NICE guidelines are the accepted standard for determining the management of hypertension in UK primary care.
To explore adherence and non-adherence to NICE hypertension guidelines, the extent to which this influences blood pressure control, and the role of ethnicity.
Design and setting
A cross-sectional study was conducted based on primary care data from Lambeth DataNet, a database of primary care records in one inner-city London borough.
NICE guidelines were used to determine adherence to recommended treatment options for four groups of patients with hypertension: aged <55 years on monotherapy; aged ≥55 years on monotherapy; any age on dual therapy; any age and with comorbid diabetes. Blood pressure control was determined for each treatment category and ethnic group. The study controlled for age, sex, social deprivation, and clustering within general practices.
A total of 32 183 patients were identified with a current diagnosis of hypertension. Ethnic coding was available for 28 320 (88.0%). Overall, 13 546 patients with ethnicity coding could be allocated to one of the four clinical categories of hypertension; 44% of these patients received non-guideline-adherent treatment; ethnicity was not a significant determinant. Mean arterial pressure did not differ significantly between those receiving ‘correct’ or ‘incorrect’ hypotensive therapy.
Evidence-based guidelines for the management of hypertension were not followed in a relatively large proportion of patients included in this study. Nevertheless, no evidence was found that failure to follow treatment recommendations resulted in poorer blood pressure control. Further work is needed to determine the reasons for non-implementation of guideline recommendations in primary care.
ethnicity; guidelines; hypertension; primary care
The Dominantly Inherited Alzheimer Network (DIAN) is a collaborative effort of international Alzheimer disease (AD) centers that are conducting a multifaceted prospective biomarker study in individuals at-risk for autosomal dominant AD (ADAD). DIAN collects comprehensive information and tissue in accordance with standard protocols from asymptomatic and symptomatic ADAD mutation carriers and their non-carrier family members to determine the pathochronology of clinical, cognitive, neuroimaging, and fluid biomarkers of AD. This article describes the structure, implementation, and underlying principles of DIAN, as well as the demographic features of the initial DIAN cohort.
Alzheimer disease; autosomal dominant; biomarkers of Alzheimer disease; PSEN1; PSEN2; APP; amyloid-beta; preclinical Alzheimer disease
To determine the frequency of a hexanucleotide repeat expansion in C9ORF72, a gene of unknown function implicated in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), in Australian FTD patient cohorts and to examine the clinical and neuropathologic phenotypes associated with this expansion.
We examined a clinically ascertained FTD cohort (n = 89) and a neuropathologically ascertained cohort of frontotemporal lobar degeneration cases with TDP-43 pathology (FTLD-TDP) (n = 22) for the C9ORF72 hexanucleotide repeat expansion using a repeat primed PCR assay. All expansion-positive patients were genotyped for rs3849942, a surrogate marker for the chromosome 9p21 risk haplotype previously associated with FTD and ALS.
The C9ORF72 repeat expansion was detected in 10% of patients in the clinically diagnosed cohort, rising to 29% in those with a positive family history of early-onset dementia or ALS. The prevalence of psychotic features was significantly higher in expansion-positive cases (56% vs 14%). In the pathology cohort, 41% of TDP-43-positive cases harbored the repeat expansion, and all exhibited type B pathology. One of the 17 expansion-positive probands was homozygous for the “nonrisk” G allele of rs3849942.
The C9ORF72 repeat expansion is a relatively common cause of FTD in Australian populations, and is especially common in those with FTD-ALS, psychotic features, and a strong family history. Detection of a repeat expansion on the 9p21 putative “nonrisk” haplotype suggests that not all mutation carriers are necessarily descended from a common founder and indicates that the expansion may have occurred on multiple haplotype backgrounds.
