Efficacy of haloperidol to decrease the burden of delirium in adult critically ill patients:the EuRIDICE randomized clinical trial

Background:The role of haloperidol as treatment for ICU delirium and related symptoms remains controversial despite two recent large controlled trials evaluating its efficacy and safety. We sought to determine whether haloperidol when compared to placebo in critically ill adults with delirium reduces days with delirium and coma and improves delirium-related sequelae.Methods:This multi-center double-blind, placebo-controlled randomized trial at eight mixed medical-surgical Dutch ICUs included critically ill adults with delirium (Intensive Care Delirium Screening Checklist ≥ 4 or a positive Confusion Assessment Method for the ICU) admitted between February 2018 and January 2020. Patients were randomized to intravenous haloperidol 2.5 mg or placebo every 8 h, titrated up to 5 mg every 8 h if delirium persisted until ICU discharge or up to 14 days. The primary outcome was ICU delirium- and coma-free days (DCFDs) within 14 days after randomization. Predefined secondary outcomes included the protocolized use of sedatives for agitation and related behaviors, patient-initiated extubation and invasive device removal, adverse drug associated events, mechanical ventilation, ICU length of stay, 28-day mortality, and long-term outcomes up to 1-year after randomization.Results:The trial was terminated prematurely for primary endpoint futility on DSMB advice after enrolment of 132 (65 haloperidol; 67 placebo) patients [mean age 64 (15) years, APACHE IV score 73.1 (33.9), male 68%]. Haloperidol did not increase DCFDs (adjusted RR 0.98 [95% CI 0.73–1.31], p = 0.87). Patients treated with haloperidol (vs. placebo) were less likely to receive benzodiazepines (adjusted OR 0.41 [95% CI 0.18–0.89], p = 0.02). Effect measures of other secondary outcomes related to agitation (use of open label haloperidol [OR 0.43 (95% CI 0.12–1.56)] and other antipsychotics [OR 0.63 (95% CI 0.29–1.32)], self-extubation or invasive device removal [OR 0.70 (95% CI 0.22–2.18)]) appeared consistently more favorable with haloperidol, but the confidence interval also included harm. Adverse drug events were not different. Long-term secondary outcomes (e.g., ICU recall and quality of life) warrant further study.Conclusions:Haloperidol does not reduce delirium in critically ill delirious adults. However, it may reduce rescue medication requirements and agitation-related events in delirious ICU patients warranting further evaluation.Trial registration: ClinicalTrials.gov (#NCT03628391), October 9, 2017

The Edinburgh Postnatal Depression Scale (EPDS): translation and validation study of the Iranian version

BACKGROUND: The Edinburgh Postnatal Depression Scale (EPDS) is a widely used instrument to measure postnatal depression. This study aimed to translate and to test the reliability and validity of the EPDS in Iran. METHODS: The English language version of the EPDS was translated into Persian (Iranian language) and was used in this study. The questionnaire was administered to a consecutive sample of 100 women with normal (n = 50) and caesarean section (n = 50) deliveries at two points in time: 6 to 8 weeks and 12 to 14 weeks after delivery. Statistical analysis was performed to test the reliability and validity of the EPDS. RESULTS: Overall 22% of women at time 1 and 18% at time 2 reported experiencing postpartum depression. In general, the Iranian version of the EPDS was found to be acceptable to almost all women. Cronbach's alpha coefficient (to test reliability) was found to be 0.77 at time 1 and 0.86 at time 2. In addition, test-rest reliability was performed and the intraclass correlation coefficient was found to be 0.80. Validity as performed using known groups comparison showed satisfactory results. The questionnaire discriminated well between sub-groups of women differing in mode of delivery in the expected direction. The factor analysis indicated a three-factor structure that jointly accounted for 58% of the variance. CONCLUSION: This preliminary validation study of the Iranian version of the EPDS proved that it is an acceptable, reliable and valid measure of postnatal depression. It seems that the EPDS not only measures postpartum depression but also may be measuring something more

Relatively higher norms of blood flow velocity of major intracranial arteries in North-West Iran

