Tim Wilkinson

Outcome After Conservative Management or Intervention for Unruptured Brain Arteriovenous Malformations

IMPORTANCE Whether conservative management is superior to interventional treatment for unruptured brain arteriovenous malformations (bAVMs) is uncertain because of the shortage of long-term comparative data. OBJECTIVE To compare the long-term outcomes of conservative management vs intervention for unruptured bAVM. DESIGN, SETTING, AND POPULATION Population-based inception cohort study of 204 residents of Scotland aged 16 years or older who were first diagnosed as having an unruptured bAVM during 1999-2003 or 2006-2010 and followed up prospectively for 12 years. EXPOSURES Conservative management (no intervention) vs intervention (any endovascular embolization, neurosurgical excision, or stereotactic radiosurgery alone or in combination). MAIN OUTCOMES AND MEASURES Cox regression analyses, with multivariable adjustment for prognostic factors and baseline imbalances if hazards were proportional, to compare rates of the primary outcome (death or sustained morbidity of any cause by Oxford Handicap Scale [OHS] score ≥2 for ≥2 successive years [0 = no symptoms and 6 = death]) and the secondary outcome (nonfatal symptomatic stroke or death due to bAVM, associated arterial aneurysm, or intervention). RESULTS Of 204 patients, 103 underwent intervention. Those who underwent intervention were younger, more likely to have presented with seizure, and less likely to have large bAVMs than patients managed conservatively. During a median follow-up of 6.9 years (94% completeness), the rate of progression to the primary outcome was lower with conservative management during the first 4 years of follow-up (36 vs 39 events; 9.5 vs 9.8 per 100 person-years; adjusted hazard ratio, 0.59; 95% CI, 0.35-0.99), but rates were similar thereafter. The rate of the secondary outcome was lower with conservative management during 12 years of follow-up (14 vs 38 events; 1.6 vs 3.3 per 100 person-years; adjusted hazard ratio, 0.37; 95% CI, 0.19-0.72). CONCLUSIONS AND RELEVANCE Among patients aged 16 years or older diagnosed as having unruptured bAVM, use of conservative management compared with intervention was associated with better clinical outcomes for up to 12 years. Longer follow-up is required to understand whether this association persists.

Identifying dementia cases with routinely-collected health data: a systematic review

Prospective, population‐based studies can be rich resources for dementia research. Follow‐up in many such studies is through linkage to routinely collected, coded health‐care data sets. We evaluated the accuracy of these data sets for dementia case identification.

Accuracy of routinely-collected healthcare data for identifying motor neurone disease cases: A systematic review

Background Motor neurone disease (MND) is a rare neurodegenerative condition, with poorly understood aetiology. Large, population-based, prospective cohorts will enable powerful studies of the determinants of MND, provided identification of disease cases is sufficiently accurate. Follow-up in many such studies relies on linkage to routinely-collected health datasets. We systematically evaluated the accuracy of such datasets in identifying MND cases. Methods We performed an electronic search of MEDLINE, EMBASE, Cochrane Library and Web of Science for studies published between 01/01/1990-16/11/2015 that compared MND cases identified in routinely-collected, coded datasets to a reference standard. We recorded study characteristics and two key measures of diagnostic accuracy—positive predictive value (PPV) and sensitivity. We conducted descriptive analyses and quality assessments of included studies. Results Thirteen eligible studies provided 13 estimates of PPV and five estimates of sensitivity. Twelve studies assessed hospital and/or death certificate-derived datasets; one evaluated a primary care dataset. All studies were from high income countries (UK, Europe, USA, Hong Kong). Study methods varied widely, but quality was generally good. PPV estimates ranged from 55–92% and sensitivities from 75–93%. The single (UK-based) study of primary care data reported a PPV of 85%. Conclusions Diagnostic accuracy of routinely-collected health datasets is likely to be sufficient for identifying cases of MND in large-scale prospective epidemiological studies in high income country settings. Primary care datasets, particularly from countries with a widely-accessible national healthcare system, are potentially valuable data sources warranting further investigation.

