Aspects of control and substance use among middle‐aged and older adults with bipolar disorder

High prevalence rates of alcohol and substance use disorders have been reported among persons with bipolar disorder (BD). In the present study, we explored the daily experiences of middle‐aged and older adults living with BD who reported regular substance use and the ways in which participants expressed ‘control’ in relation to their use of alcohol and other substances. Semistructured, in‐depth interviews were conducted with 12 participants (nine women and three men), aged 36–57 years of age (mean = 49 years). Thematic analyses identified emergent themes and patterns in participants’ life histories. The theme of ‘control’ emerged as central to participants’ reports, and was organized into four categories: (i) substance use to control BD symptoms; (ii) substance use provides a sense of being in control; (iii) methods of controlled substance use; and (iv) not having control: overreliance on substances. Implications of the present study include the need for nurses to openly discuss the use of alcohol and other drugs with persons with BD, provide health information and screening, and determine whether persons with BD feel they have control over their substance use. Several lines of research with persons who have BD and use substances are suggested.     

Use of non‐conventional nurses’ attire in a paediatric hospital: a quasi‐experimental study

Aims:  To test the impact of a multi‐coloured non‐conventional attire on a population of children admitted to a paediatric hospital. Design:  Quasi‐experimental before‐after controlled study. Background:  It has been suggested that non‐conventional nurses’ uniforms in paediatric settings may contribute to lowering children’s distrust towards healthcare providers and reduce fear. Little formal research has investigated on the impact of nursing attire in a paediatric setting. No study has so far analysed the effects in actual use of a non‐conventional, other than the traditional type of uniform, on a paediatric hospitalised population. Design:  A quasi‐experimental study. Methods:  We introduced multi‐coloured nurses’ attire in two wards of a paediatric hospital. Using open questions and semantic differential scales (SDS), we evaluated the effects of this non‐conventional attire on a group of hospitalised children, compared to sex‐and‐age‐matched controls interviewed before the introduction. Parents were also interviewed. Results:  One hundred and twelve hospitalised children and their parents (n = 112) were studied. The percentage of positive words used by children to define their nurse was higher in children interviewed after the introduction of non‐conventional uniforms (96·2% vs. 81·8%, p = 0·01). Children’s perception of nurses was significantly improved by the use of multi‐coloured attire (‘bad’–‘good’ SDS: p = 0·01; ‘disagreeable’–‘nice’ SDS: p = 0·001). Children’s perceptions regarding hospital environment did not change. Parents’ perception of nurses’ uniform adequacy to the role and capability to reassure resulted improved (p < 0·0001, p = 0·0003). Conclusions:  Multi‐coloured non‐conventional attire were preferred by hospitalised children and their parents. Their introduction improved the perception children have of their nurses. Moreover, the coloured uniforms improve the parents perception about the reliability of the nurse. Relevance to clinical practice:  The use of non‐conventional nurses’ attire can contribute to improve the child–nurse relation, which has the potential to ease the discomfort experienced by children due to hospitalisation.     

Major bleeding with antithrombotic agents: a 2012–2015 study using the French nationwide Health Insurance database linked to emergency department records within five areas – rationale and design of SACHA study

Bleeding represents the most recognized and feared complications of antithrombotic drugs including oral anticoagulants. Previous studies showed inconsistent results on the safety profile. Among explanations, bleeding definition could vary and classification bias exists related to the lack of medical evaluation. To quantify the risk of major haemorrhagic event and event‐free survival associated with antithrombotic drugs (vitamin K antagonist [VKA], non‐VKA anticoagulant [NOAC], antiplatelet agent, parenteral anticoagulant) in 2012–2015, we linked the French nationwide Health Insurance database (SNIIRAM) with a local ‘emergency database’ (clinical and biological data collected in clinical records). In the VKA‐NOAC comparison, a Cox regression analysis will be used to estimate the hazard ratio of major haemorrhagic event adjusted on gender, modified HAS‐BLED score and comorbidities. A distinction on the type of major haemorrhagic event (intracranial, gastrointestinal and other haemorrhagic events) was made. We present here the study protocol and the database linkage results. Using six linkage keys, among 3 837 557 hospital visits identified in SNIIRAM, 5264 have been matched with a major haemorrhagic event identified in the ‘emergency database’, thus clinically confirmed. The 1090 unmatched haemorrhagic events could be explained by the fact that patients were not extracted in the SNIIRAM database (patients living in accommodation establishment with internal use of pharmacy, military people with specific insurance…). We showed the value of SNIIRAM enrichment with a clinical database, a necessary step to categorize haemorrhagic events by a clinically relevant definition and medical validation; it will allow to estimate more accuracy each type of haemorrhagic event.     

