Efficacy of Canakinumab (ACZ885), a Fully Human Anti-Interleukin (IL)-1beta Monoclonal Antibody, in the Prevention of Flares in Gout Patients Initiating Allopurinol Therapy

Background: Gout patients initiating urate lowering therapy have an increased risk of flares. Inflammation in gouty arthritis is induced by IL-1b. Canakinumab targets and inhibits IL-1b effectively in clinical studies. This study compared different doses of canakinumab vs colchicine in preventing flares in gout patients initiating allopurinol therapy.Methods: In this 24 week double blind study, gout patients (20-79 years) initiating allopurinol were randomized (1:1:1:1:1:1:2) to canakinumab s.c. single doses of 25, 50, 100, 200, 300 mg, or 150 mg divided in doses every 4 weeks (50+50+25+25 mg [q4wk]) or colchicine 0.5 mg p.o. daily for 16 weeks. Primary outcome was to determine the canakinumab dose giving comparable efficacy to colchicine with respect to the number of gout flares occurring during first 16 weeks. Secondary outcomes included number of patients with gout flares and C-reactive protein (CRP) levels during the first 16 weeks.Results: 432 patients were randomized and 391 (91%) completed the study. All canakinumab doses were better than colchicine in preventing flares and therefore, a canakinumab dose comparable to colchicine could not be determined. Based on a negative binomial model, all canakinumab groups, except 25 mg, reduced the flare rate ratio per patient significantly compared to colchicine group (rate ratio estimates 25 mg 0.60, 50 mg 0.34, 100 mg 0.28, 200 mg 0.37, 300 mg 0.29, q4wk 0.38; p<=0.05). The percentage of patients with flares was lower for all canakinumab groups (25 mg 27.3%, 50 mg 16.7%, 100 mg 14.8%, 200 mg 18.5%, 300 mg 15.1%, q4wk 16.7%) compared to colchicine group (44.4%). All patients taking canakinumab were significantly less likely to experience at least one gout flare than patients taking colchicine (odds ratio range [0.22 - 0.47]; p<=0.05 for all). The median baseline CRP levels were 2.86 mg/L for 25 mg, 3.42 mg/L for 50 mg, 1.76 mg/L for 100 mg, 3.66 mg/L for 200 mg, 3.21 mg/L for 300 mg, 3.23 mg/L for q4wk canakinumab groups and 2.69 mg/L for colchicine group. In all canakinumab groups with median CRP levels above the normal range at baseline, median levels declined within 15 days of treatment and were maintained at normal levels (ULN=3 mg/L) throughout the 16 week period. Adverse events (AEs) occurred in 52.7% (25 mg), 55.6% (50 mg), 51.9% (100 mg), 51.9% (200 mg), 54.7% (300 mg), and 58.5% (q4wk) of patients on canakinumab vs 53.7% of patients on colchicine. Serious AEs (SAE) were reported in 2 (3.6%; 25 mg), 2 (3.7%, 50 mg), 3 (5.6%, 100 mg), 3 (5.6%, 200 mg), 3 (5.7%, 300 mg) and 1 (1.9%, q4wk) patients on canakinumab and in 5 (4.6%) patients on colchicine. One fatal SAE (myocardial infarction, not related to study drug) occurred in colchicine group.Conclusion: In this large randomized, double-blind active controlled study of flare prevention in gout patients initiating allopurinol therapy, treatment with canakinumab led to a statistically significant reduction in flares compared with colchicine (standard of care), and was well tolerated.

Iowa Veterans Home Building A Future On The Foundation Of Our Past FY 2012 Annual,

Annual report for the Iowa Veterans Home. To provide a continuum of care to Iowa’s veterans and their spouses in an environment focusing on individualized services to enhance their quality of life.

Partnership for fragility bone fracture care provision and prevention program (P4Bones): study protocol for a secondary fracture prevention pragmatic controlled trial.

