Angioedema induced by cardiovascular drugs: new players join old friends

During the last years, two new cardiovascular drug classes, namely inhibitors of DPP IV or neprilysin, have been developed. In both cases, there is clinical evidence for their potential to induce angioedema as known already from blockers of the renin–angiotensin–aldosterone system (RAAS). The majority of angioedema induced by DPP IV inhibitors occurs during concomitant treatment with ACEi and is therefore likely mediated by overactivation of bradykinin type 2 receptors (B2). In striking contrast, the molecular pathways causing angioedema induced by neprilysin inhibitors, that is, sacubitril, are unclear, although a contribution of bradykinin appears likely. Nevertheless, there is no clinical evidence suggesting that inhibition of B2 might relieve the symptoms and/or prevent invasive treatment including coniotomy or tracheotomy in angioedema caused by these drugs. Therefore, the risk of angioedema should always be considered, especially in ambulatory care situations where patients have no rapid access to intensive care.     

An implantable MEMS drug delivery device for rapid delivery in ambulatory emergency care

We introduce the first implantable drug delivery system based on MEMS (Micro-Electro-Mechanical-Systems) technology specifically designed as a platform for treatment in ambulatory emergency care. The device is named IRD³ (implantable rapid drug delivery device) and allows rapid delivery of drugs. Vasopressin was used as a model drug for in vitro tests as it is a commonly used drug for cardiac resuscitation. Experimental results reveal that the IRD³ provides an effective method for rapid delivery without significant drug degradation. Several medical uses and delivery modalities for IRD³ are proposed. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. N. M. Elman and H. L. Ho Duc contributed equally to this work.     

Understanding the relationship between market competition and students' ratings of the managed care content of their undergraduate medical education.

PURPOSE: The increase in managed care has led to questions about the inadequacy of instruction undergraduate medical students receive in curricular areas related to managed care. This study examined (1) the percentages of graduating medical students who felt they had received inadequate instruction in six curricular content areas (CCAs): primary care, care of ambulatory patients, health promotion and disease prevention, medical care cost control, teamwork with other health professionals, and cost-effective medical practice; and (2) whether the market competitiveness of these students' medical schools affected their reports of inadequacy of instruction in these CCAs. METHOD: Data from the Association of American Medical Colleges' Graduation Questionnaires (GQs) from 1994 to 1997 were analyzed. The GQ asked graduating students to rate the adequacy of instruction they had received in the six CCAs. Students' ratings were collapsed into the dichotomous variables "inadequate" and "not inadequate." The market competitiveness of medical schools was determined using the four-stage Market Evolution Model developed by the University HealthSystem Consortium. Only responses from students graduating from medical schools that could be staged for all four years of the study were analyzed. Statistical analyses were performed to determine trends for each CCA by year, across the entire study period, by market stage, and by market stage across the entire study period. RESULTS: A total of 39,136 respondents from 86 medical schools were used in the study. The percentages of graduating medical students who reported inadequate instruction decreased over the study period for five of the six CCAs: primary care (27.6% in 1994 to 13.7% in 1997), ambulatory care (37.4% to 23. 9%), medical care cost control (62.9% to 52.9%) cost-effectiveness of medical practice (62.7% to 53.9%), and health promotion and disease prevention (44.4% to 23.7%); all at p <0.001. The responses for inadequacy of instruction for teamwork with other health professionals remained steady from 1994 to 1996 (10.2% to 10.6%), then increased 21.8% in 1997. Over the course of the study, students graduating from schools in more competitive markets (Stage 3 or Stage 4) were more likely to report inadequate instruction in three CCAs, primary care, ambulatory care, and health promotion and disease prevention, than were those graduating from schools in less competitive markets (Stage 1 and Stage 2). Conversely, students graduating from schools in the more competitive health care markets were less likely to report inadequate instruction in cost-effectiveness and cost control than were students from schools in less competitive markets. CONCLUSION: Graduating students' reports of inadequacy of instruction decreased over the study period for five of the six CCAs, increasing only for teamwork with other professionals. Findings were mixed with regard to the relationship of medical schools' market competitiveness and graduating students' reports of inadequacy of instruction. More research is needed to confirm graduating students' perceptions of the inadequacy of their instruction in CCAs related to managed care, particularly once they have gained experience treating patients in managed care environments.     

