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Recently, attention has focused on a potential link between schizophrenia and diabetes, with speculation that this potential associationis stronger in patients who are prescribed atypical antipsychotics. Pharmacoepidemiological studies can help to evaluate this potential association. Source data on the incidence of diabetes in patients treated with antipsychotics is available in the FDA MedWatch database, prescription claims databases and other patient registries. These data indicate that antipsychotic drugs may increase the risk of developing diabetes and that there may be an interaction with age. However, current data are insufficient to accurately assess potential differences in the risk of diabetes between users of individual antipsychotic medications. In addition, antipsychotic treatment-emergent diabetes has several distinct features, notably relating to age of onset, gender ratio, rate of deterioration of glycaemic control, and independence from initial treatment emergent weight gain. Nonetheless, guidelines for the control of risk factors for diabetes developed for the general population appear to be applicable to patients with schizophrenia.
Adding another antipsychotic to a treatment regimen was previously used in evaluating the medication's efficacy. Supplementation of depot antipsychotics with oral antipsychotics is particularly meaningful because depot formulations are typically chosen for patients struggling with adherence to oral antipsychotics. This post-hoc analysis assessed supplementation of olanzapine long-acting injection (olanzapine-LAI) with oral olanzapine.
Subjects and methods
We used 12 months of data from an open-label, single-arm extension study of patients with schizophrenia or schizoaffective disorder (N = 931) treated with olanzapine-LAI. The prevalence, duration, time to first supplementation, and best predictors of oral supplementation were assessed.
Oral supplementation occurred in 21% of patients for a median of 31 days with mean modal dose of 10.8 mg/day. Mean time to first supplementation was shorter for patients who were at least moderately ill at baseline compared to less ill patients (47 vs. 97 days, p < 0.001). Best predictors of oral supplementation included a more severe illness profile at baseline, lower olanzapine-LAI dose prior to oral supplementation, supervised living arrangements, and being African-American.
Supplementation of olanzapine-LAI appears to be infrequent, of relatively short duration, and reserved for more severely ill patients who may require a targeted rescue medication due to signs of impending relapse.
Agitation is a common symptom in schizophrenia and bipolar mania, causing marked distress and posing considerable risks for patients. Intramuscular formulations of psychotropic medication can provide a fast acting treatment of severe agitation in patients with acute episodes of schizophrenia or mania. As effective as these treatments are, particular antipsychotics can be associated with a heightened risk of dystonia and related Extrapyramidal Symptoms (EPS). Patients presenting to emergency care settings are also likely to have coexisting intoxications and medical conditions that may contribute to this risk.
The aim of this observational prospective study was to document the safety and effectiveness of all IM psychotropic drugs during the 24 hours following an initial injection in acutely agitated patients suffering from schizophrenia or bipolar disorder under naturalistic conditions.
Two-hundred-thirty-two (232) participating investigator sites (12 European countries) observed 1940 patients (mean age: 39 y, 42% female, 66% schizophrenia diagnosis). The primary endpoint was the occurrence of extrapyramidal symptoms (EPS), further endpoints were clinical severity measured by PANSS-EC and CGI-S. A total of 1311 (68%) patients received a monotherapy injection at baseline. Within 24 hours after the first injection, 190 (10%) of all 1940 patients experienced EPS. All intramuscular psychotropic drugs were shown to be effective in reducing measures of acute agitation.
This study provides favourable results on EPS related adverse events and effectiveness of intramuscular psychotropic medication for the management of acute agitation in patients within a naturalistic setting during the first 24 hours of treatment.
To compare CATIE, a randomized double blind study, and SOHO, a 3-year prospective non-randomized observational European study of outpatients with schizophrenia, on the Number Needed to Treat (NNT) for all-cause medication discontinuation. NNTs place data into a clinically meaningful context - the number of patients needed to be treated with one antipsychotic instead of another to prevent one negative outcome, defined here as one additional medication discontinuation for any cause.
Rate of medication discontinuation for any cause during the 18 months post initiation was calculated for patients newly initiated on olanzapine (N=4247), risperidone (N=1549), quetiapine (N=583), amisulpride (N=256), clozapine (N=274), oral typicals (N=471) or depot typicals (N=348). Cox models were employed to adjust for treatment group differences at baseline. NNTs with their 95% confidence intervals were calculated and compared with published NNTs for CATIE (Phase 1).