ABSTRACT: BACKGROUND: Fractures associated with bone fragility in older adults signal the potential for secondary fracture. Fragility fractures often precipitate further decline in health and loss of mobility, with high associated costs for patients, families, society and the healthcare system. Promptly initiating a coordinated, comprehensive pharmacological bone health and falls prevention program post-fracture may improve osteoporosis treatment compliance; and reduce rates of falls and secondary fractures, and associated morbidity, mortality and costs.Methods/design: This pragmatic, controlled trial at 11 hospital sites in eight regions in Quebec, Canada, will recruit community-dwelling patients over age 50 who have sustained a fragility fracture to an intervention coordinated program or to standard care, according to the site. Site study coordinators will identify and recruit 1,596 participants for each study arm. Coordinators at intervention sites will facilitate continuity of care for bone health, and arrange fall prevention programs including physical exercise. The intervention teams include medical bone specialists, primary care physicians, pharmacists, nurses, rehabilitation clinicians, and community program organizers.The primary outcome of this study is the incidence of secondary fragility fractures within an 18-month follow-up period. Secondary outcomes include initiation and compliance with bone health medication; time to first fall and number of clinically significant falls; fall-related hospitalization and mortality; physical activity; quality of life; fragility fracture-related costs; admission to a long term care facility; participants' perceptions of care integration, expectations and satisfaction with the program; and participants' compliance with the fall prevention program. Finally, professionals at intervention sites will participate in focus groups to identify barriers and facilitating factors for the integrated fragility fracture prevention program.This integrated program will facilitate knowledge translation and dissemination via the following: involvement of various collaborators during the development and set-up of the integrated program; distribution of pamphlets about osteoporosis and fall prevention strategies to primary care physicians in the intervention group and patients in the control group; participation in evaluation activities; and eventual dissemination of study results.Study/trial registration: Clinical Trial.Gov NCT01745068Study ID number: CIHR grant # 267395.

Children's experience regarding the quality of their hospital stay: the development of an assessment questionnaire for children

A questionnaire assessing the satisfaction of children with their hospital stay has been developed and tested with 136 children (aged 6-12 years) at 2 Swiss hospital sites. Three out of 4 children were satisfied overall with their hospital stay. Their relationships with the professional medical staff, explanations they received, games they played, and environment, all received positive evaluations. The most critical points were pain, fear, and the absence of relatives. Ninety percent of the children appreciated that their opinions were sought. These results reinforce the importance of having questionnaires available for the children to consider their opinions to enhance the quality of care.

EURECCA colorectal: multidisciplinary mission statement on better care for patients with colon and rectal cancer in Europe

Background: Care for patients with colon and rectal cancer has improved in the last twenty years however still considerable variation exists in cancer management and outcome between European countries. Therefore, EURECCA, which is the acronym of European Registration of cancer care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012 the first multidisciplinary consensus conference about colon and rectum was held looking for multidisciplinary consensus. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries. Methods: The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Experts commented and voted on the two web-based online voting rounds before the meeting (between 4th and 25th October and between the 20th November and 3rd December 2012) as well as one online round after the meeting (4th20th March 2013) and were invited to lecture on the subjects during the meeting (13th15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. All sentences that were voted on are available on the EURECCA website www.canceraudit.eu. The consensus document was divided in sections describing evidence based algorithms of diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and stage IV separately. Consensus was achieved using the Delphi method. Results: The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members. Conclusions: It is feasible to achieve European Consensus on key diagnostic and treatment issues using the Delphi method. This consensus embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe.

Long-Term Care Choices

Consumers today have many choices when it comes to considering long-term care – whether they wish to remain in their home or community or move into an assisted living program or nursing home. Choosing a long-term care option that best fits your individual situation can depend on the level of care you need, your location preferences, your lifestyle needs and your ability to pay. The best time to begin exploring your options is long before the need arises. That way, you can communicate your preferences to your loved ones and create a plan that meets your needs as well as your wishes.

