GetReal in network meta-analysis: a review of the methodology.

Pairwise meta-analysis is an established statistical tool for synthesizing evidence from multiple trials, but it is informative only about the relative efficacy of two specific interventions. The usefulness of pairwise meta-analysis is thus limited in real-life medical practice, where many competing interventions may be available for a certain condition and studies informing some of the pairwise comparisons may be lacking. This commonly encountered scenario has led to the development of network meta-analysis (NMA). In the last decade, several applications, methodological developments, and empirical studies in NMA have been published, and the area is thriving as its relevance to public health is increasingly recognized. This article presents a review of the relevant literature on NMA methodology aiming to pinpoint the developments that have appeared in the field. Copyright © 2016 John Wiley & Sons, Ltd.

Patient-Rated Outcomes of Lumbar Fusion in Patients with Degenerative Disease of the Lumbar Spine: Does Age Matter?

STUDY DESIGN Single centre retrospective study of prospectively collected data, nested within the Eurospine Spine Tango data acquisition system. OBJECTIVE The aim of this study was to assess the patient-rated outcome and complication rates associated with lumbar fusion procedures in three different age groups. SUMMARY OF BACKGROUND DATA There is a general reluctance to consider spinal fusion procedures in elderly patients due to the increased likelihood of complications. METHODS Before and at 3, 12, and 24 months after surgery, patients completed the multidimensional Core Outcome Measures Index (COMI). At the 3-, 12-, and 24-month follow-ups they also rated the Global Treatment Outcome (GTO) and their satisfaction with care. Patients were divided into three age groups: younger (≥50y < 65y; n = 317), older (≥65y < 80y; n = 350), and geriatric (≥ 80y; n = 40). RESULTS 707 consecutive patients were included. The preoperative comorbidity status differed significantly (p < 0.0001) between the age groups, with the highest scores in the geriatric group. Medical complications during surgery were lower in the younger age group (7%) than in the older (13.4%; p = 0.006) and geriatric groups (17.5%; p = 0.007); surgical complications tended to be higher in the elderly group (younger, 6.3%; older, 6.0%; geriatric, 15.0%; p = 0.09). There were no significant group differences (p > 0.05) for the scores on any of the COMI domains, GTO, or patient-rated satisfaction at either 3-, 12-, and 24-months follow-up. CONCLUSIONS Despite greater comorbidity and complication rates in geriatric patients, the patient-rated outcome was as good in the elderly as it was in younger age groups up to two years after surgery. These data indicate that geriatric age needs careful consideration of associated risks but is not per se a contraindication for fusion for lumbar degenerative disease. LEVEL OF EVIDENCE 4.

Haematopoietic stem cell transplantation in Switzerland. Report from the Swiss Transplant Working Group Blood and Marrow Transplantation (STABMT) Registry 1997-2003

In 1997, the Swiss Transplant Working Group Blood and Marrow Transplantation (STABMT) initiated a mandatory national registry for all haematopoietic stem cell transplants (HSCT) in Switzerland. As of 2003, information was collected of 2010 patients with a first HSCT (577 allogeneic (29%) and 1433 autologous (71%) HSCT) and 616 additional re-transplants. This included 1167 male and 843 female patients with a median age of 42.4 years (range 0.2-76.6 years). Main indications were leukaemias (592; 29%) lymphoproliferative disorders (1,061; 53%), solid tumours (295; 15%) and non-malignant disorders (62; 3%). At the time of analysis 1,263 patients were alive (63%), 747 had died (37%). Probability of survival, transplant related mortality or relapse at 5 years was 52%, 21%, 36% for allogeneic and 54%, 5%, 60% for autologous HSCT. Outcome depended on indication, donor type, stem cell source and age of patient. HSCT is an established therapy in Switzerland. These data describe current practice and outcome.

