Effects of Testicular and Ovarian Inhibin‐Like Activity, Using In Vitro and In Vivo Systems

Inhibin‐like activities in charcoal‐treated bovine follicular fluid (FF) and medium from cultured Sertoli cells (SCCM) were assayed in an in vitro bioassay system, using cultured pituitary cells. Addition of both fluids resulted in parallel dose‐dependent decreases of the concentration of follicle‐stimulating hormone (FSH) in the medium, both in the presence or absence of luteinizing hormone‐releasing hormone (LH‐RH). A single injection of FF into immature and adult male and female rats resulted in decreased peripheral levels of FSH, but not of LH, after 4 or 8 h. This decrease was larger and occurred faster in adult female rats than in prepubertal female animals. Injection of FF into adult female rats, immediately after unilateral ovariectomy (ULO) prevented the specific increase of FSH levels, occurring in control animals. This suppression could not be obtained after treatment with steroids. Daily treatment of adult female or immature male rats for periods longer than 5 days did not result in prolonged suppression of circulating FSH concentrations; LH levels were significantly increased. The female animals showed cyclic vaginal smear changes and normal ovulation; in the male rats testis weight and numbers of spermatogenic cells were reduced. It is concluded that testicular and ovarian inhibin‐like activities have similar properties. Injections of FF into male and female rats cause similar effects on FSH and LH. The effect of FF in ULO‐animals suggests that inhibin could play a role in the short‐term regulation of the number of developing follicles in the ovary. Injection of FF into male rats causes a probably transient impairment of spermatogenesis through an initial suppression of FSH. Copyrigh

Web-based guided insulin self-titration in patients with type 2 diabetes: the Di@log study. Design of a cluster randomised controlled trial [TC1316]

<p>Abstract</p> <p>Background</p> <p>Many patients with type 2 diabetes (T2DM) are not able to reach the glycaemic target level of HbA1c < 7.0%, and therefore are at increased risk of developing severe complications. Transition to insulin therapy is one of the obstacles in diabetes management, because of barriers of both patient and health care providers. Patient empowerment, a patient-centred approach, is vital for improving diabetes management. We developed a web-based self-management programme for insulin titration in T2DM patients. The aim of our study is to investigate if this internet programme helps to improve glycaemic control more effectively than usual care.</p> <p>Methods/Design</p> <p>T2DM patients (n = 248), aged 35–75 years, with an HbA1c ≥ 7.0%, eligible for treatment with insulin and able to use the internet will be selected from general practices in two different regions in the Netherlands. Cluster randomisation will be performed at the level of general practices. Patients in the intervention group will use a self-developed internet programme to assist them in self-titrating insulin. The control group will receive usual care.</p> <p>Primary outcome is the difference in change in HbA1c between intervention and control group. Secondary outcome measures are quality of life, treatment satisfaction, diabetes self-efficacy and frequency of hypoglycaemic episodes. Results will be analysed according to the intention-to-treat principle.</p> <p>Discussion</p> <p>An internet intervention supporting self-titration of insulin therapy in T2DM patients is an innovative patient-centred intervention. The programme provides guided self-monitoring and evaluation of health and self-care behaviours through tailored feedback on input of glucose values. This is expected to result in a better performance of self-titration of insulin and consequently in the improvement of glycaemic control. The patient will be enabled to 'discover and use his or her own ability to gain mastery over his/her diabetes' and therefore patient empowerment will increase. Based on the self-regulation theory of Leventhal, we hypothesize that additional benefits will be achieved in terms of increases in treatment satisfaction, quality of life and self-efficacy.</p> <p>Trial registration</p> <p>Dutch Trial Register TC1316.</p

The effectiveness of case management for comorbid diabetes type 2 patients; the CasCo study. Design of a randomized controlled trial

