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Studies have been carried out to investigate the disposition of nicardipine hydrochloride following intravenous and oral administration to male volunteers. Following oral administration of a radiolabelled dose, nicardipine was shown to be rapidly and extensively metabolised and to be rapidly eliminated from plasma. After intravenous infusion of nicardipine at 5 mg-1 for 3 h, plasma levels declined biexponentially, and clearance values were of the same order as hepatic blood flow. With repeated oral administration, 20 mg three times daily for 28 days, plasma levels rose over the first 3 days of administration and then declined to some extent. Possible reasons for this decline are discussed. Steady-state plasma levels and bioavailability show a nonlinear relationship with doses over the range 10-40 mg three times daily. Food consumption has been shown to reduce the bioavailability of nicardipine when the food is taken before or at the same time as nicardipine administration. [ABSTRACT FROM AUTHOR]

Background: Partial wrist arthrodesis (PWA) is a salvage procedure used in advanced wrist arthritis and has traditionally been performed via an open dorsal approach. In recent years, surgeons have moved towards arthroscopic fusions to minimise soft tissue damage and preserve vascular supply, increase union rates and hasten recovery. The purpose of this study is to synthesise the current literature on the outcomes of arthroscopic PWA. Methods: A systematic review was performed to survey the literature regarding outcomes of PWA. English language studies that reported original data and commented on at least one postoperative measure of function were eligible for inclusion. Data collected included patient demographics, operation time and technique, complications and postoperative patient outcomes in the form of patient-rated surveys, grip strength, range of motion and the pain visual analogue scale (VAS). Results: Twelve studies were eligible for inclusion, with a total of 191 patients. 94% of patients achieved union, with a mean time to fusion of 12.5 weeks. VAS, Disabilities of the Arm, Shoulder and Hand (DASH) and Mayo Wrist scores were significantly improved after the procedure, and complication rates were comparable to open procedures. Range of motion varied greatly across studies, due to heterogeneity in carpal intervals fused. Conclusions: Arthroscopic PWA is a safe and effective procedure in the treatment of advanced arthritis of the wrist. Further comparative studies would be useful in assessing benefits of arthroscopic arthrodesis over an open approach. Level of Evidence: Level III (Therapeutic).

Importance: Acute respiratory failure (ARF) associated with antipsychotic use has been documented through case reports and population-based studies., Objective: To assess whether the recent use of antipsychotics is associated with an increased risk of ARF in U.S. Medicare beneficiaries with chronic obstructive pulmonary disease., Design, Setting, and Participants: Case-crossover study conducted among U.S. Fee-for-Service Medicare beneficiaries with chronic obstructive pulmonary disease hospitalized with ARF, from January 1, 2007, through December 31, 2019., Exposure: Oral antipsychotics., Main Outcome(s) and Measure(s): Adjusted odds ratios (aOR) and 95% confidence intervals (CI) for ARF requiring invasive mechanical ventilation associated with the use of antipsychotics in the case period (days -14 to -1) compared to the control period (days -75 to -88)., Results: We identified 145,018 cases (mean age 69.4 years, 57.2% female). Of these, 2,003 had antipsychotic use only during the case period and 1,728 only during the control period. The aOR of ARF within 14 days after antipsychotic use was 1.13 (95% CI, 1.06, 1.20). The risk increased with increasing age, being statistically significant in patients ages 75-84 years (aOR: 1.37 [95% CI, 1.17, 1.60]) and 85 + years (aOR: 1.50 [95% CI, 1.20, 1.89]), but not in beneficiaries under 75 years of age (aOR 18-49 years: 1.01 [95% CI, 0.85, 1.20]; 50-64 years: 1.03 [95% CI, 0.92, 1.15]; 65-74 years: 1.12 [95% CI, 0.98, 1.27])., Conclusions and Relevance: Recent antipsychotic use by Medicare beneficiaries with chronic obstructive pulmonary disease was associated with an increased risk of ARF in those aged 75 years and older., Competing Interests: Declarations:. Financial Support:: The U.S. Food and Drug Administration funded this study through an interagency agreement with the Centers for Medicare & Medicaid Services (Contract number: GS-10F-0133S). The authors who were employees or contractors of the U.S. Food and Drug Administration and the Centers for Medicare & Medicaid Services played a role in the design; however, other officials at the U.S. Food and Drug Administration and the Centers for Medicare & Medicaid Services had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Conflict of Interest:: Amy Brehm’s spouse owns stocks in Bristol Myers, Abbvie, and Johnson & Johnson. All other authors have no conflicts of interest to disclose. Previous Presentation:: Preliminary results of this work were presented at CHEST Annual Meeting 2022, October 16–19, 2022, Nashville, TN, USA. Disclaimer:: The manuscript was subject to administrative review before submission, but this