Low serum fetuin‐A concentration predicts poor outcome only in the presence of inflammation in prevalent haemodialysis patients

Background Fetuin‐A, a negative acute phase protein that inhibits vascular calcification, has a controversial association with mortality in chronic kidney disease (CKD) patients. Chronic inflammation, which is common in CKD, may promote vascular calcification. Materials and methods We investigated the impact of inflammation on the relationship between serum fetuin‐A and mortality (42 months) in 222 prevalent haemodialysis (HD) patients. Results Serum fetuin correlated negatively with comorbidity score (assessed by Davies score) and circulating inflammatory markers. Patients with low fetuin‐A levels (< median) had higher mortality (Hazard ratio ‘HR’ 2·2; CI 1·4–3·5, P < 0·001), but this association was lost after adjustment for age, gender, comorbidities score, dialysis vintage and inflammation (CRP > median). In inflamed patients with low fetuin a significantly independent association with mortality (HR 2·3; CI 1·2–4·5, P = 0·01) was observed compared to non‐inflamed patients with high fetuin‐A, after adjusting for the same variables. Non‐inflamed patients with low fetuin‐A and inflamed patients with high fetuin‐A did not have increased mortality compared to non‐inflamed patients with high fetuin‐A. Conclusions The results show that low levels of serum fetuin‐A are associated with increased mortality in HD patients only in the presence of inflammation. This suggests that coexistence of a low serum fetuin‐A level and low‐grade inflammation exerts an additive effect on the risk of death in HD patients.     

Antidepressant‐like effect of bis‐eugenol in the mice forced swimming test: evidence for the involvement of the monoaminergic system

Dehydrodieugenol, known as bis‐eugenol, is a eugenol ortho dimer, and both compounds were able to exhibit anti‐inflammatory and antioxidant activities in previous studies. Furthermore, eugenol showed antidepressant‐like effect; however, the biological actions of bis‐eugenol on experimental models for screening antidepressant activity are still unknown. The present study investigated a possible antidepressant‐like activity of bis‐eugenol in the forced swimming test (FST) and tail suspension test (TST) in mice and the involvement in the monoaminergic system in this effect. In addition, a neurochemical analysis on brain monoamines of mice acutely treated with bis‐eugenol was also conducted. Bis‐eugenol decreased the immobility time in the FST and TST without accompanying changes in ambulation in the open field test at 10 mg/kg, i.p.. Nevertheless, it induced ambulation at 25 and 50 mg/kg doses. The anti‐immobility effect of bis‐eugenol (10 and 50 mg/kg, i.p.) was prevented by pretreatment of mice with p‐chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), yohimbine (1 mg/kg, i.p., an α2‐adrenoceptor antagonist), SCH23390 (15 μg/kg, s.c., a dopamine D1 receptor antagonist) and sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist). Monoamines analysis using high‐performance liquid chromatograph revealed significant increase in the 5‐HT, NE and DA levels in brain striatum. The present study indicates that bis‐eugenol possesses antidepressant‐like activity in FST and TST by altering dopaminergic, serotonergic and noradrenergic systems function.     

ERCC1 and XPD/ERCC2 Polymorphisms’ Predictive Value of Oxaliplatin‐Based Chemotherapies in Advanced Colorectal Cancer has an Ethnic Discrepancy: A Meta‐analysis

