Epidemiology of amyotrophic lateral sclerosis and effect of riluzole on disease course.

OBJECTIVES: To assess the epidemiology of ALS in Austria and to evaluate the long-term effect of riluzole treatment on survival. METHODS: Hospital discharge and riluzole prescription databases were used to identify ALS cases from January 2008 to June 2012. Using the capture-recapture method we evaluated the incidence and prevalence of ALS and patients' survival in dependence of age, gender and riluzole treatment. RESULTS: The corrected incidence and prevalence of ALS were 3.13/100,000 person-years (95% CI, 2.77 to 3.50) and 9.14/100,000 persons (95% CI, 8.53 to 9.79), respectively. Median survival from diagnosis was 676 days (95% CI, 591 to 761). A younger age at diagnosis was associated with a longer survival. Gender did not appear to affect survival time. Riluzole therapy was associated with a survival advantage only for the initial treatment period. The adjusted hazard ratio of mortality for using riluzole increased continually over time resulting in an apparent reversal of its beneficial effect after 6 months of therapy. CONCLUSIONS: We report incidence and prevalence estimates that are on the upper end of the wide range discussed in literature. Riluzole seems to exert a beneficial effect only in the first 6 months of therapy.

Michigan Oncology Medical Home Demonstration Project: first-year results.

Launched in May 2012, the Michigan Oncology Medical Home Demonstration Project is an innovative multipractice oncology medical home model supported by payment reform. In the first year of the project, four oncology practices (29 physicians) participated and enrolled 85 patients receiving chemotherapy for a cancer diagnosis (96 new chemotherapy starts). By creating an oncology medical home for patients, the project reduced costs associated with unnecessary emergency room visits and inpatient admissions, with an average estimated cost savings of $550 per patient, while also enhancing payments to providers. The total estimated cost savings for year 1 was $46,228. In addition to the financial savings realized through reductions in emergency room visits and hospitalizations, the program also demonstrated that participating practices had high adherence to national and practice-selected guidelines, instituted advance care planning, and provided effective and standardized symptom management. The results are promising and provide evidence that community oncology practices will embrace the transformation to a patient-centered model with properly aligned incentives and administrative assistance.

Michigan Oncology Medical Home Demonstration Project: First-Year Results.

PURPOSE: The Michigan Oncology Medical Home Demonstration Project (MOMHDP) is an innovative multipractice oncology medical home model, supported by payment reform. Sponsored by Priority Health, Physician Resource Management, and ION Solutions, MOMHDP includes four oncology practices and 29 physicians. METHODS: Oncology practices used existing technologies, with MOMHDP providing evidence-based treatment guideline selection and compliance tracking, automated physician order entry, a patient portal, symptom management/standardized nurse triage, and advance care planning. To support changes in care and administrative models and to focus on quality, MOMHDP modifies provider payments. The program replaces the average sales price payment methodology with a drug acquisition reimbursement plus a care management fee, calculated to increase total drug reimbursement. Additionally, it reimburses for chemotherapy and treatment planning and advance care planning consultation. There is also a shared savings opportunity. MOMHDP will be enhanced in its second year to include a survivorship program, patient distress screening, imaging guidelines, and standardized patient satisfaction surveys. Priority Health patients receiving chemotherapy for a cancer diagnosis were recruited to the program. Results for this group were compared with a control group of patients from a prior period. RESULTS: In addition to the financial results, the project also accomplished the following: (1) adherence to practice-selected guidelines, (2) institution of advance care planning, (3) effective and standardized symptom management; and (4) payment reform. CONCLUSION: We have identified a number of critical success factors: strong payer/provider collaboration built on trust through transparent use and cost data; timing of clinical standardization must come from the practices, so they can effectively absorb new approaches; having comprehensive, written program documentation and consistently applied training facilitate practice understanding; existing, off-the-shelf technologies help control costs; independent clinical, administrative, and technical coordination improves provider/payer collaboration; everything takes longer than anticipated, including practice commitment, contracting, and technology implementation. Practices are willing to take on clinical standardization with payment reform. Neither practice size nor technology platform variation was a barrier to participation or success in the project. These results represent preliminary reporting from the first multipractice oncology medical home in the United States, to our knowledge, with payer support that includes payment reform. The results are promising, and the concept warrants further study, review, and reporting. [Table: see text].