review did not alter its content. The views expressed are those of the authors and not necessarily those of the Department of Health and Human Services, the U.S. Food and Drug Administration, or the Centers for Medicare & Medicaid Services., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: There is a paucity of data on treatment of osteoporosis in patients with advanced chronic kidney disease (CKD)., Objective: To assess the risk for emergently treated hypocalcemia with denosumab by stage of CKD and presence of CKD-mineral and bone disorder (CKD-MBD)., Design: Target trial emulation., Setting: Medicare fee-for-service data with prescription drug coverage, 2012 to 2020., Participants: Female patients aged 65 years or older initiating denosumab, oral bisphosphonates, or intravenous (IV) bisphosphonates for osteoporosis., Measurements: Hospital and emergency department admissions (that is, emergent care) for hypocalcemia were assessed in the first 12 treatment weeks. Inverse probability of treatment weighted cumulative incidence and weighted risk differences (RDs) were calculated., Results: A total of 361 453 patients treated with denosumab, 829 044 treated with oral bisphosphonates, and 160 413 treated with IV bisphosphonates were identified. Risk for emergently treated hypocalcemia with denosumab versus oral bisphosphonates increased with worsening CKD stage ( P  < 0.001), with greatest risk among dialysis-dependent (DD) patients (3.01% vs. 0.00%; RD, 3.01% [95% CI, 2.27% to 3.77%]) and non-dialysis-dependent (NDD) patients with CKD stages 4 and 5 (0.57% vs. 0.03%; RD, 0.54% [CI, 0.41% to 0.68%]). Among patients with stages 4 and 5 CKD (NDD + DD), denosumab had a greater risk for emergently treated hypocalcemia versus oral bisphosphonates in those with CKD-MBD (1.53% vs. 0.02%; RD, 1.51% [CI, 1.21% to 1.78%]) than in those without CKD-MBD (0.22% vs. 0.03%; RD, 0.19% [CI, 0.08% to 0.31%]). Denosumab also showed increased risk compared with IV bisphosphonates., Limitation: Generalizability to men and non-Medicare populations., Conclusion: Risk for emergently treated hypocalcemia with denosumab increased with worsening CKD stage and was highest in DD patients and those with CKD-MBD., Primary Funding Source: U.S. Food and Drug Administration., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0013.

Objective: To identify subgroups of parents' food choice value systems and evaluate associations with restaurant eating behaviors of children., Design: Cross-sectional survey., Participants: Parents with low income and children aged 2-11 years who were frequent restaurant visitors before the coronavirus disease 2019 pandemic (n = 1,146)., Main Outcome Measure(s): Past week restaurant meals and the healthfulness of child meal orders., Analysis: We used latent class analysis to identify patterns of stated food choice values (convenience, taste, cost, cooking, nutrition, locality, socialization, and food safety reputation) among parents. Logistic and linear regression models evaluated differences in child restaurant eating behaviors across classes., Results: Three classes of parents' stated food choice values were identified: hassle-free, indulgent, and multifaceted consumers (7.94%, 54.97%, and 37.09% of parents, respectively). The children of the hassle-free consumers class were 91% less likely to select a healthy entree than an unhealthy entree and were even less likely to select a healthy entree than those of the indulgent and multifaceted consumer classes (P < 0.02). The multifaceted consumers class ate from restaurants the most in the last week (2.4 vs 2.1 and 1.9 times; P < 0.02)., Conclusions and Implications: This subgroup approach could inform future restaurant interventions by tailoring to differences in parents' food choice values., (Copyright © 2024 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Objectives. To characterize cannabis-related disorder medical encounter trends in the US Medicare population during 2017 to 2022. Methods. We conducted a descriptive study, which included 56 624 432 beneficiaries aged 65 years or older and 10 247 953 aged 18 to 64 years with disability. All were continuously enrolled in Medicare (Fee-for-Service or Advantage) for 183 or more days before the first day of the calendar year. We identified cannabis-related disorder encounters using International Classification of Diseases, 10th Revision, Clinical Modification diagnosis codes and computed annual encounter rates per 10 000 beneficiaries. We used the Mann-Kendall test to analyze trends over time. Results. Annual cannabis-related disorder encounter trends among beneficiaries aged 65 years or older ranged from 15.9 (95% confidence interval [CI] = 15.8, 16.0) to 39.3 (95% CI = 39.1, 39.5) per 10 000. Rates among beneficiaries aged 18 to 64 years with disability ranged from 274.8 (95% CI = 273.6, 276.0) to 373.7 (95% CI = 372.3, 375.2) per 10 000. Rates increased over time across both groups, with average annual increases of 4.3 (95% CI = 3.3, 5.3; P  = .01) and 17.1 (95% CI = 11.0, 23.2; P  = .02) per 10 000, respectively. Conclusions. Further work is needed to explore the impact of coexisting medical conditions on outcomes that result from cannabis-related disorders. ( Am J Public Health . 2024;114(S8):S694-S697. https://doi.org/10.2105/AJPH.2024.307729).

