Prader Willi syndrome: systematic review of the prevalence and nature of presentation of unipolar depression

Purpose – The purpose of this paper is to assess the prevalence and nature of presentation of unipolar depression in individuals with Prader-Willi syndrome (PWS). Design/methodology/approach – The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (2009) checklist for systematic reviews was followed where possible. Findings – Seven studies were included in the qualitative synthesis from a total of 261 records identified. The quality of the studies was then assessed: scores for each study design ranged from between 3 and 6 of a possible score total of 6. The frequency of depression ranged between studies from 4 to 22 per cent. four studies showed over 50 per cent of patients appeared to suffer from psychotic symptoms. Low mood, anhedonia and irritability were described as features of depression, although no fixed pattern of psychopathology arose from across the studies (excluding psychosis). This review has provided evidence to suggest that depression is a frequent occurrence in the PWS population. One study found that the incidence of depression differed between the genetic subtypes, raising questions regarding the relationship between genotype and behavioural phenotypes. A high proportion of individuals with depression suffered from psychotic symptoms. Research limitations/implications – The small number of heterogeneous studies included in this study precluded meta-analysis of the results. This highlights the need for further original research in this field. Practical implications – An increased awareness of the frequency of depressive symptoms within the PWS population will aid in the timely diagnosis and management of the disorder which will reduce psychiatric morbidity. The noted high proportion of psychotic symptoms associated with depression should raise the index of suspicion with clinicians and aid appropriate management decisions. Originality/value – This review has provided preliminary evidence for the nature of presentation of unipolar depression in PWS. It has highlighted the possibility of an increased propensity towards depression with psychotic symptoms. There is some suggestion of a differing presentation and course of unipolar depression between the common genetic subtypes of PWS which warrants further investigation

Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer

Background Selective cyclooxygenase inhibitors may retard the progression of cancer, but they have enhanced thrombotic potential. We report on cardiovascular adverse events in patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer. Methods All serious adverse events that were cardiovascular thrombotic events were reviewed in 2434 patients with stage II or III colorectal cancer participating in a randomized, placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated prematurely owing to worldwide withdrawal of rofecoxib. To examine possible persistent risks, we examined cardiovascular thrombotic events reported up to 24 months after the trial was closed. Results The median duration of active treatment was 7.4 months. The 1167 patients receiving rofecoxib and the 1160 patients receiving placebo were well matched, with a median follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months (27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events, 16 occurred in the rofecoxib group during or within 14 days after the treatment period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards model; 95% confidence interval [CI], 1.03 to 6.86; P = 0.04). Analysis of the Antiplatelet Trialists’ Collaboration end point (the combined incidence of death from cardiovascular, hemorrhagic, and unknown causes; of nonfatal myocardial infarction; and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative risk of 1.60 (95% CI, 0.57 to 4.51; P = 0.37). Fourteen more cardiovascular thrombotic events, six in the rofecoxib group, were reported within the 2 years after trial closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94; P = 0.24). Four patients in the rofecoxib group and two in the placebo group died from thrombotic causes during or within 14 days after the treatment period, and during the follow-up period, one patient in the rofecoxib group and five patients in the placebo group died from cardiovascular causes. Conclusions Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular events among patients with a median study treatment of 7.4 months’ duration. (Current Controlled Trials number, ISRCTN98278138.

Methodological Issues in Evaluating Workplace Interventions to Reduce Work-related Musculoskeletal Disorders Through Mechanical Exposure Reduction

Researchers of work-related musculoskeletal disorders are increasingly asked about the evidentiary base for mechanical exposure reductions. Mixed messages can arise from the different disciplinary cultures of evidence, and these mixed messages make different sets of findings incommensurate. Interventions also operate at different levels within workplaces and result in different intensities of mechanical exposure reduction. Heterogeneity in reporting intervention processes and in measuring relevant outcomes makes the synthesis of research reports difficult. As a means of synthesizing the current understanding of measures, this paper describes a set of intervention and observation nodes for which relevant workplace indicators prior to, during, and after mechanical exposure reduction can provide useful information. On the basis of this path of impacts from exposure reduction, an approach to the evaluation of multilevel ergonomic interventions is described that can assist fellow researchers in producing evidence relevant to the challenges faced by workplace parties and policy makers

The impact of hyperhidrosis on patients' daily life and quality of life : A qualitative investigation