Frontotemporal dementia (FTD) is associated with motor neurone disease (FTD-MND), corticobasal syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS). Together, this group of disorders constitutes a major cause of young-onset dementia. One of the three clinical variants of FTD is progressive nonfluent aphasia (PNFA), which is focused on in this study. The steroid hormone progesterone (PROG) is known to have an important role as a neurosteroid with potent neuroprotective and promyelination properties. In a case-control study of serum samples (39 FTD, 91 controls), low serum PROG was associated with FTD overall. In subgroup analysis, low PROG levels were significantly associated with FTD-MND and CBS, but not with PSPS or PNFA. PROG levels of >195 pg/ml were significantly correlated with lower disease severity (frontotemporal dementia rating scale) for individuals with CBS. In the human neuroblastoma SK-N-MC cell line, exogenous PROG (9300–93,000 pg/ml) had a significant effect on overall Tau and nuclear TDP-43 levels, reducing total Tau levels by ∼1.5-fold and increasing nuclear TDP-43 by 1.7- to 2.0-fold. Finally, elevation of plasma PROG to a mean concentration of 5870 pg/ml in an Ala315Thr (A315T) TARDBP transgenic mouse model significantly reduced the rate of loss of locomotor control in PROG-treated, compared with placebo, mice. The PROG treatment did not significantly increase survival of the mice, which might be due to the limitation of the transgenic mouse to accurately model TDP-43-mediated neurodegeneration. Together, our clinical, cellular and animal data provide strong evidence that PROG could be a valid therapy for specific related disorders of FTD.
The microtubule-associated protein tau gene (MAPT) codes for a protein that plays an integral role in stabilisation of microtubules and axonal transport in neurons. As well as its role in susceptibility to neurodegeneration, previous studies have found an association between the MAPT haplotype and intracranial volume and regional grey matter volumes in healthy adults. The glycogen synthase kinase-3β gene (GSK3B) codes for a serine/threonine kinase that phosphorylates various proteins, including tau, and has also been associated with risk for neurodegenerative disorders and schizophrenia. We examined the effects of MAPT and two functional promoter polymorphisms in GSK3B (rs3755557 and rs334558) on total grey matter and intracranial volume in three independent cohorts totaling 776 neurologically healthy individuals. In vitro analyses revealed a significant effect of rs3755557 on gene expression, and altered binding of at least two transcription factors, Octamer transcription factor 1 (Oct-1) and Pre-B-cell leukemia transcription factor 1 (Pbx-1), to the GSK3B promoter. Meta-analysis across the three cohorts revealed a significant effect of rs3755557 on total grey matter volume (summary B = 0.082, 95% confidence interval = 0.037–0.128) and intracranial volume (summary B = 0.113, 95% confidence interval = 0.082–0.144). No significant effect was observed for MAPT H1/H2 diplotype or GSK3B rs334558 on total grey matter or intracranial volume. Our genetic and biochemical analyses have identified a role for GSK3B in brain development, which could have important aetiological implications for neurodegenerative and neurodevelopmental disorders.
Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans.
This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures.
Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity.
Measurements and Main Results
In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function.
After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function.
The order and magnitude of pathologic processes in Alzheimer’s disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer’s disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease.
In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant’s age at baseline assessment and the parent’s age at the onset of symptoms of Alzheimer’s disease to calculate the estimated years from expected symptom onset (age of the participant minus parent’s age at symptom onset). We conducted cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes.
Concentrations of amyloid-beta (Aβ)42 in the CSF appeared to decline 25 years before expected symptom onset. Aβ deposition, as measured by positron-emission tomography with the use of Pittsburgh compound B, was detected 15 years before expected symptom onset. Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset. Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset. Global cognitive impairment, as measured by the Mini–Mental State Examination and the Clinical Dementia Rating scale, was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset.
We found that autosomal dominant Alzheimer’s disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer’s disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer’s disease. (Funded by the National Institute on Aging and others; DIAN ClinicalTrials.gov number, NCT00869817.)