Efficacy of a carrageenan nasal spray in patients with common cold: a randomized controlled trial.

BACKGROUND: The common cold is the most widespread viral infection in humans. Iota-carrageenan has previously shown antiviral effectiveness against cold viruses in clinical trials. This study investigated the efficacy of a carrageenan-containing nasal spray on the duration of the common cold and nasal fluid viral load in adult patients. METHODS: In a randomized, double-blind, placebo-controlled trial, 211 patients suffering from early symptoms of the common cold were treated for seven days. Application was performed three times daily with either a carrageenan-supplemented nasal spray or saline solution as placebo with an overall observation period of 21 days. The primary endpoint was the duration of disease defined as the time until the last day with symptoms followed by all other days in the study period without symptoms. During the study, but prior unblinding, the definition of disease duration was adapted from the original protocol that defines disease duration as the time period of symptoms followed by 48 hours without symptoms. RESULTS: In patients showing a laboratory-confirmed cold virus infection and adherence to the protocol, alleviation of symptoms was 2.1 days faster in the carrageenan group in comparison to placebo (p = 0.037). The primary endpoint that had been prespecified but was changed before unblinding was not met. Viral titers in nasal fluids showed a significantly greater decrease in carrageenan patients in the intention-to-treat population (p = 0.024) and in the per protocol population (p = 0.018) between days 1 and 3/4. CONCLUSIONS: In adults with common cold virus infections, direct local administration of carrageenan with nasal sprays reduced the duration of cold symptoms. A significant reduction of viral load in the nasal wash fluids of patients confirmed similar findings from earlier trials in children and adults. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80148028.

Oncology comparative effectiveness research: a multistakeholder perspective on principles for conduct and reporting.

Comparative effectiveness research (CER) can assist patients, clinicians, purchasers, and policy makers in making more informed decisions that will improve cancer care and outcomes. Despite its promise, the factors that distinguish CER from other types of evidence remain mysterious to many oncologists. One concern is whether CER studies will improve decision making in oncology or only add to the massive amount of research information that decision makers must sift through as part of their professional responsibilities. In this report, we highlight several issues that distinguish CER from the most common way evidence is generated for cancer therapy-phase I-III clinical trials. To identify the issues that are most relevant to busy decision makers, we assembled a panel of active professionals with a wide range of roles in cancer care delivery. This panel identified five themes that they considered most important for CER in oncology, as well as fundamental threats to the validity of individual CER studies-threats they termed the "kiss of death" for their applicability to practice. In discussing these concepts, we also touched upon the notion of whether cancer is special among health issues with regard to how evidence is generated and used.

Reflux symptom index and reflux finding score in otolaryngologic practice.

OBJECTIVES: To evaluate whether patients with abnormal Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) benefit from proton pump inhibitor (PPI) therapy. STUDY DESIGN: Open, multicenter, prospective longitudinal cohort study. METHODS: Patients with suspected reflux-associated laryngologic symptoms were evaluated by 40 community practice otolaryngologists using RSI and RFS. Patients were treated with pantoprazole 40-80 mg/d for 8-12 weeks if RSI was greater than 9 and RFS greater than 7. Pre- and posttherapeutic RSI and RFS were compared using Wilcoxon signed rank test and additionally controlled with the symmetry test of Bowker. RESULTS: A total of 1044 patients were included over a period of 20 months. Median total score of RSI before therapy was 12 and decreased to 3 (P≪0.001). Median total score of RFS before therapy was 16 and decreased to 6 (P≪0.001). Assessment of the treatment effect by otolaryngologists and patients was judged as being excellent in at least 50%. In 2% of the patients, gastrointestinal side effects were documented. CONCLUSION: RSI and RSF are easy to administer in the routine care of patients suspected of having laryngopharyngeal reflux. Patients identified by positive results of these tests have a high likelihood of excellent improvement after 8-12 weeks of PPI treatment. By implementation of RFS and RSI in daily use, most patients may not need time-consuming and cost-intensive examinations in the first-line assessment of LPR. These examinations can be reserved for nonresponders, and uncontrolled prescription of PPIs can be restricted.

