Precision oncology: a clinical and patient perspective.

Molecular characterization of tumors has shifted cancer treatment strategies away from nonspecific cytotoxic treatment of histology-specific tumors toward targeting of actionable mutations that can be found across multiple cancer types. The development of high-throughput technologies such as next-generation sequencing, combined with decision support applications and availability of patient databases, has provided tools that optimize disease management. Precision oncology has proven success in improving outcomes and quality of life, as well as identifying and overcoming mechanisms of drug resistance and relapse. Addressing challenges that impede its use will improve matching of therapies to patients. Here we review the current status of precision oncology medicine, emphasizing its impact on patients - what they understand about precision oncology medicine and their hopes for the future.

Lay abstract Precision oncology offers individualized treatment of cancer on a per-patient basis, based on the unique DNA fingerprint of a patient's cancer. New, advanced technologies for DNA sequencing have led to rapid advancement in developing novel therapies. Decision-making tools have followed pace, leading to improved matching of therapy to patient, ultimately improving outcomes (including quality of life), building trust between patient and physician, and increasing hope for the future.

Update on the ESCEO recommendation for the conduct of clinical trials for drugs aiming at the treatment of sarcopenia in older adults.

BACKGROUND: In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. AIMS: The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. METHODS: This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. RESULTS: The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure. CONCLUSION: The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.

A single intra-articular injection of 2.0% non-chemically modified sodium hyaluronate vs 0.8% hylan G-F 20 in the treatment of symptomatic knee osteoarthritis: A 6-month, multicenter, randomized, controlled non-inferiority trial.

OBJECTIVES: The aim of the study was to demonstrate the non-inferiority of a single intra-articular injection of 2.0% non-chemically modified sodium hyaluronate (SH) vs 0.8% hylan G-F 20 (control) in symptomatic knee osteoarthritis. DESIGN: This was a double-blind, randomized, controlled trial conducted in patients with painful tibiofemoral osteoarthritis (American College of Rheumatology criteria) with insufficient response or intolerance to first-line analgesics and regular non-steroidal anti-inflammatory drugs. Subjects received a single intra-articular injection of either SH or hylan G-F 20. The primary outcome was the 6-month change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale (WOMAC A), with a pre-specified lower margin for non-inferiority of 8 mm. RESULTS: Of the 292 patients randomized (SH: 144), 288 received an injection (SH: 142), 266 completed the study (SH: 134). In the Per Protocol dataset (SH: 113, control: 112), the WOMAC A change at 6 months was -34.3 mm (95% confidence interval (CI): -37.8, -30.8) and -36.2 mm (95% CI: -40.3, -32.1) for the SH and hylan G-F 20 patients, respectively (P = 0.5). The intergroup difference was -1.9 mm (95% CI: -7.3, 3.5). Results were similar in the Full Analysis Set (SH: 139, control: 141) with a difference between the groups of -2.9 mm (95% CI: -7.9, 2.2). A total of 31.3% of the injected patients reported a treatment-emergent adverse event, including injection site reactions (pain, inflammation or effusion) which occurred in 8.5% of the SH patients vs 13.0% of the hylan G-F 20 patients. No serious reactions were reported. CONCLUSIONS: This clinical trial demonstrated the non-inferiority of a single intra-articular injection of SH vs hylan G-F 20 on the WOMAC A change from baseline at 6 months.

Moving Towards Accountability for Reasonableness - A Systematic Exploration of the Features of Legitimate Healthcare Coverage Decision-Making Processes Using Rare Diseases and Regenerative Therapies as a Case Study.

