Sleeping Beauty Syndrome

Kleine Levin Syndrome (KLS), also known as Sleeping Beauty Syndrome, is characterized by progressive drowsiness and sleep for most days and nights. It is a rare neurological disorder with a prevalence of one to five cases per million. Those with KLS have recurring periods of excessive sleep, altered behavior, and a reduced understanding of the world. KLS primarily occurs in adolescents, boys more frequently than girls with a higher prevalence in Ashkenazi Jews. The exact cause of KLS is unknown but damage or malfunction of the hypothalamus may be involved. Although there is no definitive treatment for KLS, pharmaceuticals such as stimulants have been used to combat the sleepiness. However, these can cause irritability and mood swings, so alternatives to pharmaceuticals are also considered. Recent research suggests that a mutation in the gene LMOD3 may be the cause of KLS. LMOD proteins are structural proteins and appear to be developmentally regulated. In this poster, we will present the molecular mechanism for the disease and potential therapeutic targets for treatment on this disease

Data capture by digital pen in clinical trials: A qualitative and quantitative study.

International audienceOBJECTIVES: To investigate the use of the digital pen (DP) system to collect data in a clinical trial. To assess the accuracy of the system in this setting. DESIGN: Qualitative study based on semistructured interviews and a focus group. Quantitative study comparing the DP system and a double manual data-entry system in accuracy of acquiring data by variable type (tick boxes, dates, numbers, letters). SETTING: An ongoing randomised multicentric clinical trial in tertiary care in France. PARTICIPANTS: 27 investigators involved in the trial (anaesthetists) who did or did not include patients, 4 study monitors and the study coordinator. RESULTS: Six key findings emerged: 1) the DP system was easy to use; its utilisation was intuitive, even for investigators inexperienced in informatics; 2) despite its portability, the DP was not always used in front of patients; 3) the DP system did not affect patient recruitment; 4) most of the technical problems of the system occurred during setup (compatibility, password access, antivirus software); 5) the main advantage was quickness of data availability for the study coordination staff and the main hindrance was the extra time required for online verification; and 6) all investigators were ready to use the system again. The investigators had to check 16% of data obtained by the DP system during the verification step. There is no relevant difference between the number of errors for the DP and the double manual data-entry systems: 8/5022 versus 6/5022 data entries. 5 out of 8 DP-system failures were due to the intelligent character recognition system. CONCLUSION: The DP system has a good acceptability among all investigators in a clinical setting, whether they are experienced with computers or not, and a good accuracy, as compared with double manual data entry

Non-Financial Conflicts of Interest in Academic Grant Evaluation: A Qualitative Study of Multiple Stakeholders in France

International audienceBACKGROUND: Peer review is the most widely used method for evaluating grant applications in clinical research. Criticisms of peer review include lack of equity, suspicion of biases, and conflicts of interest (CoI). CoIs raise questions of fairness, transparency, and trust in grant allocation. Few observational studies have assessed these issues. We report the results of a qualitative study on reviewers' and applicants' perceptions and experiences of CoIs in reviews of French academic grant applications. METHODOLOGY AND PRINCIPAL FINDINGS: We designed a qualitative study using semi-structured interviews and direct observation. We asked members of assessment panels, external reviewers, and applicants to participate in semi-structured interviews. Two independent researchers conducted in-depth reviews and line-by-line coding of all transcribed interviews, which were also subjected to Tropes® software text analysis, to detect and qualify themes associated with CoIs. Most participants (73/98) spontaneously reported that non-financial CoIs predominated over financial CoIs. Non-financial CoIs mainly involved rivalry among disciplines, cronyism, and geographic and academic biases. However, none of the participants challenged the validity of peer review. Reviewers who felt they might be affected by CoIs said they reacted in a variety of ways: routine refusal to review, routine attempt to conduct an impartial review, or decision on a case-by-case basis. Multiple means of managing non-financial CoIs were suggested, including increased transparency throughout the review process, with public disclosure of non-financial CoIs, and careful selection of independent reviewers, including foreign experts and methodologists. CONCLUSIONS: Our study underscores the importance of considering non-financial CoIs when reviewing research grant applications, in addition to financial CoIs. Specific measures are needed to prevent a negative impact of non-financial CoIs on the fairness of resource allocation. Whether and how public disclosure of non-financial CoIs should be accomplished remains debatable