Our purpose is to evaluate the predictive value of the genetic polymorphisms of Excision repair cross‐complementing group 1 (ERCC1) and xeroderma pigmentosum group D/excision repair cross‐complementing group 2 (XPD/ERCC2) in patients with advanced colorectal cancer receiving oxaliplatin‐based chemotherapy, and we performed a meta‐analysis in order to obtain a more precise estimation for a more optimizing individual chemotherapy. The relevant cohort studies were identified by searching the electronic databases of MEDLINE, EMBASE, and CNKI. We used ‘‘colorectal,’’ ‘‘cancer,’’ ‘‘carcinoma,’’ ‘‘ERCC1,’’ ‘‘XPD or ERCC2,’’ ‘‘polymorphism,’’ ‘‘oxaliplatin,’’ ‘‘treatment,’’ or ‘‘chemotherapy’’ as key words. Inclusion criteria were patients with advanced colorectal cancer receiving oxaliplatin‐based chemotherapy, evaluation of polymorphism of ERCC1 and XPD/ ERCC2, and overall response rate (ORR). In this meta‐analysis, a total of seven studies were selected according to the inclusion criteria. Five studies investigated ERCC1 codon 118 polymorphisms and three studies evaluated XPD/ERCC2 codon 751 polymorphisms. For ERCC1 codon C118T polymorphism, the ORR to oxaliplatin‐based chemotherapy in patients with C/C wild genotype was 77.27% and it was 69.30% for C/T and T/T variant genotype. The pooled odds ratio (OR) for C/C wild‐type vs. C/T and T/T genotype was 1.11 (95% CI, 0.86–1.42; P = 0.42). For XPD/ERCC2 Lys751Gln polymorphism, the response rate was 86.58 and 67.57% in patients with the A/A and either one or two C alleles (A/C or C/C) respectively, and the pooled OR was 1.15 (95% CI, 1.01–1.30; P = 0.03). Furthermore, we chose subgroup analysis in order to find the difference between the Caucasian and Asian ethnicity. The results indicated that Oxaliplatin sensitivity was significantly associated with ERCC1 C118T polymorphism in Asian people. XPD/ERCC2 Lys751Gln polymorphism had the predictive value especially for the patients from the America and Europe.     

Factors associated with change in health‐related quality of life among individuals treated with long‐term mechanical ventilation,a 6‐year follow‐up study

Aims

To examine changes and explanatory variables for changes in health‐related quality of life in patients treated with long‐term mechanical ventilation over a 6‐year period.

Background

Long‐term mechanical ventilation is a treatment for individuals with chronic hypercapnic respiratory failure, primarily caused by neuromuscular diseases, obesity hypoventilation syndrome, chronic obstructive pulmonary and restrictive thoracic diseases. Studies on long‐term outcome on health‐related quality of life and factors influencing it are lacking.

Design

Prospective cohort study.

Methods

Data were collected from the Norwegian Long‐Term‐Mechanical‐Ventilation Registry and from patient‐reported questionnaire in 2008 and 2014. Health‐related quality of life was measured by the Severe Respiratory Insufficiency questionnaire, containing 49 items and seven subdomains. Linear mixed effects models were used to measure changes and identify factors for changes.

Results

After 6 years, 60 patients were still participating, out of 127 at baseline. Health‐related quality of life improved significantly in the total score and in four subdomains of the questionnaire. Satisfaction with training in long‐term mechanical ventilation was an explanatory variable for improved ‘psychological well‐being’ and follow‐up for improvement of ‘anxiety’. Side effects of the treatment like facial soreness were associated with the total score. High age and high forced vital capacity were related to lower ‘physical function’ and improved ‘social functioning’, respectively.

Conclusion

Long‐term mechanical ventilation over 6 years improved health‐related quality of life in most patients. Patient training, follow‐up and reduction of side effects, largely delivered by trained nurses, contribute to achieve the main goal of the treatment—improved health‐related quality of life.     

Efficacy and safety of ustekinumab and etanercept for the treatment of psoriasis

Importance of the field: TNF-α inhibitors such as etanercept have been used for psoriasis for years. A fairly well defined efficacy and safety profile has developed. A new biologic agent, ustekinumab, an IL-12 and IL-23 inhibitor, has recently been released in the US for the treatment of moderate-to-severe psoriasis. The purpose of this article is to compare the efficacy and safety profiles of ustekinumab and etanercept.

Areas covered in this review: We examined safety and efficacy data regarding ustekinumab and etanercept from clinical reports, a head-to-head trial, review articles, and databases and registries from the last 20 years.

What the reader will gain: Evidence is reviewed about the efficacy for the treatment of psoriasis as well as the safety profiles for both agents, ustekinumab and etanercept.