A hexanucleotide repeat expansion in C9ORF72 has been established as a common cause of frontotemporal dementia (FTD). However, the minimum repeat number necessary for disease pathogenesis is not known. The aims of our study were to determine the frequency of the C9ORF72 repeat expansion in two FTD patient collections (one Australian and one Spanish, combined n = 190), to examine C9ORF72 expansion allele length in a subset of FTD patients, and to examine C9ORF72 allele length in ‘non-expansion’ patients (those with <30 repeats). The C9ORF72 repeat expansion was detected in 5–17% of patients (21–41% of familial FTD patients). For one family, the expansion was present in the proband but absent in the mother, who was diagnosed with dementia at age 68. No association was found between C9ORF72 non-expanded allele length and age of onset and in the Spanish sample mean allele length was shorter in cases than in controls. Southern blotting analysis revealed that one of the nine ‘expansion-positive’ patients examined, who had neuropathologically confirmed frontotemporal lobar degeneration with TDP-43 pathology, harboured an ‘intermediate’ allele with a mean size of only ∼65 repeats. Our study indicates that the C9ORF72 repeat expansion accounts for a significant proportion of Australian and Spanish FTD cases. However, C9ORF72 allele length does not influence the age at onset of ‘non-expansion’ FTD patients in the series examined. Expansion of the C9ORF72 allele to as little as ∼65 repeats may be sufficient to cause disease.
Numerous families exhibiting both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) have been described, and although many of these have been shown to harbour a repeat expansion in C9ORF72, several C9ORF72-negative FTD-ALS families remain. We performed neuropathological and genetic analysis of a large European Australian kindred (Aus-12) with autosomal dominant inheritance of dementia and/or ALS. Affected Aus-12 members developed either ALS or dementia; some of those with dementia also had ALS and/or extrapyramidal features. Neuropathology was most consistent with frontotemporal lobar degeneration with type B TDP pathology, but with additional phosphorylated tau pathology consistent with corticobasal degeneration. Aus-12 DNA samples were negative for mutations in all known dementia and ALS genes, including C9ORF72 and FUS. Genome-wide linkage analysis provided highly suggestive evidence (maximum multipoint LOD score of 2.9) of a locus on chromosome 16p12.1–16q12.2. Affected individuals shared a chromosome 16 haplotype flanked by D16S3103 and D16S489, spanning 37.9 Mb, with a smaller suggestive disease haplotype spanning 24.4 Mb defined by recombination in an elderly unaffected individual. Importantly, this smaller region does not overlap with FUS. Whole-exome sequencing identified four variants present in the maximal critical region that segregate with disease. Linkage analysis incorporating these variants generated a maximum multipoint LOD score of 3.0. These results support the identification of a locus on chromosome 16p12.1–16q12.2 responsible for an unusual cluster of neurodegenerative phenotypes. This region overlaps with a separate locus on 16q12.1–q12.2 reported in an independent ALS family, indicating that this region may harbour a second major locus for FTD-ALS.
Electronic supplementary material
The online version of this article (doi:10.1007/s00401-013-1078-9) contains supplementary material, which is available to authorized users.
Frontotemporal dementia; Amyotrophic lateral sclerosis; Motor neuron disease; Corticobasal degeneration; Tau; TDP-43
Changes in the cortical expression of small non-coding microRNA (miRNA) have been observed in postmortem analysis of psychotic disorders. Antipsychotic drugs (APDs) are the most effective treatment option for these disorders and have been associated with changes in gene expression. MicroRNA regulate numerous genes involved in brain development and function. It is therefore plausible to question whether miRNA expression is also altered and hence whether they take part in the neuroleptic mechanism of action.
We sought to investigate whether treatment with APDs induces changes in miRNA expression and query the functional implications of such changes. Furthermore, we investigated the possible functional interplay of miRNA–gene regulatory interactions.
High-throughput miRNA profiling of the whole brain of C57BL/6 mice treated with haloperidol, olanzapine or clozapine for 7 days was performed. Functional analysis was conducted on the putative targets of altered microRNA. Significant miRNA–gene regulatory interactions were evaluated by the integration of genome-wide mRNA expression analysis using the Bayesian networks with splitting–averaging strategy and functional analysis conducted.
