CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes.

The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5-6, 2024 ( http://www.cvot.org ).

CVOT Summit 2022 Report: new cardiovascular, kidney, and glycemic outcomes.

The 8th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Kidney, and Glycemic Outcomes was held virtually on November 10-12, 2022. Following the tradition of previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed outcomes trials as well as key trials important to the cardiovascular (CV) field. This year's focus was on the results of the DELIVER, EMPA-KIDNEY and SURMOUNT-1 trials and their implications for the treatment of heart failure (HF) and chronic kidney disease (CKD) with sodium-glucose cotransporter-2 (SGLT2) inhibitors and obesity with glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. A broad audience of primary care physicians, diabetologists, endocrinologists, cardiologists, and nephrologists participated online in discussions on new consensus recommendations and guideline updates on type 2 diabetes (T2D) and CKD management, overcoming clinical inertia, glycemic markers, continuous glucose monitoring (CGM), novel insulin preparations, combination therapy, and reclassification of T2D. The impact of cardiovascular outcomes on the design of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) trials, as well as the impact of real-world evidence (RWE) studies on the confirmation of CVOT outcomes and clinical trial design, were also intensively discussed. The 9th Cardiovascular Outcome Trial Summit will be held virtually on November 23-24, 2023 ( http://www.cvot.org ).

Deintensification in older patients with type 2 diabetes: A systematic review of approaches, rates and outcomes.

AIM: To assess deintensification approaches and rates and evaluate the harm and benefits of deintensification with antidiabetic medication and other therapies among older people (≥ 65 years) with type 2 diabetes with or without cardiometabolic conditions. METHODS: We identified relevant studies in a literature search of MEDLINE, Embase, Web of Science and Cochrane databases to 30 October 2018. Data were extracted on baseline characteristics, details on deintensification and outcomes, and was synthesized using a narrative approach. RESULTS: Ten studies (observational cohorts and interventional studies) with data on 26 558 patients with comorbidities were eligible. Deintensification approaches included complete withdrawal, discontinuation, reducing dosage, conversion, or substitution of at least one medication, but the majority of studies were based on complete withdrawal or discontinuation of antihyperglycaemic medication. Rates of deintensification approaches ranged from 13.4%-75%. The majority of studies reported no deterioration in HbA1c levels, hypoglycaemic episodes, falls or hospitalizations on deintensification. On adverse events and mortality, no significant differences were observed among the comparison groups in the majority of studies. CONCLUSION: Available but limited evidence suggests that the benefits of deintensification outweigh the harm in older people with type 2 diabetes with or without comorbidities. Given the heterogeneity of patients with diabetes, further research is warranted on which deintensification approaches are appropriate and beneficial for each specific patient population.

Disparities in prevalence and treatment of diabetes, cardiovascular and chronic kidney diseases - Recommendations from the taskforce of the guideline workshop.

There is a mounting clinical, psychosocial, and socioeconomic burden worldwide as the prevalence of diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD) continues to rise. Despite the introduction of therapeutic interventions with demonstrated efficacy to prevent the development or progression of these common chronic diseases, many individuals have limited access to these innovations due to their race/ethnicity, and/or socioeconomic status (SES). However, practical guidance to providers and healthcare systems for addressing these disparities is often lacking. In this article, we review the prevalence and impact of healthcare disparities derived from the above-mentioned chronic conditions and present broad-based recommendations for improving access to quality care and health outcomes within the most vulnerable populations.

Self-rated knowledge and competence regarding the management of chronic kidney disease in primary care: A cross-sectional European survey of primary care professionals.

