduced by CVD prevention in those with CVD, e.g. anticoagulants- COVID-19: 0.69, 0.69-0.70 and 0.92, 0.91-0.93; Long Covid: 0.59, 0.54-0.64, and 0.88, 0.84-0.92. COVID-19 vaccination, influenza vaccination and CVD drugs (Anticoagulants) averted 101117 of 193598, 2138 of 4017 and 16573 of 36847 preventable deaths among individuals after COVID-19, and 875 of 1189, 65 of 127 and 507 of 1007 preventable deaths among those with Long COVID, particularly in people with CVD. Conclusions Prior CVD and high CVD risk are associated with increased hospitalisation and mortality risk in people with COVID-19 and Long COVID. Targeted improvement in COVID-19 vaccination and CVD prevention, especially in those with CVD are priority interventions in pandemics to avoid excess hospitalisation and mortality.Baseline Characteristics and OutcomesHospitalisation/mortality by COVID vaccn

A real-world data analysis investigating the cardioprotective effects of glucagon-like peptide-1 receptor agonists among people with type 2 diabetes in England

Abstract Background Cardiovascular disease (CVD) is a common and major complication of type 2 diabetes (T2D). Anti-diabetic therapy aims to lower blood glucose, with primary clinical trial endpoints for new antidiabetic entrants focused on HbA1c. Research suggests some glucose-lowering drugs, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), can have a cardioprotective effect in people with T2D.1,2 Purpose To compare the real-world risk of major adverse cardiovascular event (MACE) in people with T2D treated with GLP-1 RAs compared to dipeptidyl peptidase-4 (DPP-4) inhibitors or basal insulin. Methods We conducted a retrospective cohort study using linked primary care data from the Clinical Practice Research Datalink Aurum, secondary care Hospital Episode Statistics and Office for National Statistics death registrations. We included patients aged ≥18 years with T2D at high-risk or very-high-risk of CVD (as defined by the European Society of Cardiology) who had ≥2 prescriptions of either GLP-1 RA (dulaglutide, liraglutide, and semaglutide), DPP-4 inhibitor (as part of line 4 therapy) or basal insulin from 01/01/2014-31/12/2018. We excluded those pregnant at therapy initiation or with type 1 diabetes. Follow-up started at second prescription of relevant therapy and ended at the earliest of two years later, pregnancy, death, end of primary care record, or 31/12/2019. We used data from patients’ medical histories to define baseline characteristics. We calculated the incidence of MACE per 100,000 person-years (PY), defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. We used Cox proportional hazards regression, using LASSO to select confounding clinical variables including BMI, prior MACE and intercurrent antidiabetic treatments, to estimate risk difference of MACE among those treated with 1) GLP1-RA and DPP-4 inhibitor and 2) GLP1-RA and basal insulin. Results We included 63,237 patients, among whom the patients treated with GLP1-RA were younger and a higher proportion were obese or severely obese than those treated with DPP-4 inhibitor or basal insulin (Table 1). The incidence of MACE was highest in those treated with DPP-4 inhibitor (high-risk 1,503.0/100,000 PY; very-high-risk 6,000.7/100,000 PY) followed by basal insulin (high-risk 1,396.9/100,000 PY; very-high-risk 5,707.1/100,000 PY), and lowest in those treated with GLP1-RA (high-risk 377.1/100,000 PY; very-high-risk 1,946.1/100,000 PY). After adjustment, the risk of MACE among patients treated with GLP1-RA was still significantly lower than those treated with either DPP-4 inhibitor (high-risk aHR: 0.42, 95% CI 0.21-0.86 and very-high-risk aHR: 0.65, 95% CI 0.58-0.73) or those treated with basal insulin (high-risk aHR: 0.36, 95% CI 0.18-0.72 and very-high-risk aHR: 0.72, 95% CI 0.64-0.81). Conclusion(s) Our study supports clinical trial and other observational research studies which find a cardioprotective effect of GLP-1 RA use in people with T2D.

