[Prescribing inappropriate medication: the new STOPP/START criteria]. / Prescription médicamenteuse inappropriée: les nouveaux critères STOPP/START.

Prescribing inappropriate medication (PIM) is a common public health problem. Mainly due to associated adverse drugs events (ADE), it results in major morbidity and mortality, as well as increased healthcare utilization. For a long time, the systematic review of medications prescribed appeared as a solution for limiting PIM and the ADE associated with such prescriptions. With this aim and since 2008, the list of STOPP-START criteria has appeared as attractive in its design, as well as logical and easy to use. The initial version has just been updated and improved. After having detailed all improvements provided to the 2008 version, we present the result of its adaptation into French language by a group of French-speaking expert from Belgium, Canada, France, and Switzerland.

Antipsychotic prescribing and drug-related readmissions in multimorbid older inpatients: a post-hoc analysis of the OPERAM population.

BACKGROUND: Limited data are available on characteristics associated with antipsychotic use in multimorbid older adults. AIM: Primary: to identify patient characteristics associated with antipsychotic prescribing in a multimorbid population of older inpatients with polypharmacy. Secondary: (1) to observe if antipsychotics use during an index hospitalisation was associated with a drug related admission (DRA) within one year, and (2) to describe these cases of antipsychotic-related readmissions. METHOD: This was a secondary analysis of the OPERAM randomized controlled trial. Multivariate analysis assessed the association between characteristics and comorbidities with antipsychotic use. An expert team assessed DRA occurring during the one-year follow-up. RESULTS: Antipsychotics were prescribed to 5.5% (n = 110) patients upon admission while 7.7% (n = 154) inpatients received antipsychotics at any time (i.e. upon admission, during hospitalisation, and/or at discharge). The most frequently prescribed antipsychotics were quetiapine (n = 152), haloperidol (n = 48) and risperidone (n = 22). Antipsychotic prescribing was associated with dementia (OR = 3.7 95%CI[2.2;6.2]), psychosis (OR = 26.2 [7.4;92.8]), delirium (OR = 6.4 [3.8;10.8]), mood disorders (OR = 2.6 [1.6;4.1]),  ≥ 15 drugs a day (OR = 1.7 [1.1;2.6]), functional dependency (Activities of Daily Living score < 50/100) (OR = 3.9 [2.5;6.1]) and < 2 units of alcohol per week (OR = 2.2 [1.4;3.6]). DRA occurred in 458 patients (22.8%) within one year. Antipsychotic prescribing at any time was not associated with DRA (OR = 1.0 [0.3;3.9]) however contributed to 8 DRAs, including 3 falls. CONCLUSION: In this European multimorbid polymedicated older inpatients, antipsychotics were infrequently prescribed, most often at low dosage. Besides neuro-psychiatric symptoms, risk factors for inhospital antipsychotic prescribing were lower functional status and polymedication.

Time-of-day-dependent dietary fat consumption influences multiple cardiometabolic syndrome parameters in mice.

BACKGROUND: Excess caloric intake is strongly associated with the development of increased adiposity, glucose intolerance, insulin resistance, dyslipidemia, and hyperleptinemia (that is the cardiometabolic syndrome). Research efforts have focused attention primarily on the quality (that is nutritional content) and/or quantity of ingested calories as potential causes for diet-induced pathology. Despite growing acceptance that biological rhythms profoundly influence energy homeostasis, little is known regarding how the timing of nutrient ingestion influences development of common metabolic diseases. OBJECTIVE: To test the hypothesis that the time of day at which dietary fat is consumed significantly influences multiple cardiometabolic syndrome parameters. RESULTS: We report that mice fed either low- or high-fat diets in a contiguous manner during the 12 h awake/active period adjust both food intake and energy expenditure appropriately, such that metabolic parameters are maintained within a normal physiologic range. In contrast, fluctuation in dietary composition during the active period (as occurs in human beings) markedly influences whole body metabolic homeostasis. Mice fed a high-fat meal at the beginning of the active period retain metabolic flexibility in response to dietary challenges later in the active period (as revealed by indirect calorimetry). Conversely, consumption of high-fat meal at the end of the active phase leads to increased weight gain, adiposity, glucose intolerance, hyperinsulinemia, hypertriglyceridemia, and hyperleptinemia (that is cardiometabolic syndrome) in mice. The latter perturbations in energy/metabolic homeostasis are independent of daily total or fat-derived calories. CONCLUSIONS: The time of day at which carbohydrate versus fat is consumed markedly influences multiple cardiometabolic syndrome parameters.