BACKGROUND: Diabetes is a major risk factor for chronic kidney disease (CKD), which is a leading cause of global morbidity and mortality and also associated with substantial costs to healthcare systems. Despite the current best practice standards of care, management of CKD in diabetes in the primary care setting remains an ongoing challenge. Using an online survey, we aimed to assess the self-rated knowledge and competence of primary care professionals involved in the management of CKD in diabetes in the European region. METHODS: An online anonymous survey was developed by the Primary Care Diabetes Europe research group and administered to primary care professionals involved in managing CKD in diabetes from 23rd March 2022-9 th October 2022. Descriptive statistics were used to summarise questionnaire responses. Factors influencing ability to initiate treatment strategies were evaluated using logistic regression. RESULTS: A total of 266 respondents (51.9% males) completed the questionnaire. Most respondents were GPs (82.7%) followed by nurses (9.4%). The age of respondents ranged from 25 to 72 years with a median of 51 years. About a third of respondents indicated that they were fully confident in the screening and diagnosis of CKD in diabetes. With regards to CKD presentation, staging and prognosis, 16.5-21.8% of respondents stated they were fully confident in this area; however, about 11% of respondents were not confident on how to predict CKD prognosis using established clinical guidelines. About a third of respondents stated they were confident without support regarding the complications of kidney disease in diabetes and it being a risk multiplier; just a quarter of respondents were fully confident. A third of respondents stated they were fully confident regarding appropriate management strategies for preventing or slowing down the progression of CKD and the initiation of newer agents. In multivariable analyses, confidence in the knowledge of the stages of kidney disease and criteria for the diagnosis of kidney disease were each associated with an increased odds in the confidence to select and initiate appropriate management strategies. CONCLUSIONS: With regards to almost all aspects of management of CKD in diabetes, only up to a third of primary care professionals stated they are fully confident and are able to teach others; the majority are confident but would like to know more or require extra support. This may be a contributor to the challenges faced in providing optimal CKD care in people with diabetes in the primary care setting. Effective interventions that can promote the uptake of best practice clinical guidelines in primary care are urgently needed.

Associations of blood pressure with cardiovascular and mortality outcomes in over 2 million older persons with or without diabetes mellitus: A systematic review and meta-analysis of 45 cohort studies.

BACKGROUND: The impact of blood pressure on cardiovascular disease (CVD) and mortality outcomes in older people with diabetes mellitus (DM) is not well quantified. Using a systematic review and meta-analysis of observational cohort studies, we aimed to compare the associations of blood pressure levels with cardiovascular and mortality outcomes in older people aged ≥ 65 years with or without DM. METHODS: Studies were identified from MEDLINE, Embase, Web of Science, and search of bibliographies to July 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. RESULTS: Forty-five unique observational cohort studies (n = 2305,189 participants) assessing the associations of systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) levels with adverse cardiovascular outcomes were included. In the general population, the pooled RRs (95% CIs) of SBP ≥ 140 vs < 140 mmHg and per 10 mmHg increase for composite CVD/MACE were 1.26 (0.96-1.64) and 1.15 (1.08-1.23), respectively. The respective estimates were 1.56 (1.04-2.34) and 1.10 (1.04-1.18) for patients with DM. SBP ≥ 130 vs < 130 mmHg was not associated with an increased risk of adverse cardiovascular outcomes in both populations. SBP < 120 vs ≥ 120 mmHg was associated with an increased risk of all cause-mortality in the general population (n = 10 studies). DBP ≥ 90 mmHg was associated with an increased risk of some adverse cardiovascular outcomes in both populations. Interaction analyses suggested similar risk of outcomes in both populations. CONCLUSIONS: Observational evidence suggests SBP and DBP confer similar cardiovascular and mortality risk in older adults in the general population and those with DM. A blood pressure target range of > 130/80 to < 140/90 mmHg may be optimal for patients ≥ 65 years with DM, but specific targets may need to be individualised based on patients' unique circumstances. Furthermore, findings do not support stringent blood pressure control in this population group. Definitive RCTs are needed to support these observational findings.

