What proportion of initially prescribed antidepressants is still being prescribed chronically after 5 years in general practice? A longitudinal cohort analysis

Objectives Antidepressant prescribing almost doubled in the Netherlands between 1996 and 2012, which could be accounted for by longer continuation after the first prescription. This might be problematic given a growing concern of large-scale antidepressant dependence. We aimed to assess the extent and determinants of chronic antidepressant prescribing among patient aged 18 years and older. We hypothesise a relatively large prevalence of chronic (&gt;2 years) prescription.Design A longitudinal observational study based on routinely registered prescription data from general practice.Setting 189 general practices in the Netherlands.Participants 326 025 patients with valid prescription data for all 5 years of the study.Outcome measures Primary outcome measure: the number of patients (N) receiving at least four antidepressant prescriptions in 2011, as well as during each of the four subsequent years. Secondary outcome measure: the above, but specified for selective serotonin reuptake inhibitors and for tricyclic antidepressants.Results Antidepressants were prescribed to almost 7% of our 326 025 participants each year. They were prescribed for depression (38%), anxiety (17%), other psychological disorders (20%) and non-psychological indications (25%). Antidepressants were prescribed in all 5 years to the 42% of the population who had at least four prescriptions dispensed in 2011. Chronic prescribing was higher among women than men, for those aged 45-64 years than for those aged &gt; 65 years and for those treated for depression or anxiety than for non-psychological indications (eg, neuropathic pain). Chronic prescribing also varied markedly among general practices.Conclusion Chronic antidepressant use is common for depression and for anxiety and non-psychological diagnoses. Once antidepressants have been prescribed, general practitioners and other prescribers should be aware of the risks associated with long-term use and should provide annual monitoring of the continued need for therapy.</p

Changes in the quality of doctor–patient communication between 1982 and 2001: an observational study on hypertension care as perceived by patients and general practitioners

Background: The rise of evidence-based medicine may have implications for the doctor–patient interaction. In recent decades, a shift towards a more task-oriented approach in general practice indicates a development towards more standardised healthcare. Objective: To examine whether this shift is accompanied by changes in perceived quality of doctor–patient communication. Design: GP observers and patient observers performed quality assessments of Dutch General Practice consultations on hypertension videotaped in 1982–1984 and 2000–2001. In the first cohort (1982–1984) 81 patients were recorded by 23 GPs and in the second cohort (2000–2001) 108 patients were recorded by 108 GPs. The GP observers and patient observers rated the consultations on a scale from 1 to 10 on three quality dimensions: medical technical quality, psychosocial quality and quality of interpersonal behaviour. Multilevel regression analyses were used to test whether a change occurred over time. Results: The findings showed a significant improvement over time on all three dimensions. There was no difference between the quality assessments of GP observers and patient observers. The three different dimensions were moderately to highly correlated and the assessments of GP observers showed less variability in the second cohort. Conclusions: hypertension consultations in general practice in the Netherlands received higher quality assessments by general practitioners and patients on medical technical quality, psychosocial quality and the quality of interpersonal behaviour in 2000–2001 as compared with the 1980s. The shift towards a more task-oriented approach in hypertension consultations does not seem to detract from individual attention for the patient. In addition, there is less variation between general practitioners in the quality assessments of more recent consultations. The next step in this line of research is to unravel the factors that determine patients' quality assessments of doctor–patient communication. (aut.ref.