Evaluation of an intravitreal fluocinolone acetonide implant versus standard systemic therapy in noninfectious posterior uveitis.

PURPOSE: To evaluate the safety and efficacy of an intravitreal fluocinolone acetonide (FA) implant compared with standard therapy in subjects with noninfectious posterior uveitis (NIPU). DESIGN: Randomized, controlled, phase 2b/3, open-label, multicenter superiority trial. PARTICIPANTS: Subjects with unilateral or bilateral NIPU. METHODS: One hundred forty subjects received either a 0.59-mg FA intravitreal implant (n = 66) or standard of care (SOC; n = 74) with either systemic prednisolone or equivalent corticosteroid as monotherapy (> or =0.2 mg/kg daily) or, if judged necessary by the investigator, combination therapy with an immunosuppressive agent plus a lower dose of prednisolone or equivalent corticosteroid (> or =0.1 mg/kg daily). MAIN OUTCOME MEASURES: Time to first recurrence of uveitis. RESULTS: Eyes that received the FA intravitreal implant experienced delayed onset of observed recurrence of uveitis (P<0.01) and a lower rate of recurrence of uveitis (18.2% vs. 63.5%; P< or =0.01) compared with SOC study eyes. Adverse events frequently observed in implanted eyes included elevated intraocular pressure (IOP) requiring IOP-lowering surgery (occurring in 21.2% of implanted eyes) and cataracts requiring extraction (occurring in 87.8% of phakic implanted eyes). No treatment-related nonocular adverse events were observed in the implant group, whereas such events occurred in 25.7% of subjects in the SOC group. CONCLUSIONS: The FA intravitreal implant provided better control of inflammation in patients with uveitis compared with systemic therapy. Intraocular pressure and lens clarity of implanted eyes need close monitoring in patients receiving the FA intravitreal implant.

Medical and pharmacological direct costs of a 9-week smoking cessation programme.

Background: Medical and pharmacological direct costs of cigarette smoking cessation programmes are not covered by health insurance in several countries despite documented cost-effectiveness. Design: prospective cost identification study of a 9-week programme in Switzerland. Methods: A total of 481 smokers were followed-up for 9 weeks. Socio-demographic characteristics, number of outpatient visits, dosage and frequency of use of nicotine replacement therapy (NRT) as well as date of relapse were prospectively collected. Individual cost of care until relapse or programme end as well as cost per week of follow-up were computed. Comparisons were carried out between the groups with or without relapse at the end of the programme. Results: Of the 209 men and 272 women included, 347 patients (72%) finished the programme. Among them, 240 patients (70%) succeeded in quitting and 107 patients (30%) relapsed. As compared with the group relapsing by the end of the programme, the group succeeding in quitting was more often living in a couple (68% vs. 55%, p = 0.029). Their mean weekly costs of visits were higher (CHF 81.2 ± 6.1 vs. 78.4 ± 7.6, p = 0.001), while their mean weekly costs for NRT were similar (CHF 24.2 ± 12.6 vs. 25.4 ± 15.9, p = 0.711). Mean total costs per week were similar (CHF 105.4 ± 15.4 vs. 103.8 ± 19.4, p = 0.252). More intensive NRT at week 4 increased the probability not to relapse at the end of the programme. Conclusions: Over 9 weeks, medical and pharmacological costs of stopping smoking are low. Good medical and social support as well as adequate NRT seem to play a role in successful quitting.

Meanings and perceptions of patient-centeredness in social work, nursing and medicine: A comparative study.