Cost-effectiveness of implementing new guidelines for treatment of hypertension in general practice.

BACKGROUND: Hypertension is a major public health concern and, as the population ages, the size of the problem is likely to increase. However, detection rates and treatment of hypertension have been low. The introduction of new guidelines for the detection and treatment of hypertension have been encouraged but without any consideration to their cost-effectiveness. AIM: To assess the potential cost-effectiveness of implementing new guidelines for the treatment of hypertension in general practice. Design of study: Model examining the incremental costs and effects of the new guidelines compared with the old. SETTING: A large general practice in north Yorkshire. METHOD: Two thousand and twenty-three patients reporting for a new health patient check had the costs and outcomes under the old and new guidelines estimated. RESULTS: Implementing new guidelines for the detection, management, and treatment of hypertension in a primary care setting is more costly than the implementation of previous guidelines, but more effective in reducing the risk of cardiovascular disease. The incremental cost per cardiovascular disease event avoided is ?30 000, although sensitivity analysis shows that the estimate is subject to considerable uncertainty. CONCLUSIONS: Compared with previous guidelines, introducing new guidelines for the management and treatment of hypertension in new patients in general practice is likely to be cost-effective. However, the workforce implications for general practitioners (GPs) and practice nurses should be considered.     

Rheumatology and musculoskeletal medicine

Musculoskeletal disease accounts for a large proportion of a general practitioner's (GP's) workload. Proper management can not only improve quality of care, but also increase job satisfaction and reap rewards under the new contract. Osteoporosis creates a huge socioeconomic burden of disease and disability. Identifying high-risk groups in primary care and using preventative treatment can result in a substantial reduction in morbidity and mortality. GPs can help by presenting a unified lifestyle message, advising on fall prevention, and providing effective treatment; in particular, calcium and vitamin D for female nursing home residents. Osteoarthritis is eminently treatable in primary care with a number of management options for GPs, in addition to drug therapy. Glucosamine and chondroitin have few side effects and are worth recommending to patients with mild knee osteoarthritis. Rheumatoid arthritis can cause significant disability, which can be limited by early diagnosis, referral, and treatment. Severe refractory rheumatoid arthritis may warrant referral for consideration of biologic therapy. Assessment of the cardiovascular risk and possible use of statins in rheumatoid patients may reduce their cardiovascular mortality. GPs should aim to help patients to achieve optimum quality of life by using a holistic approach and by allowing maximum choice and control over their disease.     

Meeting the National Service Framework for coronary heart disease: which patients have untreated high blood pressure?

BACKGROUND: The National Service Framework for coronary heart disease requires primary care teams to identify patients who are at high risk of cardiovascular events and treat those with high blood pressure. However, there are no data on how many must be assessed, how much cardiovascular disease can be prevented or which patients are most likely to benefit. AIM: To estimate the potential number of patients who are eligible for blood pressure assessment, the number of preventable cardiovascular disease events and the relative efficiency of the strategy in different age groups. DESIGN OF STUDY: Modelling exercise. SETTING: Hypothetical population of 100,000. METHOD: The age-sex specific prevalence of cardiovascular risk factors and of current anti-hypertensive treatment were obtained from published sources and combined with published estimates of the effectiveness of anti-hypertensive treatment. From these data were calculated numbers of persons eligible for assessment and treatment, and numbers of preventable cardiovascular events. RESULTS: There were 79,607 persons eligible for assessment and 5888 eligible for treatment. Treatment could prevent between 101 and 139 cardiovascular events annually. There were 11,571 persons aged over 65 years and eligible for assessment and 4655 eligible for treatment. Treatment could prevent 85 to 117 cardiovascular events annually. No cardiovascular events are prevented in persons aged under 45 years. CONCLUSION: Confining assessment to the 16% who are aged over 65 years prevents 85% of the population's avoidable cardiovascular disease. Primary care teams should assess and treat persons aged over 65 years before assessing younger patients. No health benefit results from assessing persons aged under 45 years.     