Benefits and harms of sodium-glucose co-transporter-2 inhibitors (SGLT2-I) and renin-angiotensin-aldosterone system inhibitors (RAAS-I) versus SGLT2-Is alone in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: It is uncertain if the combination of sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) and renin-angiotensin-aldosterone system inhibitors (RAAS-Is) provides better cardio-renal clinical outcomes in people with type 2 diabetes mellitus (T2DM) compared with SGLT2-Is alone. Using a systematic review and meta-analysis of randomized controlled trials (RCTs), we evaluated the efficacy and safety with respect to cardio-renal outcomes of the combination of SGLT2 and RAAS inhibitors vs SGLT2-Is in patients with T2DM. METHODS: Studies were identified from MEDLINE, Embase, the Cochrane Library and search of bibliographies to May 2021. The Cochrane risk of bias tool was used to assess the risk of bias of each study. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. Quality of the evidence was assessed using GRADE. RESULTS: Nine articles comprising 8 RCT evaluations (n = 34,551 participants) that compared SGLT2-Is with placebo in patients with T2DM against a background of standard care and reported subgroup results for those treated with or without RAAS-Is at baseline were included. No RCT specifically investigated the combination of SGLT2 and RAAS inhibitors compared with SGLT2-Is alone. The RRs (95% CIs) for composite cardiovascular outcome and composite CVD death/heart failure hospitalization comparing SGLT2-Is vs placebo in patients on RAAS-Is were 0.93 (0.85-1.01) and 0.88 (0.76-1.02), respectively. The corresponding estimates for patients not on RAAS-Is were 0.78 (0.65-0.93) and 0.73 (0.65-0.82), respectively. There was no evidence of interactions between RAAS-I status and the effects of SGLT2-Is for both outcomes. Single study results showed that SGLT2-Is vs placebo reduced the risk of composite kidney outcome and cardiovascular death in patients with RAAS inhibition. The effect of SGLT2 inhibition vs placebo on kidney parameters, genital infections, volume depletion, hyperkalaemia, hypokalaemia, hypoglycaemia and other adverse events was similar in patients with or without RAAS inhibition. The quality of the evidence ranged from very low to moderate. CONCLUSIONS: Aggregate published data suggest that the combination of SGLT2 and RAAS inhibitors in the treatment of patients with T2DM may be similar in efficacy and safety if not superior to SGLT2-Is alone. Head-to-head comparisons of the two interventions are warranted to inform T2DM management. The use of SGLT2 inhibition as a first-line therapy in T2DM or its early use in the prevention of renal deterioration and cardiovascular complications in addition to its glycaemic control deserves further study.

Residents' views about family medicine specialty education in Turkey.

BACKGROUND: Residents are one of the key stakeholders of specialty training. The Turkish Board of Family Medicine wanted to pursue a realistic and structured approach in the design of the specialty training programme. This approach required the development of a needs-based core curriculum built on evidence obtained from residents about their needs for specialty training and their needs in the current infrastructure. The aim of this study was to obtain evidence on residents' opinions and views about Family Medicine specialty training. METHODS: This is a descriptive, cross-sectional study. The board prepared a questionnaire to investigate residents' views about some aspects of the education programme such as duration and content, to assess the residents' learning needs as well as their need for a training infrastructure. The questionnaire was distributed to the Family Medicine Departments (n = 27) and to the coordinators of Family Medicine residency programmes in state hospitals (n = 11) by e-mail and by personal contact. RESULTS: A total of 191 questionnaires were returned. The female/male ratio was 58.6%/41.4%. Nine state hospitals and 10 university departments participated in the study. The response rate was 29%. Forty-five percent of the participants proposed over three years for the residency duration with either extensions of the standard rotation periods in pediatrics and internal medicine or reductions in general surgery. Residents expressed the need for extra rotations (dermatology 61.8%; otolaryngology 58.6%; radiology 52.4%). Fifty-nine percent of the residents deemed a rotation in a private primary care centre necessary, 62.8% in a state primary care centre with a proposed median duration of three months. Forty-seven percent of the participants advocated subspecialties for Family Medicine, especially geriatrics. The residents were open to new educational methods such as debates, training with models, workshops and e-learning. Participation in courses and congresses was considered necessary. The presence of a department office and the clinical competency of the educators were more favored by state residents. CONCLUSIONS: This study gave the Board the chance to determine the needs of the residents that had not been taken into consideration sufficiently before. The length and the content of the programme will be revised according to the needs of the residents.