BACKGROUND: The accountability for reasonableness (A4R) framework defines 4 conditions for legitimate healthcare coverage decision processes: Relevance, Publicity, Appeals, and Enforcement. The aim of this study was to reflect on how the diverse features of decision-making processes can be aligned with A4R conditions to guide decision-making towards legitimacy. Rare disease and regenerative therapies (RDRTs) pose special decision-making challenges and offer therefore a useful case study. METHODS: Features operationalizing each A4R condition as well as three different approaches to address these features (cost-per-QALY-focused and multicriteria-based) were defined and organized into a matrix. Seven experts explored these features during a panel run under the Chatham House Rule and provided general and RDRT-specific recommendations. Responses were analyzed to identify converging and diverging recommendations. RESULTS: Regarding Relevance, recommendations included supporting deliberation, stakeholder participation and grounding coverage decision criteria in normative and societal objectives. Thirteen of 17 proposed decision criteria were recommended by a majority of panelists. The usefulness of universal cost-effectiveness thresholds to inform allocative efficiency was challenged, particularly in the RDRT context. RDRTs raise specific issues that need to be considered; however, rarity should be viewed in relation to other aspects, such as disease severity and budget impact. Regarding Publicity, panelists recommended transparency about the values underlying a decision and value judgements used in selecting evidence. For Appeals, recommendations included a life-cycle approach with clear provisions for re-evaluations. For Enforcement, external quality reviews of decisions were recommended. CONCLUSION: Moving coverage decision-making processes towards enhanced legitimacy in general and in the RDRT context involves designing and refining approaches to support participation and deliberation, enhancing transparency, and allowing explicit consideration of multiple decision criteria that reflect normative and societal objectives.

Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

BACKGROUND: Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are an important drug class in the treatment armamentarium for osteoarthritis (OA). OBJECTIVE: We aimed to re-assess the safety of various SYSADOAs in a comprehensive meta-analysis of randomized placebo-controlled trials, using, as much as possible, data from full safety reports. METHODS: We performed a systematic review and random-effects meta-analyses of randomized, double-blind, placebo-controlled trials that assessed adverse events (AEs) with various SYSADOAs in patients with OA. The databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus were searched. The primary outcomes were overall severe and serious AEs, as well as AEs involving the following Medical Dictionary for Regulatory Activities (MedDRA) system organ classes (SOCs): gastrointestinal, cardiac, vascular, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue, renal and urinary system. RESULTS: Database searches initially identified 3815 records. After exclusions according to the selection criteria, 25 studies on various SYSADOAs were included in the qualitative synthesis, and 13 studies with adequate data were included in the meta-analyses. Next, from the studies previously excluded according to the protocol, 37 with mainly oral nonsteroidal anti-inflammatory drugs (NSAIDs) permitted as concomitant medication were included in a parallel qualitative synthesis, from which 18 studies on various SYSADOAs were included in parallel meta-analyses. This post hoc parallel inclusion was conducted because of the high number of studies allowing concomitant anti-OA medications. Indeed, primarily excluding studies with concomitant anti-OA medications was crucial for a meta-analysis on safety. The decision for parallel inclusion was made for the purpose of comparative analyses. Glucosamine sulfate (GS), chondroitin sulfate (CS) and avocado soybean unsaponifiables (ASU; Piascledine®) were not associated with increased odds for any type of AEs compared with placebo. Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of total AEs (odds ratio [OR] 2.22; 95% confidence interval [CI] 1.58-3.13; I2 = 52.8%), gastrointestinal disorders (OR 2.85; 95% CI 2.02-4.04; I2 = 62.8%) and renal and urinary disorders (OR 3.42; 95% CI 2.36-4.96; I2 = 17.0%) compared with placebo. In studies that allowed concomitant OA medications, diacerein was associated with significantly more dermatological disorders (OR 2.47; 95% CI 1.42-4.31; I2 = 0%) and more dropouts due to AEs (OR 3.18; 95% CI 1.85-5.47; I2 = 13.4%) than was placebo. No significant increase in serious or severe AEs was found with diacerein versus placebo. CONCLUSIONS: GS and CS can be considered safe treatments for patients with OA. All eligible studies on ASU included in our analysis used the proprietary product Piascledine® and allowed other anti-OA medications; thus, the safety of ASU must be confirmed in future studies without concomitant anti-OA medications. Given the safety concerns with diacerein, its usefulness in patients with OA should be assessed, taking into account individual patient characteristics.

Safety of Paracetamol in Osteoarthritis: What Does the Literature Say?

Osteoarthritis (OA) is a major cause of pain and physical disability in adults, and an increasingly common disease given its associations with aging and a growing obese/overweight population. Paracetamol is widely recommended for analgesia at an early stage in the management of OA, and, although frequently prescribed, evidence suggests the efficacy of paracetamol for OA pain is low. Furthermore, there have been recent concerns over the safety profile of paracetamol, with reports of gastrointestinal, cardiovascular, hepatic and renal adverse events. This narrative review summarizes recent literature on the benefits and harms of paracetamol for OA pain. Data on long-term paracetamol safety are derived largely from observational evidence, and are difficult to interpret given the potential biases of such data. Nonetheless, a considerable degree of toxicity is associated with paracetamol use among the general population, especially at the upper end of standard analgesic doses. Paracetamol is linked to liver function abnormalities and there is evidence for liver failure associated with non-intentional paracetamol overdose. Safety data for paracetamol use in the older population (aged >65 years) are sparse; however, there is some evidence that frail elderly people may have impaired paracetamol clearance. Given that the analgesic benefit of paracetamol in OA joint pain is uncertain and potential safety issues have been raised, more careful consideration of its use is required.