Take home message: Both drugs have data to confirm efficacy and safety in patients with moderate-to-severe psoriasis in the short-term. The limited long-term data on the safety profile of ustekinumab requires careful judgment on the clinician's part, weighing well-defined benefits and potential unknown risks.     

Brief admission for patients with emotional instability and self‐harm: A qualitative analysis of patients’ experiences during crisis

Previous studies report that individuals diagnosed with borderline personality disorder have been met by negative attitudes from healthcare professionals and their care needs have often been neglected during hospitalizations. When symptoms of emotional instability are combined with self‐harm, the resulting crisis often becomes difficult to handle for patients and healthcare professionals. To meet their care needs during these crises, an intervention called ‘brief admission’ (BA) has been developed. The purpose of BA is to provide a timeout, in situations of increased stress and threat, in order to foster self‐management in a safe environment. In the present study, we explored the following research questions: What are patients’ experiences with BA? What do patients consider to be the key components of BA? What improvements are considered relevant by patients? A qualitative design was employed, and 15 patients (13 females, 2 males; mean age 38.5 ± 12.9, range 20–67 years) were interviewed using a semi‐structured interview guide. Thematic analyses were performed, which yielded four themes related to the patients’ experiences: ‘a timeout when life is tough’, ‘it is comforting to know that help exists’, ‘encouraged to take personal responsibility’, and ‘it is helpful to see the problems from a different perspective’. Four themes also described the key components: ‘a clear treatment plan’, ‘a smooth admission procedure’, ‘a friendly and welcoming approach from the staff’, and ‘daily conversations’. Lastly, three themes described areas for improvements: ‘feeling guilty about seeking BA’, ‘room occupancy issues’, and ‘differences in staff’s competence’. Collectively, the findings indicate that BA constructively supports patients with emotional instability and self‐harm during a period of crisis.     

Adverse drug reactions to self‐medication: a study in a pharmacovigilance database

Although self‐medication is widely developed, there are few detailed data about its adverse drug reactions (ADRs). This study investigated the main characteristics of ADRs with self‐medication recorded in the Midi‐Pyrénées PharmacoVigilance between 2008 and 2014. Self‐medication included first OTC drugs and second formerly prescribed drugs later used without medical advice (reuse of previously prescribed drugs). Among the 12 365 notifications recorded, 160 (1.3%) were related to SM with 186 drugs. Around three‐forth of the ADRs were ‘serious’. Mean age was 48.8 years with 56.3% females. The most frequent ADRs were gastrointestinal and neuropsychiatric and main drug classes involved NSAIDs, analgesics, and benzodiazepines. Phytotherapy–homeopathy accounted for 9.1% of drugs.     

Validation of a clinical algorithm to identify low‐risk patients with pulmonary embolism

Summary. Background: We previously derived a clinical prognostic algorithm to identify patients with pulmonary embolism (PE) who are at low risk of short‐term mortality and who could be safely discharged early or treated entirely in an outpatient setting. Objectives: To externally validate the clinical prognostic algorithm in an independent patient sample. Methods: We validated the algorithm in 983 consecutive patients prospectively diagnosed with PE at an emergency department of a university hospital. Patients with none of the algorithm’s 10 prognostic variables (age ≥ 70 years, cancer, heart failure, chronic lung disease, chronic renal disease, cerebrovascular disease, pulse ≥ 110 min^–1, systolic blood pressure < 100 mmHg, oxygen saturation < 90%, and altered mental status) at baseline were defined as being at low risk. We compared 30‐day overall mortality among low‐risk patients, on the basis of the algorithm, between the validation sample and the original derivation sample. We also assessed the rate of PE‐related and bleeding‐related mortality among low‐risk patients. Results: Overall, the algorithm classified 16.3% of patients with PE as being at low risk. Mortality at 30 days was 1.9% among low‐risk patients, and did not differ between the validation sample and the original derivation sample. Among low‐risk patients, only 0.6% died from definite or possible PE, and 0% died from bleeding. Conclusions: This study validates an easy‐to‐use, clinical prognostic algorithm for PE that accurately identifies patients with PE who are at low risk of short‐term mortality. Patients who are at low risk according to our algorithm are potential candidates for less costly outpatient treatment.     