Orthostatic blood pressure drop and cardiovascular and psychotropic medication dosages in acutely ill geriatric inpatients.

OBJECTIVES: . To investigate the dose-response relationship between cardiovascular or psychotropic medication dosages and falling orthostatic blood pressure in geriatric inpatients. METHODS: . This cross-sectional study included 100 consecutive geriatric inpatients of a Belgian hospital. The end points were the maximum changes of systolic (sBP) and diastolic (dBP) blood pressure in a standing up position at one or three minutes. The dosages of six classes of vascular and five classes of psychotropic medications were expressed in terms of a proportion of defined daily doses (DDD). Bivariate and multivariate linear regression models were used. RESULTS: . The 100 geriatric patients (85 ± 5 years, 58 % women) received 7.7 ± 4 medications (mean DDD: vascular = 1.0, psychotropic = 0.74) on the day of an orthostatic test (lying sBP: 136 ± 21; dBP: 72 ± 14 mm Hg). In a standing position, sBP and dBP fell by 12 ± 17 and 11 ± 5 mmHg, respectively. At the individual level, BP change was not correlated with vascular DDD (sBP: p = 0.07, r2 = 0.04; dBP: p = 0.59; r2 = 0.004) nor with psychotropic DDD (sBP: p = 0.14, r2 = 0.02; dBP: p = 0.82; r2 = 0.0). In multivariate analysis, sBP drop was positively associated with age, diabetes, falls history, and number of medications, but not with the DDD of any of the medication classes, while dBP drop was positively associated with age, diabetes, stroke and anaemia, but again with the DDD of any of the medication classes. CONCLUSION: . No correlation was found between vascular and psychotropic medication dosages and the orthostatic blood pressure drop expressed as a continuous variable.

High body mass index is associated with increased risk of treatment failure and surgery in biologic-treated patients with ulcerative colitis.

BACKGROUND: Though pharmacokinetic studies suggest accelerated biologic drug clearance with increasing body weight, evidence of obesity's impact on clinical outcomes in biologic-treated patients with ulcerative colitis (UC) is inconsistent. AIM: To evaluate the impact of obesity on real world response to biological therapy in patients with UC. METHODS: In a single-centre retrospective cohort study between 2011-2016 of biologic-treated patients with UC, we evaluated treatment response by baseline body mass index (BMI). Primary outcome was treatment failure (composite outcome of IBD-related surgery/hospitalisation or treatment modification including dose escalation, treatment discontinuation or addition of corticosteroids); secondary outcomes were risk of IBD-related surgery/hospitalisation and endoscopic remission. We conducted multivariate Cox proportional hazard analyses to evaluate the independent impact of BMI on clinical outcomes. Stratified analysis by weight-based regimens (infliximab) or fixed-dose regimens (adalimumab, golimumab, vedolizumab, certolizumab pegol) was performed. RESULTS: We included 160 biologic-treated UC patients (50% males, 55% on infliximab) with median (IQR) age 36 y (26-52) and BMI 24.3 kg/m2 (21.4-28.7). On multivariate analysis, each 1 kg/m2 increase in BMI was associated with 4% increase in the risk of treatment failure (adjusted hazard ratio [aHR], 1.04 [95% CI, 1.00-1.08]) and 8% increase in the risk of surgery/hospitalisation (aHR, 1.08 [1.02-1.14]). The effect on treatment failure was seen in patients on weight-based dosing regimens or fixed-dose therapies. CONCLUSION: BMI is independently associated with increased risk of treatment failure in biologic-treated patients with UC, independent of dosing regimen.

Organizing pneumonia. Features and prognosis of cryptogenic, secondary, and focal variants.