The NNTs for all-cause discontinuation of olanzapine vs. each studied atypical antipsychotic during the 18 month following medication initiation in SOHO were comparable to CATIE: 4.3(95% CI: 3.6–5.3) for olanzapine vs. quetiapine (5.5 in CATIE); 16.1(11.0–28.1) for olanzapine vs. risperidone (10.1 in CATIE); 6.9(5.2–10.1) for olanzapine vs. oral typicals (9.0 in CATIE for olanzapine vs. perphenazine).
The NNTs for all-cause medication discontinuation based on CATIE appeared comparable to NNTs based on SOHO. The NNTs for olanzapine therapy were consistently better when compared to each studied atypical antipsychotic (except clozapine) and when compared to typical antipsychotics. Results should be interpreted conservatively, due to the observational design of SOHO.
To contrast the outcomes of olanzapine- and valproate-treated patients in an observational study of acute mania with the results of a RCT assessing the same treatments (Tohen et al., 2002).
EMBLEM (European Mania in Bipolar Evaluation of Medication) was a 2-year, prospective, observational study of health outcomes associated with treatment of mania. Severity of mania and depression was assessed at baseline and 6 weeks using the YMRS and 5-item version of the HAMD, respectively. The RCT was a 3-week, randomised, double-blind comparison of olanzapine (n=125) and divalproate-treated (n=123) patients hospitalised for acute manic or mixed episodes. The YMRS and HAMD were used to quantify manic and depressive symptoms, respectively.
621 EMBLEM patients were analysed (n=107 valproate, n=514 olanzapine). Both observed groups improved from baseline to 6 weeks in mean YMRS and HAMD-5 total scores, with significantly greater mean improvements in the olanzapine compared with the valproate group using linear regression to adjust for baseline differences. The RCT reported significantly greater mean YMRS improvement (but not HAMD) in the olanzapine-treated group. EMBLEM patients treated with olanzapine experienced significantly greater weight gain than patients treated with valproate, similar to RCT results. There was a significantly greater incidence of treatment-emergent gastrointestinal adverse events in EMBLEM patients treated with valproate.
The EMBLEM results support those of the RCT, which suggest that olanzapine monotherapy may be more effective than valproate monotherapy in the treatment of acute mania. Contrasting observational and RCT results present methodological challenges but can provide important complementary information.
This naturalistic, observational pan-European study assessed the safety and early effectiveness of intramuscular (IM) psychotropic treatments in patients with acute agitation suffering from schizophrenia or bipolar mania. One thousand nine hundred and forty of 1945 patients completed the 24-hour observation period after initial IM treatment. Patients from 12 European countries were included (mean age 39 years; 58% male, 66% schizophrenia). IM treatment was at the physician's discretion. The primary objective was to describe the acute tolerability of IM psychotropic therapies in clinical practice, with particular emphasis on EPS. At baseline, 68% of the patients received IM monotherapy, with IM olanzapine most commonly prescribed (36%). During the first 24hours, 190 (9.8%) patients experienced EPS. The occurrence of EPS was statistically significantly lower in patients treated with IM olanzapine compared to those treated with other IM psychotropic medications (mainly typical antipsychotics and benzodiazepines): acute dystonia: 1.1%, 95% CI 0.5–2.3 and 2.9%, CI 2.0–4.0; akathisia: 2.3%, CI 1.3–3.7 and 5.5%, CI 4.3–6.9; Parkinsonism: 2.9%, CI 1.8–4.4 and 7.8%, CI 6.4–9.4, respectively. Anticholinergic treatment was given to 12% IM olanzapine versus 31% non-olanzapine treated patients. Acute agitation after 24hours was reduced by 1.68 (95% CI 1.46–1.91) points on the Clinical Global Impression of Severity (CGI-S) in IM olanzapine patients and 1.51 (95% CI 1.30–1.73) points in non-olanzapine patients. Additional psychotropic medication was required for 90% of the patients during the first 24hours of treatment. Results provide naturalistic evidence for low EPS rates and improvement of agitation with IM psychotropic medications during acute states of patients suffering from acute mania or schizophrenia.
The patient portal may be an effective method for administering surveys regarding participant research experiences but has not been systematically studied.
We evaluated 4 methods of delivering a research participant perception survey: mailing, phone, email, and patient portal. Participants of research studies were identified (n=4013) and 800 were randomly selected to receive a survey, 200 for each method. Outcomes included response rate, survey completeness, and cost.