Osteoarthritis and the rule of halves

<b>Background</b> Symptomatic osteoarthritis poses a major challenge to primary health care but no studies have related accessing primary care ("detection"), receiving recommended treatments ("treatment"), and achieving adequate control ("control").<p></p> <b>Objective</b> To provide estimates of detection, treatment, and control within a single population adapting the approach used to determine a Rule of Halves for other long-term conditions.<p></p> <b>Setting</b> General population.<p></p> <b>Participants</b> 400 adults aged 50+ years with prevalent symptomatic knee osteoarthritis.<p></p> <b>Design</b> Prospective cohort with baseline questionnaire, clinical assessment, and plain radiographs, and questionnaire follow-up at 18 and 36 months and linkage to primary care medical records.<p></p> <b>Outcome measures</b> "Detection" was defined as at least one musculoskeletal knee-related GP consultation between baseline and 36 months. "Treatment" was self-reported use of at least one recommended treatment or physiotherapy/hospital specialist referral for their knee problem at all three measurement points. Pain was "controlled" if characteristic pain intensity <5 out of 10 on at least two occasions.<p></p> <b>Results</b> In 221 cases (55.3%; 95%CI: 50.4, 60.1) there was evidence that the current problem had been detected in general practice. Of those detected, 164 (74.2% (68.4, 80.0)) were receiving one or more of the recommended treatments at all three measurement points. Of those detected and treated, 45 (27.4% (20.5, 34.3)) had symptoms under control on at least two occasions. Using narrower definitions resulted in substantially lower estimates.<p></p> <b>Conclusion</b> Osteoarthritis care does not conform to a Rule of Halves. Symptom control is low among those accessing health care and receiving treatment

Short-Term Efficacy of Rofecoxib and Diclofenac in Acute Shoulder Pain: A Placebo-Controlled Randomized Trial

OBJECTIVES: To evaluate the short-term symptomatic efficacy of rofecoxib and diclofenac versus placebo in acute episodes of shoulder pain. DESIGN: Randomized controlled trial of 7 days. SETTING: Rheumatologists and/or general practitioners totaling 47. PARTICIPANTS: Acute shoulder pain. INTERVENTIONS: Rofecoxib 50 mg once daily, diclofenac 50 mg three times daily, and placebo. OUTCOME MEASURES: Pain, functional impairment, patient's global assessment of his/her disease activity, and local steroid injection requirement for persistent pain. The primary variable was the Kaplan-Meier estimates of the percentage of patients at day 7 fulfilling the definition of success (improvement in pain intensity and a low pain level sustained to the end of the 7 days of the study; log-rank test). RESULTS: There was no difference in the baseline characteristics between the three groups (rofecoxib n = 88, placebo n = 94, and diclofenac n = 89). At day 7, the Kaplan-Meier estimates of successful patients was higher in the treatment groups than in the placebo (54%, 56%, and 38% in the diclofenac, rofecoxib, and placebo groups respectively, p = 0.0070 and p = 0.0239 for placebo versus rofecoxib and diclofenac, respectively). During the 7 days of the study, there was a statistically significant difference between placebo and both active arms (rofecoxib and diclofenac) in all the evaluated outcome measures A local steroid injection had to be performed in 33 (35%) and 19 (22%) patients in the placebo and rofecoxib group respectively. Number needed to treat to avoid such rescue therapy was 7 patients (95% confidence interval 5–15). CONCLUSION: This study highlights the methodological aspects of clinical trials, e.g., eligibility criteria and outcome measures, in acute painful conditions. The data also establish that diclofenac and rofecoxib are effective therapies for the management of acute painful shoulder and that they reduce the requirement for local steroid injection

Clinical course and prognosis of musculoskeletal pain in patients referred for physiotherapy: does pain site matter?

Background: Danish patients with musculoskeletal disorders are commonly referred for primary care physiotherapy treatment but little is known about their general health status, pain diagnoses, clinical course and prognosis. The objectives of this study were to 1) describe the clinical course of patients with musculoskeletal disorders referred to physiotherapy, 2) identify predictors associated with a satisfactory outcome, and 3) determine the influence of the primary pain site diagnosis relative to those predictors. Methods: This was a prospective cohort study of patients (n = 2,706) newly referred because of musculoskeletal pain to 30 physiotherapy practices from January 2012 to May 2012. Data were collected via a web-based questionnaire 1–2 days prior to the first physiotherapy consultation and at 6 weeks, 3 and 6 months, from clinical records (including primary musculoskeletal symptom diagnosis based on the ICPC-2 classification system), and from national registry data. The main outcome was the Patient Acceptable Symptom State. Potential predictors were analysed using backwards step-wise selection during longitudinal Generalised Estimating Equation regression modelling. To assess the influence of pain site on these associations, primary pain site diagnosis was added to the model. Results: Of the patients included, 66% were female and the mean age was 48 (SD 15). The percentage of patients reporting their symptoms as acceptable was 32% at 6 weeks, 43% at 3 months and 52% at 6 months. A higher probability of satisfactory outcome was associated with place of residence, being retired, no compensation claim, less frequent pain, shorter duration of pain, lower levels of disability and fear avoidance, better mental health and being a non-smoker. Primary pain site diagnosis had little influence on these associations, and was not predictive of a satisfactory outcome. Conclusion: Only half of the patients rated their symptoms as acceptable at 6 months. Although satisfactory outcome was difficult to predict at an individual patient level, there were a number of prognostic factors that were associated with this outcome. These factors should be considered when developing generic prediction tools to assess the probability of satisfactory outcome in musculoskeletal physiotherapy patients, because the site of pain did not affect that prognostic association

Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer

International audienceBackgroundNon-muscle-invasive bladder cancer (NMIBC) is a high incidence form of bladder cancer (BCa), where genetic and epigenetic alterations occur frequently. We assessed the performance of associating a FGFR3 mutation assay and a DNA methylation analysis to improve bladder cancer detection and to predict disease recurrence of NMIBC patients.MethodsWe used allele specific PCR to determine the FGFR3 mutation status for R248C, S249C, G372C, and Y375C. We preselected 18 candidate genes reported in the literature as being hypermethylated in cancer and measured their methylation levels by quantitative multiplex-methylation specific PCR. We selected HS3ST2, SLIT2 and SEPTIN9 as the most discriminative between control and NMIBC patients and we assayed these markers on urine DNA from a diagnostic study consisting of 167 NMIBC and 105 controls and a follow-up study consisting of 158 NMIBC at diagnosis time’s and 425 at follow-up time. ROC analysis was performed to evaluate the diagnostic accuracy of each assay alone and in combination.ResultsFor Diagnosis: Using a logistic regression analysis with a model consisting of the 3 markers’ methylation values, FGFR3 status, age and known smoker status at the diagnosis time we obtained sensitivity/specificity of 97.6 %/84.8 % and an optimism-corrected AUC of 0.96. With an estimated BCa prevalence of 12.1 % in a hematuria cohort, this corresponds to a negative predictive value (NPV) of 99.6 %. For Follow-up: Using a logistic regression with FGFR3 mutation and the CMI at two time points (beginning of the follow-up and current time point), we got sensitivity/specificity/NPV of 90.3 %/65.1 %/97.0 % and a corrected AUC of 0.84. We also tested a thresholding algorithm with FGFR3 mutation and the two time points as described above, obtaining sensitivity/specificity/NPV values of, respectively, 94.5 %/75.9 %/98.5 % and an AUC of 0.82.ConclusionsWe showed that combined analysis of FGFR3 mutation and DNA methylation markers on urine can be a useful strategy in diagnosis, surveillance and for risk stratification of patients with NMIBC. These results provide the basis for a highly accurate noninvasive test for population screening and allowing to decrease the frequency of cystoscopy, an important feature for both patient quality of life improvement and care cost reduction

Lack of control of hypertension in primary cardiovascular disease prevention in Europe: Results from the EURIKA study

Background The prevalence of and factors associated with uncontrolled hypertension and apparent resistant hypertension were assessed in the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA; NCT00882336). Methods EURIKA was a cross-sectional observational study including patients being treated for the primary prevention of cardiovascular disease in 12 European countries. Patients were assessed if they were being treated for hypertension (N = 5220). Blood pressure control was defined according to European guidelines, with sensitivity analysis taking account of patients' age and diabetes status. Associated factors were assessed using multivariate analysis. Results In the primary analysis, a total of 2691 patients (51.6%) had uncontrolled hypertension. Factors significantly associated with an increased risk of having uncontrolled hypertension included female sex (odds ratio [OR]: 2.29; 95% confidence interval [CI]: 1.93-2.73), body mass index (BMI; OR per kg/m2: 1.03; 95% CI: 1.01-1.04), and geographic location. A total of 749 patients (14.3%) had apparent resistant hypertension. Factors significantly associated with an increased risk of having apparent resistant hypertension included BMI (OR per kg/m2: 1.06; 95% CI: 1.04-1.08), diabetes (OR: 1.28; 95% CI: 1.06-1.53), use of statins (OR: 1.36; 95% CI: 1.15-1.62), serum uric acid levels (OR: 1.16; 95% CI: 1.09-1.23), and geographic location. Similar results were seen in sensitivity analyses. Conclusions Over 50% of patients treated for hypertension continued to have uncontrolled blood pressure and 14.3% had apparent resistant hypertension. Positive associations were seen with other cardiovascular risk factors