Background: An understanding of the daily life impacts of hyperhidrosis and how patients deal with them, based on qualitative research, is lacking. This study investigated the impact of hyperhidrosis on the daily life of patients using a mix of qualitative research methods. Methods: Participants were recruited through hyperhidrosis patient support groups such as the Hyperhidrosis Support Group UK. Data were collected using focus groups, interviews and online surveys. A grounded theory approach was used in the analysis of data transcripts. Data were collected from 71 participants, out of an initial 100 individuals recruited. Results: Seventeen major themes capturing the impacts of hyperhidrosis were identified; these covered all areas of life including daily life, psychological well-being, social life, professional /school life, dealing with hyperhidrosis, unmet health care needs and physical impact. Conclusions: Psychosocial impacts are central to the overall impacts of hyperhidrosis, cutting across and underlying the limitations experienced in other areas of life.Peer reviewe

Extratropical storm inundation testbed : intermodel comparisons in Scituate, Massachusetts

Author Posting. © American Geophysical Union, 2013. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 118 (2013): 5054–5073, doi:10.1002/jgrc.20397.The Integrated Ocean Observing System Super-regional Coastal Modeling Testbed had one objective to evaluate the capabilities of three unstructured-grid fully current-wave coupled ocean models (ADCIRC/SWAN, FVCOM/SWAVE, SELFE/WWM) to simulate extratropical storm-induced inundation in the US northeast coastal region. Scituate Harbor (MA) was chosen as the extratropical storm testbed site, and model simulations were made for the 24–27 May 2005 and 17–20 April 2007 (“Patriot's Day Storm”) nor'easters. For the same unstructured mesh, meteorological forcing, and initial/boundary conditions, intermodel comparisons were made for tidal elevation, surface waves, sea surface elevation, coastal inundation, currents, and volume transport. All three models showed similar accuracy in tidal simulation and consistency in dynamic responses to storm winds in experiments conducted without and with wave-current interaction. The three models also showed that wave-current interaction could (1) change the current direction from the along-shelf direction to the onshore direction over the northern shelf, enlarging the onshore water transport and (2) intensify an anticyclonic eddy in the harbor entrance and a cyclonic eddy in the harbor interior, which could increase the water transport toward the northern peninsula and the southern end and thus enhance flooding in those areas. The testbed intermodel comparisons suggest that major differences in the performance of the three models were caused primarily by (1) the inclusion of wave-current interaction, due to the different discrete algorithms used to solve the three wave models and compute water-current interaction, (2) the criterions used for the wet-dry point treatment of the flooding/drying process simulation, and (3) bottom friction parameterizations.This project was supported by NOAA via the U.S.IOOS Office (award: NA10NOS0120063 and NA11NOS0120141) and was managed by the Southeastern Universities Research Association. The Scituate FVCOM setup was supported by the NOAA-funded IOOS NERACOOS program for NECOFS and the MIT Sea Grant College Program through grant 2012-R/RC-127.2014-04-0

Isothiourea-catalysed enantioselective pyrrolizine synthesis : synthetic and computational studies

We thank Syngenta and the EPSRC (grant code EP/K503162/1) (DGS), and the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT, grant code EP/L016419/1) (ERG,SFM, RWFK) for funding. The European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) ERC Grant Agreement No. 279850 is also acknowledged (JET). ADS thanks the Royal Society for a Wolfson Research Merit Award.The catalytic enantioselective synthesis of a range of cis-pyrrolizine carboxylate derivatives with outstanding stereocontrol (14 examples,>95:5 dr, >98:2 er) through an isothiourea-catalyzed intramolecular Michael addition-lactonisation and ring opening approach from the corresponding enone acid is reported. An optimised and straightforward three-step synthetic route to the enone acid starting materials from readily available pyrrole-2-carboxaldehydes is delineated, with benzotetramisole (5 mol%) proving the optimal catalyst for the enantioselective process. Ring-opening of the pyrrolizine dihydropyranone products with either MeOH or a range of amines leads to the desired products in excellent yield and enantioselectivity. Computation has been used to probe the factors leading to high stereocontrol, with the formation of the observed cis-steroisomer predicted to be kinetically and thermodynamically favoured.Publisher PDFPeer reviewe

Associations between cardiorespiratory fitness, physical activity and clustered cardiometabolic risk in children and adolescents: the HAPPY study

Clustering of cardiometabolic risk factors can occur during childhood and predisposes individuals to cardiometabolic disease. This study calculated clustered cardiometabolic risk in 100 children and adolescents aged 10-14 years (59 girls) and explored differences according to cardiorespiratory fitness (CRF) levels and time spent at different physical activity (PA) intensities. CRF was determined using a maximal cycle ergometer test, and PA was assessed using accelerometry. A cardiometabolic risk score was computed as the sum of the standardised scores for waist circumference, blood pressure, total cholesterol/high-density lipoprotein ratio, triglycerides and glucose. Differences in clustered cardiometabolic risk between fit and unfit participants, according to previously proposed health-related threshold values, and between tertiles for PA subcomponents were assessed using ANCOVA. Clustered risk was significantly lower (p < 0.001) in the fit group (mean 1.21 ± 3.42) compared to the unfit group (mean -0.74 ± 2.22), while no differences existed between tertiles for any subcomponent of PA. Conclusion These findings suggest that CRF may have an important cardioprotective role in children and adolescents and highlights the importance of promoting CRF in youth