Efficacy of individualized Chinese herbal medication in osteoarthrosis of hip and knee: a double-blind, randomized-controlled clinical study.

OBJECTIVES: The objective of this study was to determine the efficacy of individually designed herbal formulas according to the rules of Traditional Chinese Medicine (TCM) in patients with osteoarthritis of the hip and knee. DESIGN: This was a randomized, controlled, double-blind study with two parallel groups. SETTINGS/LOCATION: This study was conducted at the University-centre in Gars am Kamp/Austria and was organized by the Institute of TCM and Complementary Medicine of the Danube University Krems /Austria. SUBJECTS: The study comprised female and male patients with osteoarthritis of hip or knee aged between 45 and 75 years. INTERVENTIONS: Patients were randomized into a treatment with individualized, water-based herbal decoctions prepared in a standardized cooking process (Verum group) or to a treatment with nonspecific presumably ineffective, water-based herbal decoctions (Control group). OUTCOME MEASURES: The primary outcome was the comparison of change between the intervention groups in the Western Ontario and McMaster Universities lower limb global index questionnaire (WOMAC global index) between baseline and week 20. Secondary outcomes included subscales of WOMAC for pain (A), stiffness (B), and functional impairment (C) and general quality of life in the form of the SF-36 questionnaire. RESULTS: Altogether, 102 patients were randomized in this trial. The demographic and medical baseline characteristics were comparable in the 2 groups. The change of the WOMAC global index and all three subscales was significant in both groups between week 20 and baseline (verum group, global WOMAC: at baseline 47 [SD ± 11.8] and at week 20: 24 (SD ± 18.3); change of mean 23; p > 0.001; control group; global WOMAC: at baseline: 48 (SD ± 14.7) and at week 20: 25 (SD ± 18.3); change of mean 23; p > 0.001). However, there was no significant difference (p = 0.783) between the treatment groups. There were significant changes in the subscales "physical functioning," "bodily pain," "vitality," "social-functioning," and "role-physical" of the SF-36 in both study groups between 20 weeks and baseline, but again no significant difference between the groups. There were no drug-related serious adverse events. CONCLUSIONS: While the individual prescription consisting of medicinal herbs according to TCM diagnosis investigated in this trial tend to improve the osteoarthritis, the same effect was also achieved with the nonspecific prescription.

Composite biclonal marginal zone lymphoma of lung and chronic lymphocytic leukemia: pathologic, phenotypic, cytogenetic, and molecular study.

The simultaneous diagnosis of marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare. This study reports a patient with composite synchronous biclonal occurrence of MALT lymphoma of the lung and CLL/SLL. The morphology of the lung and peripheral blood showed features of MALT lymphoma and CLL, respectively. The cytogenetic evaluation of the lung specimen revealed a t(1;14) (p22;q32), a frequent genetic abnormality in MALT lymphoma. Flow cytometry analysis of the lung tissue showed features of MALT lymphoma and CLL/SLL with different light chain restriction, whereas the blood showed phenotypic evidence of CLL/SLL. Fluorescence in situ hybridization study of the blood showed a deletion of 13q14 and 17p13. Immunoglobulin heavy chain (IgH) gene rearrangement study of the lung tissue and blood showed a monoclonal IgH gene rearrangement with distinct light chain restriction, suggesting that the immunophenotypically different cell populations originated from separate clones.

NIMRA-survey: NSAIDs impact on mortality. Results of an Austrian Survey in 2006.