Does urinary incontinence affect quality of life of Greek women less severely? A cross-sectional study in two Mediterranean settings.

OBJECTIVE: Numerous studies have identified a reduced health-related quality of life (QoL) in patients with urinary incontinence (UI). The aim of this study was to assess and compare QoL in women with UI in the island of Crete, Greece, and in Turkey. METHODS: Incontinent women from two community-based primary health care (PHC) groups (Greece and Turkey) and one outpatient clinic-based group were studied. RESULTS: A total of 231 (24.7%) women out of 932 women from the PHC group in Greece and Turkey reported UI whereas another 38 incontinent women visited the secondary care outpatient clinic. Mean Incontinence Quality of Life questionnaire (I-QoL) total score of women visiting PHC centers was 73.8 (SD = 23.5). There was significant difference among the three groups regarding I-QoL total and subscale scores, with women from the Greek community-based group having the highest score (mean = 81.8, SD = 20.7, P < 0.001). Impaired QoL was significantly associated with severity (P < 0.001), incontinence type (P = 0.026), seeking secondary care, and Turkey as sample setting (P < 0.001). CONCLUSION: Urinary incontinence is a frequent problem for women visiting PHC centers, affecting negatively their quality of life. Besides incontinence severity, Turkey as place of residence emerged as another essential predictor of impaired quality of life, suggesting that other social and cultural factors may also play an important role.

Factors affecting choice of specialty among first-year medical students of four universities in different regions of Turkey.

AIM: To determine the factors affecting medical students' choice of the specialty of family medicine. METHODS: The study was conducted in the period from 2004-2006 and comprised 770 first-year medical students from Ondokuz Mayis, Karadeniz Technical, Kocaeli, and Adnan Menderes Universities, Turkey. The questionnaire included questions on demographic data and 6 "yes/no" or open-ended questions on students' career aspirations and the specialty of family medicine. RESULTS: The response rate was 93.1% (n=717, 54.7% male). Nearly all students (n=714, 99.6%) showed an intention to specialize after receiving the medical doctor degree. A total of 187 students (26.2%) showed an intention to work in primary care without specialization "for a temporary period" to "gain some experience." Family medicine was the least preferred specialty (n=7, 0.9%). The most important reasons for the choice of specialty were "better financial opportunities" and "prestige" (n=219, 30.5%), followed by "personal development" (n=149, 20.8%), "more benefits for the patient" (n=128, 17.9%), and "wish to work in an urban area" (n=32, 4.5%). The most preferred specialties were cardiology (n=179, 25.0%), pediatrics (n=121, 16.9%), ophthalmology (n=47, 6.6%), physical therapy and rehabilitation (n=34, 4.7%), and obstetrics and gynecology (n=32, 4.5%). CONCLUSION: Prestige, money, and personal development are important factors in career decision-making among medical students in Turkey. This should be taken into consideration when conducting reforms at the primary level.

Counselling and knowledge about contraceptive mode of action among married women; a cross-sectional study.

BACKGROUND: Family planning counselling which covers knowledge transfer about contraceptive mode of action, by enabling informed choice, improves compliance to and efficiency of contraceptive methods. The objective of this study was to investigate associations between family planning counselling, counsellor and correct knowledge about mode of action of modern contraceptive methods among married women. METHODS: For this cross-sectional study, stratified (according to current modern contraceptive method in use) random sampling was performed from the registries of two primary health care centres. Main outcomes were; prevalence of family planning counselling, professional background of the counsellor and correct knowledge about mode of action. A semi-structured questionnaire developed by the researchers was applied via face-to-face interview. The answers about mode of action were categorized as correct vs. incorrect by consensus rating. RESULTS: Prevalence of counselling and correct knowledge about mode of action was 49.0% and 39.3%, respectively. Higher educated women were significantly more likely to know the mode of action (p < 0.001). Being counselled by a physician (54.1%, n = 120) was not associated with correct knowledge about mode of action (p = 0.79). Non-barrier method users were less educated (p = 0.001), more often counselled (60.8% vs. 8.0%) and less knowledgeable (p < 0.001) about mode of action of their contraceptive method, compared to condom users. Nevertheless, counselled non-barrier method users were significantly more likely to know the correct mode of action of their chosen method (p = 0.021) than counselled condom users. CONCLUSION: The beneficial effect of counselling on knowledge about mode of action of the more complicated, medical (non-barrier) contraceptive methods suggests that the use of family planning counselling services in primary health care should be promoted; furthermore, counselling strategies and content should be re-structured for better efficacy.