Small subsets of miRNA were altered with each treatment with potential neurologically relevant influence. Metabolic pathways were enriched in olanzapine and clozapine treatments, possibly associated with their weight gain side effects. Neurologically and metabolically relevant miRNA–gene interaction networks were identified in the olanzapine treatment group.
This study is the first to suggest a role for miRNA in the mechanism of APD action and the metabolic side effects of the atypical ADPs, and adds support for their consideration in pharmacogenomics.
Electronic supplementary material
The online version of this article (doi:10.1007/s00213-012-2939-y) contains supplementary material, which is available to authorized users.
Antipsychotic drugs; MicroRNA; Schizophrenia; Olanzapine; Clozapine; Haloperidol; Pharmacogenomics
Executive functions are amongst the most heritable cognitive traits with twin studies indicating a strong genetic origin. However genes associated with this domain are unknown. Our research into the neurodevelopmental disorder Williams-Beuren syndrome (WBS) has identified a gene within the causative recurrent 1.5/1.6 Mb heterozygous microdeletion on chromosome 7q11.23, which may be involved in executive functioning. Comparative genome array screening of 55 WBS patients revealed a larger ∼1.8 Mb microdeletion in 18% of cases, which results in the loss of an additional gene, the transcription factor GTF2IRD2. The GTF gene family of transcription factors (GTF2I, GTF2IRD1 and GTF2IRD2) are all highly expressed in the brain, and GTF2I and GTF2IRD1 are involved in the pathogenesis of the cognitive and behavioural phenotypes associated with WBS. A multi-level analysis of cognitive, behavioural and psychological functioning in WBS patients showed that those with slightly larger deletions encompassing GTF2IRD2 were significantly more cognitively impaired in the areas of spatial functioning, social reasoning, and cognitive flexibility (a form of executive functioning). They also displayed significantly more obsessions and externalizing behaviours, a likely manifestation of poor cognitive flexibility and executive dysfunction. We provide the first evidence for a role for GTF2IRD2 in higher-level (executive functioning) abilities and highlight the importance of integrating detailed molecular characterisation of patients with comprehensive neuropsychological profiling to uncover additional genotype-phenotype correlations. The identification of specific genes which contribute to executive function has important neuropsychological implications in the treatment of patients with conditions like WBS, and will allow further studies into their mechanism of action.
Concerns have been raised as to the safety of bisphosphonates; in particular a possible link between bisphosphonate use and upper gastrointestinal (GI) cancer. Two published studies using different study populations but drawn from earlier versions of the same national UK database, reached differing conclusions: one finding no evidence for an increase in the risk of gastric or oesophageal cancer in bisphosphonate users and one finding a small but significantly increased risk of oesophageal cancer linked to duration of bisphosphonate use.
Methodology/ Principal Findings
Design-A case control study comparing bisphosphonate prescribing in cases of upper GI cancer from 1995 to 2007 using UK primary care electronic health records (GPRD).
Main Outcome Measure-Relative Risk (approximated to Odds Ratio for rare events) for oesophageal and gastric cancer development in bisphosphonate users compared to non–users. The odds of being a case of oesophageal cancer, adjusted for smoking status, were significantly increased in women who had had one or more bisphosphonate prescriptions, odds ratio 1·54 (95% CI 1·27–1·88) compared to non-users. There was no significant effect on gastric cancer in women, odds ratio adjusted for smoking status, 1.06 (95% CI 0.83–1.37) and also no apparent risk in men for either oesophageal or gastric cancer, odds ratio adjusted for smoking status 0.78 (95%CI 0.56–1.09) and 0.87 (95% CI 0.55–1.36) respectively.
Our results support a small but significant increased risk of oesophageal cancer in women prescribed bisphosphonates and is based on the largest number of exposed cases to date in the UK.