Chronotropic incompetence predictors in a Cardiac Rehabilitation Program following myocardial infarction

Abstract Background Chronotropic incompetence (CI) has been described in many patients after myocardial infarction (MI) and can negatively affect physical capacity, especially if negative chronotropic therapy (NCT) is prescribed. Prediction of CI after MI could be useful for tailored medical therapy and exercise training prescription. Purpose We aim to predict CI on initial exercise ECG testing (ExECG) in MI patients submitted to a Cardiac Rehabilitation Program (CRP). Methods Patients with ST-segment elevation MI (STEMI) or occlusion MI (OMI) submitted to our CRP were prospectively included. After an initial follow-up phase of clinical stabilization and medical therapy optimization, ExECG (conventional or cardiopulmonary) was performed. Peak VO2 and chronotropic reserve index [(maximum heart rate – resting heart rate) / ([220-age] – resting heart rate)] were measured. Chronotropic incompetence was defined as &amp;lt;80% chronotropic reserve index (≤62% in patients treated with NCT). Pharmacological therapy with NCT was registered in absolute and equivalent doses per bisoprolol 2.5mg units (B2.5EU). The effect of NCT on CI was studied by ANOVA test, and predictors of CI by binary logistic regression analysis. The model was tested by area under the curve (AUC) analysis in receiver operating characteristic curves. A p&amp;lt;0.05 was considered statistically significant. Results The cohort comprised 143 patients, mostly middle-aged (mean 60.3±15.8 years) males (85.3%) with anterior or inferior MI (44.8% and 44.8%, respectively). Mean left ventricular ejection fraction (LVEF) was 52.4±10.6% and 36.4% depicted LVEF&amp;lt;50%. NCT was prescribed in most patients (n=125, 87.4%), and median equivalent dose was 1 [0.5-1] B2.5EU. CI was noted on more than half of the population on initial ExECG (n=75, 52.4%). Higher NCT doses per B2.5EU associated with worse mean chronotropic reserve indexes: 72.8±24.4% in patients without NCT; 71.7±18.7% in patients with 0.5 B2.5EU; 62.8±18.2% in patients with 1 B2.5EU; and 58.7±16.9% in patients with ≥2 B2.5EU (ANOVA p=0.04). On binary logistic regression analysis, only two variables were independent predictors of CI: diabetes mellitus (HR 3.02 [1.26-7.23], p=0.01) and LVEF (0.97 [0.94-0.99] per increased %, p=0.04). However, the predictive power of the model was poor (AUC 0.62 [0.53-0.71], p=0.01). Conclusions Chronotropic incompetence after a MI is associated with lower LVEF, diabetes mellitus, and higher doses of NCT. Although significant interindividual variability exists in chronotropic response in the post-infarction period, these factors could be taken into consideration for tailored prescription (or deprescription), especially in patients who may not derive any prognostic benefit from NCT.Chronotropic incompetence in CRP

Unique regional risk profiles and cardiovascular outcomes of patients with acute coronary syndrome in the absence of standard modifiable risk factors: a systematic review and meta-analysis