Safety of Intra-articular Hyaluronic Acid Injections in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

BACKGROUND: Some controversy exists regarding the safety of intra-articular hyaluronic acid (IAHA) in the management of osteoarthritis (OA). OBJECTIVE: The objective of this study was to re-assess the safety profile of IAHA in patients with OA, through a comprehensive meta-analysis of randomized, placebo-controlled trials. METHODS: A comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with IAHA in patients with OA were eligible for inclusion. Authors and/or study sponsors were contacted to obtain the full report of AEs. The primary outcomes were overall severe and serious AEs, as well as the following MedDRA System Organ Class (SOC)-related AEs: gastrointestinal, cardiac, vascular, respiratory, nervous system, skin and subcutaneous tissue disorders, musculoskeletal, renal and urinary disorders, infections and infestations, and hypersensitivity reaction. RESULTS: Database searches initially identified 1481 records. After exclusions according to the selection criteria, 22 studies were included in the qualitative synthesis, and nine studies having adequate data were ultimately included in the meta-analysis. From the studies excluded according to the pre-specified selection criteria, 21 with other pharmacological OA treatments permitted during the trials were a posteriori included in a parallel qualitative synthesis, from which eight studies with adequate data were finally included in a parallel meta-analysis. Since this meta-analysis was designed to assess safety, the exclusion criterion on concomitant anti-OA medication was crucial. However, due to the high number of studies that allowed mainly concomitant oral non-steroidal anti-inflammatory drugs (NSAIDs), we decided to include them in a post hoc parallel analysis in order to compare the results from the two analyses. No statistically significant difference in odds was found between IAHA and placebo for all types of SOC-related disorders, except for infections and infestations, for which significantly lower odds were found with IAHA compared with placebo, both overall (odds ratio [OR] = 0.61, 95% confidence interval [CI] 0.40-0.93; I2 = 0%) and in studies without concomitant anti-OA medication (OR = 0.49, 95% CI 0.27-0.89). There were significant increased odds of reporting serious AEs with IAHA compared with placebo, both overall (OR = 1.78, 95% CI 1.21-2.63; I2 = 0%) and in studies with concomitant anti-OA medication (OR = 1.78, 95% CI 1.10-2.89), but not in studies without concomitant anti-OA medication (OR = 1.78, 95% CI 0.92-3.47). CONCLUSIONS: Using the available data on studies without any concomitant anti-OA medication permitted during clinical trials, IAHA seems not to be associated with any safety issue in the management of OA. However, this evidence was associated with only a "low" to "moderate" certainty. A possible association with increased risk of serious AEs, particularly when used with concomitant OA medications, requires further investigation.

Effect of unloading brace treatment on pain and function in patients with symptomatic knee osteoarthritis: the ROTOR randomized clinical trial.

Evidence is still inconclusive for the benefits of bracing in patients with knee osteoarthritis. To assess the effect of REBEL RELIEVER unloading knee brace in conservative treatment of knee osteoarthritis, a randomized controlled trial was conducted in 67 patients with symptomatic medial knee osteoarthritis, who randomly received 6-week treatment with either REBEL RELIVER unloading knee brace + usual care (Brace group, N = 32) or usual care alone (Control group, N = 35). Primary outcome was the global last 24h-pain relief (100-mm visual analogic scale [VAS]) at 6 weeks. Secondary endpoints included pain on motion (100-mm VAS), function (Lequesne index), safety and observance. At 6 weeks, mean [SD] last 24h-pain decreased significantly more in Brace group versus Control group (-41.35 [3.37] vs -15.37 [3.23], difference -25.98, 95% CI -41.64 to -10.33, P < 0.0001). Higher mean [SD] pain on motion decrease (-51.91 [3.49] vs -19.91 [3.34], difference -32.01, 95% CI -48.21 to -15.80, P < 0.0001) and better improvement of Lequesne index score (-5.8 [0.5] vs -2.3 [0.5], difference -3.5, 95% CI -5.0 to -2.0, P < 0.0001) were observed in Brace group. Safety and observance to the brace were excellent. The additive clinical benefit of wearing REBEL RELIEVER unloading knee brace was demonstrated in knee osteoarthritis patients.