Among those aged <65 years, response rates did not differ between mail, phone, and patient portal (22%, 29%, 30%, p>0.07). Among these methods, the patient portal was the lowest-cost option. Response rates were significantly lower using email (10%, p<0.01), the lowest-cost option. In contrast, among those aged 65+ years, mail was superior to the electronic methods (p<0.02).
The patient portal was among the most effective ways to reach research participants, and was less expensive than surveys administered by mail or telephone.
A study was carried out, from 2012 to 2015, in 10 French départements to estimate the serological prevalence of Q fever and the frequency of abortive episodes potentially related to Coxiella burnetii in a large sample of cattle, sheep and goat herds. The serological survey covered 731 cattle, 522 sheep and 349 goat herds, randomly sampled. The frequency of abortive episodes potentially related to C. burnetii was estimated by investigating series of abortions in 2695 cattle, 658 sheep and 105 goat herds using quantitative polymerase chain reaction analyses and complementary serological results when needed. The average between-herd seroprevalence was significantly lower for cattle (36·0%) than for sheep (55·7%) and goats (61·0%) and significantly higher for dairy herds (64·9% for cattle and 75·6% for sheep) than for meat herds (18·9% for cattle and 39·8% for sheep). Within-herd seroprevalence was also significantly higher for goats (41·5%) than for cattle (22·2%) and sheep (25·7%). During the study period, we estimated that 2·7% (n = 90), 6·2% (n = 48) and 16·7% (n = 19) of the abortive episodes investigated could be ‘potentially related to C. burnetii’in cattle, sheep and goat herds, respectively. Overall, strong variability was observed between départements and species, suggesting that risk factors such as herd density and farming practices play a role in disease transmission and maintenance.
Bodily isomerism, also referred to as heterotaxy, involves predominantly the thoracic organs, although other organs are usually abnormally positioned. Previously assessed on the basis of splenic anatomy, it is now understood that isomerism is better segregated on the basis of atrial appendage morphology. This allows for anticipation of associated findings. We aimed to assess the accuracy of segregation based on the morphology of the atrial appendages and other structures more easily identified by echocardiography.
We reviewed postmortem specimens of hearts from the archives at four institutions categorised as obtained from patients with “heterotaxy”. The cardiac structures were analysed using sequential segmental analysis. Non-cardiac structures were also examined if available. Statistical analyses were performed to compare differences in the settings of right as opposed to left isomerism.
Specimens were available from 188 patients. Of these, 57 had left isomerism, and 131 had right isomerism. Atrial appendages were isomeric in all patients. A coronary sinus was found only in left isomerism, whereas a terminal crest, or a Eustachian valve, was found only in right isomerism. Interruption of the inferior caval vein was associated with left isomerism, whereas totally anomalous pulmonary venous connection was associated with right isomerism.
Isomerism is uniformly segregated on the basis of the morphology of the atrial appendages, itself defined by the extent of the pectinate muscles. Other features such as the presence of a coronary sinus and systemic venous return can further help with such segregation of isomerism.
To examine temporal trends and determinants of discretionary salt use in the USA.
Multiple logistic regression was used to assess temporal trends in discretionary salt use at the table and during home cooking/preparation, adjusting for demographic characteristics, using data from the National Health and Nutrition Examination Survey 2003–2012. Prevalence and determinants of discretionary salt use in 2009–2012 were also examined.
Participants answered salt use questions after completing a 24 h dietary recall in a mobile examination centre.
Nationally representative sample of non-institutionalized US children and adults, aged ≥2 years.
From 2003 to 2012, the proportion of the population who reported using salt ‘very often’ declined; from 18 % to 12 % for use at the table (P<0·01) and from 42 % to 37 % during home cooking (P<0·02). While one-third of the population reported never adding salt at the table, most used it during home cooking/preparation (93 %). Use of discretionary salt was least commonly reported among young children and older adults and demographic and health subgroups at risk of CVD.
While most people reported using salt during home cooking/preparation, a minority reported use at the table. Reported ‘very often’ discretionary salt use has declined. That discretionary salt use is less common among those at risk of CVD suggests awareness of messages to limit Na intake.