Are lipid‐lowering drugs associated with a risk of cataract? A pharmacovigilance study

Some reports have raised concerns regarding a potential risk of cataracts associated with statins. However, clinical and observational studies evaluating the risk led to conflicting results. We assessed whether lipid‐lowering drugs (LLD) use is associated with an increased risk of cataract using the WHO's Individual Case Safety Reports database, VigiBase^®. We performed a disproportionality analysis with all reports between 1/1/1988 and 12/31/2018 to measure the reporting risk of ‘cataract’ in patients ≥45 years. Primary analysis compared LLD users to non‐users. To mitigate some potential confounding bias, we performed several sensitivity analyses excluding reports (i) with an association of at least two LLD, (ii) with antidiabetic and glucocorticoids and (iii) with lovastatin. We also analyzed the data according to the different classes of age limiting the period of study to years 2002–2012. We identified 14 664 reports of cataract (3 049 in LLD users, 66% women, 66 ± 20 years). Statins (84%, atorvastatin, simvastatin, rosuvastatin and lovastatin) were mostly reported, followed by fibrates (5.7%), nicotinic acid (3%), bile acid sequestrants (2%), herbal cholesterol and triglyceride reducers (2%) and others (ezetimibe, PCSK9 inhibitors, 15%). LLD users were associated with a greater risk of reports than non‐users (ROR 2.47, 95% CI 2.37–2.57). This association was also found for statins in general, fibrates, bile sequestrants, nicotinic acid, herbal drugs and others. Similar trends were observed in sensitivity analyses (except for fibrates and nicotinic acid after exclusion of reports with at least two LLD or in older patients ≥75 years). Using a large real‐life database (>18.5 million reports), we found a signal of cataract for LLD as a whole and statins, bile sequestrants and herbal drugs in particular. The signal disappeared for fibrates and nicotinic acid in older patients. No definite conclusions can be made for ezetimibe or PCSK9 inhibitors (evolocumab and alirocumab). This suggests that a decrease in cholesterol could be important in the pathophysiology of cataract in patients exposed to the main LLD.     

INR targets and site‐level anticoagulation control: results from the Veterans AffaiRs Study to Improve Anticoagulation (VARIA)

Summary. Background: Not all clinicians target the same International Normalized Ratio (INR) for patients with a guideline‐recommended target range of 2–3. A patient’s mean INR value suggests the INR that was actually targeted. We hypothesized that sites would vary by mean INR, and that sites of care with mean values nearest to 2.5 would achieve better anticoagulation control, as measured by per cent time in therapeutic range (TTR).Objectives: To examine variations among sites in mean INR and the relationship with anticoagulation control in an integrated system of care.Patients/Methods: We studied 103 897 patients receiving oral anticoagulation with an expected INR target between 2 and 3 at 100 Veterans Health Administration (VA) sites from 1 October 2006 to 30 September 2008. Key site‐level variables were: proportion near 2.5 (that is, percentage of patients with mean INR between 2.3 and 2.7) and mean risk‐adjusted TTR.Results: Site mean INR ranged from 2.22 to 2.89; proportion near 2.5, from 30 to 64%. Sites’ proportions of patients near 2.5, below 2.3 and above 2.7 were consistent from year to year. A 10 percentage point increase in the proportion near 2.5 predicted a 3.8 percentage point increase in risk‐adjusted TTR (P < 0.001).Conclusions: Proportion of patients with mean INR near 2.5 is a site‐level ‘signature’ of care and an implicit measure of targeted INR. This proportion varies by site and is strongly associated with site‐level TTR. Our study suggests that sites wishing to improve TTR, and thereby improve patient outcomes, should avoid the explicit or implicit pursuit of non‐standard INR targets.     