Systematic reviews: guidance relevant for studies of older people

Abstract Systematic reviews and meta-analyses are increasingly common. This article aims to provide guidance for people conducting systematic reviews relevant to the healthcare of older people. An awareness of these issues will also help people reading systematic reviews to determine whether the results will influence their clinical practice. It is essential that systematic reviews are performed by a team which includes the required technical and clinical expertise. Those performing reviews for the first time should ensure they have appropriate training and support. They must be planned and performed in a transparent and methodologically robust way: guidelines are available. The protocol should be written—and if possible published—before starting the review. Geriatricians will be interested in a table of baseline characteristics, which will help to determine if the studied samples or populations are similar to their patients. Reviews of studies of older people should consider how they will manage issues such as different age cut-offs; non-specific presentations; multiple predictors and outcomes; potential biases and confounders. Systematic reviews and meta-analyses may provide evidence to improve older peoples care, or determine where new evidence is required. Newer methodologies, such as meta-analyses of individual level data, network meta-analyses and umbrella reviews, and realist synthesis, may improve the reliability and clinical utility of systematic reviews.

The diagnosis, burden and prognosis of dementia: A record-linkage cohort study in England

Objectives Electronic health records (EHR) might be a useful resource to study the risk factors and clinical care of people with dementia. We sought to determine the diagnostic validity of dementia captured in linked EHR. Methods and findings A cohort of adults in linked primary care, hospital, disease registry and mortality records in England, [CALIBER (CArdiovascular disease research using LInked Bespoke studies and Electronic health Records)]. The proportion of individuals with dementia, Alzheimer’s disease, vascular and rare dementia in each data source was determined. A comparison was made of symptoms and care between people with dementia and age-, sex- and general practice-matched controls, using conditional logistic regression. The lifetime risk and prevalence of dementia and mortality rates in people with and without dementia were estimated with random-effects Poisson models. There were 47,386 people with dementia: 12,633 with Alzheimer’s disease, 9540 with vascular and 1539 with rare dementia. Seventy-four percent of cases had corroborating evidence of dementia. People with dementia were more likely to live in a deprived area (conditional OR 1.26;95%CI:1.20–1.31 most vs least deprived), have documented memory impairment (cOR = 11.97;95%CI:11.24–12.75), falls (cOR = 2.36;95%CI:2.31–2.41), depression (cOR = 2.03; 95%CI:1.98–2.09) or anxiety (cOR = 1.27; 95%CI:1.23–1.32). The lifetime risk of dementia at age 65 was 9.2% (95%CI:9.0%-9.4%), in men and 14.9% (95%CI:14.7%-15.1%) in women. The population prevalence of recorded dementia increased from 0.3% in 2000 to 0.7% in 2010. A higher mortality rate was observed in people with than without dementia (IRR = 1.56;95%CI:1.54–1.58). Conclusions Most people with a record of dementia in linked UK EHR had some corroborating evidence for diagnosis. The estimated 10-year risk of dementia was higher than published population-based estimations. EHR are therefore a promising source of data for dementia research.

Relative risk of hemorrhage during pregnancy in patients with brain arteriovenous malformations

Background It is unclear whether the risk of bleeding from brain arteriovenous malformations is higher during pregnancy, delivery, or puerperium. We compared occurrence of brain arteriovenous malformation hemorrhage in women during this period with occurrence of hemorrhage outside this period during their fertile years. Methods We included all women with ruptured brain arteriovenous malformations (16–41 years) from a retrospective database of patients with brain arteriovenous malformations in four Dutch university hospitals (n = 95) and from the population-based Scottish Audit of Intracranial Vascular Malformations (n = 44). We estimated the relative rate of brain arteriovenous malformation rupture (before any treatment) during exposed time (pregnancy, delivery, puerperium) versus non-exposed time during fertile years, using the case-crossover design as primary analysis, and the self-controlled case-series design as secondary analysis. Results In 17 of 95 Dutch women and in 3 of 44 Scottish women, hemorrhages occurred while pregnant; none occurred during delivery or puerperium. In Dutch women, the relative rate of brain arteriovenous malformation rupture during pregnancy, delivery, or puerperium was 6.8 (95% confidence interval 3.6–13) according to the case-crossover method and 7.1 (95% confidence interval 3.4–13) using the self-controlled case-series method. In Scottish women, the relative rate was 1.3 (95% confidence interval 0.39–4.1) using the case-crossover method and 1.7 (95% confidence interval 0.0–4.4) according to the self-controlled case-series method. Because of limited overlap of confidence intervals, we refrained from pooling the cohorts. Conclusions Case-crossover and self-controlled case series analyses reveal an increase in relative rate of brain arteriovenous malformation rupture during pregnancy in the Dutch cohort but not in the Scottish cohort. Since point estimates varied between both cohorts and numbers are relatively small, the clinical implications of our findings are uncertain.