This study uses the eigenvalues of the local velocity gradient tensor to categorize the local flow structures in incompressible turbulent flows into different types of saddle nodes and vortices and investigates their effect on the local collision kernel of heavy particles. Direct numerical simulation (DNS) results show that most of the collisions occur in converging regions with real and negative eigenvalues. Those regions are associated not only with a stronger preferential clustering of particles, but also with a relatively higher collision kernel. To better understand the DNS results, a conceptual framework is developed to compute the collision kernel of individual flow structures. Converging regions, where two out of three eigenvalues are negative, posses a very high collision kernel, as long as a critical amount of rotation is not exceeded. Diverging regions, where two out of three eigenvalues are positive, have a very low collision kernel, which is governed by the third and negative eigenvalue. This model is not suited for particles with Stokes number
, where the contribution of particle collisions from caustics is dominant.
To examine the association between overweight and obesity and serum ferritin among women of reproductive age (15–49 years) in Nicaragua, considering the effect of α1-acid glycoprotein (AGP), a marker of inflammation.
We analysed data from the 2004–05 Nicaraguan Integrated Surveillance System for Nutrition Interventions. Three logistic regression models were analysed with low serum ferritin (<15 μg/l) as the dependent variable: (i) overweight or obese status and covariates; (ii) model 1 plus AGP; and (iii) model 1 restricted to only women with normal AGP levels (≤1·0 g/l).
Included in this analysis were 832 non-pregnant mother/caregivers (15–49 years) surveyed in 2004–2005.
In the sample, prevalence of overweight and obesity was 31·8 % and 19·2 %, respectively, and 27·6 % had low serum ferritin. In model 1, the adjusted OR of low serum ferritin was 0·74 (95 % CI 0·52, 1·05) for overweight women and 0·42 (95 % CI 0·26, 0·65) for obese women. In model 2, AGP was significantly independently associated with low serum ferritin (adjusted OR=0·56, 95 % CI 0·34, 0·92) while the adjusted OR for overweight and obesity were largely unchanged. Excluding women with elevated AGP did not appreciably affect the relationship between overweight or obesity and low serum ferritin (model 3).
Overall, in this population of reproductive-age women, obese women were less likely to have low serum ferritin levels, and this was independent of inflammation as measured by AGP.
A prevalence survey of methicillin-resistant Staphylococcus aureus (MRSA) was performed in 2010 in 19 long-term care facilities in Luxembourg. Of the 954 participating residents, 69 (7·2%) were colonized by MRSA. Previous history of MRSA [odds ratio (OR) 7·20, 95% confidence interval (CI) 3·19–16·27], quinolone therapy in the previous year (OR 2·27, 95% CI 1·17–4·41) and ⩾24 h care administered per week (OR 4·29, 95% CI 1·18–15·56) were independent risk factors for MRSA colonization. More than 75% of strains were of clonal complex (CC)5, mainly spa-type t003 or sequence type (ST)225 and ST710, which is a rapidly emerging lineage prevalent in central Europe. Five residents were colonized by livestock-associated genotypes belonging to CC398. Previously dominant CC8 strains have recently been replaced by more resistant CC5 strains in Luxembourg.
The first UK epizootic of highly pathogenic (HP) H5N1 influenza in wild birds occurred in 2008, in a population of mute swans that had been the subject of ornithological study for decades. Here we use an innovative combination of ornithological, phylogenetic and immunological approaches to investigate the ecology and age structure of HP H5N1 in nature. We screened samples from swans and waterbirds using PCR and sequenced HP H5N1-positive samples. The outbreak's origin was investigated by linking bird count data with a molecular clock analysis of sampled virus sequences. We used ringing records to reconstruct the age-structure of outbreak mortality, and we estimated the age distribution of prior exposure to avian influenza. Outbreak mortality was low and all HP H5N1-positive mute swans in the affected population were <3 years old. Only the youngest age classes contained an appreciable number of individuals with no detectable antibody responses to viral nucleoprotein. Phylogenetic analysis indicated that the outbreak strain circulated locally for ∼1 month before detection and arrived when the immigration rate of migrant waterbirds was highest. Our data are consistent with the hypothesis that HP H5N1 epizootics in wild swans exhibit limited mortality due to immune protection arising from previous exposure. Our study population may represent a valuable resource for investigating the natural ecology and epidemiology of avian influenza.
We prove that the quantum cohomology ring of any minuscule or cominuscule homogeneous space, specialized at $q\,=\,1$, is semisimple. This implies that complex conjugation defines an algebra automorphism of the quantum cohomology ring localized at the quantum parameter. We check that this involution coincides with the strange duality defined in our previous article. We deduce Vafa–Intriligator type formulas for the Gromov–Witten invariants.