The PRO-AGE study: an international randomised controlled study of health risk appraisal for older persons based in general practice

BACKGROUND: This paper describes the study protocol, the recruitment, and base-line data for evaluating the success of randomisation of the PRO-AGE (PRevention in Older people-Assessment in GEneralists' practices) project. METHODS/DESIGN: A group of general practitioners (GPs) in London (U.K.), Hamburg (Germany) and Solothurn (Switzerland) were trained in risk identification, health promotion, and prevention in older people. Their non-disabled older patients were invited to participate in a randomised controlled study. Participants allocated to the intervention group were offered the Health Risk Appraisal for Older Persons (HRA-O) instrument with a site-specific method for reinforcement (London: physician reminders in electronic medical record; Hamburg: one group session or two preventive home visits; Solothurn: six-monthly preventive home visits over a two-year period). Participants allocated to the control group received usual care. At each site, an additional group of GPs did not receive the training, and their eligible patients were invited to participate in a concurrent comparison group. Primary outcomes are self-reported health behaviour and preventative care use at one-year follow-up. In Solothurn, an additional follow-up was conducted at two years. The number of older persons agreeing to participate (% of eligible persons) in the randomised controlled study was 2503 (66.0%) in London, 2580 (53.6%) in Hamburg, and 2284 (67.5%) in Solothurn. Base-line findings confirm that randomisation of participants was successful, with comparable characteristics between intervention and control groups. The number of persons (% of eligible) enrolled in the concurrent comparison group was 636 (48.8%) in London, 746 (35.7%) in Hamburg, and 1171 (63.0%) in Solothurn. DISCUSSION: PRO-AGE is the first large-scale randomised controlled trial of health risk appraisal for older people in Europe. Its results will inform about the effects of implementing HRA-O with different methods of reinforcement.

Sweat testing practice in Swiss hospitals

AIMS: To determine whether the current practice of sweat testing in Swiss hospitals is consistent with the current international guidelines. METHODS: A questionnaire was mailed to all children's hospitals (n = 8), regional paediatric sections of general hospitals (n = 28), and all adult pulmonology centres (n = 8) in Switzerland which care for patients with cystic fibrosis (CF). The results were compared with published "guidelines 2000" of the American National Committee for Clinical Laboratory Standards (NCCLS) and the UK guidelines of 2003. RESULTS: The response rate was 89%. All 8 children's hospitals and 18 out of 23 answering paediatric sections performed sweat tests but none of the adult pulmonology centres. In total, 1560 sweat tests (range: 5-200 tests/centre/year, median 40) per year were done. 88% (23/26) were using Wescor systems, 73% (19/26) the Macroduct system for collecting sweat and 31% (8/26) the Nanoduct system. Sweat chloride was determined by only 62% (16/26) of all centres; of these, only 63% (10/16) indicated to use the recommended diagnostic chloride-CF-reference value of >60 mmol/l. Osmolality was measured in 35%, sodium in 42% and conductivity in 62% of the hospitals. Sweat was collected for maximal 30-120 (median 55) minutes; only three centres used the maximal 30 minutes sample time recommended by the international guidelines. CONCLUSIONS: Sweat testing practice in Swiss hospitals was inconsistent and seldom followed the current international guidelines for sweat collection, analyzing method and reference values. Only 62% were used the chloride concentration as a diagnostic reference, the only accepted diagnostic measurement by the NCCLS or UK guidelines.

Management of acute bronchiolitis: can evidence based guidelines alter clinical practice?

BACKGROUND: Acute bronchiolitis is the most common lower respiratory tract infection in infants and there is no evidence that drug treatment alters its natural course. Despite this, most Swiss paediatricians reported in 2001 prescribing bronchodilators and inhaled corticosteroids (ICS). This situation led to the creation of national guidelines followed by a tailored implementation programme. The aim of this study was to examine if treatment practices changed after the implementation of the new guidelines. METHODS: A questionnaire on treatment of bronchiolitis was sent to all Swiss paediatricians before (2001) and after (2006) creation and implementation of national guidelines (2003-2005). Guidelines were created in collaboration with all paediatric pulmonologists and implemented carefully using a multifaceted approach. RESULTS: Questionnaires were returned by 541 paediatricians (58%) in 2001 and by 639 (54%) in 2006. While both surveys showed a wide variation in the treatment of bronchiolitis between physicians, reported drug prescription decreased significantly between the two surveys. For outpatients, general use (for all patients) of bronchodilators dropped from 60% to 23%, and general use of ICS from 34% to 6%. For inpatients, general use of bronchodilators and ICS dropped from 55% to 18% and from 26% to 6%, respectively (all p<0.001). The decrease was evident in all regions, among hospital and primary care physicians, and among general paediatricians and paediatric pulmonologists. CONCLUSIONS: National guidelines together with a tailored implementation programme can have a major impact on medical management practices in a country.

Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice

BACKGROUND: Microarray genome analysis is realising its promise for improving detection of genetic abnormalities in individuals with mental retardation and congenital abnormality. Copy number variations (CNVs) are now readily detectable using a variety of platforms and a major challenge is the distinction of pathogenic from ubiquitous, benign polymorphic CNVs. The aim of this study was to investigate replacement of time consuming, locus specific testing for specific microdeletion and microduplication syndromes with microarray analysis, which theoretically should detect all known syndromes with CNV aetiologies as well as new ones. METHODS: Genome wide copy number analysis was performed on 117 patients using Affymetrix 250K microarrays. RESULTS: 434 CNVs (195 losses and 239 gains) were found, including 18 pathogenic CNVs and 9 identified as "potentially pathogenic". Almost all pathogenic CNVs were larger than 500 kb, significantly larger than the median size of all CNVs detected. Segmental regions of loss of heterozygosity larger than 5 Mb were found in 5 patients. CONCLUSIONS: Genome microarray analysis has improved diagnostic success in this group of patients. Several examples of recently discovered "new syndromes" were found suggesting they are more common than previously suspected and collectively are likely to be a major cause of mental retardation. The findings have several implications for clinical practice. The study revealed the potential to make genetic diagnoses that were not evident in the clinical presentation, with implications for pretest counselling and the consent process. The importance of contributing novel CNVs to high quality databases for genotype-phenotype analysis and review of guidelines for selection of individuals for microarray analysis is emphasised.

Learner preferences regarding integrating, sequencing and aligning virtual patients with other activities in the undergraduate medical curriculum: A focus group study

CONTEXT: E-learning resources, such as virtual patients (VPs), can be more effective when they are integrated in the curriculum. To gain insights that can inform guidelines for the curricular integration of VPs, we explored students' perceptions of scenarios with integrated and non-integrated VPs aimed at promoting clinical reasoning skills. METHODS: During their paediatric clerkship, 116 fifth-year medical students were given at least ten VPs embedded in eight integrated scenarios and as non-integrated add-ons. The scenarios differed in the sequencing and alignment of VPs and related educational activities, tutor involvement, number of VPs, relevance to assessment and involvement of real patients. We sought students' perceptions on the VP scenarios in focus group interviews with eight groups of 4-7 randomly selected students (n = 39). The interviews were recorded, transcribed and analysed qualitatively. RESULTS: The analysis resulted in six themes reflecting students' perceptions of important features for effective curricular integration of VPs: (i) continuous and stable online access, (ii) increasing complexity, adapted to students' knowledge, (iii) VP-related workload offset by elimination of other activities, (iv) optimal sequencing (e.g.: lecture--1 to 2 VP(s)--tutor-led small group discussion--real patient) and (V) optimal alignment of VPs and educational activities, (vi) inclusion of VP topics in assessment. CONCLUSIONS: The themes appear to offer starting points for the development of a framework to guide the curricular integration of VPs. Their impact needs to be confirmed by studies using quantitative controlled designs.

Building a global consensus approach to chordoma: a position paper from the medical and patient community

Chordomas are very rare bone malignant tumours that have had a shortage of effective treatments for a long time. New treatments are now available for both the local and the metastatic phase of the disease, but the degree of uncertainty in selecting the most appropriate treatment remains high and their adoption remains inconsistent across the world, resulting in suboptimum outcomes for many patients. In December, 2013, the European Society for Medical Oncology (ESMO) convened a consensus meeting to update its clinical practice guidelines on sarcomas. ESMO also hosted a parallel consensus meeting on chordoma that included more than 40 chordoma experts from several disciplines and from both sides of the Atlantic, with the contribution and sponsorship of the Chordoma Foundation, a global patient advocacy group. The consensus reached at that meeting is shown in this position paper.