Abstract Background With differences in prevalence, risk profile, cardiovascular complications, and mortality of patients with acute coronary syndrome (ACS) in the absence of standard modifiable risk factors (SMuRF-less) worldwide, this study examines the regional differences and the unique risk profiles of this often-understudied group of patients. Purpose We hypothesize that differences in non-traditional risk factor profiles may lead to unique ACS-related presentations, complication rates, and secondary preventative strategies across regions. Hence this study was undertaken to assess the cross-regional comparisons of patient characteristics, risk profile, angiographic characteristics that may provide insights into disparate cardiovascular outcomes observed in the SMuRF-less ACS population. Methods Medline and Embase databases were searched in November 2022 to identify relevant literature relating to the prevalence of risk factors in SMuRF-less patients with ACS. A single-arm meta-analysis of proportion and means was conducted on baseline and presentation characteristics, outcomes and complications, management, and risk factors in SMuRF-less ACS patients, stratified according to geographical region (Asia-Pacific, Europe, and North America). Risk of bias was assessed using the Newcastle-Ottawa scale. Results A total of 25 studies comprising of 1,393,184 individuals with ACS were included, of which 242,929 patients were SMuRF-less. Within this SMuRF-less ACS group, mortality rates were similar across the regions (Asia-Pacific:15.8%, Europe:17.5%, p=0.861), cardiac arrest (6.3%, 95%CI:2.3% to 16.3%, p=0.001) and major bleeding (5.2%, 95%CI:2.9% to 9.2%, p=0.001) were more prevalent in Asia-Pacific, and heart failure more common in Europe (21.7%, 95%CI:18.2% to 25.7%, p&amp;lt;0.001). Prevalence of chronic obstructive lung disease (21.4%, 95%CI:21.2% to 21.6%, p&amp;lt;0.001) and peripheral artery disease (3.8%, 95%CI:3.1% to 4.7%, p=0.001) were highest in SMuRF-less ACS patients from North America, chronic liver disease most prevalent in those from Asia-Pacific (3.5%, 95%CI:2.2% to 5.6%, p&amp;lt;0.001) and family history of coronary artery disease highest in SMuRF-less ACS patients from Europe (25.2%, 95%CI:24.8% to 25.7%, p=0.024). Significantly lower rates of guideline-directed medical therapy prescriptions were observed for SMuRF-less ACS patients in Asia-Pacific compared to other regions. Conclusion This regional analysis highlights the different risk profiles, cardiovascular outcomes, and specific needs of individuals presenting with ACS in the absence of cardiovascular risk factors, across Asia-Pacific, Europe, and North America. Whilst unravelling novel pathomechanistic pathways of atherosclerosis will prove beneficial on a global scale, understanding the unique regional profile of these individuals will aid policymakers strategize effective and tailored clinical pathways in the management of SMuRF-less ACS.Graphical AbstractKey Outcomes

Nodal radiotherapy for prostate adenocarcinoma recurrence: predictive factors for efficacy

BackgroundNodes are the second site for prostate cancer recurrence. Whole-pelvic radiotherapy (WPRT) has shown superiority over nodal stereotactic body radiotherapy (SBRT) in two retrospective cohorts. We aimed to compare both modalities and assess factors associated with treatment outcomes.Materials and methodsThis retrospective multicentric cohort study included patients from five institutions spanning from 2010 to 2022. Patients had a history of prostatic adenocarcinoma classified as N0 M0 at diagnosis with a first nodal-only pelvic castration-sensitive recurrence. Failure-free survival (FFS) was defined as the time from the end of RT to the first failure event–biochemical or imaging recurrence, or death.ResultsA total of 147 patients (pts) were analyzed, mainly treated for a recurrence after initial prostatectomy (87%), with 64 (43.5%) undergoing SBRT and 83 (56.5%) undergoing WPRT. SBRT was chosen mainly for dosimetric constraints (67%) and was associated with a lower rate of concomitant androgen deprivation therapy (ADT) prescription. With a median follow-up of 68 months [inter-quartile range (IQR) = 51], FFS was significantly lower in the SBRT group (p &amp;lt; 0.0001). In multivariable analysis, WPRT and ADT were associated with a longer FFS. Factors associated with a longer FFS after SBRT included associated ADT, lower prostate-specific antigen (PSA) levels, a PSA doubling time &amp;gt;6 months, and a Gleason score &amp;lt;8. SBRT was associated with a lower rate of genitourinary and gastrointestinal grade ≥2 complications.DiscussionFor an isolated pelvic nodal prostate cancer recurrence, SBRT is associated with a shorter FFS compared to WPRT. SBRT is often more convenient for patients and leaves further pelvic salvage options available, so it can be explored as an option for well-informed patients.

Medication Burden Before and After Prescription of Biologics in Patients with Inflammatory Bowel Disease