Effect of an Institutional Medication Adherence Program for Long-Acting Injectable Risperidone on Adherence and Psychiatric Hospitalizations: Evidence from a Prospective Cohort Study.

BACKGROUND: Long-acting injectable (LAI) atypical antipsychotics are associated with improved adherence and reduced relapse rates in schizophrenia but reminder-based interventions may further improve outcomes. OBJECTIVES: To assess an institutional medication adherence program's (IMAP) effectiveness on adherence and psychiatric hospitalizations among schizophrenia patients taking risperidone LAI (RLAI). METHODS: Between 2009 and 2010, we recruited patients meeting DSM-IV criteria for schizophrenia treated with RLAI receiving outpatient care from psychiatric centres in France. The IMAP consisted of calling patients 48 hours prior to their scheduled RLAI injections and within 3 days of a missed appointment. Centres applying the IMAP to ≥50% of scheduled patient injections were deemed compliant. Patients were followed up to one year for adherence (≥80% of scheduled RLAI injections received within 5 days of the scheduled date) and psychiatric hospitalizations. RESULTS: Among 506 patients recruited from 36 centres, the hospitalization rate was 32.5 per 100 person-years. 15 centres treating 243 patients were IMAP compliant and 21 centres treating 263 patients were not. IMAP compliance was associated with lower psychiatric hospitalization rates (crude RR: 0.64 [95% CI: 0.44-0.93]; adjusted RR: 0.78 [95% CI: 0.47-1.27]). Nearly 75% of patients were adherent to RLAI. While patient adherence had little impact on hospitalization rates (adjusted RR: 0.92 [95% CI: 0.59-1.44]), IMAP compliance was more effective among non-adherent (adjusted RR: 0.45 [95% CI: 0.16-1.28]) than adherent (adjusted RR: 0.88 [95% CI: 0.51-1.53]) patients. CONCLUSIONS: IMAPs may improve patient adherence and reduce psychiatric hospitalizations, particularly among patients with difficulties adhering to LAI antipsychotics.

Homeopathic medical practice for anxiety and depression in primary care: the EPI3 cohort study.

BACKGROUND: The purpose of the study was to compare utilization of conventional psychotropic drugs among patients seeking care for anxiety and depression disorders (ADDs) from general practitioners (GPs) who strictly prescribe conventional medicines (GP-CM), regularly prescribe homeopathy in a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho). METHODS: This was one of three epidemiological cohort studies (EPI3) on general practice in France, which included GPs and their patients consulting for ADDs (scoring 9 or more in the Hospital Anxiety and Depression Scale, HADS). Information on all medication utilization was obtained by a standardised telephone interview at inclusion, 1, 3 and 12 months. RESULTS: Of 1562 eligible patients consulting for ADDs, 710 (45.5 %) agreed to participate. Adjusted multivariate analyses showed that GP-Ho and GP-Mx patients were less likely to use psychotropic drugs over 12 months, with Odds ratio (OR) = 0.29; 95 % confidence interval (CI): 0.19 to 0.44, and OR = 0.62; 95 % CI: 0.41 to 0.94 respectively, compared to GP-CM patients. The rate of clinical improvement (HADS <9) was marginally superior for the GP-Ho group as compared to the GP-CM group (OR = 1.70; 95 % CI: 1.00 to 2.87), but not for the GP-Mx group (OR = 1.49; 95 % CI: 0.89 to 2.50). CONCLUSIONS: Patients with ADD, who chose to consult GPs prescribing homeopathy reported less use of psychotropic drugs, and were marginally more likely to experience clinical improvement, than patients managed with conventional care. Results may reflect differences in physicians' management and patients' preferences as well as statistical regression to the mean.

Utilization of psychotropic drugs by patients consulting for sleeping disorders in homeopathic and conventional primary care settings: the EPI3 cohort study.