Molecular pathology of lung cancer: key to personalized medicine

The majority of lung adenocarcinoma patients with epidermal growth factor receptor- (EGFR) mutated or EML4-ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors. Both primary and acquired resistance in a significant number of those patients to these therapies remains a major clinical problem. The specific molecular mechanisms associated with tyrosine kinase inhibitor resistance are not fully understood. Clinicopathological observations suggest that molecular alterations involving so-called 'driver mutations' could be used as markers that aid in the selection of patients most likely to benefit from targeted therapies. In this review, we summarize recent developments involving the specific molecular mechanisms and markers that have been associated with primary and acquired resistance to EGFR-targeted therapy in lung adenocarcinomas. Understanding these mechanisms may provide new treatment avenues and improve current treatment algorithms.     

阿司匹林对高血压患者心血管疾病一级预防作用的Meta分析

目的 评价阿司匹林对高血压患者心血管疾病一级预防的作用与风险。方法 计算机网络检索PubMed、Web of Science、Cochrane Library、维普数据库、中国知网、万方数据库、中国生物医学数据库中关于阿司匹林用于高血压患者心血管事件一级预防的相关研究,检索时间范围为建库至2019年9月,提取文献数据、检验发表偏倚后,使用STATA 12.0软件进行Meta分析。结果 阿司匹林用于高血压患者心血管疾病一级预防中能够降低多种心血管事件的发生风险（RR=0.93,95%CI:0.90~0.97,P＜0.001）;亚组分析显示,作为一级预防,阿司匹林主要降低非致命性心血管事件的发生风险;对于致死性心血管事件,阿司匹林并没有预防作用;口服阿司匹林组相较于安慰剂组增加了出血风险（RR=1.30,95%CI:1.20~1.40,P＜0.001）。结论 阿司匹林用于高血压患者心血管事件的一级预防确实能够降低非致命性心血管事件的发生风险,但阿司匹林在发挥该作用的同时会诱发出血风险。     

Preventing diabetes-related morbidity and mortality in the primary care setting

Diabetes is the leading cause of blindness, end-stage renal failure, non-traumatic limb amputations, and cardiovascular morbidity and mortality. The vast majority of patients with diabetes receive routine care from primary care providers who are not endocrinologists. Primary care providers, including internists, family practice physicians, and physician extenders with advanced skills, face the important task of implementing standards of care recommendations for persons with diabetes. These recommendations draw upon an emerging body of compelling evidence regarding the prevention and management diabetes and its complications. The challenge of diabetes must be tackled on three fronts: Primary prevention, secondary prevention (of diabetes complications), and tertiary prevention (of morbidity and mortality from established complications). There is now abundant evidence that type 2 diabetes, which accounts for greater than 90% of diabetes world-wide, is preventable. Moreover, the complications of diabetes are preventable by a policy of tight glycemic control and comprehensive risk reduction. Even after complications have set in, intensive glucose control dramatically reduces the risk of progression of complications. The challenge, therefore, is the identification of strategies that enable translation of existing scientific data to pragmatic benefits. This article proposes 10 strategies for preventing or reducing diabetes-related morbidity and mortality at the primary care level. These strategies include provider education; patient empowerment through promotion of lifestyle and self-care practices; surveillance for microvascular complications; cardiovascular risk reduction; efficient use of medications; goal setting; and stratification of patients and triaging of those with poor glycemic control for more intensive management.     

