Integrating novel agents into multiple myeloma treatment - current status in Switzerland and treatment recommendations.

The treatment of multiple myeloma has undergone significant changes in the recent past. The arrival of novel agents, especially thalidomide, bortezomib and lenalidomide, has expanded treatment options and patient outcomes are improving significantly. This article summarises the discussions of an expert meeting which was held to debate current treatment practices for multiple myeloma in Switzerland concerning the role of the novel agents and to provide recommendations for their use in different treatment stages based on currently available clinical data. Novel agent combinations for the treatment of newly diagnosed, as well as relapsed multiple myeloma are examined. In addition, the role of novel agents in patients with cytogenetic abnormalities and renal impairment, as well as the management of the most frequent side effects of the novel agents are discussed. The aim of this article is to assist in treatment decisions in daily clinical practice to achieve the best possible outcome for patients with multiple myeloma.

Can routine offering of influenza vaccination in office-based settings reduce racial and ethnic disparities in adult influenza vaccination?

BACKGROUND: Influenza vaccination remains below the federally targeted levels outlined in Healthy People 2020. Compared to non-Hispanic whites, racial and ethnic minorities are less likely to be vaccinated for influenza, despite being at increased risk for influenza-related complications and death. Also, vaccinated minorities are more likely to receive influenza vaccinations in office-based settings and less likely to use non-medical vaccination locations compared to non-Hispanic white vaccine users. OBJECTIVE: To assess the number of "missed opportunities" for influenza vaccination in office-based settings by race and ethnicity and the magnitude of potential vaccine uptake and reductions in racial and ethnic disparities in influenza vaccination if these "missed opportunities" were eliminated. DESIGN: National cross-sectional Internet survey administered between March 4 and March 14, 2010 in the United States. PARTICIPANTS: Non-Hispanic black, Hispanic and non-Hispanic white adults living in the United States (N = 3,418). MAIN MEASURES: We collected data on influenza vaccination, frequency and timing of healthcare visits, and self-reported compliance with a potential provider recommendation for vaccination during the 2009-2010 influenza season. "Missed opportunities" for seasonal influenza vaccination in office-based settings were defined as the number of unvaccinated respondents who reported at least one healthcare visit in the Fall and Winter of 2009-2010 and indicated their willingness to get vaccinated if a healthcare provider strongly recommended it. "Potential vaccine uptake" was defined as the sum of actual vaccine uptake and "missed opportunities." KEY RESULTS: The frequency of "missed opportunities" for influenza vaccination in office-based settings was significantly higher among racial and ethnic minorities than non-Hispanic whites. Eliminating these "missed opportunities" could have cut racial and ethnic disparities in influenza vaccination by roughly one half. CONCLUSIONS: Improved office-based practices regarding influenza vaccination could significantly impact Healthy People 2020 goals by increasing influenza vaccine uptake and reducing corresponding racial and ethnic disparities.

Pre-hospital tracheal intubation in patients with traumatic brain injury: systematic review of current evidence.

BACKGROUND: We reviewed the current evidence on the benefit and harm of pre-hospital tracheal intubation and mechanical ventilation after traumatic brain injury (TBI). METHODS: We conducted a systematic literature search up to December 2007 without language restriction to identify interventional and observational studies comparing pre-hospital intubation with other airway management (e.g. bag-valve-mask or oxygen administration) in patients with TBI. Information on study design, population, interventions, and outcomes was abstracted by two investigators and cross-checked by two others. Seventeen studies were included with data for 15,335 patients collected from 1985 to 2004. There were 12 retrospective analyses of trauma registries or hospital databases, three cohort studies, one case-control study, and one controlled trial. Using Brain Trauma Foundation classification of evidence, there were 14 class 3 studies, three class 2 studies, and no class 1 study. Six studies were of adults, five of children, and three of both; age groups were unclear in three studies. Maximum follow-up was up to 6 months or hospital discharge. RESULTS: In 13 studies, the unadjusted odds ratios (ORs) for an effect of pre-hospital intubation on in-hospital mortality ranged from 0.17 (favouring control interventions) to 2.43 (favouring pre-hospital intubation); adjusted ORs ranged from 0.24 to 1.42. Estimates for functional outcomes after TBI were equivocal. Three studies indicated higher risk of pneumonia associated with pre-hospital (when compared with in-hospital) intubation. CONCLUSIONS: Overall, the available evidence did not support any benefit from pre-hospital intubation and mechanical ventilation after TBI. Additional arguments need to be taken into account, including medical and procedural aspects.