BACKGROUND: Utilization of sedative hypnotic drugs for sleeping disorders (SD) raises concerns, particularly among older people. This study compared utilization of conventional psychotropic drugs for SD among patients seeking care from general practitioners (GPs) who strictly prescribe conventional medications (GP-CM), regularly prescribe homeopathy in a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho). METHODS: This was a French population-based cohort study of GPs and their patients consulting for SD, informed through the Pittsburgh sleep quality index (PSQI) questionnaire. Information on psychotropic drugs utilization was obtained from a standardized telephone interview at inclusion, one, three and 12 months. RESULTS: 346 patients consulting for SD were included. Patients in the GP-Ho group experienced more often severe SD (41.3%) than patients in the GP-CM group (24.3%). Adjusted multivariate analyses showed that patients who chose to be managed by GP-Ho were less likely to use psychotropic drugs over 12 months as opposed to the GP-CM group, with Odds ratio (OR) = 0.25; 95% confidence interval (CI): 0.14 to 0.42. Patients in the GP-Mx group also used less psychotropic drugs but the result was not statistically significant (OR = 0.67; 95% CI: 0.39-1.16). Rates of clinical improvement of the SD did not differ between groups. CONCLUSIONS: Patients with SD who chose to consult GPs certified in homeopathy consumed less psychotropic drugs and had a similar evolution of their condition to patients treated with conventional medical management. This result may translate in a net advantage with reduction of adverse events related to psychotropic drugs.

Post-approval studies in France, challenges facing medical devices.

Medical devices are characterized notably by a wide heterogeneity (from tongue depressors to hip prostheses, and from non-implantable to invasive devices), a short life cycle with recurrent incremental innovations (from 18 months to 5 years), and an operator-dependent nature. The objective of the current round table was to develop proposals and recommendations concerning the prerequisites needed in order to meet the French health authorities expectations concerning requests for post-approval studies for medical devices, required in cases where short and long-term consequences are unknown. These studies, which are the responsibility of the manufacturer or the distributor of the medical device, are designed to confirm the role of the medical device in the therapeutic management strategy in a real-life setting. There are currently approximately 150 post-approval studies underway, mainly concerning class III devices, and the majority face difficulties implementing the study or meeting the study objectives. In light of this, the round table endeavored to clearly identify the conditions for implementation of post-approval studies specific to the characteristics of medical devices. Various areas of progress have been envisaged to improve the performance of these studies, and by consequence, the efficiency of reimbursement of medical devices by the national health insurance. These include providing manufacturers with the opportunity to better anticipate post-approval requirements, defining a study-specific primary objective, integrating a phase allowing dialogue between the manufacturer, the health authorities and the scientific committee, and increasing awareness and training of health professionals on the impact of post-approval clinical studies in terms of the reimbursement of medical devices by the national insurance.

Characterization of knee osteoarthritis in Latin America. A comparative analysis of clinical and health care utilization in Argentina, Brazil, and Mexico / Características de la artrosis de la rodilla en América Latina. Análisis comparativo de la utilización de servicio clínicos y cuidados de la salud en Argentina, Brasil y México

Background: The burden of knee osteoarthritis (OA) in Latin America is unknown. Objective: To determine the demographic, clinical, and therapeutic characteristics of patients with OA in Argentina, Brazil, and Mexico. Material and methods: This is an observational, cross-sectional study of patients with symptomatic knee OA referred from first care medical centers to Rheumatology departments. Results: We included 1210 patients (Argentina 398, Brazil 402, Mexico 410; mean age 61.8 [12] years; 80.8% females). Knee OA pain lasted for 69 months; the duration and severity of the last episode were 190 days and (SD 5.2 [3.3]; 74% had functional limitations, but very few patients lost their job because of knee OA. Around 71% had taken medications, but 63% relied on their own pocket to afford knee OA cost. Most demographic and clinical variables differed across countries, particularly the level of pain, disability, treatment, and access to care. The variable country of origin influenced the level of pain, disability, and NSAIDs use in logistic regression models; age, pain, treatment, and health care access influenced at least 2 of the models. Conclusions: The burden of knee OA in Latin American depends on demographic, clinical, and therapeutic variables. The role of such variables differs across countries. The level of certain variables is significantly influenced by country of origin and health care system