Parents' knowledge and behaviour concerning sunning their babies; a cross-sectional, descriptive study.

BACKGROUND: For centuries, sunlight has been used for therapeutic purposes. Parents still sun their infants to treat neonatal jaundice, nappy rash or mostly to supply vitamin D for bone development as a consequence of health beliefs. In this study we aimed to assess knowledge and behaviour of parents about benefits of sunlight and sun protection. METHODS: In this study, parents attending to governmental primary healthcare units for their children's routine vaccinations, upon their informed consent, were consecutively enrolled during one month. Data were collected by a semi-structured questionnaire. RESULTS: The mean age of 118 enrolled parents and their babies were 27.9 +/- 6.5 years and 8.3 +/- 5.8 months, respectively. Most of the participants were mothers (93.2%), housewives (81.4%) with an educational level of > or =6 years (71.2%). Sunlight was considered beneficial for bone development (86.4%), diaper rash (5.9%) and neonatal jaundice (12.7%). In case of neonatal jaundice 72.0% of the participants reported that they would consult a physician. Most of the participants (82.2%) were sunning their babies outdoors. Nearly half (49.7%) of them got this information from medical staff. Fifty two percent of the parents were sunning their babies before 10-11 a.m. and/or after 3 p.m. Only 13.6% of parents reported using sunscreen for their babies, and the majority of them were using sun protecting factor > or = 15. One forth of the sunscreen users was using sunscreen according to their physicians' advice. CONCLUSION: Most of the participants were aware of the benefits of sunlight; especially for bone development. However they were displaying inappropriate behaviour while sunning their babies for health reasons. More education should be given to parents about the danger of sunlight at primary health care units while advising to sun their babies, if any.

Risk factors for urinary incontinence in Turkish women. A cross-sectional study.

OBJECTIVE: To explore the association between conventional risk factors and urinary leakage among a random sample of adult Turkish women. METHODS: Six hundred and fifty patients (mean age 33.2 +/- 10.6 years; range 17-65 years) attending 6 Primary Health Care Centers in the Eastern Marmara Region, Turkey were randomly enrolled in this study, between September 2005 and December 2005. After signing their informed consent, all patients filled in a questionnaire consisting of questions inquiring any kind of urinary leakage, related symptomatology and personal medical history. RESULTS: One hundred and six women (16.4%) with urinary incontinence (UI) were reported. The most frequent type of incontinence was mixed UI (n=65, 61.3%). The prevalence of stress UI among all incontinent women was 20.8% (n=22) and urge UI 17.9% (n=19). The prevalence was associated with age, body mass index and parity. Number of pregnancies was positively correlated with prevalence of incontinence (r=0.30, p<0.001). Women who had >2 deliveries had a higher risk of UI (odds ratio = 4.04, 95% confidence interval, 2.37 to 6.89, p<0.001). CONCLUSION: The results of this study supported previous reports revealing that age, body mass index, type of deliveries and number of pregnancies/deliveries are risk factors of UI, and showed that age, body mass index and number of pregnancies should be regarded as independent risk factors.

Intentional sun exposure in infancy in Sakarya, Turkey.