Ambulatory oral surgery: 1-year experience with 11?680 patients from Zagreb district,Croatia

Aim

To examine the types and frequencies of oral surgery diagnoses and ambulatory oral surgical treatments during one year period at the Department of Oral Surgery, University Hospital Dubrava in Zagreb, Croatia.

Methods

Sociodemographic and clinical data on 11 680 ambulatory patients, treated between January 1 and of December 31, 2011 were retrieved from the hospital database using a specific protocol. The obtained data were subsequently analyzed in order to assess the frequency of diagnoses and differences in sex and age.

Results

The most common ambulatory procedure was tooth extraction (37.67%) and the most common procedure in ambulatory operating room was alveolectomy (57.25%). The test of proportions showed that significantly more extractions (P < 0.001) and intraoral incisions (P < 0.001) were performed among male patients, whereas significantly more alveolectomies and apicoectomies were performed among female patients (P < 0.001). A greater prevalence of periodontal disease was found in patients residing in Zagreb than in patients residing in rural areas.

Conclusion

The data from this study may be useful for planning of ambulatory oral surgery services, budgeting, and sustaining quality improvement, enhancing oral surgical curricula, training and education of primary health care doctors and oral surgery specialists, and promoting patients’ awareness of the importance of oral health.Oral health is essential to general health and well-being, and tooth loss is an important indicator of oral health status. Reduction of tooth loss is one of the targets for achieving global goals for oral health (1).Croatian dental health system, along with general health care, is regulated by the Health Care Law and divided into three levels of care: primary, secondary, and tertiary. Primary dental health care is performed by doctors of dental medicine with the help of dental assistants; it includes prevention, detection, and treatment of oral diseases, as well as rehabilitation of the masticatory system. Secondary or specialist outpatient dental health care treats patients in need of expert opinion, advice, or treatment. Tertiary care provides care only for patients requiring hospitalization.In order for the system to work properly and without overload, levels of health care must cooperate. Most patients with oral needs visit a primary health care system dentist, so further education of these professionals is essential for a better system of specialist referrals and a more efficient health care system. In Croatia, there are no data about the types and frequencies of oral surgery treatment so the aim of this study was to gain insight into the types and frequencies of diagnoses and ambulatory surgical treatments at the Department of Oral Surgery at University Hospital Dubrava in Zagreb, Croatia. We also investigated whether there was a significant difference in clinical diagnoses and procedures according to sex, age, and place of residence.     

Patients' responsiveness to a decision support tool for primary prevention of cardiovascular diseases in primary care

OBJECTIVE: Assessment of patients' responsiveness to a decision support tool for primary prevention of cardiovascular diseases (CVDs). The booklet focuses on barriers at patient level. METHODS: Process evaluation of an intervention in primary care. Patients at high or potentially high-cardiovascular risk were asked by their GP to prepare themselves for a second consultation in order to participate in decisions on risk management. OUTCOMES: Patients' actually having read the booklet and returning for the second consultation; comprehension and perceived relevance of the information; perceived reassurance. RESULTS: 17 GPs, in the intervention arm of a cluster RCT, issued 276 decision support tools during the first consultation and were instructed to ask them to return for a second consultation to discuss their CVD risk. Patients had a mean age of 54 years, 47% were male and 19% actually had a high cardiovascular risk. Data on 239 patients, a mixture of returnees and non-returnees, showed that they all read the booklet; comprehension was fair to good; 85% perceived the information as relevant; 68% of the patients felt reassured by the information. Satisfaction with the first consultation was higher in the non-returnees. CONCLUSIONS: Cardiovascular prevention spread over two consultations with use of a decision support tool for patients is not easily applicable for GPs. However, based on the findings of good patients' responsiveness, we recommend further development and implementation of decision support tools in primary care. PRACTICE IMPLICATIONS: Decision support for primary CV-prevention is welcomed by patients but needs further adjustment of both the GP and the organization of CV-prevention in primary care. Sharing information between professional and patient on a personal CV-risk management plan is difficult, more training is needed.     