Answering patients' evolving, more complex needs has been recognized as a main incentive for the development of interprofessional care. Thus, it is not surprising that patient-centered practice (PCP) has been adopted as a major outcome for interprofessional education. Nevertheless, little research has focused on how PCP is perceived across the professions. This study aimed to address this issue by adopting a phenomenological approach and interviewing three groups of professionals: social workers (n = 10), nurses (n = 10) and physicians (n = 8). All the participants worked in the same department (the General Internal Medicine department of a university affiliated hospital). Although the participants agreed on a core meaning of PCP as identifying, understanding and answering patients' needs, they used many dimensions to define PCP. Overall, the participants expressed value for PCP as a philosophy of care, but there was the sense of a hierarchy of patient-centeredness across the professions, in which both social work and nursing regarded themselves as more patient-centered than others. On their side, physicians seemed inclined to accept their lower position in this hierarchy. Gieryn's concept of boundary work is employed to help illuminate the nature of PCP within an interprofessional context.

Hour of birth as a prognostic factor for perinatal death.

The analysis of the 220,540 births and 2152 perinatal deaths recorded in Switzerland between 1979 and 1981 showed a variation of perinatal mortality rates (PMR) according to the hour of birth. The PMR for babies born between 4 pm and 2 am was 12 per 1000, contrasting with a figure of 8.4 per 1000 for babies born between 2 am and 4 pm. This pattern, which was fairly constant throughout the week, was characterised by a slow and steady increase from the very early morning, reaching a maximum in the late evening. There was also an hour-to-hour variation in the proportion of babies born weighing less than 2500 g, with a maximum in the evening and a less pronounced peak in the morning: the mortality rates by birthweight were raised only in the evening. Since the availability of hospital staff and equipment also follows a circadian rhythm, the variation in PMR may be related to a circadian rhythm of quality of care or possibly to chronobiological or selection factors.

Dramatic response of vemurafenib-induced cutaneous lesions upon switch to dual BRAF/MEK inhibition in a metastatic melanoma patient.

BRAF inhibitory therapy is the mainstream treatment for BRAF mutant advanced melanoma. However vemurafenib, a type I mutant BRAF V600 inhibitor, induces an array of proliferative skin disorders from keratosis pilaris-like and keratoacanthoma-like lesions to locally aggressive cutaneous squamous cell carcinoma (cuSCC). Dual BRAF/MEK inhibition is known to lower the incidence of such manifestations, but it is not known whether it can counteract established lesions. Here we show, for the first time, a dramatic response and a restitution ad integro upon dual inhibition of a widespread proliferative affection induced by BRAF monotherapy. A 75-year-old woman was diagnosed with a BRAF V600E mutated metastatic melanoma. Following dacarbazine (DTIC) and ipilimumab, the patient was started on 960 mg twice daily vemurafenib (Zelboraf), which resulted in complete response, but the patient also developed grade IV skin toxicity. Despite dose-reduction to 720 mg twice daily the side effects persisted. We hypothesized that a switch to double inhibition of the mitogen-activated protein kinase pathway with dabrafenib and trametinib could lead to improvement of the skin lesions, while preserving tumor control. The patient was closely followed for changes in skin lesions. We witnessed a rapid regression followed by complete disappearance of all side effects of vemurafenib except for grade I fatigue. The biopsied skin lesions show regression of established keratoacanthoma-like lesions with signs of apoptosis. Switching from the current standard of care vemurafenib therapy to the double BRAF/MEK inhibition in BRAF mutant melanoma patients results in rapid disappearance of established proliferative skin disorders.

Clinically relevant quality measures for risk factor control in primary care: a retrospective cohort study.