OBJECTIVE: To determine the extent of intentional sun exposure in infancy, and the prevalence of maternal belief that potentially increases the children's harm risk from ultraviolet radiation. The major determinants of mothers' beliefs and behaviors regarding sunning were also assessed. METHODS: Three hundred and ninety six Caucasian women mothering 0-12 month old infants, attending to Sakarya State Hospital Healthy Infant outpatient clinic in November 2003, filled in the questionnaire after giving their informed consent. Each mother was asked 11 structured questions regarding maternal education, beliefs regarding benefits or harms of sun exposure, use of sunlight for therapeutic purposes, use of sun protection, and source of knowledge. RESULTS: The mean age of the mothers was 27.37 +/- 5.36 years and the children was 5.71 +/- 3.53 months. Two hundred and thirty-five mothers (64.1%) believed that sunlight is harmful, but 296 (79.7%) named one benefit of intentional baby sunning. Sun causes cutaneous diseases was the most frequently (n=83/126) mentioned harm and sun strengthens bones and teeth was the number one (n=250/296) benefit according to the mothers. The leading source of knowledge for the beneficial effects of the sun was health care professionals (physician, midwife, nurse) 45.7% (130/284). There was no significant correlation between mothers' sunning behavior and age, education level, being advised so by a health care professional or believing that the sun was harmful. CONCLUSION: As these results display being the leading source of knowledge and initiative of healthy/risky behaviors, primary health care physicians/workers have to be informed regarding the vitamin D supplementation and risks of sun exposure.

Efficacy of sibutramine, orlistat and combination therapy on short-term weight management in obese patients.

OBJECTIVES: To compare changes in anthropometric measures [body mass index (BMI), body weight] of obese patients treated with diet and exercise alone or additionally sibutramine, orlistat or the combination of both drugs, respectively. To describe encountered adverse effects. METHODS: Short-term (12 weeks), randomized, open-labeled trial. A total of 86 patients (18.6% male, age 41.1 +/- 8.7 years, BMI: 36.11 +/- 4.34 kg/m(2)) were randomized to (1) sibutramine group (10 mg/d, n = 22), or (2) orlistat group (3 x 120 mg/d, n = 25), or (3) combination group (10 mg sibutramine/d + 3 x 120 mg orlistat/d, n = 20), or (4) diet group (n = 19). The primary outcome parameter was a decrease in BMI. Additionally patient-reported adverse effects were reported. RESULTS: The four interventional groups displayed decreases in BMI as follows: (1) -4.41 +/- 1.26 kg/m(2); (2) -3.64 +/- 0.97 kg/m(2); (3) -5.12 +/- 1.44 kg/m(2) and (4) -2.52 +/- 1.36 kg/m(2); with the diet group showing the significantly lowest decrease in BMI compared to the orlistat (P = 0.004), sibutramine (P < 0.001) or the combination groups (P < 0.001), respectively. Decreases in BMI did not statistically differed between the sibutramine group and the combination therapy group (P = 0.072). However, both treatment groups were significantly more efficient in decreasing BMI than the orlistat group (P < 0.001). In addition to well-known side effects, such as gastrointestinal disturbances, headache and dry mouth, newly described adverse effects were self-reported hypermenorrhea (13.6%, n = 3) with sibutramine and forgetfulness with orlistat (24%, n = 6). CONCLUSION: In our study pharmacotherapy showed significant better results in the short-term management of obesity than dietary regimens alone. Sibutramine and sibutramine in combination with orlistat seemed to be equally effective in terms of weight reduction compared to orlistat monotherapy. Attention should be paid to the possibility of adverse effects.

Series: The research agenda for general practice/family medicine and primary health care in Europe. Part 6: reaction on commentaries - how to continue with the Research Agenda?

The Research Agenda should be used as a key reference point to which new research should relate its usefulness and added value. Primary care evolves towards more interdisciplinary care, and research should focus more on the core competency of person-centred team care. There is an urgent need to develop clear definitions and appropriate research instruments for this domain. It will be a particular challenge to study comprehensive approaches in primary-care patients with multi-morbidity. The Research Agenda and the commentaries on it show future directions for primary care research. There are challenges related to a changing society, the shared responsibility and guidance of research by professionals and citizens (patients), and the need to fully integrate research as part of primary healthcare provision. There will be a need for a prioritization of spearheads to guide primary care research for the next decade: translational research, research on equity and health differences, on chronic disease and health systems research. This can not be realized without the development and maintenance of a solid research infrastructure: easily maintained and accessed observational databases, helpful information technology, strategies and techniques for patient involvement, advanced research training possibilities, and the development and validation of appropriate research instruments and outcome measures to capture the different challenges. Worldwide, primary care not only is a priority for health care policy, but it needs to become a research priority as well.

