Intrinsic dissolution simulation of highly and poorly soluble drugs for BCS solubility classification

Intrinsic dissolution testing allows characterizing drug substances through its dissolution rate when exposed to a specified surface area in a specific dissolution media, This can be used to determine if a drug substance is highly or poorly soluble. In this work. DDDPlus version 4.0 (Simulations Plus, Inc.) was used to simulate intrinsic dissolution experiments for pyrimethamine and metronidazole. These drugs have low and high solubility properties. Predicted intrinsic dissolution rates (IDR) were compared to observed in vitro IDR. Physicochemical parameters from literature and the experimental conditions of the intrinsic dissolution tests for each drug were used as input data into the software. The program was able to predict the IDR of pyrimethamine and metronidazole within a pH range of 1.0 to 7.2. Observed and predicted IDR values for both drugs showed high correlations (R-2 > 0.9424), The IDR values from simulations showed the pH-dependent solubility of pyrimethamine and metronidazole, allowing us to classify the solubility according to the Biopharmaceutics Classification System (BCS). Intrinsic dissolution test simulations using DDDPlus can be used to obtain a BCS solubility classification of a drug substance, helping to reduce the number of laboratory experiments.National Council of Scientific and Technological Development (CNPq/Brazil)Univ Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, Sao Paulo, BrazilUniv Fed Sao Paulo UNIFESP, Inst Environm Chem & Pharmaceut Sci, Dept Exact & Earth Sci, Sao Paulo, BrazilUniv Alberta, Ctr Pharm & Hlth Res, Fac Pharm & Pharmaceut Sci, Edmonton, AB, CanadaUniv Fed Sao Paulo UNIFESP, Inst Environm Chem & Pharmaceut Sci, Dept Exact & Earth Sci, Sao Paulo, BrazilCNPq: 400455/2014-5Web of Scienc

Muscle contractile exercise through a belt electrode device prevents myofiber atrophy, muscle contracture, and muscular pain in immobilized rat gastrocnemius muscle

Purpose: Immobilization of skeletal muscles causes muscle atrophy, muscle contracture, and muscle pain, the mechanisms of which are related to macrophage accumulation. However, muscle contractile exercise through a belt electrode device may mitigate macrophage accumula-tion. We hypothesized that such exercise would be effective in preventing myofiber atrophy, muscle contracture, and muscular pain. This study tested this hypothesis in immobilized rat gastrocnemius muscle.Materials and methods: A total of 32 rats were divided into the following control and experimental groups: immobili-zation (immobilized treatment only), low-frequency (LF; immobilized treatment and muscle contractile exercise with a 2 s (do) /6 s (rest) duty cycle), and high-frequency (HF; immobi-lized treatment and muscle contractile exercise with a 2 s (do)/2 s (rest) duty cycle). Electri-cal stimulation was performed at 50 Hz and 4.7 mA, and muscle contractile exercise was applied to the lower limb muscles for 15 or 20 min/session (once daily) for 2 weeks (6 times/ week). After the behavioral tests, the bilateral gastrocnemius muscles were collected for analysis.Results: The number of macrophages, the Atrogin-1 and MuRF-1 mRNA expression, and the hydroxyproline content in the HF group were lower than those in the immobilization and LF groups. The cross-sectional area (CSA) of type IIb myofibers in the superficial region, the PGC-1α mRNA expression, and the range of motion of dorsiflexion in the HF group were significantly higher than those in the immobilization and LF groups. The pressure pain thresholds in the LF and HF groups were significantly higher than that in the immobilization group, and the nerve growth factor (NGF) content in the LF and HF groups was significantly lower than that in the immobilization group.Conclusion: Muscle contractile exercise through the belt electrode device may be effective in preventing immobilization-induced myofiber atrophy, muscle contracture, and muscular pain in the immobilized rat gastrocnemius muscle

Effect of exercise and/or educational interventions on physical activity and pain in patients with hip/knee osteoarthritis: A systematic review with meta-analysis

Objective: To investigate the effectiveness of exercise and/or educational intervention on physical activity and pain in patients with hip/knee osteoarthritis (OA) using systematic review and meta-analysis.Methods: We searched randomized controlled trials that investigated physical activity and pain and compared exercise and/or educational intervention with usual care in patients with hip/knee OA in MEDLINE (PubMed), ProQuest, Scopus, and the Physiotherapy Evidence Database (PEDro), including all those published by April 30, 2022 and written in English. Studies that newly applied analgesics after onset of the intervention were excluded. The revised Cochrane risk-of-bias tool for randomized trials was used to assess the methodological qualities. The random-effects model was used for meta-analysis with standard mean differences using RevMan version 5.4. The body of evidence for each study was synthesized using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.Results: Twenty studies including 2,350 patients were included (7 exercise studies, 8 educational intervention studies and 5 combination studies). The meta-analysis demonstrated that there is very low evidence that combination therapy of exercise and educational intervention improve the physical activity level at the endpoint (4 articles; SMD 0.33, 95% CI 0.04 to 0.51, P = 0.03). Low evidence was observed for combination therapy reducing pain (4 articles; SMD -0.15, 95% CI -0.29 to -0.02, P = 0.03).Discussion: The current evidence indicated that combination therapy of exercise and educational intervention leads to improved physical activity and pain reduction in hip/knee OA patients, but the risk of bias in each study, especially in allocation concealment, downgraded the evidence level. These findings support the use of a combination therapy of exercise and educational intervention to promote physical activity levels in patients with hip/knee OA.Trail registration: There was no financial support for this research. The protocol was registered at the International Prospective Register of Systematic Reviews (registration code: CRD42020205804)

Adherence to blood pressure measurement guidelines in long-term care facilities: A cross sectional study