Background: Concerns have been raised regarding proton pump inhibitor (PPI) use and risk of severe coronavirus disease 2019 (COVID-19). Observational studies have yielded heterogeneous results and were subject to important methodological limitations., Aims: To examine the association between the receipt of PPIs and risk of COVID-19 hospitalizations and severe in-hospital outcomes or death., Methods: Case-control study among Medicare fee-for-service beneficiaries 66+ years old with gastroesophageal reflux disorder (GERD). Within this population, we identified cases by an incident hospital discharge diagnosis of COVID-19 from April 1 to December 11, 2020, using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) U07.1, and randomly selected up to 10 controls per case, matched on date and neighborhood. We defined PPI use as a prescription providing ≥15 days of supply in the 30 days before admission, with H2-receptor antagonist (H2RA) use as the reference to account for indication. We analyzed uncomplicated hospitalizations and hospitalizations with severe outcomes (intensive/coronary care unit admission, invasive mechanical ventilation, or death), estimating odds ratios (ORs), and 95% confidence intervals (CIs) with multinomial conditional logistic regression adjusted for demographics, comorbidities, chronic medications, and health care utilization., Results: We matched 25,867 uncomplicated and 12,954 severe hospitalized COVID-19 cases to 146,972 and 73,104 controls, respectively. Cases tended to be older and have more comorbidities. Relative to H2RA use, we found no association of PPI use with uncomplicated COVID-19 hospitalization (OR 0.99, 95% CI 0.93-1.06) or severe COVID-19 hospitalization (OR 1.00, 95% CI 0.91-1.10)., Conclusions: Relative to H2RA use, PPI use was not associated with uncomplicated or severe COVID-19 hospitalizations among Medicare beneficiaries with GERD., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Objective: To compare the risk of intentional self-harm (ISH) and suicide in older men using 5-α reductase inhibitors (5-ARIs) and alpha-blockers for benign prostatic hyperplasia (BPH). Observational research of older men with BPH suggested an increase in ISH with 5-ARI use compared with nonuse; we aimed to address potential confounding by indication with an active comparator reference group., Methods: Using Medicare data linked to the National Death Index (NDI) from 2007-2016, we implemented a retrospective cohort design in males aged ≥65 years who initiated 5-ARI or alpha-blocker use for BPH. ISH was identified using ICD-9-CM and ICD-10-CM diagnosis codes. Suicides were identified through cause-of-death information from the NDI. We used inverse probability of treatment weighted Cox proportional hazards regression to compare time-to-event between treatment groups, with robust variance estimation., Results: The event rates for ISH and suicide, respectively, were 0.314 and 0.308 per 1000 person-years (PY) among 5-ARI users (n = 181,675), and 0.364 and 0.382 per 1000PY among alpha-blocker users (n = 850,476). For 5-ARI use relative to alpha-blocker use, hazard ratios (HRs) for ISH and suicide, respectively, were 0.88 (95% CI:0.62-1.25) and 0.82 (95% CI:0.54-1.24); for the composite outcome (non-fatal ISH or suicide), the HR was 0.88 (95% CI:0.66-1.16). Subgroup and sensitivity analyses supported these results., Conclusion: 5-ARI use was not associated with an increased risk for ISH or suicide compared to alpha-blocker use in older men with BPH. Study limitations included low event rates and potentially low sensitivity for ISH events., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare. SA, KBN, NF, MW and TEM were employees of Acumen, LLC at the time the study was conducted. This study was funded in full by the U.S. Food and Drug Administration, through an interagency agreement with the Centers for Medicare & Medicaid Services, for which Acumen, LLC is a contractor., (Published by Elsevier Inc.)