Concerns voiced by patients and GPs' responses during psychosocial visits in primary care:a historical cross-sectional study

Background: In a recent study comparing psychosocial consultations prior to and after the implementation of national clinical guidelines in the Netherlands, we found that general practitioners (GPs) showed less empathy in the more recent consultations. As a consequence, patients possibly have less scope to express their worries. The objective is to investigate whether patients have become more reluctant to open up about their concerns during psychosocial consultations and how GPs respond. Methods: Consultations from previous study samples videotaped between 1977 and 2008 and categorized by GPs as ‘completely psychosocial’ were selected for the present study. These consultations were observed using the Verona Coding Definitions of Emotional Sequences (VR-CoDES) to capture cues and concerns expressed by patients and GPs’ immediate responses. We compared consultations prior to (N = 121) and after (N = 391) introduction of national clinical guidelines in the 1990s. Results: In 92% of the consultations, patients presented at least one worry. These were most often expressed implicitly. However, the proportion of consultations containing at least one explicit concern changed from 24% to 37% over time. The increased number of expressed cues and concerns was partly explained by a change in GP characteristics; the latter sample contained more female and more experienced GPs. Furthermore, cues and concerns were more often expressed during later phases of consultations in recent years. Conclusions: Our study shows that patients have become somewhat more explicit in expressing their worries. However, GPs need to be aware that, still, most worries are expressed implicitly and that new concerns may appear towards the end of consultations. (aut. ref.

Health beliefs and perceived need for mental health care of anxiety and depression - The patients' perspective explored

Patients' illness representations and beliefs about treatment for depression and anxiety, as well as their perceived needs, are important for treatment. A systematic review was conducted of 71 studies describing the beliefs or perceived needs of patients and non-patients. Patients give multi-dimensional explanations for depression and see both psychological and medication treatment as helpful. People who suffer from depression have more positive beliefs about biological etiology and medication treatment than healthy people, or those with less severe depressive symptoms. Anxiety patients view psychological interventions as their best treatment option. Between 49% and 84% of the patients with depression or anxiety perceive a need for treatment, mostly for counseling and medication. All patients prefer psychological treatment forms to medication. A majority of patients view antidepressants as addictive and many perceive stigma and see practical and economic barriers to care. The most vulnerable groups in terms of seeking and receiving mental health care for depression and anxiety seem to be minority groups, as well as younger and older patients. More research is required into the specific needs of anxiety and depression patients. Open communication between patient and provider could lead to valuable improvements in treatment. (aut. ref.

A new approach to child mental healthcare within general practice

Background: Child and adolescent mental health problems are frequently not identified and properly treated within general practice. Politicians in the Netherlands are promoting more primary healthcare treatment for mental health problems. The current study aims to evaluate an integrated primary mental healthcare approach for child and adolescent emotional and behavioural problems. This integrated approach allows general practitioners (GPs) to comprehensively explore the request for help, followed by an informed decision to refer, offer short-term treatment within general practice or postpone a decision by asking for additional consultations with youth mental health specialists. Method: The study is a naturalistic evaluation of Dutch general practices with pre-test and post-test comparison with controls based on data from Electronic Medical Records (EMR). The intervention started in September 2010. EMR data of all GP contacts with children aged 4 to 18 (including diagnosis, prescriptions, referrals) from practices involved in the intervention was used from 1 January 2009 to 31 December 2012. Extra codes were added to the EMR to record aspects of the intervention. Comparable EMR data was used in control practices in 2011. Results: GPs in the intervention group were able to identify more emotional and behavioural problems after the integrated service had started. They also identified more problems than GPs in the control practices. They were already reluctant to prescribe psychopharmacological medication to children before the intervention, and levels of prescription at intervention GP practices remained low for psychotropic drugs compared to control practices. Referral rates to mental healthcare remained relatively steady after the introduction of the integrated service, but referrals switched from specialized to primary mental healthcare. Conclusion: An integrated mental healthcare approach within general practice may lead to an increase in detected psychosocial problems among children, and these problems can mainly be treated within the primary care setting

Sedentary aging results in structural impairment of the neuromuscular junction and may be attenuated by voluntary endurance exercise

