The cardiac autonomic dysfunction in the absence of any significant changes in vascular dynamics, 4 but not 8 weeks after induction of type 2 diabetes, suggests that the diabetic autonomic neuropathy may precede arterial stiffening and cardiac hypertrophy in the STZ- and NA-treated rats.
To supplement previous state-of-art reviews on anti-tuberculosis treatment and to pave the way forward with reference to the current status, we systematically reviewed published literature on clinical research on tuberculosis (TB) over the past decade in the treatment of drug-susceptible and multidrug-resistant TB (MDR-TB), with a focus on drugs, dosing factors and regimens. Our review was restricted to Phase II/III clinical trials, cohort and case-control studies, and systematic reviews of clinical studies. TB programmatic and patient behavioural factors, non-TB drugs, adjunctive surgery, new vaccines, immunotherapy, antiretroviral therapy and management of latent tuberculous infection are outside the scope of this review. An algorithm was used to systematically search PubMed for relevant articles published in English from 1 January 2005 to 31 December 2014. Articles without evaluated factors (drugs, dosing factors and regimens) or comparative analysis of specified anti-tuberculosis treatment outcomes were excluded. Of the 399 articles initially identified, 294 were excluded. The main findings of the remaining 105 articles are described under two categories: presumed drug-susceptible TB and MDR-TB. Fifty-nine articles included under drug-susceptible TB were divided into 12 subcategories: isoniazid, rifampicin, pyrazinamide, fluoroquinolones, fixed-dose combination drugs, dosing frequency, treatment phases, treatment duration, experimental regimens for pulmonary (surrogate markers vs. clinical outcomes) and extra-pulmonary TB. Forty-nine articles included under MDR-TB were divided into seven subcategories: fluoroquinolones, pyrazinamide, second-line injectable drugs, World Health Organization Group 4 and Group 5 drugs, MDR-TB regimens and novel drugs. Clinical research in the last decade and ongoing trials might furnish new paradigms for improving the treatment of this recalcitrant ancient disease.
Aim and objectives To determine the association between PDE5i exposure and incident dementia in PCa patients treated with ADT. Material and methods We conducted a retrospective cohort study using the Chang Gung Research Database (CGRD) in Taiwan. We included PCa patients newly receiving ADT between 2009 and 2016. We conducted a three step matching and modified landmark approach to identify PDE5i users and non-users after ADT use. The landmark date was defined as 1 year following the start of ADT, and we defined PDE5i users as patients initiating PDE5i before and after the landmark date. We matched PDE5i users to non-users by (1) age, (2) prostatic specific antigen and (3) 1:4 propensity scores for comorbidity and co-medication. We followed the patients from the landmark date until the incident diagnosis of dementia, last date of clinical visit or 31 December 2019. We performed multivariate Cox proportional hazard models to compare the dementia risk between PDE5i users and nonusers.Results We included 4557 PCa patients starting ADT treatment, with a mean age of 69.5 (SD 7.0) years. After matching, we identified 161 PDE5i users and 644 non-PDE5i users. A total of 5.1 person years of PDE5i users and 4.6 person years of PDE5i non-users were included. Compared with non-users of PDE5i, PCa patients treated with ADT initiating PDE5i had a lower risk of dementia (adjusted HR=0.17, 95% CI 0.04 to 0.70) in the modified landmark analyses. Conclusion and relevance PDE5i use in PCa patients treated with ADT was associated with a decreased risk of subsequent dementia. Future large scale studies are suggested to confirm our findings.
Background and importance The management of investigational health products (IHPs) is a major part of conducting clinical trials (CTs). It presents specific risks all along the circuit, with data integrity and patient safety issues. However, few standardised tools are available, and no national inventory has been conducted in hospital pharmacies. Aim and objectives The aim of this work was to make an inventory of the current situation in our country, and then to prioritise risk reduction standardised tools to develop. Material and methods A national survey was developed by a regional working group including four clinical research pharmacists (CRPs), a coordinating pharmacist and a pharmacy resident. The 76 questions dealt with the quality approach and the proposal of new tools. The online anonymous survey was emailed to CRPs in health facilities and activated for 2 months. Results 94 pharmacists participated, allowing a response rate of 70%: 35 non-university hospitals, 25 university hospital centres, 12 private clinics, 11 cancer centres, 10 not-for-profit private hospitals and 1 academic cancer institute. The results regarding the features of quality approach were: documentation system (76/94), adverse drug event reporting system (77/ 94), prior risk assessment (24/94), training and empowering staff (42/94), using means of evaluation and monitoring (49/ 94, including 13 conducting internal audits) and ISO 9001 certification (10/94). All of these features were synthesised into an overall score: from I (basic quality approach) to IV (ISO certification). Score II was the most frequent (38/94). The score depends on the type of health facility (p<0.0005) and increases with the number of active CTs (p<0.0005). 88/ 94 pharmacists were interested in standardised tools. All nine proposed tools were useful for over two-thirds of pharmacists. Two tools with the highest utility scores were self-assessment (p<0.001) and the internal audit grids. Conclusion and relevance All types of facilities conducting CTs were represented and the response rate suggested an overall interest in this topic of management of IHPs. The quality approach was heterogeneous in hospital pharmacies and depended on the level of activity. The needs identified justify prioritising the self-assessment and traceability audit tools which are being validated for dissemination. Such tools will help to harmonise practices in hospital pharmacies by identifying the specific risks and improving the circuit for IHPs. References and/or acknowledgements Conflict of interest No conflict of interest
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