BACKGROUND: Organizing pneumonia (OP) is a non-specific response to many types of lung injury. Clinicians frequently encounter pathology reports of OP in patients with no underlying condition (cryptogenic OP, also known as BOOP or bronchiolitis obliterans OP) or in association with drugs or nonpulmonary disease. The goals of this study are to describe the clinical course and outcomes in patients with 3 clinical variants of OP. METHODS: A retrospective study of patients with OP seen at the Mayo Clinic, Rochester, Minn, from January 1, 1984, through June 30, 1994, was conducted. Initial features were obtained from medical records. Chest radiographs and pathology specimens were reviewed for this study. Resolution, relapse, and survival were obtained from medical records and a follow-up patient questionnaire. RESULTS: Seventy-four patients had pathologically confirmed OP. Organizing pneumonia was classified into 3 clinical groups: symptomatic cryptogenic OP; symptomatic OP related to underlying hematologic malignant neoplasm, collagen vascular disease, or drugs (secondary OP); and asymptomatic OP presenting as a focal nodule (focal OP). Thirty-seven patients (50%) had cryptogenic OP and 27 patients (36%) had secondary OP. No difference was found between cryptogenic and secondary OP in type or severity of symptoms, signs, laboratory and pulmonary function tests, or radiologic or pathologic findings. Corticosteroids were given at a similar initial dose (prednisone, about 50 mg/d). Resolution of symptoms was more frequent in patients with cryptogenic OP than those with secondary OP. Relapse was infrequent in both of these groups. Five-year survival was higher in patients with cryptogenic OP (73%) than in secondary OP (44%), and respiratory-related deaths were more frequent in patients with secondary OP. Organizing pneumonia was an asymptomatic focal rounded opacity in 10 patients (14%), most often detected on chest radiograph and diagnosed on lung biopsy done for suspicion of lung cancer. Patients with focal OP required no treatment and had no relapse or respiratory-related deaths. CONCLUSIONS: Clinical classification of OP is useful to predict clinical course and outcome. Cryptogenic OP most often was a symptomatic bilateral lung process that had an overall favorable prognosis with prolonged corticosteroid therapy. Patients with secondary OP had a high mortality rate when the disease was associated with predisposing conditions or drugs. Patients with asymptomatic focal OP had an excellent prognosis.

Training and manpower issues for specialist registrars in paediatrics. How are we doing and where are we going?

All Irish paediatric higher specialist trainees' opinions about the paediatric higher specialist training (HST) scheme and related manpower issues were surveyed. Information was obtained on 1) trainees' level of satisfaction with HST, 2) their ultimate career ambitions including location of final posts, 3) attitudes to both flexible training and consultancies and 4) demographics to assess the significance of gender variations. Fifty-two eligible trainees were identified using the Royal College of Physicians of Ireland database. The survey was administered as an anonymous postal survey. The response rate was 88%. Results indicated a high level of satisfaction with HST (78%) overall although problems were noted with the half-day release programme as only 63% were facilitated. Only 30% wish to practice as subspecialists, 76% of trainees wish to work in an urban hospital and 43.5% desire a flexible consultancy suggesting an incompatibility of trainees' desires with current Irish medical manpower policy. To address these difficulties we suggest establishing more rigorous audit of training posts to ensure deficiencies are corrected and the establishment of flexible training to address gender imbalance and to promote the concept of consultant job sharing.

[From PICO to search terms on the Internet: how to find relevant information? New coxibs: do they have a better gastrointestinal safety?]. / Du PICO aux termes de recherche par Internet: comment accéder à l'information pertinente? Les nouveaux coxibs: ont-ils réellement une meilleure sécurité digestive?

In the first article of this series, we have shown how to translate a clinical problem into a well built question, by creating a PICO (Patient--Intervention--Comparison--Outcome). In this second article, we will explain how to transform the PICO in English search terms for use on the internet. We use these terms in the different databases to find the answer to the following clinical problem: "In patients aged 65 or over with hip osteoarthritis, and a history of peptic ulcer, is the risk of a new peptic ulcer less using a cox-2 inhibitor than with a classic nonsteroidal anti-inflammatory drug?"

Adult safeguarding; guidance for dental professionals.

The legal responsibilities of all those involved in the care of adults at risk of harm were set out in the 'Care Act 2014' which became law in England in April 2015. In the same month, the General Dental Council (GDC) announced that 'safeguarding vulnerable adults' was to become a recommended topic for continuing professional development (CPD), along with 'safeguarding children and young people.' This paper updates on relevant legislation, and outlines the role of dental professionals in adult safeguarding. It then advises on issues surrounding safeguarding concerns, using three scenarios for illustration. Rather than covering the very broad topic of abuse of adults in general, the paper focusses on 'adults at risk' to whom statutory safeguarding law applies.

Orthostatic hypotension and associated conditions in geriatric inpatients.

