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Background: People with schizophrenia spectrum disorders (SSD) engage less in physical activity than healthy individuals. The impact of subjectively assessed physical fitness levels on motivation for sports engagement and its relation to objective fitness parameters in SSD is unclear. Methods: 25 patients with SSD (P-SSD) and 24 healthy controls (H-CON) participated in a randomized controlled study. Individual anaerobic thresholds (AT) were determined by an incremental exercise test and on separate days, aerobic exercise (cycling at 80% of workload at AT) and non-exercise control (sitting on an ergometer without cycling) sessions were performed. Demographic, clinical and objective physical fitness data (i.e., weekly physical activity, workload at AT, heart rate) were collected. Subjective physical fitness parameters were assessed before and after exercise and control sessions. Results: Weekly physical activity in P-SSD was lower than in H-CON (p < 0.05) attributed to reduced engagement in sport activities (p < 0.001). Workload and percentage of predicted maximal heart rate at AT were also reduced in P-SSD compared to H-CON (both p < 0.05). Although objective and subjective physical fitness parameters were related in H-CON (p < 0.01), this relationship was absent in P-SSD. However, during exercise sessions subjective physical fitness ratings increased to a stronger extent in P-SSD than H-CON (p < 0.05). Conclusion: The missing relationship between subjective and objective physical fitness parameters in people with SSD may represent a barrier for stronger engagement in physical activity. Accordingly, supervised exercise interventions with individually adjusted workload intensity may support realistic subjective fitness estimations and enhance motivation for sports activity in individuals with SSD. [ABSTRACT FROM AUTHOR]

Clofazimine is included in drug regimens to treat rifampicin/drug-resistant tuberculosis (DR-TB), but there is little information about its interaction with other drugs in DR-TB regimens. We evaluated the pharmacokinetic interaction between clofazimine and isoniazid, linezolid, levofloxacin, and cycloserine, dosed as terizidone. Newly diagnosed adults with DR-TB at Klerksdorp/Tshepong Hospital, South Africa, were started on the then-standard treatment with clofazimine temporarily excluded for the initial 2 weeks. Pharmacokinetic sampling was done immediately before and 3 weeks after starting clofazimine, and drug concentrations were determined using validated liquid chromatography-tandem mass spectrometry assays. The data were interpreted with population pharmacokinetics in NONMEM v7.5.1 to explore the impact of clofazimine co-administration and other relevant covariates on the pharmacokinetics of isoniazid, linezolid, levofloxacin, and cycloserine. Clofazimine, isoniazid, linezolid, levofloxacin, and cycloserine data were available for 16, 27, 21, 21, and 6 participants, respectively. The median age and weight for the full cohort were 39 years and 52 kg, respectively. Clofazimine exposures were in the expected range, and its addition to the regimen did not significantly affect the pharmacokinetics of the other drugs except levofloxacin, for which it caused a 15% reduction in clearance. A posteriori power size calculations predicted that our sample sizes had 97%, 90%, and 87% power at P < 0.05 to detect a 30% change in clearance of isoniazid, linezolid, and cycloserine, respectively. Although clofazimine increased the area under the curve of levofloxacin by 19%, this is unlikely to be of great clinical significance, and the lack of interaction with other drugs tested is reassuring., Competing Interests: The authors declare no conflict of interest.

