Kate Walters

Prediagnostic presentations of Parkinson's disease in primary care: a case-control study

BACKGROUND Parkinsons disease has an insidious onset and is diagnosed when typical motor features occur. Several motor and non-motor features can occur before diagnosis, early in the disease process. We aimed to assess the association between first presentation of several prediagnostic features in primary care and a subsequent diagnosis of Parkinsons disease, and to chart the timeline of these first presentations before diagnosis. METHODS We identified individuals with a first diagnosis of Parkinsons disease and those without Parkinsons disease from Jan 1, 1996, to Dec 31, 2012, from The Health Improvement Network UK primary care database. Codes were extracted for a range of possible prediagnostic or early symptoms, comprising motor features (tremor, rigidity, balance impairments, neck pain or stiffness, and shoulder pain or stiffness), autonomic features (constipation, hypotension, erectile dysfunction, urinary dysfunction, and dizziness), neuropsychiatric disturbances (memory problems, late-onset anxiety or depression, cognitive decline, and apathy), and additional features (fatigue, insomnia, anosmia, hypersalivation and rapid-eye-movement sleep behaviour disorder) in the years before diagnosis. We report the incidence of symptoms recorded in more than 1% of cases per 1000 person-years and incidence risk ratios (RRs) for individuals with and without Parkinsons disease at 2, 5, and 10 years before diagnosis. FINDINGS 8166 individuals with and 46,755 individuals without Parkinsons disease were included in the study. Apathy, REM sleep behaviour disorder, anosmia, hypersalivation, and cognitive decline were all reported in less than 1% of people per 1000 person-years and were excluded from further analyses. At 2 years before Parkinsons disease diagnosis, the incidence of all studied prediagnostic features except neck pain or stiffness was higher in patients who went on to develop Parkinsons disease (n=7232) than in controls (n=40,541). At 5 years before diagnosis, compared with controls (n=25,544), patients who went on to develop Parkinsons disease (n=4769) had a higher incidence of tremor (RR 13·70, 95% CI 7·82-24·31), balance impairments (2·19, 1·09-4·16), constipation (2·24, 2·04-2·46), hypotension (3·23, 1·85-5·52), erectile dysfunction (1·30, 1·11-1·51), urinary dysfunction (1·96, 1·34-2·80), dizziness (1·99, 1·67-2·37), fatigue (1·56, 1·27-1·91), depression (1·76, 1·41-2·17), and anxiety (1·41, 1·09-1·79). At 10 years before diagnosis of Parkinsons disease, the incidence of tremor (RR 7·59, 95% CI 1·11-44·83) and constipation (2·01, 1·62-2·49) was higher in those who went on to develop Parkinsons disease (n=1680) than in controls (n=8305). INTERPRETATION A range of prediagnostic features can be detected several years before diagnosis of Parkinsons disease in primary care. These data can be incorporated into ongoing efforts to identify individuals at the earliest stages of the disease for inclusion in future trials and to help understand progression in the earliest phase of Parkinsons disease. FUNDING Parkinsons UK.

Survival of people with clinical diagnosis of dementia in primary care: cohort study

Objectives To estimate survival after a diagnosis of dementia in primary care, compared with people without dementia, and to determine incidence of dementia. Design Cohort study using data from The Health Improvement Network (THIN), a primary care database. Setting 353 general practices in the United Kingdom providing data to THIN. Participants All adults aged 60 years or over with a first ever code for dementia from 1990 to 2007 (n=22 529); random sample of five participants without dementia for every participant with dementia matched on practice and time period (n=112 645). Main outcome measures Median survival by age and sex; mortality rates; incidence of dementia by age, sex, and deprivation. Results The median survival of people with dementia diagnosed at age 60-69 was 6.7 (interquartile range 3.1-10.8) years, falling to 1.9 (0.7-3.6) years for those diagnosed at age 90 or over. Adjusted mortality rates were highest in the first year after diagnosis (relative risk 3.68, 95% confidence interval 3.44 to 3.94). This dropped to 2.49 (2.29 to 2.71) in the second year. The incidence of recorded dementia remained stable over time (3-4/1000 person years at risk). The incidence was higher in women and in younger age groups (60-79 years) living in deprived areas. Conclusions Median survival was much lower than in screened populations. These clinically relevant estimates can assist patients and carers, clinicians, and policy makers when planning support for this population. The high risk of death in the first year after diagnosis may reflect diagnoses made at times of crisis or late in the disease trajectory. Late recording of diagnoses of dementia in primary care may result in missed opportunities for potential early interventions.