This survey is based on a sample of over two thousand patients who were in the first eight months of the year 2006 hospitalised due to a diagnosis of coronary heart disease (CHD) or rheumatic diseases (RD). Their demographic, anamnestic data were assessed according to a prospectively defined analysis plan together with the associated mortality. The main survey questions--whether the data suggest an association between rheumatism as compared to CHD and mortality and which conclusions with respect to NSAID (non-steroidal anti-inflammatory drug) consumption can be drawn in this pilot project--can be answered with some degree of statistical robustness bearing in mind the sampling uncertainties and the omnipresent fuzziness of medical data including mortality. Rheumatism is generally associated with a lower risk of death (1%) as compared to CHD patients with a death risk of 3% (p < 0.01). As there are many confounding risk factors which show statistically highly significant effects and might be associated with substantial interactions on the mortality outcome it seems advisable to interpret the available data with caution and take this as the main results of a survey which is characterised mainly by its pilot nature. Additional research in this area with more sophisticated tools and based on much larger samples is judged to provide final and conclusive epidemiologic evidence. For the time being NSAIDs did not imply any relevant increases in mortality in RD or CHD patients as compared to patients who were not prescribed NSAIDs. Coronary heart diseases constitute a relevant and significant prognostic factor for an increased mortality as compared to rheumatic diseases.

A meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis.

BACKGROUND: This systematic meta-analysis on randomized controlled trials with diacerein was performed to provide an evidence-based assessment of its symptomatic efficacy in the treatment of osteoarthritis. METHODS: Electronic databases were searched for randomized controlled trials with diacerein. A manual review of the literature, abstracts, and posters was also conducted. Unpublished final reports were obtained from the manufacturer. Only studies performed in knee and/or hip osteoarthritis were chosen for review. Study inclusion, quality scoring, and data extraction were performed by 2 reviewers independently. Objectives for analysis comprised pain, function, escape medication use, global efficacy, and safety ratings by patients and investigators. Specific study periods, such as the active treatment period and the treatment-free follow-up period (when present), were analyzed. Statistical analyses were based on the intention-to-treat principle as far as possible, and acknowledged tests were used for data analysis. RESULTS: A total of 23 studies were identified, 19 of which were included. Diacerein was significantly superior to placebo during the active treatment phase (Glass score, 1.50 [95% confidence interval, 0.80-2.20]). Both diacerein and nonsteroidal anti-inflammatory drugs (NSAIDs) were similarly efficacious during the treatment period; however, diacerein, but not NSAIDs, showed a carryover effect, persisting up to 3 months after treatment, with a significant analgesic-sparing effect during the follow-up period (Glass score, 2.06 [95% confidence interval, 0.66-3.46]). Tolerability assessment revealed no differences between diacerein and NSAIDs, although the latter showed more severe events. CONCLUSION: This systematic meta-analysis provides evidence for the symptomatic efficacy of diacerein in the treatment of knee and hip osteoarthritis, with reasonable tolerability.

Changes in management techniques and patterns of disease recurrence over time in patients with breast carcinoma treated with breast-conserving therapy at a single institution.