Congenital nonprogressive spinocerebellar ataxia is characterized by early gross motor delay, hypotonia, gait ataxia, mild dysarthria and dysmetria. The clinical presentation remains fairly stable and may be associated with cerebellar atrophy. To date, only a few families with autosomal dominant congenital nonprogressive spinocerebellar ataxia have been reported. Linkage to 3pter was demonstrated in one large Australian family and this locus was designated spinocerebellar ataxia type 29. The objective of this study is to describe an unreported Canadian family with autosomal dominant congenital nonprogressive spinocerebellar ataxia and to identify the underlying genetic causes in this family and the original Australian family.
Methods and Results
Exome sequencing was performed for the Australian family, resulting in the identification of a heterozygous mutation in the ITPR1 gene. For the Canadian family, genotyping with microsatellite markers and Sanger sequencing of ITPR1 gene were performed; a heterozygous missense mutation in ITPR1 was identified.
ITPR1 encodes inositol 1,4,5-trisphosphate receptor, type 1, a ligand-gated ion channel that mediates calcium release from the endoplasmic reticulum. Deletions of ITPR1 are known to cause spinocerebellar ataxia type 15, a distinct and very slowly progressive form of cerebellar ataxia with onset in adulthood. Our study demonstrates for the first time that, in addition to spinocerebellar ataxia type 15, alteration of ITPR1 function can cause a distinct congenital nonprogressive ataxia; highlighting important clinical heterogeneity associated with the ITPR1 gene and a significant role of the ITPR1-related pathway in the development and maintenance of the normal functions of the cerebellum.
Congenital nonprogressive spinocerebellar ataxia; Spinocerebellar ataxia type 29; Cerebellar atrophy; ITPR1; Gene identification
Bisphenol A is widely used in food and drinks packaging. There is evidence of associations between raised urinary bisphenol A (uBPA) and increased incidence of reported cardiovascular diagnoses.
To estimate associations between BPA exposure and angiographically graded coronary atherosclerosis. 591 patients participating in The Metabonomics and Genomics in Coronary Artery Disease (MaGiCAD) study in Cambridgeshire UK, comparing urinary BPA (uBPA) with grades of severity of coronary artery disease (CAD) on angiography. Linear models were adjusted for BMI, occupational social class and diabetes status. Severe (one to three vessel) CAD was present in 385 patients, 86 had intermediate disease (n = 86) and 120 had normal coronary arteries. The (unadjusted) median uBPA concentration was 1.28 ng/mL with normal coronary arteries, and 1.53 ng/mL with severe CAD. Compared to those with normal coronary arteries, uBPA concentration was significantly higher in those with severe CAD (OR per uBPA SD = 5.96 ng/ml OR = 1.43, CI 1.03 to 1.98, p = 0.033), and near significant for intermediate disease (OR = 1.69, CI 0.98 to 2.94, p = 0.061). There was no significant uBPA difference between patients with severe CAD (needing surgery) and the remaining groups combined.
BPA exposure was higher in those with severe coronary artery stenoses compared to those with no vessel disease. Larger studies are needed to estimate true dose response relationships. The mechanisms underlying the association remain to be established.
We previously identified a significant bipolar spectrum disorder linkage peak on 15q25-26 using 35 extended families with a broad clinical phenotype, including bipolar disorder (types I and II), recurrent unipolar depression and schizoaffective disorder. However, the specific gene(s) contributing to this signal had not been identified. By a fine mapping association study in an Australian case-control cohort (n = 385), we find that the sialyltransferase 8B (ST8SIA2) gene, coding for an enzyme that glycosylates proteins involved in neuronal plasticity which has previously shown association to both schizophrenia and autism, is associated with increased risk to bipolar spectrum disorder. Nominal single point association was observed with SNPs in ST8SIA2 (rs4586379, P = 0.0043; rs2168351, P = 0.0045), and a specific risk haplotype was identified (frequency: bipolar vs controls = 0.41 vs 0.31; χ2 = 6.46, P = 0.011, OR = 1.47). Over-representation of the specific risk haplotype was also observed in an Australian schizophrenia case-control cohort (n = 256) (χ2 = 8.41, P = 0.004, OR = 1.82). Using GWAS data from the NIMH bipolar disorder (n = 2055) and NIMH schizophrenia (n = 2550) cohorts, the equivalent haplotype was significantly over-represented in bipolar disorder (χ2 = 5.91, P = 0.015, OR = 1.29), with the same direction of effect in schizophrenia, albeit non-significant (χ2 = 2.3, P = 0.129, OR = 1.09). We demonstrate marked down-regulation of ST8SIA2 gene expression across human brain development and show a significant haplotype×diagnosis effect on ST8SIA2 mRNA levels in adult cortex (ANOVA: F(1,87) = 6.031, P = 0.016). These findings suggest that variation the ST8SIA2 gene is associated with increased risk to mental illness, acting to restrict neuronal plasticity and disrupt early neuronal network formation, rendering the developing and adult brain more vulnerable to secondary genetic or environmental insults.