BACKGROUND: More than half of the patients with type 2 diabetes (T2DM) patients are diagnosed with one or more comorbid disorders. They can participate in several single-disease oriented disease management programs, which may lead to fragmented care because these programs are not well prepared for coordinating care between programs. Comorbid patients are therefore at risk for suboptimal treatment, unsafe care, inefficient use of health care services and unnecessary costs. Case management is a possible model to counteract fragmented care for comorbid patients. It includes evidence-based optimal care, but is tailored to the individual patients' preferences.The objective of this study is to examine the effectiveness of a case management program, in addition to a diabetes management program, on the quality of care for comorbid T2DM patients. METHODS/DESIGN: The study is a randomized controlled trial among patients with T2DM and at least one comorbid chronic disease (N=230), who already participate in a diabetes management program. Randomization will take place at the level of the patients in general practices. Trained practice nurses (case managers) will apply a case management program in addition to the diabetes management program. The case management intervention is based on the Guided Care model and includes six elements; assessing health care needs, planning care, create access to other care providers and community resources, monitoring, coordinating care and recording of all relevant information. Patients in the control group will continue their participation in the diabetes management program and receive care-as-usual from their general practitioner and other care providers. DISCUSSION: We expect that the case management program, which includes better structured care based on scientific evidence and adjusted to the patients' needs and priorities, will improve the quality of care coordination from both the patients' and caregivers' perspective and will result in less consumption of health care services. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR1847. (aut. ref.

Effect of educational outreach on general practice prescribing of antibiotics and antidepressants: a two-year randomised controlled trial

Objective. Prescribing of broad spectrum antibiotics and antidepressants in general practice often does not accord with guidelines. The aim was to determine the effectiveness of educational outreach in improving the prescribing of selected antibiotics and antidepressants, and whether the effect is sustained for two years. Design. Single blind randomized trial. Setting. Twenty-eight general practices in Leicestershire, England. Intervention. Educational outreach visits were undertaken, tailored to barriers to change, 14 practices receiving visits for reducing selected antibiotics and 14 for improving antidepressant prescribing. Main outcome measures. Number of items prescribed per 1000 registered patients for amoxicillin with clavulanic acid (co-amoxiclav) and quinolone antibiotics, and average daily quantities per 1000 patients for lofepramine and fluoxetine antidepressants, measured at the practice level for six-month periods over two years. Results. There was no effect on the prescribing of co-amoxiclav, quinolones, or fluoxetine, but prescribing of lofepramine increased in accordance with the guidelines. The increase persisted throughout two years of follow-up. Conclusion. A simple, group-level educational outreach intervention, designed to take account of identified barriers to change, can have a modest but sustained effect on prescribing levels. However, outreach is not always effective. The context in which change in prescribing practice is being sought, the views of prescribers concerning the value of the drug, or other unrecognised barriers to change may influence the effectiveness of outreach

Effect of medication review and cognitive behaviour treatment by community pharmacists of patients discharged from the hospital on drug related problems and compliance: design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Drug related problems (DRPs) are common among elderly patients who are discharged from the hospital and are using several drugs for their chronic diseases. Examples of drug related problems are contra-indications, interactions, adverse drug reactions and inefficacy of treatment. Causes of these problems include prescription errors and non-compliance with treatment. The aim of this study is to examine the effect of <it>medication review </it>and <it>cognitive behaviour therapy </it>of discharged patients by community pharmacists to minimize the occurrence of drug related problems.</p> <p>Methods/Design</p> <p>A randomized controlled trial will be performed. Community pharmacists will be randomized into a control group and an intervention group. 342 Patients, aged over 60 years, discharged from general and academic hospitals, using five or more prescription drugs for their chronic disease will be asked by their pharmacy to participate in the study.</p> <p>Patients randomized to the control group will receive usual care according to the Dutch Pharmacy Standard. The medication of patients randomised to the intervention group will be reviewed by the community pharmacist with use of the national guidelines for the treatment of diseases, when patients are discharged from the hospital. The Pharmaceutical Care network Europe Registration form will be used to record drug related problems. Trained pharmacy technicians will counsel patients at home at baseline and at 1,3,6,9 and 12 months, using Cognitive Behaviour Treatment according to the Theory of Planned Behaviour. The patient's attitude towards medication and patient's adherence will be subject of the cognitive behaviour treatment. The counselling methods that will be used are <it>motivational interviewing </it>and <it>problem solving treatment</it>. Patients adherence towards drug use will be determined with use of the Medication Adherence Report Scale Questionnaire. There will be a follow-up of 12 months.</p> <p>The two primary outcome measures are the difference in occurrence of DRPs between intervention and control group and adherence with drug use. Secondary endpoints are attitude towards drug use, incidence of Re-hospitalisations related to medicines, functional status of the patient, quality of life and the cost-effectiveness of this intervention.</p> <p>Discussion</p> <p>Combining both medication review and Cognitive Behaviour Treatment may decrease DRPs and may result in more compliance with drug use among patients discharged from the hospital and using 5 or more chronic drugs.</p> <p>Trial registration</p> <p>Dutch Trial Register NTR1194</p