Series: The research agenda for general practice/family medicine and primary health care in Europe. Part 4. Results: specific problem solving skills.

The 'Research Agenda for General Practice/Family Medicine and Primary Health Care in Europe' summarizes the evidence relating to the core competencies and characteristics of the Wonca Europe definition of GP/FM, and its implications for general practitioners/family doctors, researchers and policy makers. The European Journal of General Practice publishes a series of articles based on this document. The previous articles presented background, objectives, and methodology, as well results on 'primary care management' and 'community orientation' and the person-related core competencies of GP/FM. This article reflects on the general practitioner's 'specific problem solving skills'. These include decision making on diagnosis and therapy of specific diseases, accounting for the properties of primary care, but also research questions related to quality management and resource use, shared decision making, or professional education and development. Clinical research covers most specific diseases, but often lacks pragmatism and primary care relevance. Quality management is a stronghold of GP/FM research. Educational interventions can be effective when well designed for a specific setting and situation. However, their message that 'usual care' by general practitioners is insufficient may be problematic. GP and their patients need more research into diagnostic reasoning with a step-wise approach to increase predictive values in a setting characterized by uncertainty and low prevalence of specific diseases. Pragmatic comparative effectiveness studies of new and established drugs or non-pharmaceutical therapy are needed. Multi-morbidity and complexity should be addressed. Studies on therapy, communication strategies and educational interventions should consider impact on health and sustainability of effects.

The research agenda for general practice/family medicine and primary health care in Europe. Part 3. Results: person centred care, comprehensive and holistic approach.

The recently published 'Research Agenda for General Practice/Family Medicine and Primary Health Care in Europe' summarizes the evidence relating to the core competencies and characteristics of the Wonca Europe definition of GP/FM, and its implications for general practitioners/family doctors, researchers and policy makers. The European Journal of General Practice publishes a series of articles based on this document. In a first article, background, objectives, and methodology were discussed. In a second article, the results for the two core competencies 'primary care management' and 'community orientation' were presented. This article reflects on the three core competencies, which deal with person related aspects of GP/FM, i.e. 'person centred care', 'comprehensive approach' and 'holistic approach'. Though there is an important body of opinion papers and (non-systematic) reviews, all person related aspects remain poorly defined and researched. Validated instruments to measure these competencies are lacking. Concerning patient-centredness, most research examined patient and doctor preferences and experiences. Studies on comprehensiveness mostly focus on prevention/care of specific diseases. For all domains, there has been limited research conducted on its implications or outcomes.

Series: The research agenda for general practice/family medicine and primary health care in Europe. Part 5: Needs and implications for future research and policy.

The recently published 'Research Agenda for General Practice/Family Medicine and Primary Health Care in Europe' summarizes the evidence relating to the core competencies and characteristics of the Wonca Europe definition of GP/FM, and highlights related needs and implications for future research and policy. The European Journal of General Practice publishes a series of articles based on this document. In a first article, background, objectives, and methodology were discussed. In three subsequent, articles the results for the six core competencies of the European Definition of GP/FM were presented. This article formulates the common aims for further research and appropriate research methodologies, based on the missing evidence and research gaps identified form the comprehensive literature review. In addition, implications of this research agenda for general practitioners/family doctors, researchers, research organizations, patients and policy makers are presented. The concept of six core competencies should be abandoned in favour of a model with four dimensions, including clinical, person related, community oriented and management aspects. Future research and policy should consider more the involvement and rights of patients; more attention should be given to how new treatments or technologies are effectively translated into routine patient care, in particular primary care. There is a need for a European ethics board. The promotion of GP/FM research demands a good infrastructure in each country, including access to literature and databases, appropriate funding and training possibilities.