The olfactory bulb (OB) receives extensive cholinergic input from the basal forebrain and is affected very early in Alzheimer’s disease (AD). We speculated that an olfactory ‘stress test’ (OST), targeting the OB, might be used to unmask incipient AD. We investigated if change in olfactory performance following intranasal atropine was associated with several known antecedents or biomarkers of AD.
We measured change in performance on the University of Pennsylvania Smell Identification Test (UPSIT) in the left nostril before (20-items) and after (remaining 20-items) intranasal administration of 1 mg of atropine. We administered cognitive tests, measured hippocampal volume from MRI scans and recorded Apolipoprotein E genotype as indices relevant to underlying AD.
In a convenience sample of 56 elderly individuals (14 probable AD, 13 cognitive impairment no dementia, 29 cognitively intact) the change in UPSIT score after atropine (‘atropine effect’ = AE) correlated significantly with demographically scaled episodic memory score (r = 0.57, p < 0.001) and left hippocampal volume (LHCV) (r = 0.53, p < 0.001). Among non-demented individuals (n = 42), AE correlated with episodic memory (r = 0.52, p < 0.001) and LHCV (r = 0.49, p < 0.001) and hierarchical linear regression models adjusted for age, gender, education, and baseline UPSIT showed that the AE explained more variance in memory performance (24%) than did LHCV (15%). The presence of any APOE ϵ4 allele was associated with a more negative AE (p = 0.014).
The OST using atropine as an olfactory probe holds promise as a simple, inexpensive screen for early and preclinical AD and further work, including longitudinal studies, is needed to explore this possibility.
High blood pressure is the single most important risk factor worldwide for the development of cardiovascular disease, and has been shown to affect some ethnic minority groups disproportionately.
To explore ethnic inequalities in blood pressure monitoring and control.
Data from Lambeth DataNet was used, based on case records from GP practices in one inner-city London borough. Blood pressure monitoring and control was compared using Quality and Outcomes Framework (QOF) targets for patients with: diabetes, coronary heart disease, stroke, hypertension, and chronic kidney disease. The study controlled for age, sex, social deprivation, and clustering within GP practices.
A total of 16 613 patients met the study criteria, with 5962 categorised as black/black British. Blood pressure monitoring was similar across ethnic groups and as good, if not better, for black patients compared to white. However, marked ethnic inequalities in blood pressure control were found, with black patients significantly less likely to achieve QOF targets than their white counterparts (odds ratio [OR] 0.73; 95% confidence interval [CI] = 0.64 to 0.82). Further inequalities were revealed in blood pressure control within disease groups and ethnic subgroups. In particular, blood pressure control was poor in African patients with diabetes (OR 0.63; 95% CI = 0.50 to 0.79) and Caribbean patients with coronary heart disease (OR 0.53; 95% CI = 0.37 to 0.77) when compared with white patients.
While black patients with chronic conditions are equally likely to have their blood pressure monitored, their blood pressure control is consistently poorer than that of their white counterparts. This may have important implications for cardiovascular risk management in black patients.
ethnicity/race; inequalities; health care; hypertension
The majority of patients discontinue antidepressant treatment earlier than prescribed. The factors behind this and the influences on patients' choices about whether to take medication remain poorly understood.