A systematic review of longitudinal population-based studies on the predictors of smoking cessation in adolescent and young adult smokers.

OBJECTIVE: To describe the determinants of self-initiated smoking cessation of duration of at least 6 months as identified in longitudinal population-based studies of adolescent and young adult smokers. METHODS: A systematic search of the PubMed and EMBASE databases using smoking, tobacco, cessation, quit and stop as keywords was performed. Limits included articles related to humans, in English, published between January 1984 and August 2010, and study population aged 10-29 years. A total of 4502 titles and 871 abstracts were reviewed independently by 2 and 3 reviewers, respectively. Nine articles were retained for data abstraction. Data on study location, timeframe, duration of follow-up, number of data collection points, sample size, age/grade of participants, number of quitters, smoking status at baseline, definition of cessation, covariates and analytic method were abstracted from each article. The number of studies that reported a statistically significant association between each determinant investigated and cessation were tabulated, from among all studies that assessed the determinant. RESULTS: Despite heterogeneity in methods across studies, five factors robustly predicted quitting across studies in which the factor was investigated: not having friends who smoke, not having intentions to smoke in the future, resisting peer pressure to smoke, being older at first use of cigarette and having negative beliefs about smoking. CONCLUSIONS: The literature on longitudinal predictors of cessation in adolescent and young adult smokers is not well developed. Cessation interventions for this population will remain less than optimally effective until there is a solid evidence base on which to develop interventions.

Empirical antifungal therapy in neutropaenic cancer patients with persistent fever

Invasive fungal infections are frequent and severe complications in leukaemic patients with prolonged neutropaenia. Empirical antifungal therapy has become the standard of care in patients with persistent fever despite treatment with broad-spectrum antibiotics. For decades amphotericin B deoxycholate has been the sole option for empirical antifungal therapy. Recently, several new antifungal agents became available. The choice of the most appropriate drug should be guided by efficacy and safety criteria. The recommendations from the First European Conference on Infections in Leukaemia (ECIL-1) on empirical antifungal therapy in neutropaenic cancer patients with persistent fever have been developed by an expert panel after assessment of clinical practices in Europe and evidence-based review of the literature. Many antifungal regimens can now be recommended for empirical therapy in neutropaenic cancer patients. However, persistent fever lacks specificity for initiation of therapy. Development of empirical and pre-emptive strategies using new clinical parameters, laboratory markers and imaging techniques for early diagnosis of invasive mycoses are needed.

Population based screening - the difficulty of how to do more good than harm and how to achieve it.

Screening people without symptoms of disease is an attractive idea. Screening allows early detection of disease or elevated risk of disease, and has the potential for improved treatment and reduction of mortality. The list of future screening opportunities is set to grow because of the refinement of screening techniques, the increasing frequency of degenerative and chronic diseases, and the steadily growing body of evidence on genetic predispositions for various diseases. But how should we decide on the diseases for which screening should be done and on recommendations for how it should be implemented? We use the examples of prostate cancer and genetic screening to show the importance of considering screening as an ongoing population-based intervention with beneficial and harmful effects, and not simply the use of a test. Assessing whether screening should be recommended and implemented for any named disease is therefore a multi-dimensional task in health technology assessment. There are several countries that already use established processes and criteria to assess the appropriateness of screening. We argue that the Swiss healthcare system needs a nationwide screening commission mandated to conduct appropriate evidence-based evaluation of the impact of proposed screening interventions, to issue evidence-based recommendations, and to monitor the performance of screening programmes introduced. Without explicit processes there is a danger that beneficial screening programmes could be neglected and that ineffective, and potentially harmful, screening procedures could be introduced.