ObjectiveTo assess the extent to which long‐term care facilities in Japan adhere to blood pressure (BP) measurement guidelines.DesignCross‐sectional, observational survey.SettingJapan (nationwide).ParticipantsGeriatric health service facilities that responded to a questionnaire among 701 facilities that provide short‐time daycare rehabilitation services in Japan.MethodsA written questionnaire that asked about types of measurement devices, number of measurements used to obtain an average BP, resting time prior to measurement, and measurement methods when patients’ arms were covered with thin (eg, a light shirt) or thick sleeves (eg, a sweater) was administered.Main outcome measureProportion of geriatric health service facilities adherent to BP measurement guidelines.ResultsThe response rate was 63.2% (443/701). Appropriate upper‐arm BP measurement devices were used at 302 facilities (68.2%). The number of measurements was appropriate at 7 facilities (1.6%). Pre‐measurement resting time was appropriate (≥5 minutes) at 205 facilities (46.3%). Of the 302 facilities that used appropriate BP measurement devices, 4 (1.3%) measured BP on a bare arm if it was covered with a thin sleeve, while 266 (88.1%) measured BP over a thin sleeve. When arms were covered with thick sleeves, BP was measured on a bare arm at 127 facilities (42.1%) and over a sleeve at 78 facilities (25.8%).ConclusionsBP measurement guidelines were not necessarily followed by long‐term care service facilities in Japan. Modification of guidelines regarding removing thick sweaters and assessing BP on a visit‐to‐visit basis might be needed

Detection of SARS-CoV-2 using qRT-PCR in saliva obtained from asymptomatic or mild COVID-19 patients, comparative analysis with matched nasopharyngeal samples

Objectives: The accurate detection of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) is essential for the diagnosis of coronavirus disease 2019 (COVID-19). We compared the quantitative RT-PCR results between nasopharyngeal swabs and saliva specimens.Methods: A COVID-19 outbreak occurred on a cruise ship at Nagasaki port, Japan. We obtained 123 nasopharyngeal swabs and saliva each from asymptomatic or mild patients in the late phase of infection.Results: The intervals from the diagnosis to the sampling were 25.5 days for nasopharyngeal swabs and 28.9 days for saliva. The positive rate was 19.5% (24/123) for nasopharyngeal swabs and 38.2% (47/123) for saliva (P = 0.48). The quantified viral copies (mean ± SEM copies/5 μl) were 9.3±2.6 in nasopharyngeal swabs and 920±850 in saliva (P = 0.0006).Conclusions: The advantages of saliva specimens include positive rate improvement and accurate viral load detection. Saliva may be used as a reliable sample for SARS-CoV-2 detection

Association between Excessive Alcohol Use and Alcohol-Related Injuries in College Students: A Multi-Center Cross-Sectional Study in Japan

Alcohol-related injuries in college students are a major public health problem worldwide. We clarified the association between excessive drinking and alcohol-related injuries in Japanese college students. This was a cross-sectional study with a self-administered questionnaire. From January to March 2013, we sampled all college students and graduate students aged 20 years or older during annual health examinations at three colleges in Mie Prefecture in Japan. The questionnaire assessed the frequency of alcohol drinking, amount of alcohol consumed per day, binge drinking during the past year, alcohol-related injuries during the past year, and demographic data. Logistic regression analysis was conducted on the association between excessive alcohol use and alcohol-related injuries. A total of 2,842 students underwent health examinations, of whom 2,177 (76.6%) completed the questionnaire. Subjects included 1,219 men (56.0%) and 958 women (44.0%). Eighty-eight men (7.2%) and 93 women (9.7%) were classified as excessive weekly drinkers, while 693 men (56.8%) and 458 women (47.8%) were determined to be binge drinkers. Eighty-one men (6.6%) and 26 women (2.7%) had experienced alcohol-related injuries during the past year. In the logistic regression analysis, binge drinkers (odds ratio 25.6 [8.05-81.4]) and excessive weekly drinkers (odds ratio 3.83 [2.41-6.09]) had a history of significantly more alcohol-related injuries, even after adjusting for age and sex. In conclusion, alcohol-related injuries in college students in Japan were strongly associated with excessive drinking. As a strategy for preventing such injuries in this population, an interventional study is required to identify effective methods for reducing excessive alcohol use

Evaluation of a Triage Checklist for Mild COVID-19 Outpatients in Predicting Subsequent Emergency Department Visits and Hospitalization during the Isolation Period: A Single-Center Retrospective Study

Managing mild illness in COVID-19 and predicting progression to severe disease are concerning issues. Here, we investigated the outcomes of Japanese patients with mild COVID-19, and identified triage risk factors for further hospitalization and emergency department (ED) visits at a single tertiary hospital. A triage checklist with 30 factors was used. Patients recommended for isolation were followed up for 10 days for subsequent ED visits or hospital admission. Overall, 338 patients (median age, 44.0; 45% women) visited the clinic 5.0 days (median) after symptom onset. Thirty-six patients were immediately hospitalized following triage; others were isolated. In total, 72 non-hospitalized patients visited the ED during their isolation, and 30 were hospitalized after evaluation for oxygen desaturation. The median ED visit and hospitalization durations after symptom onset were 5.0 and 8.0 days, respectively. The checklist factors associated with hospitalization during isolation were age > 50 years, body mass index > 25 kg/m2, hypertension, tachycardia with pulse rate > 100/min or blood pressure > 135 mmHg at triage, and >3-day delay in hospital visit after symptom onset. No patients died. Altogether, 80% of patients with mild COVID-19 could be safely isolated at home. Age, BMI, underlying hypertension, date after symptom onset, tachycardia, and systolic blood pressure at triage might be related to later hospitalization