Antecedentes: La carga de la artrosis de rodilla (OA) en América Latina se desconoce. Objetivo: Determinar las características demográficas, clínicas y terapéuticas de los pacientes con OA en Argentina, Brasil y México. Material y métodos: Se trata de un estudio observacional, transversal, de pacientes con OA sintomática que son derivados de centros de atención primeria a los departamentos de reumatología. Resultados: Se incluyeron 1.210 pacientes (Argentina 398, Brasil 402, México 410), con una media de edad de 61,8 (12) años; el 80,8% eran mujeres. El dolor de la OA de rodilla se prolongó durante 69 meses, la duración y la gravedad del último episodio fueron 190 días, y (DS 5,2 [3,3]; el 74% tenían limitaciones funcionales, pero muy pocos pacientes perdieron su empleo a causa de la OA de rodilla. El 71% había tomado medicamentos, pero el 63% lo pagó de su propio bolsillo. La mayoría de las variables demográficas y clínicas difieren entre los países, en particular el nivel de dolor, la discapacidad, el tratamiento y el acceso a la atención. La variable de país de origen influyó en el nivel de dolor, discapacidad y AINE a utilizar en los modelos de regresión logística; la edad, el dolor, el tratamiento y el acceso a la atención de salud influyó por lo menos a 2 de los modelos. Conclusiones: La carga de la OA de rodilla en América Latina depende de las variables demográficas, clínicas y terapéuticas. El papel de estas variables difiere entre países. El nivel de ciertas variables se ve influido significativamente por el país de origen y el sistema de atención de la salud (AU)

Management of upper respiratory tract infections by different medical practices, including homeopathy, and consumption of antibiotics in primary care: the EPI3 cohort study in France 2007-2008.

BACKGROUND: Prescribing of antibiotics for upper respiratory tract infections (URTI) varies substantially in primary care. OBJECTIVES: To describe and compare antibiotic and antipyretic/anti-inflammatory drugs use, URTI symptoms' resolution and occurrence of potentially-associated infections in patients seeking care from general practitioners (GPs) who exclusively prescribe conventional medications (GP-CM), regularly prescribe homeopathy within a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho). METHOD: The EPI3 survey was a nationwide population-based study of a representative sample of 825 GPs and their patients in France (2007-2008). GP recruitment was stratified by self-declared homeopathic prescribing preferences. Adults and children with confirmed URTI were asked to participate in a standardized telephone interview at inclusion, one-, three- and twelve-month follow up. Study outcomes included medication consumption, URTI symptoms' resolution and potentially-associated infections (sinusitis or otitis media/externa) as reported by patients. Analyses included calibration to account for non-respondents and groups were compared using multivate analyses adjusting for baseline differences with a propensity score. RESULTS: 518 adults and children with URTI (79.3% rhinopharyngitis) were included (36.9% response rate comparable between groups). As opposed to GP-CM patients, patients in the GP-Ho group showed significantly lower consumption of antibiotics (Odds ratio (OR) = 0.43, 95% confidence interval (CI): 0.27-0.68) and antipyretic/anti-inflammatory drugs (OR = 0.54, 95% CI: 0.38-0.76) with similar evolution in related symptoms (OR = 1.16, 95% CI: 0.64-2.10). An excess of potentially-associated infections (OR = 1.70, 95% CI: 0.90-3.20) was observed in the GP-Ho group (not statistically significant). No difference was found between GP-CM and GP-Mx patients. CONCLUSION: Patients who chose to consult GPs certified in homeopathy used less antibiotics and antipyretic/anti-inflammatory drugs for URTI than those seen by GPs prescribing conventional medications. No difference was observed in patients consulting GPs within mixed-practice. A non-statistically significant excess was estimated through modelling for associated infections in the GP-Ho group and needs to be further studied.

Characteristics of patients consulting their regular primary care physician according to their prescribing preferences for homeopathy and complementary medicine.

BACKGROUND: Homeopathic care has not been well documented in terms of its impact on patients' utilization of drugs or other complementary and alternative medicines (CAM). The objective of this study was to describe and compare patients who visit physicians in general practice (GPs) who prescribe only conventional medicines (GP-CM), regularly prescribe homeopathy within a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho). MATERIAL AND METHODS: The EPI3-LASER study was a nationwide observational survey of a representative sample of GPs and their patients from across France. Physicians recorded their diagnoses and prescriptions on participating patients who completed a self-questionnaire on socio-demographics, lifestyle, quality of life Short Form 12 (SF-12) and the complementary and alternative medicine beliefs inventory (CAMBI). RESULTS: A total of 6379 patients (participation rate 73.1%) recruited from 804 GP practices participated in this survey. Patients attending a GP-Ho were slightly more often female with higher education than in the GP-CM group and had markedly healthier lifestyle. They did not differ greatly in their comorbidities or quality of life but exhibited large differences in their beliefs in holistic medicine and natural treatments, and in their attitude toward participating to their own care. Similar but less striking observations were made in patients of the GP-Mx group. CONCLUSION: Patients seeking care with a homeopathic GP did not differ greatly in their socio-demographic characteristics but more so by their healthier lifestyle and positive attitude toward CAM. Further research is needed to explore the directionality of those associations and to assess the potential economic benefits of homeopathic management in primary care.

[Influenza, influenza-like illness: from theory to practice]. / Grippe, syndrome grippal : de la théorie à la pratique.

In France, there are large discrepancies regarding flu between the severe disease described by Health Authorities and the disease that people face, considered as usual and benign. Flu prevention is useful, mainly through vaccination. For a well-established influenza-like illness, both individual measures dedicated to the limitation of the disease propagation and symptomatic treatment are to be initiated. Few clinical data are available regarding the most often used treatments for influenza-like illness (paracetamol, homeopathic and symptomatic treatments). The analysis did not show any decrease in the chances of success for patients with more often used drugs, either being under medical prescription, pharmacist advice or self-medication. In front of an influenza-like illness, the recommendations for daily practice can be based on 2 well-defined clinical situations: a specific management for patients at risk, and the influenza-like illness symptoms relief for the others, using a treatment specific for each patient.

Characterization of knee osteoarthritis in Latin America. A comparative analysis of clinical and health care utilization in Argentina, Brazil, and Mexico.

BACKGROUND: The burden of knee osteoarthritis (OA) in Latin America is unknown. OBJECTIVE: To determine the demographic, clinical, and therapeutic characteristics of patients with OA in Argentina, Brazil, and Mexico. MATERIAL AND METHODS: This is an observational, cross-sectional study of patients with symptomatic knee OA referred from first care medical centers to Rheumatology departments. RESULTS: We included 1210 patients (Argentina 398, Brazil 402, Mexico 410; mean age 61.8 [12] years; 80.8% females). Knee OA pain lasted for 69 months; the duration and severity of the last episode were 190 days and (SD 5.2 [3.3]; 74% had functional limitations, but very few patients lost their job because of knee OA. Around 71% had taken medications, but 63% relied on their own pocket to afford knee OA cost. Most demographic and clinical variables differed across countries, particularly the level of pain, disability, treatment, and access to care. The variable country of origin influenced the level of pain, disability, and NSAIDs use in logistic regression models; age, pain, treatment, and health care access influenced at least 2 of the models. CONCLUSIONS: The burden of knee OA in Latin American depends on demographic, clinical, and therapeutic variables. The role of such variables differs across countries. The level of certain variables is significantly influenced by country of origin and health care system.

Who seeks primary care for sleep, anxiety and depressive disorders from physicians prescribing homeopathic and other complementary medicine? Results from the EPI3 population survey.

OBJECTIVES: To describe and compare patients seeking treatment for sleep, anxiety and depressive disorders (SADD) from physicians in general practice (GPs) with three different practice preferences: strictly conventional medicine (GP-CM), mixed complementary and conventional medicine (GP-Mx) and certified homeopathic physicians (GP-Ho). DESIGN AND SETTING: The EPI3 survey was a nationwide, observational study of a representative sample of GPs and their patients, conducted in France between March 2007 and July 2008. PARTICIPANTS: 1572 patients diagnosed with SADD. PRIMARY AND SECONDARY OUTCOMES: The patients' attitude towards complementary and alternative medicine; psychotropic drug utilisation. RESULTS: Compared to patients attending GP-CM, GP-Ho patients had healthier lifestyles while GP-Mx patients showed similar profiles. Psychotropic drugs were more likely to be prescribed by GP-CM (64%) than GP-Mx (55.4%) and GP-Ho (31.2%). The three groups of patients shared similar SADD severity. CONCLUSION: Our results showed that patients with SADD, while differing principally in their sociodemographic profiles and conventional psychotropic prescriptions, were actually rather similar regarding the severity of SADD in terms of comorbidities and quality of life. This information may help to better plan resource allocation and management of these common health problems in primary care.