Das GRADE-System: ein internationaler Ansatz zur Vereinheitlichung der Graduierung von Evidenz und Empfehlungen in Leitlinien. [The GRADE System: an international approach to standardize the graduation of evidence and recommendations in guidelines]

Clinical practice guidelines have become an important source of information to support clinicians in the management of individual patients. However, current guideline methods have limitations that include the lack of separating the quality of evidence from the strength of recommendations. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) working group, an international collaboration of guideline developers, methodologists, and clinicians have developed a system that addresses these shortcomings. Core elements include transparent methodology for grading the quality of evidence, the distinction between quality of the evidence and strength of a recommendation, an explicit balancing of benefits and harms of health care interventions, an explicit recognition of the values and preferences that underlie recommendations. The GRADE system has been piloted in various practice settings to ensure that it captures the complexity involved in evidence assessment and grading recommendations while maintaining simplicity and practicality. Many guideline organizations and medical societies have endorsed the system and adopted it for their guideline processes.

Systematic review of evidence and consensus on diverticulitis: an analysis of national and international guidelines.

AIM: The study aimed to analyse the currently available national and international guidelines for areas of consensus and contrasting recommendations in the treatment of diverticulitis and thereby to design questions for future research. METHOD: MEDLINE, EMBASE and PubMed were systematically searched for guidelines on diverticular disease and diverticulitis. Inclusion was confined to papers in English and those < 10 years old. The included topics were classified as consensus or controversy between guidelines, and the highest level of evidence was scored as sufficient (Oxford Centre of Evidence-Based Medicine Level of Evidence of 3a or higher) or insufficient. RESULTS: Six guidelines were included and all topics with recommendations were compared. Overall, in 13 topics consensus was reached and 10 topics were regarded as controversial. In five topics, consensus was reached without sufficient evidence and in three topics there was no evidence and no consensus. Clinical staging, the need for intraluminal imaging, dietary restriction, duration of antibiotic treatment, the protocol for abscess treatment, the need for elective surgery in subgroups of patients, the need for surgery after abscess treatment and the level of the proximal resection margin all lack consensus or evidence. CONCLUSION: Evidence on the diagnosis and treatment of diverticular disease and diverticulitis ranged from nonexistent to strong, regardless of consensus. The most relevant research questions were identified and proposed as topics for future research.

Involvement of family physicians in structured programs for chronic diseases or multi-morbidity in Switzerland.

The increasing prevalence of chronic diseases and multi-morbidity represents challenges for health systems worldwide. In that perspective, the current organization of healthcare delivery, fragmentation of care, limited use of evidence-based guidelines and patients'insufficient empowerment are some reasons explaining the current limited effectiveness of the management of chronically ill patients. Based on theoretical models such as the Chronic Care Model (CCM), initiatives targeting improvements in the care of patients with chronic diseases have been implemented worldwide since more than a decade. Their development in Switzerland, a health system where more than half of practices are still single handed [6], is only recent and infrequent. Structured programs for patients with chronic diseases or multimorbidity usually propose patient-centered interventions and consider an integrative multidisciplinary approach. Currently, little is known on the existence of such programs and on the role of family physicians (FPs)within these programs, in Switzerland. The objective of this study was to identify and describe current structured programs targeting chronic diseases or multi-morbidity in Switzerland. This may help in examining innovative approaches that are only developed locally but would deserve wider interest for further implementation. We conducted a telephone-based survey between June and November 2013 and contacted systematically key institutions, informants and stakeholders nationwide and in the 26 cantons...