An audit and feedback intervention for reducing antibiotic prescribing in general dental practice:the RAPiD Cluster Randomised Controlled Trial

Acknowledgments: We thank the TRiaDS Research Methodology Group, including Irene Black, Debbie Bonetti, Heather Cassie, Martin Eccles, Sandra Eldridge, Jill J. Francis, Jeremy M. Grimshaw, Lorna Macpherson, Lorna McKee, Susan Michie, Nigel Pitts, Derek Richards, Douglas Stirling, Colin Tilley, Carole Torgerson, Shaun Treweek, Luke Vale, and Alan Walker for their guidance and contribution to the design and development of the study. We also thank Maria Prior for overseeing the running of the study, drafting of the published protocol, and her contribution to the design and analysis of the process evaluation. Thanks are also extended to Jill Farnham, Jenny Eades, Sarah Blackburn, and Lorna Barnsley for providing invaluable administrative support for this study. The views expressed in this article are those of the authors and may not reflect those of the funder. Funding: This study was conducted as part of the TRiaDS programme of implementation research which is funded by NHS Education for Scotland (NES). The Health Services Research Unit which is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates supported the study. The funder had no influence over the design, conduct, analysis and write up of the study. Data Availability: Researchers can request to access the data from the Information Services Division of NHS National Services Scotland http://www.isdscotland.org/. Some restrictions may apply for the protection of privacy and appropriate usage of the data.Peer reviewedPublisher PD

Diagnostic labelling as determinant of antibiotic prescribing for acute respiratory tract episodes in general practice

<p>Abstract</p> <p>Background</p> <p>Next to other GP characteristics, diagnostic labelling (the proportion of acute respiratory tract (RT) episodes to be labelled as infections) probably contributes to a higher volume of antibiotic prescriptions for acute RT episodes. However, it is unknown whether there is an independent association between diagnostic labelling and the volume of prescribed antibiotics, or whether diagnostic labelling is associated with the number of presented acute RT episodes and consequently with the number of antibiotics prescribed per patient per year.</p> <p>Methods</p> <p>Data were used from the Second Dutch National Survey of General Practice (DNSGP-2) with 163 GPs from 85 Dutch practices, serving a population of 359,625 patients. Data over a 12 month period were analysed by means of multiple linear regression analysis. Main outcome measure was the volume of antibiotic prescriptions for acute RT episodes per 1,000 patients.</p> <p>Results</p> <p>The incidence was 236.9 acute RT episodes/1,000 patients. GPs labelled about 70% of acute RT episodes as infections, and antibiotics were prescribed in 41% of all acute RT episodes. A higher incidence of acute RT episodes (beta 0.67), a stronger inclination to label episodes as infections (beta 0.24), a stronger endorsement of the need of antibiotics in case of white spots in the throat (beta 0.11) and being male (beta 0.11) were independent determinants of the prescribed volume of antibiotics for acute RT episodes, whereas diagnostic labelling was not correlated with the incidence of acute RT episodes.</p> <p>Conclusion</p> <p>Diagnostic labelling is a relevant factor in GPs' antibiotic prescribing independent from the incidence of acute RT episodes. Therefore, quality assurance programs and postgraduate courses should emphasise to use evidence based prognostic criteria (e.g. chronic respiratory co-morbidity and old age) as an indication to prescribe antibiotics in stead of single inflammation signs or diagnostic labels.</p

Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care: study protocol for a randomised controlled trial and baseline characteristics of participating general practitioners [ISRCTN73182671]

BACKGROUND: Acute respiratory tract infections (ARTI) are among the most frequent reasons for consultations in primary care. Although predominantly viral in origin, ARTI often lead to the prescription of antibiotics for ambulatory patients, mainly because it is difficult to distinguish between viral and bacterial infections. Unnecessary antibiotic use, however, is associated with increased drug expenditure, side effects and antibiotic resistance. A novel approach is to guide antibiotic therapy by procalcitonin (ProCT), since serum levels of ProCT are elevated in bacterial infections but remain lower in viral infections and inflammatory diseases. The aim of this trial is to compare a ProCT-guided antibiotic therapy with a standard approach based on evidence-based guidelines for patients with ARTI in primary care. METHODS/DESIGN: This is a randomised controlled trial in primary care with an open intervention. Adult patients judged by their general practitioner (GP) to need antibiotics for ARTI are randomised in equal numbers either to standard antibiotic therapy or to ProCT-guided antibiotic therapy. Patients are followed-up after 1 week by their GP and after 2 and 4 weeks by phone interviews carried out by medical students blinded to the goal of the trial. Exclusion criteria for patients are antibiotic use in the previous 28 days, psychiatric disorders or inability to give written informed consent, not being fluent in German, severe immunosuppression, intravenous drug use, cystic fibrosis, active tuberculosis, or need for immediate hospitalisation. The primary endpoint is days with restrictions from ARTI within 14 days after randomisation. Secondary outcomes are antibiotic use in terms of antibiotic prescription rate and duration of antibiotic treatment in days, days off work and days with side-effects from medication within 14 days, and relapse rate from the infection within 28 days after randomisation. DISCUSSION: We aim to include 600 patients from 50 general practices in the Northwest of Switzerland. Data from the registry of the Swiss Medical Association suggests that our recruited GPs are representative of all eligible GPs with respect to age, proportion of female physicians, specialisation, years of postgraduate training and years in private practice

The @RISK Study: Risk communication for patients with type 2 diabetes: design of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Patients with type 2 diabetes mellitus (T2DM) have an increased risk to develop severe diabetes related complications, especially cardiovascular disease (CVD). The risk to develop CVD can be estimated by means of risk formulas. However, patients have difficulties to understand the outcomes of these formulas. As a result, they may not recognize the importance of changing lifestyle and taking medication in time. Therefore, it is important to develop risk communication methods, that will improve the patients' understanding of risks associated with having diabetes, which enables them to make informed choices about their diabetes care.</p> <p>The aim of this study is to investigate the effects of an intervention focussed on the communication of the absolute 10-year risk to develop CVD on risk perception, attitude and intention to change lifestyle behaviour in patients with T2DM. The conceptual framework of the intervention is based on the Theory of Planned Behaviour and the Self-regulation Theory.</p> <p>Methods</p> <p>A randomised controlled trial will be performed in the Diabetes Care System West-Friesland (DCS), a managed care system. Newly referred T2DM patients of the DCS, younger than 75 years will be eligible for the study. The intervention group will be exposed to risk communication on CVD, on top of standard managed care of the DCS. This intervention consists of a simple explanation on the causes and consequences of CVD, and possibilities for prevention. The probabilities of CVD in 10 year will be explained in natural frequencies and visualised by a population diagram. The control group will receive standard managed care. The primary outcome is appropriateness of risk perception. Secondary outcomes are attitude and intention to change lifestyle behaviour and illness perception. Differences between baseline and follow-up (2 and 12 weeks) between groups will be analysed according to the intention-to-treat principle. The study was powered on 120 patients in each group.</p> <p>Discussion</p> <p>This innovative risk communication method based on two behavioural theories might improve patient's appropriateness of risk perception and attitude concerning lifestyle change. With a better understanding of their CVD risk, patients will be able to make informed choices concerning diabetes care.</p> <p>Trail registration</p> <p>The trial is registered as NTR1556 in the Dutch Trial Register.</p