Use of drugs for hyperlipidaemia and diabetes and risk of primary and secondary brain tumours: nested case-control studies using the UK Clinical Practice Research Datalink (CPRD).

OBJECTIVES: Previous studies have suggested that fibrates and glitazones may have a role in brain tumour prevention. We examined if there is support for these observations using primary care records from the UK Clinical Practice Research Datalink (CPRD). DESIGN: We conducted two nested case-control studies using primary and secondary brain tumours identified within CPRD between 2000 and 2016. We selected cases and controls among the population of individuals who had been treated with any anti-diabetic or anti-hyperlipidaemic medication to reduce confounding by indication. SETTING: Adults older than 18 years registered with a general practitioner in the UK contributing data to CPRD. RESULTS: We identified 7496 individuals with any brain tumour (4471 primary; 3025 secondary) in total. After restricting cases and controls to those prescribed any anti-diabetic or anti-hyperlipidaemic medication, there were 1950 cases and 7791 controls in the fibrate and 480 cases with 1920 controls in the glitazone analyses. Longer use of glitazones compared with all other anti-diabetic medications was associated with a reduced risk of primary (adjusted OR (aOR) 0.89 per year, 95% CI 0.80 to 0.98), secondary (aOR 0.87 per year, 95% CI 0.77 to 0.99) or combined brain tumours (aOR 0.88 per year, 95% CI 0.81 to 0.95). There was little evidence that fibrate exposure was associated with risk of either primary or secondary brain tumours. CONCLUSIONS: Longer exposure to glitazones was associated with reduced primary and secondary brain tumour risk. Further basic science and population-based research should explore this finding in greater detail, in terms of replication and mechanistic studies.

Verbal fluency as a quick and simple tool to help in deciding when to refer patients with a possible brain tumour.

BACKGROUND: Patients with brain tumours often present with non-specific symptoms. Correctly identifying who to prioritise for urgent brain imaging is challenging. Brain tumours are amongst the commonest cancers diagnosed as an emergency presentation. A verbal fluency task (VFT) is a rapid triage test affected by disorders of executive function, language and processing speed. We tested whether a VFT could support identification of patients with a brain tumour. METHODS: This proof-of-concept study examined whether a VFT can help differentiate patients with a brain tumour from those with similar symptoms (i.e. headache) without a brain tumour. Two patient populations were recruited, (a) patients with known brain tumour, and (b) patients with headache referred for Direct-Access Computed-Tomography (DACT) from primary care with a suspicion of a brain tumour. Semantic and phonemic verbal fluency data were collected prospectively. RESULTS: 180 brain tumour patients and 90 DACT patients were recruited. Semantic verbal fluency score was significantly worse for patients with a brain tumour than those without (P < 0.001), whether comparing patients with headache, or patients without headache. Phonemic fluency showed a similar but weaker difference. Raw and incidence-weighted positive and negative predictive values were calculated. CONCLUSION: We have demonstrated the potential role of adding semantic VFT score performance into clinical decision making to support triage of patients for urgent brain imaging. A relatively small improvement in the true positive rate in patients referred for DACT has the potential to increase the timeliness and efficiency of diagnosis and improve patient outcomes.

Economic evaluation of GPs' direct access to computed tomography for identification of brain tumours.

BACKGROUND: When GPs suspect a brain tumour, a referral for specialist assessment and subsequent brain imaging is generally the first option. NICE has recommended that GPs have rapid direct access to brain imaging for adults with progressive sub-acute loss of central nervous function; however, no studies have evaluated the cost-effectiveness. METHODS: We developed a cost-effectiveness model based on data from one region of the UK with direct access computed tomography (DACT), routine data from GP records and the literature, to explore whether unrestricted DACT for patients with suspected brain tumour might be more cost-effective than criteria-based DACT or no DACT. RESULTS: Although criteria-based DACT allows some patients without brain tumour to avoid imaging, our model suggests this may increase costs of diagnosis due to non-specific risk criteria and high costs of diagnosing or 'ruling out' brain tumours by other pathways. For patients diagnosed with tumours, differences in outcomes between the three diagnostic strategies are small. CONCLUSIONS: Unrestricted DACT may reduce diagnostic costs; however, the evidence is not strong and further controlled studies are required. Criteria-based access to CT for GPs might reduce demand for DACT, but imperfect sensitivity and specificity of current risk stratification mean that it will not necessarily be cost-effective.