Background: Lopinavir/ritonavir plasma concentrations are profoundly reduced when co-administered with rifampicin. Super-boosting of lopinavir/ritonavir is limited by nonavailability of single-entity ritonavir, while double-dosing of co-formulated lopinavir/ritonavir given twice-daily produces suboptimal lopinavir concentrations in young children. We evaluated whether increased daily dosing with modified 8-hourly lopinavir/ritonavir 4:1 would maintain therapeutic plasma concentrations of lopinavir in children living with HIV receiving rifampicin-based antituberculosis treatment., Methods: Children with HIV/tuberculosis coinfection weighing 3.0 to 19.9 kg, on rifampicin-based antituberculosis treatment were commenced or switched to 8-hourly liquid lopinavir/ritonavir 4:1 with increased daily dosing using weight-band dosing approach. A standard twice-daily dosing of lopinavir/ritonavir was resumed 2 weeks after completing antituberculosis treatment. Plasma sampling was conducted during and 4 weeks after completing antituberculosis treatment., Results: Of 20 children enrolled; 15, 1-7 years old, had pharmacokinetics sampling available for analysis. Lopinavir concentrations (median [range]) on 8-hourly lopinavir/ritonavir co-administered with rifampicin (n = 15; area under the curve 0-24 55.32 mg/h/L [0.30-398.7 mg/h/L]; C max 3.04 mg/L [0.03-18.6 mg/L]; C 8hr 0.90 mg/L [0.01-13.7 mg/L]) were lower than on standard dosing without rifampicin (n = 12; area under the curve 24 121.63 mg/h/L [2.56-487.3 mg/h/L]; C max 9.45 mg/L [0.39-26.4 mg/L]; C 12hr 3.03 mg/L [0.01-17.7 mg/L]). During and after rifampicin cotreatment, only 7 of 15 (44.7%) and 8 of 12 (66.7%) children, respectively, achieved targeted pre-dose lopinavir concentrations ≥1mg/L., Conclusions: Modified 8-hourly dosing of lopinavir/ritonavir failed to achieve adequate lopinavir concentrations with concurrent antituberculosis treatment. The subtherapeutic lopinavir exposures on standard dosing after antituberculosis treatment are of concern and requires further evaluation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The prevalence of type 2 diabetes is reaching epidemic proportions. First line therapy approaches are lifestyle interventions including exercise. Although a vast amount of studies reports on beneficial effects of exercise on metabolism in humans per se, overall data are contradictory which makes it difficult to optimize interventions. Innovative exercise strategies and its underlying mechanism are needed to elucidate in order to close this therapeutic gap. The skeletal muscle produces and secretes myokines and microRNAs in response to exercise and both are discussed as mechanisms linking exercise and metabolic adaptation. Aspects of chronophysiology such as diurnal variation in insulin sensitivity or exercise as a signal to reset dysregulated peripheral clocks are of growing interest in the context of impaired metabolism. Deep insight of how exercise timing determines metabolic adaptations is required to optimize exercise interventions. This review aims to summarize the current state of research on the interaction between timing of exercise and metabolism in humans, providing insights into proposed mechanistic concepts focusing on myokines and microRNAs. First evidence points to an impact of timing of exercise on health outcome, although data are inconclusive. Underlying mechanisms remain elusive. It is currently unknown if the timed release of mykokines depends on time of day when exercise is performed. microRNAs have been found as an important mediator of processes associated with exercise adaptation. Further research is needed to evaluate their full relevance. In conclusion, it seems to be too early to provide concrete recommendations on timing of exercise to maximize beneficial effects., (© 2023 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Objectives: The 2018-2019 Rwanda Population-based HIV Impact Assessment (RPHIA) was conducted to measure national HIV incidence and prevalence. District-level estimates were modeled to inform resources allocation., Methods: RPHIA was a nationally representative cross-sectional household survey. Consenting adults were interviewed and tested for HIV using the national diagnostic algorithm followed by laboratory-based confirmation of HIV status and testing for viral load (VL), limiting antigen (LAg) avidity, and presence of antiretrovirals. Incidence was calculated using normalized optical density ≤ 1·5, VL ≥ 1,000 copies/mL, and undetectable antiretrovirals. Survey and programmatic data were used to model district-level HIV incidence and prevalence., Results: Of 31,028 eligible adults, 98·7% participated in RPHIA and 934 tested HIV positive. HIV prevalence among adults in Rwanda was 3·0% (95% CI:2·7-3·3). National HIV incidence was 0·08% (95% CI:0·02-0·14) and 0·11% (95% CI:0·00-0·26) in the City of Kigali (CoK). Based on district-level modeling, HIV incidence was greatest in the 3 CoK districts (0·11% to 0·15%) and varied across other districts (0·03% to 0·10%)., Conclusions: HIV prevalence among adults in Rwanda is 3.0%; HIV incidence is low at 0.08%. District-level modeling has identified disproportionately affected urban hotspots: areas to focus resources., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Primary hyperparathyroidism is caused by an ectopically located parathyroid adenoma in a small percentage of cases. Parathyroid adenomas located within the retrosternal area of the anterior mediastinum account for a large proportion of failed initial cervical explorations. Current surgical approach to these lesions is via median sternotomy, with the discomfort, hospitalization, and morbidity associated with a major thoracic operation. We report a new technique for the resection of these ectopic parathyroid adenomas after successful radiologic localization: a minimally invasive subxiphoid laparoscopic approach. The procedure was performed in a symptomatic patient with documented primary hyperparathyroidism who had failed three previous neck operations. The ectopic parathyroid adenoma was successfully resected endoscopically, with resolution of the hypercalcemia. The patient was discharged on the third postoperative day, avoiding completely the morbidity of a median sternotomy.