Background: Biologics are a cornerstone in the treatment of severe cases of inflammatory bowel disease (IBD) and aim to control the disease and improve quality of life. This study investigated changes in nonbiologic medication prescriptions for IBD patients initiating biologic therapy in Germany. Methods: This study used data from anonymized pharmacy records in the German longitudinal prescription (LRx) database and included biologic-naive IBD patients who received their first biologic therapy prescription between 2016 and 2022. Changes in prescription rates and pill counts for nonbiologic medications (corticosteroids, 5-aminosalicylates (5-ASA), proton pump inhibitors, analgesics, immunosuppressants, Vitamin D, iron, and antibiotics) before and after the initiation of biologic therapy were assessed using descriptive statistics, McNemar’s tests, and Poisson regression models, adjusting for age and sex. Results: A total of 29,559 biologic-naive IBD patients were included. Prior to index, 91.2% received at least one nonbiologic medication prescription, where corticosteroids and 5-ASA were the most common. Postindex, the overall prescription rate decreased to 87.7%, with significant reductions in prescriptions observed for corticosteroids, 5-ASA, and immunosuppressants (p-values &lt; 0.001). The mean (SD) pill count dropped from 704 (1712) to 514 (1651), with the largest mean differences (95% CI) having been for corticosteroids (−77.9 [−80.3 to −75.5]), 5-ASA (−61.6 [−65.2 to −58.1]), and immunosuppressants (−55.0 [−57.5 to −52.6]). Older patients tended to have greater decreases in pill counts for corticosteroids and 5-ASA, while males showed statistically significant reductions in pill count for immunosuppressants compared with females. Conclusion: This study demonstrates that the prescription of nonbiologic medications significantly decreased after biologic therapy initiation. The use of biologics may therefore lead to improved disease management and potentially better patient outcomes.

Long-term mortality in patients with chronic obstructive pulmonary disease requiring acute non-invasive ventilation with and without obstructive sleep apnoea

IntroductionChronic obstructive pulmonary disease (COPD)/obstructive sleep apnoea (OSA) overlap syndrome (OVS) is associated with higher mortality compared with COPD alone in stable outpatients. However, the prognosis of patients hospitalised with...

Pharmacological therapies for male infertility.

Male factor infertility is a multifaceted problem that affects approximately 50% of couples suffering from infertility. Causes of male infertility include endocrine disturbances, gonadotoxins, genetic abnormalities, varicocele, malignancies, infections, congenital or acquired urogenital abnormalities, iatrogenic factors, immunological factors, and idiopathic reasons. There are a variety of treatment options for male infertility, depending on the underlying cause(s). These can include surgical treatments, medical/hormonal therapies, and assisted reproductive techniques (ART), which can be combined with surgical sperm retrieval (SSR) if necessary. In this review article, the pharmacological therapies for male infertility are grouped by their underlying causes. Some of these therapies are targeted and specific, while others are used empirically to treat idiopathic male infertility. This will include treatments to optimize infertility in patients who have hypogonadism, ejaculatory dysfunction, infections, or idiopathic male infertility. Finally, we will provide an overview of the future directions of pharmacological therapies for male infertility. Significance Statement Male infertility is a significant worldwide problem. Detailed knowledge of the pharmacological therapies available will ensure the prescription of appropriate therapy and avoid the use of unnecessary or harmful treatments.

Alzheimer's Disease and (Phyto) Estrogen Treatment: Modification of Effects by Age, Type of Treatment, and Duration of Use.

There is a continued debate on whether menopausal hormone therapy (MHT) protects women against Alzheimer's disease (AD). It is also unclear whether phytoestrogen could be an alternative treatment for AD. To investigate whether mixed study findings may be due to differences in age at initiation of MHT and duration of prescription of different types of MHT using meta-analyses. After a systematic literature search, meta-analyses were carried out using Cochrane Revman 5.4.1.software including data from large nationwide studies of registered medically diagnosed AD and prescribed MHT. These analyses were stratified for duration and type of treatment, by age at start of prescription of therapy. Insufficient quality data were available for phytoestrogen treatment and AD meta-analyses. A total of 912,157 women were included from five registries, of whom 278,495 had developed AD during follow-up. Meta-analyses suggested a small increased AD risk after 5-10 years prescription of combination MHT regardless of age, and over 10 years only in women younger than 60 years of age. No association was seen for estrogen alone for women younger than 60 years of age, but AD risk did increase for women over 60 years of age for up to 5 years of MHT prescriptions. Combination MHT should probably be prescribed for less than 5 years after menopause to reduce risk for AD, while estrogen alone should not be prescribed to women over 60. For phytoestrogen, small treatment trials suggested some benefit of tempeh (fermented soy), which should be investigated further.

Altered Expressions of IL-15, IFNG, and HPRT1 Genes in the Thin Endometria of Patients with Reproductive Disorders: A Prospective Comparative Study

Reproductive disorders are common events in modern reproductive medicine, occurring both in spontaneous and assisted pregnancies. Studies on the molecular mechanisms of implantation disorders in thin endometria, including the study of gene transcriptional activities, have shed light on the identification of the potential biological markers of endometrial receptivity. Background/Objectives: The goal of this study was to reveal the significantly dysregulated selected gene expressions between RIF and RPL patients with thin endometria. Methods: Endometrial samples were collected from RIF patients (n = 20) and RPL patients (n = 19) during the implantation window days (LH + 7—LH + 10) of their natural menstrual cycles. Ten genes were chosen as the target genes regarding their possible relations with the implantation process. The total RNA was purified and reverse-transcribed, and gene expressions were quantified by RT-PCR. Results: The expressions of the IL-15, INFG, and HPRT1 genes were significantly decreased in the RIF patients with thin endometria compared to the RPL patients (log2 fold change = 0.92, p = 0.023 for IL-15; log2 fold change = 1.24, p = 0.046 for INFG; and log2 fold change = 0.579, p = 0.046 for HPRT1). There were no significant differences in the expressions of the CXCL8, CXCL1, MMP10, C4BPA, TNC, VEGFB, and HAND2 genes between the groups. Conclusions: Decreased expressions of the IL-15, INFG, and HPRT1 genes were found in patients with RIF with thin endometria compared to the endometria of women with RPL. This has practical significance for clinicians for the differentiated prescription of immunomodulatory therapy in patients undergoing ART programs.

Experience in the treatment of patients with androgenic deficiency and comorbidity pathology

Background. Age-related involution of the male reproductive system, known as testosterone deficiency syndrome, andropause, androgen deficiency in the aging male, or partial androgen deficiency in the aging male, causes clinical manifestations that impair quality of life and increase the risk of mortality, especially from cardiovascular disease. In Russia, the problem of hypodiagnosis of androgen deficiency remains up-to-date, with a low frequency of prescription of replacement therapy. Aim. At assessing the effectiveness of testosterone in the rehabilitation of patients with hypogonadism and cardiovascular pathology. Materials and methods. It involved 36 men aged 25–75 years with various cardiological pathologies. Results. As a result of the study, testosterone as a form of a transdermal gel is effective at doses of 50 mg/day. Three-month use of testosterone gel increases the level of testosterone to 2.9 nmol/l (p0.05). Conclusion. Thus, testosterone may play a key role in the treatment of hypogonadism and related cardiovascular diseases, although its safety and feasibility remain a matter of debate.

Treatment of Ocular Surface Disease in Ocular Cicatricial Pemphigoid

ABSTRACT Purpose While substantial research has focused on systemic immunomodulatory therapy for ocular cicatricial pemphigoid (OCP), limited data exist on managing associated ocular surface disease (OSD). This study evaluates treatments for OCP-related OSD at our institution. Methods We conducted a retrospective analysis of patients diagnosed with cicatrizing conjunctivitis at the University of Colorado Hospital from January 1, 2013, to October 31, 2023. Patients with cicatrizing conjunctivitis due to non-OCP conditions were excluded, and disease severity was classified using the Foster Staging System. Results Our review included 30 patients with OCP, all with at least six months of follow-up. The mean age of symptom onset (n = 19) was 62.2 years (SD = 16.4), while the mean age at diagnosis (n = 28) was 65.1 years (SD = 12.7). The most common OSD treatments at the last visit were preservative-free artificial tears (87%), topical corticosteroids (43%), autologous serum eye drops (40%), topical antibiotics (30%), and topical immunomodulators (23%). All patients used at least one treatment, with 83.3% on prescription therapies. Patients averaged 3.33 (SD: 1.4) treatments, with 1.7 (SD: 1.2) being prescriptions. Topical immunomodulators had the highest discontinuation rate at 73.1% (n = 19/26). Autologous serum eye drops and topical corticosteroids were the least discontinued treatments. Number of total treatments, prescriptions, and procedures sharply increased at stage three OCP. Conclusions The number of treatments and procedures increased with OCP severity, indicating that advanced OCP often necessitated more intensive OSD management.

Symptomatic Nonstenotic Carotids: A Topical Review.

Historically, the management of carotid artery disease has primarily focused on the degree of stenosis as the main indicator for assessing stroke etiology, risk, and need for intervention. However, accumulating evidence suggests that structural and biological features within the arterial wall, such as intraplaque hemorrhage, may have superior diagnostic, prognostic, and therapeutic values. Under current guidelines, unless an atheroma results in ≥50% stenosis, it is not considered the cause of a cerebrovascular event. This results in extensive and often unproductive diagnostic workup, prescription of ineffective medical therapy, and preclusion of patients from receiving revascularization procedures that have been shown to prevent recurrent cerebrovascular events in cases of ≥50% stenosis. A subset of embolic strokes of undetermined source, which account for up to 25% of all ischemic cerebrovascular events, are thought to be due to thromboembolic phenomena from undiagnosed plaque disruptions in nonstenotic arteries (<50% stenosis). Recently, it has been proposed to reclassify this subgroup of patients as symptomatic nonstenotic carotid if the carotid plaque ipsilateral to the cerebrovascular event presents with high-risk features including intraplaque hemorrhage, lipid-rich necrotic core, thinning/rupture of the fibrous cap, and ulceration. In this review, we first provide a historical overview of the chain of events and circumstances that resulted in the present management of carotid artery disease. Second, we embed the contemporary biomarkers of plaque vulnerability in a modern mechanistic paradigm of carotid plaque disruption and thromboembolization. Third, we review the clinically available imaging tools to detect these biomarkers, and how their use has started to shed light on the prevalence and natural history of this underdiagnosed condition. Fourth, we review recent clinical studies employing a contemporary definition of symptomatic nonstenotic carotid and discuss targeted treatments for this condition. Finally, we make a case to generate the much-needed high-level evidence to align the clinical management of patients with symptomatic nonstenotic carotid with a contemporary understanding of plaque disruption and thromboembolization.

Antihypertensive therapy in patients with arterial hypertension and concomitant diseases in real clinical practice (according to the National Registry of Arterial Hypertension, 2019-2022)

Arterial hypertension (AH) remains the leading risk factor associated with cardiovascular diseases (CVDs), cerebrovascular disease and chronic kidney disease. About 70% of patients with AH who are on monotherapy cannot achieve blood pressure (BP) targets, and therefore all quidelines for the management of AH have recently recommended prescribing combination therapy (PCT). In real clinical practice (RCP), there remains significant uncertainty in the effectiveness and rationality of therapy, despite the wide availability of antihypertensive drugs (AHD) and the presence of recommendations for a stepwise approach to prescribing combinations of specific groups of AHD in different clinical situations. Analyze the real ongoing antihypertensive therapy, including the PCT; international nonproprietary names of drugs and their dosages in RCP; compliance of therapy with clinical recommendations; changing trends in the PCT. An analysis was carried out of the data from the register of AH, the compliance of treatment in different clinical groups of patients and the achievement of BP and low-density lipoprotein cholesterol targets in the sample of 2019-2022 (n=5012). The prescription of AHD and achievement of targets values were assessed in accordance with current clinical guidelines for the management of AH and hypercholesterolemia. Data from 2010 (n=7782) and 2020 (n=3061) were analyzed to assess the dynamics of prescription of monotherapy and PCT. The greatest increase in the number of AHD was observed in patients with hypertension in combination with coronary heart disease, heart failure, and atrial fibrillation. In a small group of patients with hypertension without other CVDs, the recommended combinations of AHD were not prescribed; preference was given to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and β-adrenoblocker (β-AB). PCT mainly differed from the recommended combinations by the wider use of drugs from the β-AB group. The PCT of recommended drugs was highest in patients with hypertension and coronary artery disease - more than 90%, hypertension and heart failure in 56.2%, hypertension and atrial fibrillation - 33.3%, hypertension and chronic kidney desease - 19.6%. Achievement of BP and low-density lipoprotein cholesterol targets was insufficient in all analyzed groups. Among the international nonproprietary names of drugs, the most frequently prescribed are the following: bisoprolol, metoprolol, lisinopril, perindopril, losartan, spironolactone, amlodipine, torasemide, indapamide, hypochlorothiazide, moxonidine. The prescribed daily dosages were closer to the initial recommended ones. By 2020, the prescription of PCT with β-AB and a more uniform prescription of various combinations will come to the fore, while PCT in 2010 is characterized by the presence of one or two leaders combinations. The described features of prescribing AHD partially reproduce clinical recommendations for the management of AH. Differences in therapy provided in RCP may be associated with an attempt to intensify the treatment of hypertension in patients with other concomitant CVDs. At the same time, analysis of combinations and dosages of prescribed drugs suggests the presence of wide opportunities for further escalation of therapy. The presented data can provide insight into current patterns of antihypertensive therapy prescription in patients in RCP and lay the foundation for optimizing therapy in different categories hypertensive patients.

8228 Effect of Long-Term Testosterone Therapy on Cardiovascular Safety among Adult Male Patients with Testosterone Deficiency

Abstract Disclosure: Y. Lin: None. S. Gupta: None. L. Shi: None. V.A. Fonseca: None. Background: As testosterone therapy (TTh) prescriptions are increasing rapidly, the cardiovascular (CV) safety of TTh remains controversial among observational studies and clinical trials. Our objective is to determine the CV safety of long-term TTh in adult men with testosterone deficiency (TD) in a real-world setting. Method: This is a multi-center retrospective study comparing testosterone-treated men with untreated men diagnosed with TD. A total of 2,683 men (18+ years) with confirmed TD diagnosis and continuous enrollment were extracted from the REACHnet electronic health records data from 1/1/2013-7/1/2022. The TD was confirmed by at least 2 TD diagnoses (ICD-9/10 codes 253, 257.1, 257.2, 257.8, 257.9, E23, E29.1, E29.8, E29.9) and with the serum testosterone level less than 350 ng/dl before the first recorded TD diagnosis. We further excluded patients with a malignancy history prior to the first TD diagnosis date. Propensity score matching (PSM) by 1:1 ratio based on age, race, Charles Comorbidity Index, and serum testosterone level was conducted among men with TD. The treated group of 928 patients who were compared to the untreated group of 928 patients who opted against taking TTh. The intent to treat analysis using Kaplan-Meier curves and Cox regressions was used to examine CV risk for major adverse cardiovascular events (MACE), defined as a composite outcome of myocardial infarction, stroke, and cardiovascular death. Results: The treatment and control cohorts with 928 patients each had a median follow-up of 3 years. After PSM, only body mass index, diastolic blood pressure, hyperlipidemia, hypertension, depression, and anxiety were statistically significant between treatment and control cohorts. The log-rank test for the cumulative MACE incidence was comparable (p-value&amp;gt;0.05). There were no statistically significant associations between TTh use and increased CV risk in the univariate Cox regression (Hazard Ratio (HR) [95% CI]: 1.01 [0.75-1.36]) and Cox regressions adjusted by the pre-existing MACE (HR [95% CI]: 0.98 [0.72-1.32]) and other baseline covariates (HR [95% CI]: 0.93 [0.68-1.26]). Conclusion: TTh use among adult males with TD was not found to be associated with increased CV risk in real-world clinical practice. Further studies are needed for TTH use in a high-risk population with cardiovascular risk factors. Presentation: 6/1/2024

Prescription of quadruple therapy in heart failure with reduced ejection fraction during hospitalization

BackgroundHospitalization of patients with heart failure makes it possible to optimize drug therapy, considerably improving the prognosis of this serious condition.MethodsWe conducted a retrospective descriptive study of patients with reduced left ventricular ejection fraction (≤ 40%) in the Cardiology Department of a community hospital center in France to measure the prescription rate of heart failure medications in hospitalized patients with reduced ejection fraction heart failure and identify their limiting factors. The primary endpoint was the prescription on the discharge prescription of the following four drug classes: beta-blockers, renin–angiotensin–aldosterone system blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter inhibitors.ResultsFrom September 1, 2022, to March 31, 2023, 73 patients were included in the study. About one-third of patients were discharged with the recommended four drug classes. Those discharged with all 4 drug classes were younger and had preserved renal function.ConclusionsThe low rate of prescription of heart failure medications after hospitalization is a reminder of the need to develop a specialized follow-up structure to optimize the drug treatment of reduced ejection fraction heart failure, even in the most fragile patients.