Target Therapy in SLE

The intention of this paper is to review actual developments in target therapy in SLE. Target therapy includes both the objective of intervention and the aim of treatment. The objective should be linked to the pathophysiologic process of SLE; the aim has to be in any case an improved outcome.The current therapeutic in SLE is guided mostly by secondary prevention. In SLE, besides a BASIC concept with antimalarials, bone and sun protection, vaccination and cardiovascular risk minimising, treatment waits for new manifestations to be started to prevent secondarily damage. With the new treatment target remission, treatment should aim at ensuring long-term survival, preventing organ damage and optimizing health-related quality-of-life by controlling disease activity and minimising comorbidities and drug toxicity. First examples show that some patients are in remission and that those patients have a better outcome. But for treat-to-target a strategy needs to be developed that needs to be evaluated.     

A cluster randomised controlled trial of the effect of a treatment algorithm for hypertension in patients with type 2 diabetes

BACKGROUND: Good blood pressure (BP) control reduces the risk of complications in people with type 2 diabetes, yet many do not achieve this. Guidelines for managing hypertension recommend increasing antihypertensive medications until control is achieved, but the effect of such recommendations in routine primary care is unknown. AIM: To evaluate the effectiveness of a BP treatment algorithm in primary care patients with type 2 diabetes. DESIGN OF STUDY: A cluster randomised controlled trial of 1534 patients with type 2 diabetes. SETTING: Forty-two practices in Nottingham, UK. METHOD: Practices were randomised to continue usual care or to use a treatment algorithm designed so that practice nurses and GPs would increase antihypertensive treatment in steps until the target of 140/80 mmHg was reached. Participants were assessed by a clinical interview and case note review at recruitment and at 1 year. The primary outcome measure was the proportion of participants achieving target BP at 1 year. RESULTS: At 1 year there was no difference between the proportions of participants with well controlled BP in the intervention and control arms (36.6% versus 34.3%; P = 0.27). Mean systolic and diastolic blood pressures were identical in the two arms (143/78 mmHg). There was some evidence that participants in the intervention arm were more likely to be receiving higher doses of their antihypertensive drugs, although there was no significant difference in the number of different antihypertensive drugs prescribed. Participants in the intervention arm had a higher rate of primary care BP-related consultations over 12 months than those receiving usual care (rate ratio = 1.55, 95% confidence interval [CI] = 1.26 to 1.88, P<0.001). CONCLUSION: Despite increased monitoring and possibly higher doses of medication there was no improvement in blood pressure control. Improvements achieved by specialist nurse-led clinics in secondary care may not translate to people with type 2 diabetes in primary care settings.     

Probiotics: a complementary approach in the treatment and prevention of pediatric atopic disease

PURPOSE OF REVIEW: The goal of this article is to review recent primary research and developments in the area of probiotics and pediatric atopic disease. RECENT FINDINGS: Research developments in probiotics summarized in this article include the following: (1) the role of probiotics in primary prevention of atopic disease, (2) the effect of probiotics on cytokines involved in the allergic immune response, (3) the long-term effects of peri-natal probiotic use and (4) the relationship between the gut microflora and atopic dermatitis. SUMMARY: Probiotics continue to be an area of active investigation as our understanding evolves of the gut microbiota's role in the altered immune response of atopic patients. Physicians should be aware of these developments as probiotics may be an important complementary approach in the treatment and the natural and long-term course of various pediatric diseases. This article summarizes the research conducted over the past 10 years with a primary focus on the literature published since January 2003.     