Responding to Young People's Health Risks in Primary Care: A Cluster Randomised Trial of Training Clinicians in Screening and Motivational Interviewing.

OBJECTIVE: To evaluate the effectiveness of a complex intervention implementing best practice guidelines recommending clinicians screen and counsel young people across multiple psychosocial risk factors, on clinicians' detection of health risks and patients' risk taking behaviour, compared to a didactic seminar on young people's health. DESIGN: Pragmatic cluster randomised trial where volunteer general practices were stratified by postcode advantage or disadvantage score and billing type (private, free national health, community health centre), then randomised into either intervention or comparison arms using a computer generated random sequence. Three months post-intervention, patients were recruited from all practices post-consultation for a Computer Assisted Telephone Interview and followed up three and 12 months later. Researchers recruiting, consenting and interviewing patients and patients themselves were masked to allocation status; clinicians were not. SETTING: General practices in metropolitan and rural Victoria, Australia. PARTICIPANTS: General practices with at least one interested clinician (general practitioner or nurse) and their 14-24 year old patients. INTERVENTION: This complex intervention was designed using evidence based practice in learning and change in clinician behaviour and general practice systems, and included best practice approaches to motivating change in adolescent risk taking behaviours. The intervention involved training clinicians (nine hours) in health risk screening, use of a screening tool and motivational interviewing; training all practice staff (receptionists and clinicians) in engaging youth; provision of feedback to clinicians of patients' risk data; and two practice visits to support new screening and referral resources. Comparison clinicians received one didactic educational seminar (three hours) on engaging youth and health risk screening. OUTCOME MEASURES: Primary outcomes were patient report of (1) clinician detection of at least one of six health risk behaviours (tobacco, alcohol and illicit drug use, risks for sexually transmitted infection, STI, unplanned pregnancy, and road risks); and (2) change in one or more of the six health risk behaviours, at three months or at 12 months. Secondary outcomes were likelihood of future visits, trust in the clinician after exit interview, clinician detection of emotional distress and fear and abuse in relationships, and emotional distress at three and 12 months. Patient acceptability of the screening tool was also described for the intervention arm. Analyses were adjusted for practice location and billing type, patients' sex, age, and recruitment method, and past health risks, where appropriate. An intention to treat analysis approach was used, which included multilevel multiple imputation for missing outcome data. RESULTS: 42 practices were randomly allocated to intervention or comparison arms. Two intervention practices withdrew post allocation, prior to training, leaving 19 intervention (53 clinicians, 377 patients) and 21 comparison (79 clinicians, 524 patients) practices. 69% of patients in both intervention (260) and comparison (360) arms completed the 12 month follow-up. Intervention clinicians discussed more health risks per patient (59.7%) than comparison clinicians (52.7%) and thus were more likely to detect a higher proportion of young people with at least one of the six health risk behaviours (38.4% vs 26.7%, risk difference [RD] 11.6%, Confidence Interval [CI] 2.93% to 20.3%; adjusted odds ratio [OR] 1.7, CI 1.1 to 2.5). Patients reported less illicit drug use (RD -6.0, CI -11 to -1.2; OR 0·52, CI 0·28 to 0·96), and less risk for STI (RD -5.4, CI -11 to 0.2; OR 0·66, CI 0·46 to 0·96) at three months in the intervention relative to the comparison arm, and for unplanned pregnancy at 12 months (RD -4.4; CI -8.7 to -0.1; OR 0·40, CI 0·20 to 0·80). No differences were detected between arms on other health risks. There were no differences on secondary outcomes, apart from a greater detection of abuse (OR 13.8, CI 1.71 to 111). There were no reports of harmful events and intervention arm youth had high acceptance of the screening tool. CONCLUSIONS: A complex intervention, compared to a simple educational seminar for practices, improved detection of health risk behaviours in young people. Impact on health outcomes was inconclusive. Technology enabling more efficient, systematic health-risk screening may allow providers to target counselling toward higher risk individuals. Further trials require more power to confirm health benefits. TRIAL REGISTRATION: ISRCTN.com ISRCTN16059206.