Serum Bilirubin and Risk of Respiratory Disease and Death

CONTEXT Serum total bilirubin levels in healthy patients reflect genetic and environmental factors that could influence the risk of developing respiratory disease. OBJECTIVE To examine the relationship between bilirubin levels and respiratory disease. DESIGN, SETTING, AND PARTICIPANTS Cohort study among 504,206 adults from a UK primary care research database (the Health Improvement Network) with serum bilirubin levels recorded but no evidence of hepatobiliary or hemolytic disease. Data were recorded between January 1988 and December 2008. MAIN OUTCOME MEASURES Incidence of chronic obstructive pulmonary disease (COPD), lung cancer, and all-cause mortality. RESULTS Median bilirubin levels were 0.64 mg/dL (interquartile range, 0.47-0.88 mg/dL) in men and 0.53 mg/dL (interquartile range, 0.41-0.70 mg/dL) in women. There were 1341 cases of lung cancer, 5863 cases of COPD, and 23,103 deaths, with incidence rates of 2.5, 11.9, and 42.5 per 10,000 person-years, respectively. The incidence of lung cancer per 10,000 person-years in men was 5.0 (95% confidence interval [CI], 4.2-6.0) in the first decile category of bilirubin compared with 3.0 (95% CI, 2.3-3.8) in the fifth decile. The corresponding incidences for COPD in men were 19.5 (95% CI,17.7-21.4) and 14.4 (95% CI, 12.7-16.2). The mortality rates per 10,000 person-years in men were 51.3 (95% CI, 48.5-54.2) in the first decile category compared with 38.1 (95% CI, 35.5-40.8) in the fifth decile. The associations were similar for women. After adjusting for other important health indicators, regression estimates for incidence rate of lung cancer per 0.1-mg/dL increase in bilirubin level were an 8% decrease (95% CI, 5%-11%) for men and an 11% decrease (95% CI, 7%-14%) for women. The regression estimate for COPD in men per 0.1-mg/dL increase in bilirubin level was a 6% decrease (95% CI, 5%-7%) and for mortality in men was a 3% decrease (95% CI, 2%-3%) after accounting for other health indicators. The results for COPD and mortality in women were very similar. CONCLUSION Among patients with normal-range bilirubin levels in primary care practices, relatively higher levels of bilirubin were associated with a lower risk of respiratory disease and all-cause mortality.

Recent trends in the incidence of recorded depression in primary care

BACKGROUND There is a paucity of data describing how general practitioners (GPs) label or record depression. AIMS To determine incidence and sociodemographic variation in GP-recorded depression diagnoses and depressive symptoms. METHOD Annual incidence rates calculated using data from 298 UK general practices between 1996 and 2006, adjusted for year of diagnosis, gender, age and deprivation. RESULTS Incidence of diagnosed depression fell from 22.5 to 14.0 per 1000 person-years at risk (PYAR) from 1996 to 2006. The incidence of depressive symptoms rose threefold from 5.1 to 15.5 per 1000 PYAR. Combined incidence of diagnoses and symptoms remained stable. Diagnosed depression and symptoms were more common in women and in more deprived areas. CONCLUSIONS Depression recorded by general practitioners has lower incidence rates than depression recorded in epidemiological studies, although there are similar associations with gender and deprivation. General practitioners increasingly use symptoms rather than diagnostic labels to categorize peoples illnesses. Studies using standardised diagnostic instruments may not be easily comparable with clinical practice.

Making inferences on treatment effects from real world data: propensity scores, confounding by indication, and other perils for the unwary in observational research

Propensity score based methods are used increasingly to evaluate the effectiveness of treatments when evidence from randomised trials is not available. However, users need to be aware of their strengths and limitations

Prescribing trends in bipolar disorder: cohort study in the United Kingdom THIN primary care database 1995-2009.

Objectives To determine changes in prescribing patterns in primary care of antipsychotic and mood stabiliser medication in a representative sample of patients with bipolar disorder in the United Kingdom over a fifteen year period and association with socio-demographic factors. Methods We identified 4700 patients in the Health Improvement Network (THIN) primary care database, who had received treatment for bipolar disorder between 1995 and 2009. The proportion of time for which each individual was prescribed a particular medication was studied, along with variation by sex, age and social depravation status (quintiles of Townsend scores). The number of drugs an individual was taking within a particular year was also examined. Results In 1995, 40.6% of patients with bipolar disorder were prescribed a psychotropic medication at least twice. By 2009 this had increased to 78.5% of patients. Valproate registered with the greatest increase in use (22.7%) followed by olanzapine (15.7%) and quetiapine (9.9%). There were differences by age and sex; with young (18–30 year old) women having the biggest increase in proportion of time on medication. There were no differences by social deprivation status. By 2009, 34.2% of women of childbearing age were treated with valproate. Conclusions Lithium use overall remained relatively constant, whilst second generation antipsychotic and valproate use increased dramatically. Changes in prescribing practice preceded published trial evidence, especially with the use of second generation antipsychotics, perhaps with inferences being made from treatment of schizophrenia and use of first generation antipsychotics. Women of childbearing age were prescribed valproate frequently, against best advice.