An increasingly prominent change in the aging body is the decrease in muscle mass and strength, a condition known as sarcopenia. This is a major cause for the instability in elderly individuals leading to falls and injuries. One possible cause of sarcopenia is the reduced exercise activity of older individuals. The neuromuscular junction (NMJ) is the connection by which nerves control muscle movement. This study mainly aims to investigates the possibility that alterations in the structures of the neuromuscular junction with ageing might contribute to impaired control and physical maintenance of aging muscle. Changes in the NMJ include the loss of nerve terminal from the postsynaptic membrane leading to denervation and fragmentation of postsynaptic clusters of acetylcholine receptors (AChRs) resulting in tiny islands of receptors. Exercise in ageing animals and humans have shown to have some positive effects on sarcopenic related changes like slowing down the rate of loss in muscle mass and strength. In the neuromuscular junction of old animals and rodents that exercised the age related changes were reported to be less severe and in some cases the NMJ recovered

Spatial concordance of DNA methylation classification in diffuse glioma.

BACKGROUND: Intratumoral heterogeneity is a hallmark of diffuse gliomas. DNA methylation profiling is an emerging approach in the clinical classification of brain tumors. The goal of this study is to investigate the effects of intratumoral heterogeneity on classification confidence. METHODS: We used neuronavigation to acquire 133 image-guided and spatially separated stereotactic biopsy samples from 16 adult patients with a diffuse glioma (7 IDH-wildtype and 2 IDH-mutant glioblastoma, 6 diffuse astrocytoma, IDH-mutant and 1 oligodendroglioma, IDH-mutant and 1p19q codeleted), which we characterized using DNA methylation arrays. Samples were obtained from regions with and without abnormalities on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery MRI. Methylation profiles were analyzed to devise a 3-dimensional reconstruction of (epi)genetic heterogeneity. Tumor purity was assessed from clonal methylation sites. RESULTS: Molecular aberrations indicated that tumor was found outside imaging abnormalities, underlining the infiltrative nature of this tumor and the limitations of current routine imaging modalities. We demonstrate that tumor purity is highly variable between samples and explains a substantial part of apparent epigenetic spatial heterogeneity. We observed that DNA methylation subtypes are often, but not always, conserved in space taking tumor purity and prediction accuracy into account. CONCLUSION: Our results underscore the infiltrative nature of diffuse gliomas and suggest that DNA methylation subtypes are relatively concordant in this tumor type, although some heterogeneity exists

How about your peers? Cystic fibrosis questionnaire data from healthy children and adolescents

Contains fulltext : 97967.pdf (publisher's version ) (Open Access)BACKGROUND: The Cystic Fibrosis Questionnaire (CFQ) is widely used in research as an instrument to measure quality of life in patients with cystic fibrosis (CF). In routine patient care however, measuring quality of life is still not implemented in guidelines. One of the reasons might be the lack of consensus on how to interpret CFQ scores of an individual patient, because appropriate reference data are lacking. The question which scores reflect normal functioning and which scores reflect clinically relevant problems is still unanswered. Moreover, there is no knowledge about how healthy children and adolescents report on their quality of life (on the CFQ). With regard to quality of life the effect of normal development should be taken into account, especially in childhood and adolescence. Therefore, it is important to gain more knowledge about how healthy children and adolescents report on their quality of life and if there are any difference in a healthy populations based on age or gender. Without these data we cannot adequately interpret the CFQ as a tool in clinical care to provide patient-tailored care. Therefore this study collected data of the CFQ in healthy children and adolescents with the aim to refer health status of CF youngsters to that of healthy peers. METHODS: The CFQ was completed by 478 healthy Dutch children and adolescents (aged 6-20) in a cross-sectional study. RESULTS: The majority of healthy children (over 65%) did not reach maximum scores on most domains of the CFQ. Median CFQ-scores of healthy children and adolescents ranged from 67 to 100 (on a scale of 0-100) on the different CFQ-domains. Significant differences in quality of life exist among healthy children and adolescents, and these depend on age and gender. CONCLUSIONS: Reference data of quality of life scores from a healthy population are essential for adequate interpretation of quality of life in young patients with CF. Clinicians should be aware that the perception of health-related quality of life is not as disease-specific as one might think and also relies on factors such as age, normal maturation and gender

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies