Atrial Tachycardia Facilitating Transcatheter Edge-to-Edge Repair for Severe Functional Mitral Regurgitation.

An 89-year-old woman with paroxysmal atrial tachycardia (AT) was diagnosed with severe atrial functional mitral regurgitation. On transesophageal echocardiography, the mitral regurgitation jet appeared larger during sinus rhythm and smaller during AT. During transcatheter repair of the valve, chronotropic agents were given to induce AT, assisting with leaflet capture.

Effects of gene dosage and development on subcortical nuclei volumes in individuals with 22q11.2 copy number variations.

The 22q11.2 locus contains genes critical for brain development. Reciprocal Copy Number Variations (CNVs) at this locus impact risk for neurodevelopmental and psychiatric disorders. Both 22q11.2 deletions (22qDel) and duplications (22qDup) are associated with autism, but 22qDel uniquely elevates schizophrenia risk. Understanding brain phenotypes associated with these highly penetrant CNVs can provide insights into genetic pathways underlying neuropsychiatric disorders. Human neuroimaging and animal models indicate subcortical brain alterations in 22qDel, yet little is known about developmental differences across specific nuclei between reciprocal 22q11.2 CNV carriers and typically developing (TD) controls. We conducted a longitudinal MRI study in a total of 385 scans from 22qDel (n = 96, scans = 191, 53.1% female), 22qDup (n = 37, scans = 64, 45.9% female), and TD controls (n = 80, scans = 130, 51.2% female), across a wide age range (5.5-49.5 years). Volumes of the thalamus, hippocampus, amygdala, and anatomical subregions were estimated using FreeSurfer, and the linear effects of 22q11.2 gene dosage and non-linear effects of age were characterized with generalized additive mixed models (GAMMs). Positive gene dosage effects (volume increasing with copy number) were observed for total intracranial and whole hippocampus volumes, but not whole thalamus or amygdala volumes. Several amygdala subregions exhibited similar positive effects, with bi-directional effects found across thalamic nuclei. Distinct age-related trajectories were observed across the three groups. Notably, both 22qDel and 22qDup carriers exhibited flattened development of hippocampal CA2/3 subfields relative to TD controls. This study provides novel insights into the impact of 22q11.2 CNVs on subcortical brain structures and their developmental trajectories.

Fluoroquinolone resistance in urinary tract infections: Epidemiology, mechanisms of action and management strategies.

Background: Fluoroquinolone resistance is an issue of concern amongst physicians worldwide. In urology, fluoroquinolones are often used in the treatment of acute pyelonephritis and prostatitis, as well as infections caused by multidrug-resistant pathogens. Aims: We aim to highlight the importance of antimicrobial stewardship and the need for ongoing biomedical research to discover novel agents in our losing battle against resistant pathogens. Materials and methods: In this review, we survey the literature and summarise fluoroquinolone resistance as it pertains to pyelonephritis and prostatitis, as well as alternative treatment strategies and prevention of multidrug resistance. Results: The rise of fluoroquinolone resistance in bacteria has reduced the available treatment options, often necessitating hospital admission for intravenous antibiotics, which places an additional burden on both patients and the healthcare system. Many countries such as Australia have attempted to limit fluoroquinolone resistance by imposing strict prescribing criteria, though these efforts have not been entirely successful. Solutions to overcome resistance include prevention, combination therapy and the development of novel antimicrobial agents. Conclusions: Prevention of the proliferation of resistant organisms by antimicrobial stewardship is paramount, and urologists are obliged to be aware of responsible prescribing practices such as referring to local guidelines when prescribing. By reserving fluoroquinolones for infections in which they are truly indicated and by prescribing based on both patient and local environmental factors, we can preserve this effective resource for future use.

The Tactical Athlete: Definitions, Cardiovascular Assessment, and Management, and "Fit for Duty" Standards.

Tactical athletes are individuals in the military, law enforcement, and other professions whose occupations have significant physical fitness requirements coupled with the potential for exposure to life-threatening situations. Such exposures can have varied hemodynamic effects on the cardiovascular system. It is crucial that their clinical evaluation is inclusive of specific occupational requirements. Safety protocols regarding medical clearance are relatively more stringent for this population than for competitive athletes due to the increased impact to the tactical athlete, their team, and the population they aim to serve and protect should they experience a cardiovascular event on the job.

Effects of Gene Dosage and Development on Subcortical Nuclei Volumes in Individuals with 22q11.2 Copy Number Variations.

The 22q11.2 locus contains genes critical for brain development. Reciprocal Copy Number Variations (CNVs) at this locus impact risk for neurodevelopmental and psychiatric disorders. Both 22q11.2 deletions (22qDel) and duplications (22qDup) are associated with autism, but 22qDel uniquely elevates schizophrenia risk. Understanding brain phenotypes associated with these highly penetrant CNVs can provide insights into genetic pathways underlying neuropsychiatric disorders. Human neuroimaging and animal models indicate subcortical brain alterations in 22qDel, yet little is known about developmental differences across specific nuclei between reciprocal 22q11.2 CNV carriers and typically developing (TD) controls. We conducted a longitudinal MRI study in 22qDel (n=96, 53.1% female), 22qDup (n=37, 45.9% female), and TD controls (n=80, 51.2% female), across a wide age range (5.5-49.5 years). Volumes of the thalamus, hippocampus, amygdala, and anatomical subregions were estimated using FreeSurfer, and the effect of 22q11.2 gene dosage was examined using linear mixed models. Age-related changes were characterized with general additive mixed models (GAMMs). Positive gene dosage effects (22qDel < TD < 22qDup) were observed for total intracranial and whole hippocampus volumes, but not whole thalamus or amygdala volumes. Several amygdala subregions exhibited similar positive effects, with bi-directional effects found across thalamic nuclei. Distinct age-related trajectories were observed across the three groups. Notably, both 22qDel and 22qDup carriers exhibited flattened development of hippocampal CA2/3 subfields relative to TD controls. This study provides novel insights into the impact of 22q11.2 CNVs on subcortical brain structures and their developmental trajectories.

A Novel Intrinsic Foot Muscle Strength Dynamometer Demonstrates Moderate-To-Excellent Reliability and Validity.

Background: Intrinsic foot muscle (IFM) weakness can result in reduced foot function, making it crucial for clinicians to track IFM strength changes accurately. However, assessing IFM strength can be challenging for clinicians, as there is no clinically applicable direct measure of IFM strength that has been shown to be reliable and valid with the foot on the ground. Purpose: The purpose was to investigate the intra-rater and inter-rater reliability of a novel, budget-friendly IFM dynamometer and determine its agreement with a handheld dynamometer (HHD). The researchers also examined correlations of foot morphology and activity level to IFM strength. Study design: Descriptive Laboratory Study. Methods: Two assessors measured IFM strength of 34 healthy volunteers (4 male, 30 female; age=21.14±2.57, height=164.66 ±7.62 cm, mass=64.45±11.93 kg) on two occasions 6.62±0.78 days apart with the novel dynamometer to assess intra- and inter-rater reliability. The HHD was used to measure IFM in the first session in order to assess validity. Results: For the novel dynamometer, intra- and inter-rater reliability was moderate-to-excellent (ICC = 0.73 - 0.95), and the majority of the strength tests were within the 95% limits of agreement with the HHD. Wider foot morphology and a higher number of days walking over the prior seven days had small but significant correlations with IFM strength (dominant foot r = 0.34, non-dominant foot r = 0.39; r = -0.33, -0.39 respectively). Conclusion: This novel IFM dynamometer is a budget-friendly ($75) tool that was shown to be reliable and valid in a healthy population. Levels of evidence: Level 3©The Author(s).

US Food and Drug Administration Warning Regarding Finasteride and Suicidal Ideation: What Should Urologists Know?

Finasteride competitively inhibits 5α-reductase (5-AR) isoenzymes, which blocks dihydrotestosterone (DHT) production, thereby reducing DHT. Finasteride is used in the management of benign prostatic hyperplasia (BPH) and androgenic alopecia. Amid patient reports of suicidal ideation (SI), the Post Finasteride Syndrome advocacy group has petitioned for either a stop to selling of the drug or advertisement of stronger warnings. The US Food and Drug Administration recently added SI to the adverse effects listed for finasteride. Here we provide a brief but comprehensive review of the literature on the psychological side effects of 5-AR inhibitors (5-ARIs) to provide an opinion to help in guiding treating urologists. Most of the current evidence, obtained from the literature on dermatology, suggests that 5-ARI users experience a higher rate of depressive symptoms. However, given the lack of comprehensive randomised studies, the causal link between finasteride and SI remains unclear. Urologists prescribing 5-ARIs should be aware of the recent addition of suicide and SI risk to the list of side effects. A mental health screen should be performed and appropriate resources provided to patients commencing treatment. Furthermore, a review should be arranged with the general practitioner to assess new-onset mental health or SI symptoms. Patient summary: We provide recommendations for urologists who prescribe finasteride for the treatment of benign prostate enlargement. Urologists should be aware of the recent addition of suicidal ideation to the list of side effects for this drug. Finasteride prescription should be continued; however, we recommend a detailed medical history to screen for prior mental health and personality disorders, with discontinuation of the medication in patients with new onset of depression or suicidal symptoms. Close liaison with the patient's general practitioner is vital for management of depressive or suicidal symptoms.

Isokinetic Dynamometer Leg Extensor Peak Torque Measurement: A Time-Delayed Reliability and Score Selection Analysis Study.

The reliability of isokinetic peak torque (PT) has been reported mostly using a short-term (<~10 day) inter-trial testing time frame. However, many studies and programs utilize a long-term (several weeks to months) inter-trial testing period. Additionally, the methods by which the PT value is selected and reported from a multiple rep testing scheme have not been well investigated for both reliability and PT absolute performance comparisons. The purpose of this study was to investigate the long-term reliability of isokinetic and isometric PT of the leg extensors with an emphasis on the differences among several PT score selection methods. Thirteen men and women (age = 19.5 years) underwent two testing trials separated by 28.8 (±1.8) days. Testing included maximal voluntary contractions of three sets of three reps for two isokinetic contraction conditions of 60 (Isok60) and 240 (Isok240) deg/s velocities, and three sets of one rep of isometric contractions for the leg extensors. The PT score was derived from seven different methods (see text for descriptions). Reliability as assessed from intraclass correlation coefficients (ICCs) varied widely across contraction conditions and PT score selection parameters. The Isok60 velocity overall had lower reliability (ICCs = 0.48-0.81) than Isok240 (0.77-0.87) across the conditions whereas the isometric PT variables showed moderate reliability (0.71-0.73). Overall the set 1 PT score selection parameters were generally lower (p ≤ 0.05) than those that involved sets two and three. Systematic error (p ≤ 0.05) was shown for 6 out of the 17 PT selection variables. On a subjective interpretation basis, when taking everything into account the best overall combination of time/trial efficiency, reliability, best/highest PT score parameter, and reduced risk of systematic bias appears to be the PT variable that uses the average of the highest two reps of the first two sets of three reps-i.e., averaging the highest two values of the six total reps from the first two sets.

Meds to Beds at Hospital Discharge Improves Medication Adherence and Readmission Rates in Select Populations.

OBJECTIVES: Medication nonadherence caused by difficulty obtaining and paying for medicines can increase hospital readmissions. This project implemented Medications to Beds ("Meds to Beds," M2B), a multidisciplinary predischarge medication delivery program, at a large urban academic hospital that provided subsidized medications for uninsured and underinsured patients to reduce readmissions. METHODS: This 1-year retrospective analysis of patients discharged from the hospitalist service after implementing M2B contained two groups: one with subsidized medications (M2B-S) and one with unsubsidized medications (M2B-U). Primary analysis was 30-day readmission rates for patients, stratified by Charlson Comorbidity indexes (CCIs) of 0, 1-3, ≥4 to represent low, medium, and high comorbidity burden. Secondary analysis included readmission rates by Medicare Hospital Readmission Reduction Program diagnoses. RESULTS: Compared with controls, the M2B-S and M2B-U programs had significantly reduced readmission rates among patients with CCIs of 0 (10.5% [controls] vs 9.4% [M2B-U] and 5.1% [M2B-S], P < 0.05). A nonsignificant reduction occurred in readmissions for patients with CCIs ≥4 (20.4% [controls] vs 19.4% [M2B-U] vs 14.7% [M2B-S], P < 0.07). Patients with CCIs of 1 to 3 showed a significant increase in readmission rates in the M2B-U, but a decrease in readmission rates among the M2B-S (15.4% [controls] vs 20% [M2B-U] vs 13.1% [M2B-S], P < 0.05). Secondary analyses found no significant differences in readmission rates when patients were stratified by Medicare Hospital Readmission Reduction Program diagnosis. Cost analyses demonstrated that subsidizing medicines cost less per patient for every 1% readmission reduction than delivery alone. CONCLUSIONS: Providing medicine to patients predischarge tends to lower readmission rates for populations with no comorbidities or with a high burden of disease. This effect is amplified when prescription costs are subsidized.

The impact of psoriasis biologic therapy on HIV viral load and CD4+ cell counts in HIV-positive individuals: A real-world cohort study.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disorder that also occurs in the setting of human immunodeficiency virus (HIV). Biological therapy has transformed the treatment landscape for psoriasis; however, individuals with HIV are excluded from clinical trials. The impact of biological therapy on blood parameters in HIV is unclear and is only observed in small case series. OBJECTIVE: The aim of this study was to assess the effect of biological therapy in psoriasis vulgaris in individuals with well-controlled HIV on CD4+ cell counts, CD4+ proportion and HIV viral load over 12 months. METHODS: This retrospective cohort study was conducted at a tertiary referral centre in Sydney, Australia and included 36 HIV-positive individuals with psoriasis treated with biological therapy, compared with 144 age-, gender- and HAART-matched individuals without psoriasis seen between 2010 and 2022. Outcomes of interest included HIV viral load, CD4+ cell count and incidence of infections. RESULTS: No statistically significant difference was seen in baseline HIV viral load and CD4+ count between individuals with and without psoriasis. No significant change in CD4+ count or HIV viral load was seen over the 12-month period of analysis in the HIV cohort without psoriasis. The HIV cohort treated with biological therapy for psoriasis also did not demonstrate any significant change in HIV viral load and CD4+ counts over the 12-month period examined. Stratification by type of biological therapy used did not identify any significant changes in these parameters. Rates of infections and adverse events were also not significantly different between cohorts. It is possible that minor blips seen in the biologics cohort may be a risk factor for future virological failure, and future prospective longitudinal studies are required. CONCLUSIONS: In individuals with well-controlled HIV, the use of biological therapy for psoriasis does not significantly impact HIV viral load, CD4+ cell count, CD4+ proportion and rates of infection over the first 12 months of therapy.

Effects of Flywheel Resistance Training on Muscle Function and Sport-Specific Performance in Collegiate Club Water Polo Players.

Purpose: This study investigated the effects of flywheel squat training on lower body muscle function adaptations and sport-specific performance in collegiate club water polo players. Methods: Thirteen collegiate club water polo athletes (5 women, 8 men) performed flywheel squat training for 4 weeks. Isokinetic knee extension (KE) peak power (PP) and peak torque (PT), flywheel squat peak power (FPP) and mean power (FMP), countermovement jump (CMJ), in-water jump height (WJH) and foot speed were assessed at baseline (Pre1), 4 weeks (Pre2), and 8 weeks (Post) with the first 4 week block being a control period and the second 4 week block being the experimental training. Throughout the training period muscle soreness was assessed using a VAS scale, and FPP and FMP were assessed during every other session. Results: Isokinetic KE PP and PT increased from Pre1 to Post, and FPP and FMP increased between Pre1 and Post, and Pre2 and Post. CMJ and foot speed were unchanged. WJH displayed a change between Pre1 and Post. FPP increased 19% from session 2 to 4 and FMP increased 27% from session 2 to 6, and each remained elevated through session 8. Conclusion: 4 weeks of flywheel squat training in collegiate club water polo players elicited large gains (47-52%) in flywheel-specific squat power, but did not influence sport-specific performance measures including CMJ, WJH, and foot speed. Water-based exercises and stretch-shortening cycle movements (plyometrics) in combination with effective resistance training programs, which may include flywheel-based training, are likely needed for marked sport skill improvements.

The Effects of Minimalist Shoes on Plantar Intrinsic Foot Muscle Size and Strength: A Systematic Review.

Minimalist shoes are proposed to prevent injury and enhance performance by strengthening intrinsic foot muscles, yet there is little consensus on the effectiveness of minimalist shoes in increasing muscle strength or size. This systematic review assesses using minimalist shoes as an intervention on changes in plantar intrinsic foot muscle size and strength. PubMed, CINHAL, Scopus, and SPORT Discus were systematically searched for articles from January 2000 to March 2022. Studies were included if they had an intervention of at least 2 weeks with a control group and examined the effect of minimalist shoes on plantar intrinsic foot strength or size (either volume, cross-sectional area, or thickness). Nine studies were included. There were significant increases and percent changes in foot muscle strength, volume, cross-sectional area, and thickness. Strength increased between 9-57%, and size increased between 7.05-10.6%. Minimalist shoes may effectively increase intrinsic foot muscle size and strength in healthy individuals, and they may also be more convenient than implementing time-intensive physical therapy programs. Future research is needed to explore using minimalist shoes as an intervention in clinical populations who would benefit from increased IFM strength and function. It will also be vital to improve upon IFM assessment methods.

The Tactical Athlete: Definitions, Cardiovascular Assessment, and Management, and "Fit for Duty" Standards.

Tactical athletes are individuals in the military, law enforcement, and other professions whose occupations have significant physical fitness requirements coupled with the potential for exposure to life-threatening situations. Such exposures can have varied hemodynamic effects on the cardiovascular system. It is crucial that their clinical evaluation is inclusive of specific occupational requirements. Safety protocols regarding medical clearance are relatively more stringent for this population than for competitive athletes due to the increased impact to the tactical athlete, their team, and the population they aim to serve and protect should they experience a cardiovascular event on the job.