Screening of orthostatic hypotension (OH) was performed in 285 patients aged 75  years. Current drugs, reasons for admission, geriatric syndromes, and confounding medical conditions were collected. Patients with OH (n = 116, 41%) as compared to those without OH (n = 169) more frequently (P < 0.01) presented falls in the last 6  months (62 vs. 40%, P < 0.001), a fall as the reason for the current admission (49 vs. 26%, P < 0.001), feeling of fainting (20 vs. 6%, P = 0.002), syncope (29 vs. 4%, P < 0.001) or functional decline (71 vs. 47%, P = 0.012). No difference was observed between the two groups in terms of age (85 ± 5 vs. 84 ± 4  years), gender (59 vs. 50% female), common geriatric conditions (e.g. malnutrition 46 vs. 58%, dementia 22 vs. 26%), comorbidity or confounding conditions (dehydration 28 vs. 30%, sepsis 2 vs. 6%). No difference was detected in the use of drugs with psychotropic cardiovascular or diuretic effect, or in their associations. Orthostatic hypotension is frequent upon hospital admission and should be screened, particularly in geriatric fallers. This absence of relation between OH and drugs use suggests that non-pharmacological interventions should be first attempted in older inpatients with OH before deciding to reduce or withdraw useful drugs.

Severe adverse life events and depressive symptoms among women with, or at risk for, HIV infection in four cities in the United States of America.

OBJECTIVE: To examine frequency and predictors of severe adverse life events and depressive symptoms among HIV-infected women and a comparison group of uninfected women. DESIGN: Analysis of baseline data collected from HIV-infected and uninfected women in a prospective cohort study of HIV infection and women, the HIV Epidemiologic Research Study. METHOD: The sample of 871 HIV-infected and 439 demographically and behaviorally similar uninfected women were recruited from four metropolitan areas in the USA. Women provided interview information that included sociodemographic characteristics, sexual and drug-using behaviors, and social and psychological functioning. The outcome measures were number of severe adverse life events (e.g., insufficient money for necessities, physical attack or rape, death of a person close to them) and levels of depressive symptoms. RESULTS: HIV-infected and uninfected women reported numerous adverse life events and high levels of depressive symptoms. The two groups, however, did not differ on either outcome measure. Low socio-economic status, injecting drug and crack cocaine use, and high risk sexual activity were related to reports of more adverse events and depressive symptoms for both groups. CONCLUSIONS: HIV-infected and uninfected women in socially and economically disadvantaged environments experience many adverse events and high levels of depressive symptoms. HIV infection, at least during the early phase, may be less important than socio-environmental factors in predicting negative psychosocial outcomes for women.

Critical evaluation of cytosolic calcium determination in resting muscle fibres from normal and dystrophic (mdx) mice.

The fluorescent probe Fura-2/AM was used to determine cytosolic free calcium concentration in soleus muscle and in isolated flexor digitorum brevis fibres. This required a precise calibration; therefore, each calibration parameter was studied in situ. The influence of the dye concentration on calcium measurements was also examined. This precise calibration technique was used to compare absolute free calcium concentration in resting preparations from dystrophic (mdx) and control (C57) mice. We showed that the behavior of the dye was not similar in C57 and in mdx muscles. For this reason, we did not confirm the previous results that cytosolic free calcium concentration is increased in mdx muscles.

Yield of laboratory tests for case-finding in the ambulatory general medical examination.

PURPOSE: To examine the diagnostic and therapeutic yield of frequently obtained laboratory tests for case-finding in the comprehensive ambulatory medical examination. PATIENTS AND METHODS: A prospective cohort study was conducted in four Mayo Clinic general internal medicine divisions that provide care to community, regional, and geographically distant patients. The main outcome measurements were the diagnostic yield and therapeutic yield of the complete blood count, chemistry panel, lipid profile, thyroid tests, and urinalysis ordered for case-finding. RESULTS: Overall, 1,508 laboratory tests consisting of 7,008 individual components were obtained for case-finding in the 531 patients (mean age 63 +/- 14 years; 57% female). Thirty-six percent (544 of 1508) of the tests were abnormal, of which 6% (33 of 544) were repeated and 9% (47 of 544) led to further investigations. The 1,508 case-finding tests had a diagnostic yield of 4.8% (73 new diagnoses) and a therapeutic yield of 4.0% (60 new therapies). The therapeutic yield of each test ordered for case-finding was as follows: lipid profile (16.5%), chemistry panel (2.8%), complete blood count (0.9%), urinalysis (0.8%), and thyroid tests (0.7%). Therapeutic yield was not associated with patient's age, gender, or referral distance but was approximately twice as high in new patients compared with established patients. CONCLUSIONS: The majority of treatments for conditions identified by case-finding laboratory tests resulted from the lipid profile. The therapeutic yield of the chemistry panel was low, and the therapeutic yield of the complete blood count, thyroid tests, and urinalysis were all less than 1%. The low therapeutic yield of many routine laboratory tests ordered for case-finding should be provided to patients, physicians, and managed care organizations to set priorities for case-finding and screening.