To explore factors that influence patients' decisions about taking antidepressant medication.
Design of study
Qualitative interview study.
Interviews were conducted across three sites: London, East Lancashire, and North East England.
Semi-structured interviews were conducted with a purposive sample of 65 primary care patients who were prescribed antidepressants in the past year for depression or mixed anxiety/depression.
Participants described their first course of antidepressants as typically occurring when they had ‘hit rock bottom’, having exhausted all other possibilities; therefore, there was little sense of a positive choice at this stage. There would typically follow a period of experimentation where it was usual to stop and restart medication, often several times. Ultimately, these recurring cycles lead to participants becoming more expert about their condition and better able to make an informed decision about medication. For younger participants, recovery typically remained a goal, although for older people there was often an acceptance that their condition, and medication use, would be long term.
Participants' accounts demonstrated how they could become expert at managing their condition through a process of trial and error.
antidepressants; depression; ethnicity; primary health care; qualitative research
Psychological outcome measures are evolving into measures that depict progress over time. Interval measurement during therapy has not previously been reported for a patient-generated measure in primary care. We aimed to determine the sensitivity to change throughout therapy, using ‘PSYCHLOPS’ (Psychological Outcome Profiles), and to determine if new problems appearing during therapy diminish overall improvement.
Responses to PSYCHLOPS, pre-, during- and post-therapy were compared. Setting: patients offered brief cognitive behaviour therapy in primary care in Poland.
238 patients completed the pre-therapy questionnaire, 194 (81.5%) the during-therapy questionnaire and 142 the post-therapy questionnaire (59.7%). For those completing all three questionnaires (n = 135), improvement in total scores produced an overall Effect Size of 3.1 (2.7 to 3.4). We estimated change using three methods for dealing with missing values. Single and multiple imputation did not significantly change the Effect Size; ‘Last Value Carried Forward’, the most conservative method, produced an overall Effect Size of 2.3 (1.9 to 2.6). New problems during therapy were reported by 81 patients (60.0%): new problem and original problem scores were of similar magnitude and change scores were not significantly different when compared to patients who did not report new problems.
A large proportion of outcome data is lost when outcome measures depend upon completed end of therapy questionnaires. The use of a during-therapy measure increases data capture. Missing data still produce difficulties in interpreting overall effect sizes for change. We found no evidence that new problems appearing during therapy hampered overall recovery.
Background and Objectives
Asthma and depression are common health problems in primary care. Evidence of a relationship between asthma and depression is conflicting. Objectives: to determine 1. The incidence rate and incidence rate ratio of depression in primary care patients with asthma compared to those without asthma, and 2. The standardized mortality ratio of depressed compared to non-depressed patients with asthma.
A historical cohort and nested case control study using data derived from the United Kingdom General Practice Research Database. Participants: 11,275 incident cases of asthma recorded between 1/1/95 and 31/12/96 age, sex and practice matched with non-cases from the database (ratio 1∶1) and followed up through the database for 10 years. 1,660 cases were matched by date of asthma diagnosis with 1,660 controls. Main outcome measures: number of cases diagnosed with depression, the number of deaths over the study period.
The rate of depression in patients with asthma was 22.4/1,000 person years and without asthma 13.8 /1,000 person years. The incident rate ratio (adjusted for age, sex, practice, diabetes, cardiovascular disease, cerebrovascular disease, smoking) was 1.59 (95% CI 1.48–1.71). The increased rate of depression was not associated with asthma severity or oral corticosteroid use. It was associated with the number of consultations (odds ratio per visit 1.09; 95% CI 1.07–1.11). The age and sex adjusted standardized mortality ratio for depressed patients with asthma was 1.87 (95% CI: 1.54–2.27).