Background: The medial femoral trochlea flap has been used to resurface scaphoids with recalcitrant proximal pole fractures or avascular necrosis, providing vascularized osteochondral tissue with similar morphological characteristics. This article aims to review the contemporary literature on its use for scaphoid reconstruction., Methods: A systematic review of Embase, PubMed, Cochrane Central Register of Controlled Trials, and MEDLINE assessed the use of medial femoral trochlea flaps in scaphoids., Results: Eight studies were included, with 76 patients at a mean age of 26 years. Forty-three patients underwent clinical review, and 10 patients underwent radiographic evaluation, at a mean 23.3 months of follow-up. Flaps were generally performed for proximal pole fractures, avascular necrosis, nonunion, or failure of prior fixation; 94.4% of the flaps united. No marked change in sagittal plane motion was noted; reductions were seen in axial and coronal plane motion. The Disabilities of the Arm, Shoulder, and Hand scores improved from a mean of 25.2 to 11.5. Radiographic markers also improved. A total of 12.3% of patients had unplanned return to theater. Three patients required early revision for vascular thrombosis, and 1 patient suffered a volar carpal dislocation. Three patients underwent salvage procedures for ongoing pain., Conclusions: Although technically demanding, promising early-term to medium-term results are noted with the use of medial femoral trochlea flaps in the scaphoid., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Arthroscopic debridement is increasingly being utilised in patients with early-stage first carpometacarpal joint (FCMCJ) arthritis but has limited supportive evidence. This systematic review evaluates the literature, and reports on outcomes and adverse events following this procedure. Methods: An electronic literature search of PubMed, Embase, Medline and Cochrane Central, looking for studies describing outcomes following arthroscopic debridement in FCMCJ arthritis, was performed in November 2022. Studies where bony resection or interposition was performed as adjuncts were excluded. Reported outcomes included visual analogue scores (VAS) for pain; Disabilities of Arm, Shoulder and Hand (DASH) scores; pinch and grip strength; complications and re-operations. Results: Out of a total of 90 studies revealed from the search, only two studies were eligible for inclusion, with a cohort of 34 patients. Following arthroscopic debridement for FCMCJ osteoarthritis, the mean VAS improved by four units, mean DASH by 22 points, grip strength by 4.5 kg and pinch strength by 2 kg at mean follow-up of 18 months. The pooled complication and re-operation rates were 8.8% and 23.5%, respectively. Conclusions: There is a lack of evidence supporting the utility of FCMCJ arthroscopy and debridement in the management of patients with early arthritis. Although the limited evidence suggests that there may be some therapeutic benefit, further large-scale prospective studies need to be performed before making conclusive recommendations. Level of Evidence: Level III (Therapeutic).

Background: The optimal management of distal radius fractures remains a challenge for orthopaedic surgeons. The emergence of Artificial Intelligence (AI) and Large Language Models (LLMs), especially ChatGPT, affords significant potential in improving healthcare and research. This study aims to assess the accuracy and consistency of ChatGPT's knowledge in managing distal radius fractures, with a focus on its capability to provide information for patients and assist in the decision-making processes of orthopaedic clinicians., Methods: We presented ChatGPT with seven questions on distal radius fracture management over two sessions, resulting in 14 responses. These questions covered a range of topics, including patient inquiries and orthopaedic clinical decision-making. We requested references for each response and involved two orthopaedic registrars and two senior orthopaedic surgeons to evaluate response accuracy and consistency., Results: All 14 responses contained a mix of both correct and incorrect information. Among the 47 cited references, 13% were accurate, 28% appeared to be fabricated, 57% were incorrect, and 2% were correct but deemed inappropriate. Consistency was observed in 71% of the responses., Conclusion: ChatGPT demonstrates significant limitations in accuracy and consistency when providing information on distal radius fractures. In its current format, it offers limited utility for patient education and clinical decision-making., (© 2024 Royal Australasian College of Surgeons.)