<p>Abstract</p> <p>Background</p> <p>Transcranial Doppler (TCD) is a noninvasive, less expensive and harmless hemodynamic study of main intracranial arteries. The aim of this study was to assess normal population values of cerebral blood flow velocity and its variation over age and gender in a given population.</p> <p>Findings</p> <p>Eighty healthy volunteers including 40 people with an age range of 25-40 years (group1) and 40 persons with an age range of 41-55 years (group2) were studied. In each group 20 males and 20 females were enrolled. Peak systolic, end diastolic and mean velocities of nine main intracranial arteries were determined using TCD. Mean age of the studied volunteers was 31.6 ± 4.50 years in group one and 47.2 ± 4.3 years in group two. Mean age among males was 40 years and among females it was 39. Mean blood flow velocity in middle, anterior and posterior cerebral arteries, vertebral and basilar arteries was 60 ± 8, 52 ± 9, 42 ± 6, 39 ± 8 and 48 ± 8 cm/sec respectively. Cerebral blood flow velocities among females were relatively higher than males. Cerebral blood flow velocity of left side was relatively higher than right side.</p> <p>Conclusion</p> <p>Compared to previous studies, cerebral blood flow velocity in this population was relatively higher.</p

Detecting depressive and anxiety disorders in distressed patients in primary care; comparative diagnostic accuracy of the Four-Dimensional Symptom Questionnaire (4DSQ) and the Hospital Anxiety and Depression Scale (HADS)

BACKGROUND: Depressive and anxiety disorders often go unrecognized in distressed primary care patients, despite the overtly psychosocial nature of their demand for help. This is especially problematic in more severe disorders needing specific treatment (e.g. antidepressant pharmacotherapy or specialized cognitive behavioural therapy). The use of a screening tool to detect (more severe) depressive and anxiety disorders may be useful not to overlook such disorders. We examined the accuracy with which the Four-Dimensional Symptom Questionnaire (4DSQ) and the Hospital Anxiety and Depression Scale (HADS) are able to detect (more severe) depressive and anxiety disorders in distressed patients, and which cut-off points should be used. METHODS: Seventy general practitioners (GPs) included 295 patients on sick leave due to psychological problems. They excluded patients with recognized depressive or anxiety disorders. Patients completed the 4DSQ and HADS. Standardized diagnoses of DSM-IV defined depressive and anxiety disorders were established with the Composite International Diagnostic Interview (CIDI). Receiver Operating Characteristic (ROC) analyses were performed to obtain sensitivity and specificity values for a range of scores, and area under the curve (AUC) values as a measure of diagnostic accuracy. RESULTS: With respect to the detection of any depressive or anxiety disorder (180 patients, 61%), the 4DSQ and HADS scales yielded comparable results with AUC values between 0.745 and 0.815. Also with respect to the detection of moderate or severe depressive disorder, the 4DSQ and HADS depression scales performed comparably (AUC 0.780 and 0.739, p 0.165). With respect to the detection of panic disorder, agoraphobia and social phobia, the 4DSQ anxiety scale performed significantly better than the HADS anxiety scale (AUC 0.852 versus 0.757, p 0.001). The recommended cut-off points of both HADS scales appeared to be too low while those of the 4DSQ anxiety scale appeared to be too high. CONCLUSION: In general practice patients on sick leave because of psychological problems, the 4DSQ and the HADS are equally able to detect depressive and anxiety disorders. However, for the detection of cases severe enough to warrant specific treatment, the 4DSQ may have some advantages over the HADS, specifically for the detection of panic disorder, agoraphobia and social phobi

Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium

Aims Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. Methods and results An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. Conclusion Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints

Murine Models and Cell Lines for the Investigation of Pheochromocytoma: Applications for Future Therapies?

Pheochromocytomas (PCCs) are slow-growing neuroendocrine tumors arising from adrenal chromaffin cells. Tumors arising from extra-adrenal chromaffin cells are called paragangliomas. Metastases can occur up to approximately 60% or even more in specific subgroups of patients. There are still no well-established and clinically accepted “metastatic” markers available to determine whether a primary tumor is or will become malignant. Surgical resection is the most common treatment for non-metastatic PCCs, but no standard treatment/regimen is available for metastatic PCC. To investigate what kind of therapies are suitable for the treatment of metastatic PCC, animal models or cell lines are very useful. Over the last two decades, various mouse and rat models have been created presenting with PCC, which include models presenting tumors that are to a certain degree biochemically and/or molecularly similar to human PCC, and develop metastases. To be able to investigate which chemotherapeutic options could be useful for the treatment of metastatic PCC, cell lines such as mouse pheochromocytoma (MPC) and mouse tumor tissue (MTT) cells have been recently introduced and they both showed metastatic behavior. It appears these MPC and MTT cells are biochemically and molecularly similar to some human PCCs, are easily visualized by different imaging techniques, and respond to different therapies. These studies also indicate that some mouse models and both mouse PCC cell lines are suitable for testing new therapies for metastatic PCC