ATP induced-relaxation in the mouse bladder smooth muscle.

1. The effect of adenosine 5'-triphosphate (ATP) on the free cytosolic Ca2+ concentration ([Ca2+]i) as measured with the fluorescent Ca(2+)-indicator fura-2, and on force was investigated in the intact smooth muscle strips of the mouse urinary bladder. 2. ATP elicited, when exogenously applied, a large increase of [Ca2+]i with limited force development resulting in a marked Ca(2+)-force dissociation. 3. Release of endogenous neurotransmitters by transmural electrical stimulation (TES) for 30 s induced a steady increase of [Ca2+]i and a peak contraction, followed within 15 s by a relaxation. 4. In carbachol-prestimulated preparations, ATP elicited an initial rise of [Ca2+]i followed by a return to the initial precontraction Ca(2+)-level. Force in contrast presented a biphasic pattern, i.e. an initial contraction was followed by a sustained relaxation. 5. In the K(+)-depolarized precontracted preparation, ATP elicited a slight initial rise of [Ca2+]i. The partial relaxation of the force during depolarization was not preceded by a transient contraction. 6. The ATP-induced relaxation of the K(+)-prestimulated preparations was not inhibited by 8-phenyltheophylline, a potent P1-purinoceptor antagonist. 7. The order of potency for relaxation of the ATP analogues was 2-MeSATP > ATP > beta gamma Me-ATP, which is characteristic for P2y-purinoceptors. 8. These results indicate that, besides its activating effect, ATP also relaxes the mouse urinary bladder. It is suggested that the relaxant effect, mediated through P2y-purinoceptors, is mainly responsible for the low contractile potency of ATP in the bladder.

Post-receptor pathway of the ATP-induced relaxation in smooth muscle of the mouse vas deferens.

1. The post-receptor pathway of the ATP relaxant effect in K(+)-precontracted vas deferens smooth muscle (VD) was examined. 2. The relaxation to ATP was not antagonized either by 10 microM methylene blue, a cyclic GMP inhibitor, by 10 microM indomethacin, an inhibitor of prostaglandin synthesis or by 100 microM NG-nitro-L-arginine, an inhibitor of NO production. 3. The Rp-diastereomer of adenosine 3':5'-cyclic monophosphorothioate (Rp-cAMPS) 200 microM, a competitive inhibitor of cyclic AMP significantly diminished the relaxant response to ATP. 4. Isoprenaline 10 microM, a beta-adrenoceptor agonist, produced a sustained relaxation, inhibited by Rp-cAMPS, without a significant change in [Ca2+]i, thereby mimicking the ATP-induced relaxant effect. 5. The level of the phosphorylated myosin light chain in the precontracted VD was significantly lowered by 1000 microM ATP. 6. ATP (1000 microM) and isoprenaline (10 microM) produced the same increase (+ 50%) of [cyclic AMP] when applied to a resting VD. 7. The effect of simultaneous increases of [Ca2+]i and of [cyclic AMP] produced by externally applied ATP are discussed. 8. These results suggest that ATP-induced relaxation in K(+)-precontracted VD is mediated by the activation of adenylyl cyclase.

ATP activates P2x-contracting and P2y-relaxing purinoceptors in the smooth muscle of mouse vas deferens.

1. The mechanism for the low potency of exogenous ATP in producing contraction at the P2x-purinoceptors in the smooth muscle of the mouse vas deferens (VD) was examined. 2. The measure of the breakdown of ATP in contact with the VD showed that its degradation was limited and did not account for its weak contractile effect. 3. Externally applied, ATP induced a small and transient contraction but a marked and prolonged increase of the cytosolic Ca2+ concentration ([Ca2+]i), which suggests an efficient binding to the P2x-purinoceptors. Such a calcium-force dissociation was not observed with beta, gamma-methylene ATP (beta, gamma-Me-ATP), a structural ATP analogue. 4. The force response of precontracted VD to ATP was biphasic, consisting of a small initial contraction followed by a sustained marked relaxation. In contrast, beta, gamma-Me-ATP elicited a pronounced contraction without ensuing relaxation. 5. ATP was more potent than adenosine in producing relaxation, and the relaxation was not antagonized by 8-phenyltheophylline, suggesting the activation of P2-purinoceptors. 6. For this relaxation, the rank order of potency was 2-methyl-thio-ATP (2-MeSATP) > ATP > beta, gamma-Me-ATP, which is characteristic for the P2y-purinoceptors. 7. Reactive Blue 2, a P2y-purinoceptor antagonist, was found to reduce the relaxation mediated by ATP. 8. These results indicate that ATP acts in VD not only on contracting but also on relaxing P2-purinoceptors, eliciting thereby overlapping opposite effects. In VD, the classical low potency of ATP or contraction is thus not explained by its low bioavailability or its low binding, but rather by its low specificity for the contracting P2x-purinoceptors, leading to the activation of the relaxing P2y-purinoceptors.