Explaining variation in referral from primary to secondary care: Cohort study

Objectives To determine the extent to which referral for defined symptoms from primary care varies by age, sex, and social deprivation and whether any sociodemographic variations in referral differ according to the presence of national referral guidance and the potential of the symptoms to be life threatening. Design Cohort study using individual patient data from the health improvement network database in primary care. Setting United Kingdom. Participants 5492 patients with postmenopausal bleeding, 23 121 with hip pain, and 101 212 with dyspepsia from 326 general practices, 2001-7. Main outcome measures Multivariable associations between odds of immediate referral for postmenopausal bleeding and age and social deprivation; hazard rates of referral for hip pain or dyspepsia and age, sex, and social deprivation. Analyses for dyspepsia were stratified for people aged less than and more than 55 years because referral guidance differs by age. Results 61.4% (3374/5492) of patients with postmenopausal bleeding, 17.4% (4019/23 121) with hip pain, and 13.8% (13 944/101 212) with dyspepsia were referred. The likelihood of referral for postmenopausal bleeding declined with increasing age: the adjusted odds ratio for patients aged 85 or more compared with those aged 55-64 was 0.39 (95% confidence interval 0.31 to 0.49). Patients aged 85 or more with hip pain were also less likely to be referred than those aged 55-64 (0.68, 0.57 to 0.81). Women were less likely than men to be referred for hip pain (hazard ratio 0.90, 95% confidence interval 0.84 to 0.96). More deprived patients with hip pain or dyspepsia (if aged <55) were less likely to be referred. Adjusted hazard ratios for those in the most deprived Townsend fifth compared with the least deprived were 0.72 (95% confidence interval 0.62 to 0.82) and 0.76 (0.68 to 0.85), respectively. No socioeconomic gradient was evident in referral for postmenopausal bleeding. Conclusions Inequalities in referral associated with socioeconomic circumstances were more likely to occur in the absence of both explicit guidance and potentially life threatening conditions, whereas inequalities with age were evident for all conditions.

Identifying periods of acceptable computer usage in primary care research databases.

To examine the effect of applying different data quality filters on the incidence of disease and prescribing trends over time in a primary care research database and validate a new method for defining periods of adequate computer usage.

A systematic review and meta‐analysis of premature mortality in bipolar affective disorder

To review and complete meta‐analysis of studies estimating standardised mortality ratios (SMRs) in bipolar affective disorder (BPAD) for all‐cause and cause‐specific mortalities.

Prescribing of antipsychotics in UK primary care: a cohort study

Objective To examine the recorded indication for antipsychotic prescriptions in UK primary care. Design Cohort study. Setting Primary care. Participants Individuals prescribed antipsychotics between 2007 and 2011. Measures The proportion of individuals prescribed antipsychotics with a diagnosis of (1) psychosis and bipolar disorder, (2) other diagnoses including depression, anxiety and dementia and (3) none of these diagnoses. Results We identified 47 724 individuals prescribed antipsychotic agents. 13 941 received first-generation agents and 27 966 received second-generation agents. The rates of prescribing were higher in females (incidence rate ratio (IRR) 1.092 (95% CI 1.088 to 1.095), older people (80+ vs 40–49; IRR 2.234 (2.222 to 2.246)) and in those from the most deprived areas (most deprived vs least deprived IRR 3.487 (3.567 to 3.606). Of those receiving first-generation antipsychotics, less than 50% had a diagnosis of psychosis/bipolar disorder. For the second-generation agents, the numbers ranged from 4824 (36%) for quetiapine to 7094 (62%) for olanzapine. In patients without psychosis/bipolar disorder, common diagnoses included anxiety, depression, dementia, sleep and personality disorders. For example, in risperidone users, 14% had an anxiety code, 22% depression, 12% dementia, 11% sleep disorder and 4% personality disorder. The median daily doses and duration of treatment were greater in those with schizophrenia (eg, risperidone median daily dose 4 mg; IQR 2–6: median duration 1.2 years) than in those with non-psychotic/bipolar disorders such as depression or anxiety (eg, risperidone 1 mg; IQR 1–2: 0.6 years). A relatively large proportion (between 6% and 17%) of people receiving individual antipsychotics had none of the diagnoses stated above. Conclusions In UK primary care, a large proportion of people prescribed antipsychotics have no record of psychotic or bipolar disorder. They are often older people with conditions including dementia, non-psychotic depression, anxiety and sleep disorders.