Clinical Practice Guideline for the Therapeutic Drug Monitoring of Voriconazole in Non-Asian and Asian Adult Patients: Consensus Review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring

PurposeVoriconazole, an antifungal drug, is metabolized by a cytochrome P450 isozyme. Increased adverse effects are observed in Asians because of the high rate of poor metabolizers. In this therapeutic drug monitoring (TDM) guideline, recommendations were made according to ethnic group.MethodsFive clinical questions were used. For the preparation of the guideline, the performance of TDM in multicenter studies was surveyed (study 1). We also conducted a systematic review and meta-analysis (study 2) to establish recommendations for non-Asians and Asians.FindingsIn study 1, 401 patients were surveyed. A risk of supratherapeutic concentrations was found in Japanese patients who adhered to the recommended dose. Target trough levels were achieved in 87% of patients with dose reductions. Although the trough level measured at the onset of adverse effects (AEs) was significantly associated with hepatotoxicity, no significant correlation was found between the initial trough level and hepatotoxicity, which indicated that hepatotoxicity was successfully prevented by the trough-guided dosing. In study 2, 22 studies (11 Asian locations and 11 non-Asian locations) were included in meta-analysis for the relationship between trough cutoff level (3, 4, 5, 5.5, and 6 µg/mL) and AEs. Significant differences were found for all cutoff levels, with the highest odds ratio for 4.0 µg/mL in Asian locations. In contrast, in non-Asian locations, no more than 1 study was available for any trough cutoff level, except for 5.5 µg/mL, at which level a significant increase in AEs was found. These findings indicate that TDM is strongly recommended to prevent AEs in Asians, and TDM is generally recommended for non-Asians to address subtherapeutic concentrations. TDM on day 3 is recommended to assess pharmacokinetic properties, including loading and maintenance doses. If the patient condition permits, delaying until day 5 is suggested for Asians because of the prolonged t_½ in poor metabolizers. A trough level ≥1.0 µg/mL is strongly recommended to improve efficacy. Trough levels ≥2.0 µg/mL are suggested for invasive aspergillosis. To decrease adverse effects, trough levels <4.0 µg/mL are strongly recommended in Asians, whereas trough levels <5.5 µg/mL are generally recommended in non-Asians. Maintenance doses of 4 and 3 mg/kg twice daily are recommended in non-Asians and Asians, respectively.ImplicationsDifferent indications, timings, and target trough levels for TDM and different regimens are suggested for Asians and non-Asians.     

Women-Focused Cardiovascular Rehabilitation: An International Council of Cardiovascular Prevention and Rehabilitation Clinical Practice Guideline

Women-focused cardiovascular rehabilitation (CR; phase II) aims to better engage women, and might result in better quality of life than traditional programs. This first clinical practice guideline by the International Council of Cardiovascular Prevention and Rehabilitation (ICCPR) provides guidance on how to deliver women-focused programming. The writing panel comprised experts with diverse geographic representation, including multidisciplinary health care providers, a policy-maker, and patient partners. The guideline was developed in accordance with Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Reporting Items for practice Guidelines in HealTh care (RIGHT). Initial recommendations were on the basis of a meta-analysis. These were circulated to a Delphi panel (comprised of corresponding authors from review articles and of programs delivering women-focused CR identified through ICCPR’s audit; N = 76), who were asked to rate each on a 7-point Likert scale in terms of impact and implementability (higher scores positive). A Web call was convened to achieve consensus; 15 panelists confirmed strength of revised recommendations (Grading of Recommendations Assessment, Development, and Evaluation [GRADE]). The draft underwent external review from CR societies internationally and was posted for public comment. The 14 drafted recommendations related to referral (systematic, encouragement), setting (model choice, privacy, staffing), and delivery (exercise mode, psychosocial, education, self-management empowerment). Nineteen (25.0%) survey responses were received. For all but 1 recommendation, ≥ 75% voted to include; implementability ratings were < 5/7 for 4 recommendations, but only 1 for effect. Ultimately 1 recommendation was excluded, 1 separated into 2 and all revised (2 substantively); 1 recommendation was added. Overall, certainty of evidence for the final recommendations was low to moderate, and strength mostly strong. These recommendations and associated tools can support all programs to feasibly offer some women-focused programming.     