Background: Antegrade homodigital neurovascular island flaps (AHIFs) are a heterogeneous group of pedicled flaps used for reconstruction of traumatic digital detipping injuries. While numerous single-center studies have documented their use, there are no large or multicentre studies validating their efficacy, applicability, and functional outcomes. We performed a systematic review of the contemporary literature to establish the safety and functional outcomes of this technique., Methods: Electronic searches were performed using PubMED, Embase, and MEDLINE from inception date to October 2020, with further studies identified from study reference lists and independent searches. Relevant studies reported on complications and functional outcomes of the AHIFs, as used for digital detipping injuries. Data were then extracted and analyzed., Results: Twenty-seven studies published between 1974 and 2019 yielded 744 patients. Four studies provided incomplete epidemiologic data, resulting in a total of 559 patients with 584 digital injuries. Index and middle fingers were most frequently involved. Mean final 2-point discrimination (2-PD) was 4.9 mm static and 5.1 mm dynamic, with dynamic 2-PD reported in 2 studies. Mean total active motion of the digit was 200.3°. Mean time to return to work was 6.7 weeks in 10 studies. Flap survivorship was found to be 99.6% in 23 studies. Cold intolerance was the most common complication at 18%, followed by pain and hypersensitivity., Conclusions: Antegrade homodigital neurovascular island flaps provide a safe and effective method of treating distal finger amputations, yielding satisfactory functional outcomes across all ages. Further studies comparing outcomes between the AHIFs and other reconstructive modalities would be useful., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background:  Interposition microvascular grafting may be required to bridge arterial defects during digital replantation or revascularization and has traditionally been performed utilizing a venous autograft. Arterial interposition grafting has been shown to be superior in maintaining patency in large vessel surgery; there are case reports of its use in microsurgery., Methods:  Six fellowship-trained hand and microsurgeons performed arterial and venous interposition grafts on the femoral arteries of 40 Wistar rats. After sectioning one femoral artery a segment of the contralateral femoral artery or vein was obtained. The time was recorded per graft and patency tested 10 minutes following grafting by an independent assessor. Each surgeon also completed a questionnaire detailing regular microsurgical volume, technical ease, and conceptual preference for either graft., Results:  Time for arterial interposition (median time 51.7 minutes) was longer than venous grafting (median time 45.9 minutes, p  = 0.075). Arterial grafts were more likely to be patent or questionably patent (odds ratio [OR] = 6.77, p  = 0.031). All surgeons found arterial interposition grafting technically easier and preferred it conceptually. Improvements were noted in patency rates (OR = 11.29, p  = 0.018) and avoidance of anastomotic leak (OR = 0.19, p  = 0.029) when surgeons performed moderate levels or greater of microsurgery within their regular practice., Conclusion:  Greater immediate patency was noted with arterial interposition grafting in a rodent model when compared to venous grafting, although procedural time was greater. All surgeons found arterial grafting technically easier. Arterial microvascular grafting may be useful in the setting of digital replantation or revascularization with an arterial defect., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Intramedullary screws (IMS) have become a viable option for metacarpal fracture fixation. To further appraise their utility, this study assessed clinical and patient-reported short- and medium-term outcomes of IMS fixation for extra-articular metacarpal fractures. Methods: A retrospective cohort study was performed in a series of 32 patients (with a total of 37 fractures) who underwent metacarpal fracture fixation over a 42-month period between January 2020 and July 2023. Results: Mean time for return to work was 39.8 days; mean time for return to full function was 88.4 days; total active motion was 250.7° (range: 204.9-270.9); Quick Disabilities of the Arm, Shoulder and Hand score was 2.3 (range: 0-22.7); mean visual analogue pain score was 0.9 out of 10 (range: 0-6) and a single complication was observed. Conclusions: The use of IMS in metacarpal fracture fixation is a practicable surgical option. IMS fixations yields a satisfactory duration for return to function, good postoperative range of movement, modest pain scores and low rates of complications. Level of Evidence: Level IV (Therapeutic).

Hydrological droughts are expected to increase in frequency and severity in many regions due to climate change. Over the last two decades, several droughts occurred in Europe, including the 2018-drought, which showed major adverse impacts for nature and different sectoral uses (e.g. irrigation, drinking water). While drought impacts on water quantity are well studied, little understanding exists on the impacts on water quality, particularly regarding pharmaceutical concentrations in surface waters. This study investigates the impact of the 2018-drought on concentrations of four selected pharmaceuticals (carbamazepine, sulfamethoxazole, diclofenac and metoprolol) in surface waters in Europe, with a major focus on the Elbe and Rhine rivers. Monitoring data were analysed for the period of 2010-2020 to estimate the spatiotemporal patterns of pharmaceuticals and assess the concentration responses in rivers during the 2018-drought compared to reference years. Our results indicate an overall deterioration in water quality, which can be attributed to the extremely low flow and higher water temperatures (∼ + 1.5 °C and + 2.0 °C in Elbe and Rhine, respectively) during the 2018-drought. Our results show an increase in the concentrations of carbamazepine, sulfamethoxazole, and metoprolol, but reduced concentrations of diclofenac during the 2018-drought. Significant increases in carbamazepine concentrations (+45 %) were observed at 3/6 monitoring stations in the upstream part of the Elbe, which was mainly attributed to less dilution of chemical loads from wastewater treatment plants under drought conditions. However, reduced diclofenac concentrations could be attributed to increased degradation processes under higher water temperatures (R 2  = 0.60). Moreover, the rainfed-dominated Elbe exhibited more severe water quality deterioration than the snowmelt-dominated Rhine river, as the Elbe's reduction in dilution capacity was larger. Our findings highlight the need to account for the impacts of climate change and associated increases in droughts in water quality management plans, to improve the provision of water of good quality for ecosystems and sectoral needs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)