Evaluating the role of quality assessment of primary studies in systematic reviews of cancer practice guidelines

BACKGROUND: The purpose of this study was to evaluate the role of study quality assessment of primary studies in cancer practice guidelines. METHODS: Reliable and valid study quality assessment scales were sought and applied to published reports of trials included in systematic reviews of cancer guidelines. Sensitivity analyses were performed to evaluate the relationship between quality scores and pooled odds ratios (OR) for mortality and need for blood transfusion. RESULTS: Results found that that whether trials were classified as high or low quality depended on the scale used to assess them. Although the results of the sensitivity analyses found some variation in the ORs observed, the confidence intervals (CIs) of the pooled effects from each of the analyses of high quality trials overlapped with the CI of the pooled odds of all trials. Quality score was not predictive of pooled ORs studied here. CONCLUSIONS: Had sensitivity analyses based on study quality been conducted prospectively, it is highly unlikely that different conclusions would have been found or that different clinical recommendations would have emerged in the guidelines

Rationale, design, and results of the first screening round of a comprehensive, register-based, Chlamydia screening implementation programme in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Implementing <it>Chlamydia trachomatis </it>screening in the Netherlands has been a point of debate for several years. The National Health Council advised against implementing nationwide screening until additional data collected from a pilot project in 2003 suggested that screening by risk profiles could be effective. A continuous increase in infections recorded in the national surveillance database affirmed the need for a more active approach. Here, we describe the rationale, design, and implementation of a <it>Chlamydia </it>screening demonstration programme.</p> <p>Methods</p> <p>A systematic, selective, internet-based <it>Chlamydia </it>screening programme started in April 2008. Letters are sent annually to all 16 to 29-year-old residents of Amsterdam, Rotterdam, and selected municipalities of South Limburg. The letters invite sexually active persons to login to <url>http://www.chlamydiatest.nl</url> with a personal code and to request a test kit. In the lower prevalence area of South Limburg, test kits can only be requested if the internet-based risk assessment exceeds a predefined value.</p> <p>Results</p> <p>We sent invitations to 261,025 people in the first round. One-fifth of the invitees requested a test kit, of whom 80% sent in a sample for testing. The overall positivity rate was 4.2%.</p> <p>Conclusions</p> <p>This programme advances <it>Chlamydia </it>control activities in the Netherlands. Insight into the feasibility, effectiveness, cost-effectiveness, and impact of this large-scale screening programme will determine whether the programme will be implemented nationally.</p

Revisiting the dimensional structure of the Edinburgh Postnatal Depression Scale (EPDS): empirical evidence for a general factor

<p>Abstract</p> <p>Background</p> <p>The Edinburgh Postnatal Depression Scale (EPDS) has been proposed as a one-dimensional instrument and used as a single 10-item scale. This might be considered questionable since repeated psychometric studies have shown multi-dimensionality, which would entail using separate component subscales. This study reappraised the dimensional structure of the EPDS, with a focus on the extent of factor correlations and related factor-based discriminant validity as a foundation for deciding how to effectively scale the component items.</p> <p>Methods</p> <p>The sample comprised 811 randomly selected mothers of children up to 5 months attending primary health services of Rio de Janeiro, Brazil. Strict Confirmatory Factor Analysis (CFA) and Exploratory Factor Analysis modeled within a CFA framework (E/CFA) were sequentially used to identify best fitting and parsimonious model(s), including a bifactor analysis to evaluate the existence of a general factor. Properties concerning the related 10-item raw-score scale were also investigated using non-parametric items response theory methods (scalability and monotonicity).</p> <p>Results</p> <p>An initial CFA rejected the one-dimensional structure, while an E/CFA subscribed a three-dimensional solution. Yet, factors were highly correlated (0.66, 0.75 and 0.82). The ensuing CFA showed poor discriminant validity (some square-roots of average variance extracted below the factor correlations). A general bifactor CFA was then fit. Results suggested that, although still weakly encompassing three specific factors, the EPDS might be better described by a model encompassing a general factor (loadings ranging from 0.51 to 0.81). The related 10-item raw score showed adequate scalability (Loevinger's H coefficient = 0.4208), monotonicity e partial double monotonicity (nonintersections of Item Step Response Functions).</p> <p>Conclusion</p> <p>Although the EPDS indicated the presence of specific factors, they do not qualify as independent dimensions if used separately and should therefore not be used empirically as sub-scales (raw scores). An all-encompassing scale seems better suited and continuing its use in clinical practice and applied research should be encouraged.</p