Asthma is associated with depression. This was not related to asthma severity or oral corticosteroid use but was related to service use. This suggests that a diagnosis of depression is related to health seeking behavior in patients with asthma. There is an increased mortality rate in depressed patients with asthma. The cause of this needs further exploration. Consideration should be given to case-finding for depression in this population.
The past decade has seen rapid advances in the identification of associations between candidate genes and a range of common multifactorial disorders. This paper evaluates public attitudes towards the complexity of genetic risk prediction in psychiatry involving susceptibility genes, uncertain penetrance and gene–environment interactions on which successful molecular-based mental health interventions will depend. A qualitative approach was taken to enable the exploration of the views of the public. Four structured focus groups were conducted with a total of 36 participants. The majority of participants indicated interest in having a genetic test for susceptibility to major depression, if it was available. Having a family history of mental illness was cited as a major reason. After discussion of perceived positive and negative implications of predictive genetic testing, nine of 24 participants initially interested in having such a test changed their mind. Fear of genetic discrimination and privacy issues predominantly influenced change of attitude. All participants still interested in having a predictive genetic test for risk for depression reported they would only do so through trusted medical professionals. Participants were unanimously against direct-to-consumer genetic testing marketed through the Internet, although some would consider it if there was suitable protection against discrimination. The study highlights the importance of general practitioner and public education about psychiatric genetics, and the availability of appropriate treatment and support services prior to implementation of future predictive genetic testing services.
predictive genetic testing; psychiatric genetics; major depression; direct-to-consumer genetic testing; public opinion; mental health
Substantial variation in antibiotic prescribing rates between general practices persists, but remains unexplained at national level.
To establish the degree of variation in antibiotic prescribing between practices in England and identify the characteristics of practices that prescribe higher volumes of antibiotics.
Design of study
8057 general practices in England.
A dataset was constructed containing data on standardised antibiotic prescribing volumes, practice characteristics, patient morbidity, ethnicity, social deprivation, and Quality and Outcomes Framework achievement (2004–2005). Data were analysed using multiple regression modelling.
There was a twofold difference in standardised antibiotic prescribing volumes between practices in the 10th and 90th centiles of the sample (0.48 versus 0.95 antibiotic prescriptions per antibiotic STAR-PU [Specific Therapeutic group Age-sex weightings-Related Prescribing Unit]). A regression model containing nine variables explained 17.2% of the variance in antibiotic prescribing. Practice location in the north of England was the strongest predictor of high antibiotic prescribing. Practices serving populations with greater morbidity and a higher proportion of white patients prescribed more antibiotics, as did practices with shorter appointments, non-training practices, and practices with higher proportions of GPs who were male, >45 years of age, and qualified outside the UK.
Practice and practice population characteristics explained about one-sixth of the variation in antibiotic prescribing nationally. Consultation-level and qualitative studies are needed to help further explain these findings and improve our understanding of this variation.
antibiotics; prescriptions; primary care
OBJECTIVE—To evaluate diabetes outcomes under a national “pay-for-performance” program.
RESEARCH DESIGN AND METHODS—Data were analyzed for 98% of all English family practices. For each practice, the proportion of diabetic subjects with A1C ≤7.5%, blood pressure ≤145/85 mmHg, and cholesterol ≤5 mmol/l was determined. Practices achieving less than the 25th centile for the A1C target for 2006–2007 were classified as low performing.
RESULTS—The proportion achieving the A1C target at the median practice increased from 59.1% (interquartile range [IQR] 51.7–65.9) in 2004–2005 to 66.7% (IQR 60.6–72.7) in 2007–2008, blood pressure from 70.9% in 2004–2005 to 80.2% in 2007–2008, and cholesterol from 72.6% in 2004–2005 to 83.6% in 2007–2008. In 2004–2005, 57% of practices were low performing (range by region 42.4–69.9). In 2007–2008, 26% of practices were low performing (range 11.6–37.5).
CONCLUSIONS—Introduction of pay-for-performance may be one factor contributing to increasing achievement of targets and reducing problems of low performance.