BACKGROUND: Assessment of the proportion of patients with well controlled cardiovascular risk factors underestimates the proportion of patients receiving high quality of care. Evaluating whether physicians respond appropriately to poor risk factor control gives a different picture of quality of care. We assessed physician response to control cardiovascular risk factors, as well as markers of potential overtreatment in Switzerland, a country with universal healthcare coverage but without systematic quality monitoring, annual report cards on quality of care or financial incentives to improve quality. METHODS: We performed a retrospective cohort study of 1002 randomly selected patients aged 50-80 years from four university primary care settings in Switzerland. For hypertension, dyslipidemia and diabetes mellitus, we first measured proportions in control, then assessed therapy modifications among those in poor control. "Appropriate clinical action" was defined as a therapy modification or return to control without therapy modification within 12 months among patients with baseline poor control. Potential overtreatment of these conditions was defined as intensive treatment among low-risk patients with optimal target values. RESULTS: 20% of patients with hypertension, 41% with dyslipidemia and 36% with diabetes mellitus were in control at baseline. When appropriate clinical action in response to poor control was integrated into measuring quality of care, 52 to 55% had appropriate quality of care. Over 12 months, therapy of 61% of patients with baseline poor control was modified for hypertension, 33% for dyslipidemia, and 85% for diabetes mellitus. Increases in number of drug classes (28-51%) and in drug doses (10-61%) were the most common therapy modifications. Patients with target organ damage and higher baseline values were more likely to have appropriate clinical action. We found low rates of potential overtreatment with 2% for hypertension, 3% for diabetes mellitus and 3-6% for dyslipidemia. CONCLUSIONS: In primary care, evaluating whether physicians respond appropriately to poor risk factor control, in addition to assessing proportions in control, provide a broader view of the quality of care than relying solely on measures of proportions in control. Such measures could be more clinically relevant and acceptable to physicians than simply reporting levels of control.

Estimation of age- and stage-specific Catalan breast cancer survival functions using US and Catalan survival data

Background: During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods: Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results: We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion: Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On the other hand, we obtained detailed breast cancer survival functions that will be used for modeling the effect of screening and adjuvant treatments in Catalonia.

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...

Clinical features for diagnosis of pneumonia in children younger than 5 years: a systematic review and meta-analysis.

BACKGROUND: Pneumonia is the biggest cause of deaths in young children in developing countries, but early diagnosis and intervention can effectively reduce mortality. We aimed to assess the diagnostic value of clinical signs and symptoms to identify radiological pneumonia in children younger than 5 years and to review the accuracy of WHO criteria for diagnosis of clinical pneumonia. METHODS: We searched Medline (PubMed), Embase (Ovid), the Cochrane Database of Systematic Reviews, and reference lists of relevant studies, without date restrictions, to identify articles assessing clinical predictors of radiological pneumonia in children. Selection was based on: design (diagnostic accuracy studies), target disease (pneumonia), participants (children aged <5 years), setting (ambulatory or hospital care), index test (clinical features), and reference standard (chest radiography). Quality assessment was based on the 2011 Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. For each index test, we calculated sensitivity and specificity and, when the tests were assessed in four or more studies, calculated pooled estimates with use of bivariate model and hierarchical summary receiver operation characteristics plots for meta-analysis. FINDINGS: We included 18 articles in our analysis. WHO-approved signs age-related fast breathing (six studies; pooled sensitivity 0·62, 95% CI 0·26-0·89; specificity 0·59, 0·29-0·84) and lower chest wall indrawing (four studies; 0·48, 0·16-0·82; 0·72, 0·47-0·89) showed poor diagnostic performance in the meta-analysis. Features with the highest pooled positive likelihood ratios were respiratory rate higher than 50 breaths per min (1·90, 1·45-2·48), grunting (1·78, 1·10-2·88), chest indrawing (1·76, 0·86-3·58), and nasal flaring (1·75, 1·20-2·56). Features with the lowest pooled negative likelihood ratio were cough (0·30, 0·09-0·96), history of fever (0·53, 0·41-0·69), and respiratory rate higher than 40 breaths per min (0·43, 0·23-0·83). INTERPRETATION: Not one clinical feature was sufficient to diagnose pneumonia definitively. Combination of clinical features in a decision tree might improve diagnostic performance, but the addition of new point-of-care tests for diagnosis of bacterial pneumonia would help to attain an acceptable level of accuracy. FUNDING: Swiss National Science Foundation.