Identifying Parkinson's disease and parkinsonism cases using routinely-collected healthcare data: a systematic review

Background Population-based, prospective studies can provide important insights into Parkinson’s disease (PD) and other parkinsonian disorders. Participant follow-up in such studies is often achieved through linkage to routinely-collected healthcare datasets. We systematically reviewed the published literature on the accuracy of these datasets for this purpose. Methods We searched four electronic databases for published studies that compared PD and parkinsonism cases identified using routinely-collected data to a reference standard. We extracted study characteristics and two accuracy measures: positive predictive value (PPV) and/or sensitivity. Results We identified 18 articles, resulting in 27 measures of PPV and 14 of sensitivity. For PD, PPVs ranged from 56-90% in hospital datasets, 53-87% in prescription datasets, 81-90% in primary care datasets and was 67% in mortality datasets. Combining diagnostic and medication codes increased PPV. For parkinsonism, PPVs ranged from 36-88% in hospital datasets, 40-74% in prescription datasets, and was 94% in mortality datasets. Sensitivities ranged from 15-73% in single datasets for PD and 43-63% in single datasets for parkinsonism. Conclusions In many settings, routinely-collected datasets generate good PPVs and reasonable sensitivities for identifying PD and parkinsonism cases. Further research is warranted to investigate primary care and medication datasets, and to develop algorithms that balance a high PPV with acceptable sensitivity.

Correction: The diagnosis, burden and prognosis of dementia: A record-linkage cohort study in England

[This corrects the article DOI: 10.1371/journal.pone.0199026.].

Communication between specialities of the mind and the body

We read the recent article by Sommerlad et al. [1] with great interest. This important study showed that, for patients aged .65 years who were known to mental health services with a diagnosis of dementia and who were subsequently admitted to a general medical hospital, only 63.3% received a dementia International Classification of Diseases version 10 (ICD-10) code on discharge. Worryingly, the authors found that patients from ethnic minority groups are roughly half as likely to have a discharge ICD-10 dementia code compared with white patients. Previous European studies have reported sensitivities between 26% and 51% for the identification of dementia in hospital admissions data sets [2–6]. These studies, however, analyzed data from participants of population-based studies, meaning that theywould not necessarily be known to services with a diagnosis of dementia. In this study, all participants already had a diagnosis of dementia, which may be in part why the reported sensitivity is slightly higher. Unfortunately, this still leaves more than a third of patients who, despite being already diagnosed with dementia, do not have this diagnosis incorporated into their hospital discharge record. We agree with the authors’ recommendation that clinicians in general hospitals should do more to target groups where dementia diagnoses are disproportionately underrecorded. However, we believe that the results of this study primarily demonstrate communication failures between National Health Services (NHS) providers. In the United Kingdom, older adults with dementia are predominantly cared for by mental health services. Mental and general health services can be provided by separate NHS providers (Trusts), and communication between these providers is often suboptimal. A recent report by the National Confidential Enquiry into Patient Outcome and Death (NECPOD) [7] highlighted this issue, finding that clinicians could access both mental and physical health electronic casenotes in only 20.7% of UK hospitals. The report concluded that record sharing between mental health and general hospitals needs to be improved.

CREATING A DEMENTIA RESEARCH COHORT USING ROUTINELY COLLECTED HEALTHCARE DATA

Figure 2. Frequency of dementia subtypes within cohort Subtypes non–mutually exclusive. All-cause dementia includes unspecified dementia codes as well as subtypes codes. Mixed dementia includes participants who received both an Alzheimer’s disease and vascular dementia code at any point during follow-up. Background:The Secure Anonymised Information Linkage (SAIL) databank contains a wide range of regularly updated, anonymised, linked, routinely-collected healthcare data for the entire population of Wales, UK (3 million people). It is a valuable resource for dementia research owing to its size, long follow-up time and prospective collection of data during routine clinical care. We aimed to transform these large, coded, healthcare datasets into a flexible, ‘virtual cohort’ for dementia research. Methods:SAIL contains individual-level, linked primary care, hospital admissions, mortality and demographic data. We selected an initial observation period of 1 January 1990 to 31 March 2016, following participants from an inception date of 1 April 1997 (or first registration with a General Practitioner [GP] if that came later). We created >20 International Classification of Diseases version 10 and Read version 2 code lists for: dementia and its subtypes; comorbidities (e.g. stroke, rheuma-