Patient-physician agreement about medical diagnoses and cardiovascular risk factors in the ambulatory general medical examination.

OBJECTIVE: To describe the spectrum of medical diagnoses and cardiovascular risk factors identified by physicians during the comprehensive medical examination in ambulatory patients, to assess how accurately patients report the health problems identified by their physicians, and to determine the characteristics associated with patient and physician agreement. MATERIAL AND METHODS: We conducted a prospective study of ambulatory patients at Mayo Clinic Rochester. All 64 internists in the general internal medicine divisions who perform comprehensive medical examinations were invited to enroll 10 adult patients each; 57 physicians and 566 eligible patients participated. Complete physician and patient information on diagnosed health problems was available for 458 patient visits (81%). Diagnosed health problems were collected from both the patients and the physicians by questionnaire after the examination and classified into medical diagnoses and cardiovascular risk factors. RESULTS: Of the diagnosed health problems, 63% involved four organ system categories: (1) nutritional, endocrine, or metabolic (20%); (2) cardiovascular (18%); (3) musculoskeletal (13%); and (4) digestive (12%). Patients failed to report 68% of all health problems and 54% of the most important health problems diagnosed by the physician. Major health problems, new diagnoses, and distant residence were associated with the highest level of patient-physician agreement for diagnosed health problems. CONCLUSION: Because patients failed to report more than half of their most important health problems identified by their physicians, practitioners might consider giving problem lists or summary letters to patients to improve and reinforce communication and management of health problems.

Patient-physician agreement on reasons for ambulatory general medical examinations.

OBJECTIVE: To evaluate the physician's ability to identify patients' reasons for visits (RFVs) for a general medical examination (GME), to assess predictors of agreement between patient and physician on the RFV, and to determine whether agreement about the RFVs was associated with patient satisfaction with the visit. DESIGN: We conducted a prospective study involving patients scheduled for a GME and internists in a multispecialty group practice. MATERIAL AND METHODS: Patient-physician agreement on the RFV was independently assessed by two internists. Logistic regression was used to identify predictors of low agreement. RESULTS: The 458 patients reported a total of 848 RFVs for their GME. Patient-physician agreement on the patient's RFV was low in 20% of the visits. Female gender (odds ratio, 2.02; 95% confidence interval [CI], 1.11 to 3.66), multiple RFVs (odds ratio, 2.03; 95% CI, 1.06 to 3.91), and previous GME (odds ratio, 2.18; 95% CI, 1.07 to 4.44) were independent predictors of low agreement. Patient-physician agreement for RFVs was not associated with patient satisfaction with the medical visit. CONCLUSION: In this study, physicians correctly identified the patient's main RFV in a majority of the visits. Failures to identify the patient's main RFV occurred more frequently in female patients, in patients with multiple RFVs, and in patients with a previous comprehensive GME. Surprisingly, patient-physician agreement was not associated with patient satisfaction.

Delta 9-tetrahydrocannabinol induces the apoptotic pathway in cultured cortical neurones via activation of the CB1 receptor.

Delta 9-tetrahydrocannabinol, the principal psychoactive component of marijuana, exerts a variety of effects on the CNS, including impaired cognitive function and neurobehavioural deficits. The mechanisms underlying these neuronal responses to tetrahydrocannabinol are unclear but may involve alterations in neuronal viability. Tetrahydrocannabinol has been shown to influence neuronal survival but the role of the cannabinoid receptors in the regulation of neuronal viability has not been fully clarified. In this study we demonstrate that tetrahydrocannabinol promotes the release of cytochrome c, activates caspase-3, promotes cleavage of the DNA repair enzyme poly-ADP ribose polymerase and induces DNA fragmentation in cultured cortical neurones. These effects of tetrahydrocannabinol were completely abrogated by the CB(1) receptor antagonist AM-251. The findings of this study demonstrate that tetrahydrocannabinol induces apoptosis in cortical neurones in a manner involving the CB1 subtype of cannabinoid receptor.