Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related polices. Perspective: Safe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel following a systematic review of the evidence.

Objective To determine the prevalence of chronic and debilitating symptoms of the overactive bladder, de®ned here as the presence of chronic frequency, urgency and urge incontinence (either alone or in any combination), and presumed to be caused by involuntary detrusor contractions. Subjects and methods Data were collected using a population-based survey (conducted by telephone or direct interview) of men and women aged o 40 years, selected from the general population in France, Germany, Italy, Spain, Sweden and the United Kingdom, using a random strati®ed approach. The main outcome measures were: prevalence of urinary frequency (>8 micturitions/24 h), urgency and urge incontinence; the proportion of participants who had sought medical advice for symptoms of an overactive bladder; and current or previous therapy received for these symptoms. Results In all, 16 776 interviews were conducted in the six European countries. The overall prevalence of overactive bladder symptoms in individuals aged o 40 years was 16.6%. Frequency (85%) was the most commonly reported symptom, followed by urgency (54%) and urge incontinence (36%). The prevalence of overactive bladder symptoms increased with advancing age. Overall, 60% of respondents with symptoms had consulted a doctor but only 27% were currently receiving treatment. Conclusion Symptoms of an overactive bladder, of which frequency and urgency are as bothersome as urge incontinence, are highly prevalent in the general population. However, only a few affected individuals currently receive treatment. Taken together, such ®ndings indicate that there is considerable scope for improvement in terms of how physicians diagnose and treat this condition.

Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.

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Texture zeros in the quark Yukawa matrices generally lead to precise and simple expressions for CKM matrix elements in terms of ratios of quark masses. Using the new data on b−decays we test a particularly promising texture zero solution and show that it is at best approximate. We analyse the approximate texture zero structure and show it is consistent with experiment. We investigate the implications for the CKM unitarity triangle, measurements at BaBar and BELLE as well as for the theories which invoke family symmetries.

We investigate the growth and survival of nascent businesses by analyzing their bank records. We do not find strong evidence in favour of a taxonomy of growth paths, because we observe that every possible growth path seems to occur with roughly equal probability. However, we observe that survival depends on the business' growth path. Controlling for lagged size, we observe that longer lags of growth, and even start-up size, have significant effects on survival. JEL codes: L25

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Overactive bladder (OAB)--a syndrome characterized by urinary urgency, with or without urge incontinence, urinary frequency and nocturia--is estimated to affect 10% to 20% of the US and European populations. This study was carried out to validate a patient-administered screening awareness tool to identify patients with bothersome OAB symptoms. Patients were recruited from 12 primary care and 1 gynecology practice during regularly scheduled appointments. Enrollees completed an 8-item questionnaire assessing the amount of "bother" they associated with OAB symptoms. Clinicians then asked the patients 4 questions regarding urinary frequency, urgency, nocturia, and incontinence. If the screening was positive for symptoms of OAB or if the patient provided positive responses to the urinary symptom questions, the clinician asked additional questions regarding lifestyle and coping behaviors. The clinician then diagnosed the patient, placing him or her in the "No OAB," "Possible OAB," or "Probable OAB" category. Multivariable logistic regressions controlling for age and sex were performed to assess the applicability of the tool for identifying patients with OAB. A total of 1,299 patients were enrolled, and 1,260 provided complete data. Patients were aged 51.6+/-17.0 years, 62% were female, most (89%) were Caucasian, 22% experienced urinary urgency, and 18% experienced urge incontinence. The prevalence of Probable OAB was 12%. The c-index of the model identifying patients with a diagnosis of Probable OAB was 0.96, with a sensitivity and specificity of 98.0 and 82.7. For OAB-V8 scores >or=8, the odds ratio for Probable OAB was 95.7 (95% CI: 29.3; 312.4). The OAB-V8 performed well in helping clinicians identify patients with bothersome OAB symptoms in a primary care setting and will assist clinicians in identifying patients who may benefit from treatment.