High sensitivity cardiac troponin T and interleukin‐6 predict adverse cardiovascular events and mortality in anticoagulated patients with atrial fibrillation

Summary. There are limited data on the prognostic role of biomarkers in anticoagulated patients with atrial fibrillation (AF). We evaluated the prognostic value of high sensitivity TnT (hsTnT) and high‐sensitivity interleukin‐6 (hsIL6) in a large cohort of AF patients taking oral anticoagulant therapy (OAC) as both biomarkers have been associated with adverse cardiovascular events. Methods: We studied 930 patients (51% male; median age 76) with permanent/ paroxysmal AF who were stabilized (for at least 6 months) on OAC (INRs 2.0–3.0). Plasma hsTnT and hsIL6 levels were quantified by electrochemiluminescense immunoassay at baseline. Patients were followed‐up for up to 2 years, and adverse events (thrombotic and vascular events, mortality and major bleeding) were recorded. Results: At follow‐up, 96 patients (3.97%/year) died whilst 107 had an adverse cardiovascular event (3.14%/year). On multivariate analysis, high hsTnT and high hsIL6 remained significantly associated with prognosis even after adjusting for CHADS₂ score: HR 2.21 (1.46–3.35, P < 0.001) for high hsTnT and 1.97 (1.29–3.02, P = 0.002) for high hsIL6, for adverse cardiovascular events. For all‐cause mortality, the HRs were 1.79 (1.13–2.83, P = 0.013) and 2.48 (1.60–3.85, P < 0.001), respectively. The integrated discrimination index (IDI) values of clinical scores (CHADS₂ and CHA₂DS₂‐VASc) were improved by the addition of hsTnT and/or hsIL6 (all P < 0.05). Conclusion: In a large ‘real world’ cohort of anticoagulated AF patients, both hsTnT and hsIL6 levels provided prognostic information that was complementary to clinical risk scores for prediction of long‐term cardiovascular events and death, suggesting that these biomarkers may potentially be used to refine clinical risk stratification in AF.     

Comparison of QuantiFERON TB‐G‐test to TST for detecting latent tuberculosis infection in a high‐incidence area containing BCG‐vaccinated population

Objective Until recently, the only tool for detection of latent tuberculosis infection (LTBI) was the tuberculin skin test (TST). QuantiFERON‐TB Gold In‐Tube test (QFT) is a promising in vitro diagnostic test for LTBI that has potential advantages over the TST. In this study we aimed to compare QFT with TST for diagnosis of LTBI. Patients and methods A total of 186 BCG‐vaccinated subjects enrolled in study. They underwent TST and QFT assay. They divided in two groups. Group 1 includes individuals who were at low risk for exposure to M. tuberculosis (LRG) and Group 2 includes individuals who were likely to have been exposed to M. tuberculosis infections (HRG). Results Overall agreement between QFT and TST was 89.3% (kappa = 0.052). In LRG, agreement between the two tests was 52.6% (95% confidence interval, 44–60%) with κ‐values of 0.019. In HRG agreement between the two tests was 63.2% (95% confidence interval, 42–84%) with κ‐values of 0.28. Conclusion In conclusion, the QFT assay showed acceptable results for determining latent M. tuberculosis infection in vaccinated population. The decision to select QFT over TST will depend on the population, purpose of testing and resource availability.     

Asystole and increased serum myoglobin levels associated with ‘packing blackout’ in a competitive breath‐hold diver

Many competitive breath‐hold divers use ‘glossopharyngeal insufflation’, also called ‘lung packing’, to overfill their lungs above normal total lung capacity. This increases intrathoracic pressure, decreases venous return, compromises cardiac pumping, and reduces arterial blood pressure, possibly resulting in a syncope breath‐hold divers call ‘packing blackout’. We report a case with a breath‐hold diver who inadvertently experienced a packing blackout. During the incident, an electrocardiogram (ECG) and blood pressure were recorded, and blood samples for determinations of biomarkers of cardiac muscle perturbation (creatine kinase‐MB isoenzyme (CK‐MB), cardiac troponin‐T (TnT), and myoglobin) were collected. The ECG revealed short periods of asystole during the period of ‘packing blackout’, simultaneous with pronounced reductions in systolic, diastolic, and pulse pressures. Serum myoglobin concentration was elevated 40 and 150 min after the incident, whereas there were no changes in CK‐MB or TnT. The ultimate cause of syncope in this diver probably was a decrease in cerebral perfusion following glossopharyngeal insufflation. The asystolic periods recorded in this diver could possibly indicate that susceptible individuals may be put at risk of a serious cardiac incident if the lungs are excessively overinflated by glossopharyngeal insufflation. This concern is further substantiated by the observed increase in serum myoglobin concentration after the event.