Management of type 2 diabetes: a challenge for patient and physician

Type 2 diabetes mellitus is a chronic disease, associated with serious complications and co-morbidity and considerable costs. The number of people with diabetes mellitus is expected to increase with 40% in the next decade, due to prolonged life expectancy, the ageing of the population and developments in the health care sector, including more active screening strategies. The majority (40-60%) of type 2 diabetes patients in routine GP practice have a poor metabolic control (HbA1c > 8% or fasting blood glucose > 11 mmol/l). In this paper the obstacles in routine clinical practice for optimal type 2 diabetes care are discussed. Long-term complications are the major cause of morbidity and mortality in type 2 diabetes patients. Therefore, the primary aim of type 2 diabetes management is the prevention of complications, by lowering blood glucose levels and reducing the cardiovascular risk profile. An important component of type 2 diabetes management is an active role of the patient: diet, smoking habits, physical exercise and self-care behavior often need to change. In addition, the patient has to adhere to life long medical therapy. Motivating the patient for this active role is the challenge for health care providers. A complicating factor is that changes in lifestyle do not give immediate benefit for the patient, as the effects are seen in the reduction of the development of long-term complications. The cornerstones of health care to support active patient participation are: to guarantee the continuity of care, to integrate education in health care and to encourage the patient's attendance. It is the challenge for physicians to give type 2 diabetes patients the tools for active participation in the management of the disease.     

Chronic pain and use of ambulatory health care

Chronic pain status and health care utilization were assessed in a probability sample of 1016 adult HMO enrollees, and among 242 HMO enrollees seeking treatment for Temporomandibular Disorder (TMD) pain. Likelihood of health care contact for a painful symptom: Among persons reporting back pain, headache, chest pain, abdominal pain or temporomandibular pain in the prior six months, we evaluated whether (1) pain characteristics (severity, persistence, recency of onset), and (2) psychological distress were associated with the likelihood of recent use of health care for each pain symptom. Severity, persistence, and recency of onset of pain were generally associated with recent health care contact for a pain symptom. Females with a pain symptom were no more likely than males to report recent health care contact for the symptom after controlling for pain characteristics. The presence of psychological distress did not increase the likelihood of health care contact for individual pain symptoms. However, psychologically distressed persons were more likely to report pain at multiple anatomical sites and to report recent health care contact for one or more of the five pain symptoms (as a group). Chronic pain status and total use of ambulatory health care: Total number of health care visits (irrespective of reason for visit) was measured by automated data. Chronic pain status (summarized across all five anatomical sites) showed a modest correlation with the volume of health care use. Persons with recurrent pain and severe-persistent pain with no pain-related disability days used ambulatory care at rates close to population means. Persons with severe-persistent pain and seven or more pain related disability days used health care at rates substantially above population means. There was a statistically significant association between the volume of health care use and chronic pain after controlling for age, sex, self-rated health status, and psychological distress.     

Monoclonal antibodies in oncology.

Molecular biology has made tremendous strides over the last five years. The new biology allows us to prepare monoclonal antibodies to defined antigens; to detect, isolate and clone specific genes; and to insert these genes into defined sites in different cells giving new functions to old organisms. These revolutionary developments have been followed closely by researchers, businessmen, politicians and philosophers, as well as by those involved in the clinical care of patients. Although our understanding of human molecular biology is increasing rapidly, it is the development of monoclonal antibodies that has the most immediate application in the clinic. There have been several reports of their use in the diagnosis, localisation and treatment of human malignant disease. This review describes developments that are likely to have direct relevance to patient care in the near future.     

Overview of recent literature on undergraduate ambulatory care education and a framework for future planning.

This study provides an interpretive overview of ambulatory care undergraduate education from 1979 to 1991 and identifies two major problems for medical education: (1) the difficulties inherent in the transfer of educational techniques from the hospital to the ambulatory care setting; and (2) the misuse of and lack of agreement on definitions of ambulatory care, primary care, and community-oriented primary care. The authors distinguish various types of ambulatory care and examine factors that differentiate ambulatory care and hospital sites for educating medical students, including the setting, program management, curriculum issues, evaluation, cost, faculty time, and space. Based on concepts and issues identified in the study, the authors propose a framework for planning future ambulatory care education and research.