BACKGROUND: The authors reviewed changes in the initial clinical presentation, management techniques, and patterns of disease recurrence over time (1981-1996) in patients with breast carcinoma treated with breast-conserving therapy (BCT) at a single institution. The goals of the current study were to determine the frequency and use of optimal local and systemic therapy techniques and to evaluate the impact of these changes on treatment efficacy. METHODS: Six hundred seven patients with American Joint Committee on Cancer Stage I or II invasive breast carcinomas treated with BCT at William Beaumont Hospital (Royal Oak, MI) constituted the study population. All patients received at least an excisional biopsy of the primary tumor, an axillary lymph node staging procedure, and postoperative radiotherapy (RT) (a median tumor bed dose of 61 Gray [Gy] was administered). All sides were reviewed by one pathologist. Numerous clinicopathologic and treatment-related factors were analyzed to monitor changes that occurred over time. Changes in patterns of disease recurrence and treatment efficacy over time also were analyzed. RESULTS: Over the time period analyzed, changes at initial presentation included an increase in the mean age at diagnosis (age 56.1 years vs. 61.4 years; P < 0.001), a decrease in the number of patients with clinically palpable tumors (78% vs. 36%; P < 0.001), a decrease in the mean tumor size (2.2 cm vs. 1.6 cm; P < 0.001), but no change in the percentage of patients with negative lymph nodes (79% vs. 78%; P = 0.83). No differences over time were observed in mean tumor grade (2.0 vs. 1.9; P = 0.2) or the presence of angiolymphatic invasion (27% vs. 26%; P = 0.25). Changes in surgical management and pathologic assessment included the more frequent use of reexcision (46% vs. 81%; P < 0.001), larger mean total volumes of breast tissue specimens excised (115 cm3 vs. 189 cm3; P = 0.001), a larger percentage of patients with final negative surgical margins (74% vs. 97%; P < 0.001), and a small increase in the mean number of lymph nodes excised (13.8 lymph nodes vs. 14.1 lymph nodes; P = 0.01). The only other significant change in the pathologic management of patients over time included a doubling in the mean number of slides examined (10.6 slides vs. 21.1 slides; P < 0.001). Changes in adjuvant local and systemic therapy included an increase in the percentage of patients treated with > 60 Gy to the tumor bed (66% vs. 95%; P < 0.001), a doubling in the mean number of days from the last surgery to the start of RT (24 days vs. 50 days; P < 0.001), and a decrease in the use of regional lymph node RT (24% vs. 8%; P < 0.001). The use of adjuvant tamoxifen increased from 10% to 61% (P < 0.001). Finally, improvements were observed in the 5-year and 12-year actuarial rates of local disease recurrence (8% vs. 1% and 21% vs. 9%, respectively; P = 0.001) and distant metastases (12% vs. 4% and 22% vs. 9%, respectively; P = 0.006). No changes in the mean number of years to ipsilateral (6.5 years vs. 6.4 years; P = 0.59) or distant disease recurrence (4.6 years vs. 3.8 years; P = 0.73) were observed. CONCLUSIONS: The impact of screening mammography and substantial changes in surgical, pathologic, RT, and systemic therapy recommendations were observed over time in the study population. These changes were associated with improvements in 5-year and 12-year local and distant control rates and suggested that improvements in outcome can be realized through adherence to best practice guidelines and continuous monitoring of treatment outcome data.

[Adverse effects of non-steroidal anti-inflammatory drugs. A prevalence study in Austria]. / Unerwünschte Wirkungen unter nichtsteroidalen Antiphlogistika. Eine Prävalenzstudie aus Osterreich.

OBJECTIVE: Gastrointestinal side effects are the limiting factor in the prescription of non-steroidal antirheumatic drugs (NSAID). However, there are no recent data from Austria. The aim of this prevalence study was therefore to assess the gastrointestinal risk from NSAID in Austria. METHODS: A total of 1347 patients were observed in an outpatient setting between March 2000 and February 2001. Side effects from NSAID were documented by questionnaire at two time points with a mean interval of 31 days. Documented data were analysed descriptively using an explorative strategy. The prevalence of side effects was compared to data from literature. RESULTS: Side effects were reported by 18.1% of the patients, severe gastro-intestinal complications (ulcer, bleeding, perforation) were diagnosed in 0.7%. Prescription of effective GI-protection (proton pump inhibitors, misoprostole, famotidin in high dose) was seen in only one third of the patients at risk. CONCLUSION: The prevalence of severe gastrointestinal side effects by NSAIDs assessed in our study was clearly lower than the prevalence reported in the Anglo-American literature. This may be due to a different prescription behaviour: about 75% of the patients took Diclofenac, lbuprofen or Meloxicam, drugs which have a very low potential of gastrointestinal complications. However, more information for general practitioners is needed yet to sufficiently protect patients at gastrointestinal risk from NSAID.