The role of advanced nursing in lung cancer: A framework based development.

PURPOSE: Advanced Practice Lung Cancer Nurses (APLCN) are well-established in several countries but their role has yet to be established in Switzerland. Developing an innovative nursing role requires a structured approach to guide successful implementation and to meet the overarching goal of improved nursing sensitive patient outcomes. The "Participatory, Evidence-based, Patient-focused process, for guiding the development, implementation, and evaluation of advanced practice nursing" (PEPPA framework) is one approach that was developed in the context of the Canadian health system. The purpose of this article is to describe the development of an APLCN model at a Swiss Academic Medical Center as part of a specialized Thoracic Cancer Center and to evaluate the applicability of PEPPA framework in this process. METHOD: In order to develop and implement the APLCN role, we applied the first seven phases of the PEPPA framework. RESULTS: This article spreads the applicability of the PEPPA framework for an APLCN development. This framework allowed us to i) identify key components of an APLCN model responsive to lung cancer patients' health needs, ii) identify role facilitators and barriers, iii) implement the APLCN role and iv) design a feasibility study of this new role. CONCLUSIONS: The PEPPA framework provides a structured process for implementing novel Advanced Practice Nursing roles in a local context, particularly where such roles are in their infancy. Two key points in the process include assessing patients' health needs and involving key stakeholders.

Patterns of impact resulting from a 'sit less, move more' web-based program in sedentary office employees

Purpose Encouraging office workers to ‘sit less and move more’ encompasses two public health priorities. However, there is little evidence on the effectiveness of workplace interventions for reducing sitting, even less about the longer term effects of such interventions and still less on dual-focused interventions. This study assessed the short and mid-term impacts of a workplace web-based intervention (Walk@WorkSpain, W@WS; 2010-11) on self-reported sitting time, step counts and physical risk factors (waist circumference, BMI, blood pressure) for chronic disease. Methods Employees at six Spanish university campuses (n=264; 42±10 years; 171 female) were randomly assigned by worksite and campus to an Intervention (used W@WS; n=129; 87 female) or a Comparison group (maintained normal behavior; n=135; 84 female). This phased, 19-week program aimed to decrease occupational sitting time through increased incidental movement and short walks. A linear mixed model assessed changes in outcome measures between the baseline, ramping (8 weeks), maintenance (11 weeks) and followup (two months) phases for Intervention versus Comparison groups.A significant 2 (group) × 2 (program phases) interaction was found for self-reported occupational sitting (F[3]=7.97, p=0.046), daily step counts (F[3]=15.68, p=0.0013) and waist circumference (F[3]=11.67, p=0.0086). The Intervention group decreased minutes of daily occupational sitting while also increasing step counts from baseline (446±126; 8,862±2,475) through ramping (+425±120; 9,345±2,435), maintenance (+422±123; 9,638±3,131) and follow-up (+414±129; 9,786±3,205). In the Comparison group, compared to baseline (404±106), sitting time remained unchanged through ramping and maintenance, but decreased at follow-up (-388±120), while step counts diminished across all phases. The Intervention group significantly reduced waist circumference by 2.1cms from baseline to follow-up while the Comparison group reduced waist circumference by 1.3cms over the same period. Conclusions W@WSis a feasible and effective evidence-based intervention that can be successfully deployed with sedentary employees to elicit sustained changes on “sitting less and moving more”.

Weight of evidence

Evidence-based Medicine (EBM) has become a major source of medical knowledge. It handles complexities of virtually every method or technique used in research. The knowledge on how the EBM researcher retrieves information, judges for relevance and analyzes derived data is invaluable for the skillful reader of medical scientific reports.