Climate change adaptation in European river basins

This paper contains an assessment and standardized comparative analysis of the current water management regimes in four case-studies in three European river basins: the Hungarian part of the Upper Tisza, the Ukrainian part of the Upper Tisza (also called Zacarpathian Tisza), Alentejo Region (including the Alqueva Reservoir) in the Lower Guadiana in Portugal, and Rivierenland in the Netherlands. The analysis comprises several regime elements considered to be important in adaptive and integrated water management: agency, awareness raising and education, type of governance and cooperation structures, information management and—exchange, policy development and—implementation, risk management, and finances and cost recovery. This comparative analysis has an explorative character intended to identify general patterns in adaptive and integrated water management and to determine its role in coping with the impacts of climate change on floods and droughts. The results show that there is a strong interdependence of the elements within a water management regime, and as such this interdependence is a stabilizing factor in current management regimes. For example, this research provides evidence that a lack of joint/participative knowledge is an important obstacle for cooperation, or vice versa. We argue that there is a two-way relationship between information management and collaboration. Moreover, this research suggests that bottom-up governance is not a straightforward solution to water management problems in large-scale, complex, multiple-use systems, such as river basins. Instead, all the regimes being analyzed are in a process of finding a balance between bottom-up and top–down governance. Finally, this research shows that in a basin where one type of extreme is dominant—like droughts in the Alentejo (Portugal) and floods in Rivierenland (Netherlands)—the potential impacts of other extremes are somehow ignored or not perceived with the urgency they might deserv

Managed care and patient ratings of the quality of specialty care among patients with pain or depressive symptoms

BACKGROUND: Managed care efforts to regulate access to specialists and reduce costs may lower quality of care. Few studies have examined whether managed care is associated with patient perceptions of the quality of care provided by physician and non-physician specialists. Aim is to determine whether associations exist between managed care controls and patient ratings of the quality of specialty care among primary care patients with pain and depressive symptoms who received specialty care for those conditions. METHODS: A prospective cohort study design was conducted in the offices of 261 primary physicians in private practice in Seattle in 1997. Patients (N = 17,187) were screened in waiting rooms, yielding a sample of 1,514 patients with pain only, 575 patients with depressive symptoms only, and 761 patients with pain and depressive symptoms. Patients (n = 1,995) completed a 6-month follow-up survey. Of these, 691 patients received specialty care for pain, and 356 patients saw mental health specialists. For each patient, managed care was measured by the intensity of managed care controls in the patient's health plan and primary care office. Quality of specialty care at follow-up was measured by patient rating of care provided by the specialists. Outcomes were pain interference and bothersomeness, Symptom Checklist for Depression, and restricted activity days. RESULTS: The intensity of managed care controls in health plans and primary care offices was generally not associated with patient ratings of the quality of specialty care. However, pain patients in more-managed primary care offices had lower ratings of the quality of specialty care from physician specialists and ancillary providers. CONCLUSION: For primary care patients with pain or depressive symptoms and who see specialists, managed care controls may influence ratings of specialty care for patients with pain but not patients with depressive symptoms

The Relevance of External Quality Assessment for Molecular Testing for ALK Positive Non-Small Cell Lung Cancer:Results from Two Pilot Rounds Show Room for Optimization

Molecular profiling should be performed on all advanced non-small cell lung cancer with non-squamous histology to allow treatment selection. Currently, this should include EGFR mutation testing and testing for ALK rearrangements. ROS1 is another emerging target. ALK rearrangement status is a critical biomarker to predict response to tyrosine kinase inhibitors such as crizotinib. To promote high quality testing in non-small cell lung cancer, the European Society of Pathology has introduced an external quality assessment scheme. This article summarizes the results of the first two pilot rounds organized in 2012-2013.Tissue microarray slides consisting of cell-lines and resection specimens were distributed with the request for routine ALK testing using IHC or FISH. Participation in ALK FISH testing included the interpretation of four digital FISH images.Data from 173 different laboratories was obtained. Results demonstrate decreased error rates in the second round for both ALK FISH and ALK IHC, although the error rates were still high and the need for external quality assessment in laboratories performing ALK testing is evident. Error rates obtained by FISH were lower than by IHC. The lowest error rates were observed for the interpretation of digital FISH images.There was a large variety in FISH enumeration practices. Based on the results from this study, recommendations for the methodology, analysis, interpretation and result reporting were issued. External quality assessment is a crucial element to improve the quality of molecular testing