Prolonged restricted training,fixture congestion and player rotation: What the COVID-19 pandemic taught us about injury risk in professional collision sport

ObjectivesThe COVID19-induced suspension of the 2019-20 professional England rugby union season resulted in players being exposed to an extended restricted training period, coupled with a congested match schedule once competition resumed. We assessed the impact of these changes on match and training injuries in the final 20-weeks of the season following competition resumption.DesignEpidemiological study.MethodsThe 2019-20 season was compared to the previous three seasons (2016-19).ResultsThere was no significant difference in the mean incidence, severity and burden of training and match injuries in 2019-20 compared to 2016-19 period mean. The 2019-20 post-suspension mean match injury rate [77/1000 h (95%CIs [confidence intervals]: 67-89)] was comparable to the 2019-20 pre-suspension [93/1000 h (95%CIs: 85-101)] and significantly lower than the 2016-19 equivalent post-suspension period [97/1000 h (95CIs: 90-104) IRR [incidence rate ratio] 0.8 p=0.002]. In the 2019-20 season, there was a significantly higher rate of training injury post-suspension in comparison to pre-suspension [3.8/1000 h (95CIs: 3.3-4.4) vs 2.7/1000 h (95% CIs: 2.5-3.1) IRR 1.4 p=0.005]. There was no significant difference in the overall incidence, severity or burden of injuries sustained in fixtures with shorter (<6 days) turnarounds but there was a significantly higher burden of soft tissue injuries.ConclusionsThis is the first study to assess the effect of restricted training on injury risk in collision sports. Players were at an increased risk of training injury when returning from the suspension, but 10-weeks of preparatory training meant the incidence of match injury was not higher when competition resumed.     

Echocardiographic Evaluation of Left and Right Ventricular Function in Patients with Coronary Slow Flow Syndrome: A Comparative Study

The Coronary Slow Flow Phenomenon is a syndrome of normal coronary anatomy and delayed progression of contrast medium through the coronary vessels. This research attempts to analyze and compare the systolic and diastolic function of the left and right ventricle in primary Slow Flow and Normal Coronary Flow.Two groups of primary Slow Coronary Flow (33 people) and Normal Coronary Flow (11 people) were included and the systolic and diastolic function of the ventricles was analyzed and compared between them.In the control group 18% of patients had mild and in the case group 24.2% mild, and 3.1% had moderate left ventricular diastolic dysfunction (P >0.05). The frequency distribution of the left and right ventricular systolic dysfunction was similar in the two groups.There was no statistically significant difference between two groups and in the association of cardiac dysfunction, it may be reasonable to investigate other causes.     

Health-Related Quality of Life in Patients Under Treatment With Apixaban in Latin America

Atrial fibrillation (AF) has a strong impact on the quality of life (QOL) of patients and anticoagulation has a lot to do with it. We evaluated the QOL of patients with nonvalvular AF who start treatment with apixaban in Latin America. QOL was analyzed through a questionnaire developed to evaluate anticoagulated patients, which was completed by them 3 months after starting treatment. We included 521 patients from Uruguay, Bolivia, Ecuador, Paraguay, and Peru. A high index of general treatment satisfaction (5.34 ± 0.46) and self-efficacy (5.11 ± 0.68) were observed; the distress index was low (1.77 ± 0.88), as was the perception of daily hassles (1.35 ± 0.49) and strain social network related to medication (1.21 ± 0.34). Patients with AF who started treatment with apixaban has good satisfaction and self-efficacy scores with low index of stress, few daily limitations and social disruptions.