The usefulness of symptoms alone or combined for general practitioners in considering the diagnosis of a brain tumour: a case-control study using the clinical practice research database (CPRD) (2000-2014).

OBJECTIVES: To evaluate the utility of different symptoms, alone or combined, presented to primary care for an adult brain tumour diagnosis. DESIGN AND SETTING: Matched case-control study, using the data from Clinical Practice Research Datalink (2000-2014) from primary care consultations in the UK. METHOD: All presentations within 6 months of the index diagnosis date (cases) or equivalent (controls) were coded into 32 symptom groups. Sensitivity, specificity, positive predictive values (PPVs) and positive likelihood ratios were calculated for symptoms and combinations of symptoms with headache and cognitive features. Diagnostic odds ratios were calculated using conditional logistic regression, adjusted for age group, sex and Charlson comorbidity. Stratified analyses were performed for age group, sex and whether the tumour was of primary or secondary origin. RESULTS: We included 8,184 cases and 28,110 controls. Seizure had the highest PPV of 1.6% (95% CI 1.4% to 1.7%) followed by weakness 1.5% (1.3 to 1.7) and confusion 1.4% (1.3 to 1.5). Combining headache with other symptoms increased the PPV. For example, headache plus combined cognitive symptoms PPV 7.2% (6.0 to 8.6); plus weakness 4.4% (3.2 to 6.2), compared with headache alone PPV 0.1%. The diagnostic ORs were generally larger for patients <70 years; this was most marked for confusion, seizure and visual symptoms. CONCLUSION: We found seizure, weakness and confusion had relatively higher predictive values than many other symptoms. Headache on its own was a weak predictor but this was enhanced when combined with other symptoms especially in younger patients. Clinicians need to actively search for other neurological symptoms such as cognitive problems.

Symptoms in primary care with time to diagnosis of brain tumours.

Background: Brain tumours often present with varied, non-specific features with other diagnoses usually being more likely. Objective: To examine how different symptoms and patient demographics predict variations in time to brain tumour diagnosis. Methods: We conducted a secondary analysis of brain tumour cases from National Audit of Cancer Diagnosis in Primary Care. We grouped neurological symptoms into six domains (headache, behavioural/cognitive change, focal neurology, 'fits, faints or falls', non-specific neurological, and other/non-specific) and calculated times for patient presentation, GP referral, specialist consultation and total pathway interval. We calculated odds ratios (ORs) for symptom domains comparing the slowest to other quartiles. Results: Data were available for 226 cases. Median (interquartile range) time for the total pathway interval was 24 days (7-65 days). The most common presentation was focal neurology (33.2%) followed by 'fits, faints or falls' and headache (both 20.8%). Headache only (OR = 4.11, 95% CI = 1.10, 15.5) and memory complaints (OR = 4.82, 95% CI = 1.15, 20.1) were associated with slower total pathway compared to 'fits, faints or falls'. GPs were more likely to consider that there had been avoidable delays in referring patients with headache only (OR = 4.17, 95% CI = 1.14, 15.3). Conclusion: Patients presenting to primary care with headache only or with memory complaints remain problematic with potentially avoidable delays in referral leading to a longer patient pathway. This may or may not impact on the efficacy and morbidity of therapies. Additional aids are required to help doctors differentiate when to refer headaches and memory complaints urgently for a specialist opinion.

Dietary pattern, inflammation and cognitive decline: The Whitehall II prospective cohort study.

BACKGROUND & AIMS: Low-grade inflammation appears to play an etiological role in cognitive decline. However the association between an inflammatory dietary pattern and cognitive decline has not been investigated. We aimed to investigate dietary patterns associated with inflammation and whether such diet is associated with cognitive decline. METHODS: We analyzed 5083 participants (28.7% women) from the Whitehall II cohort study. Diet and serum interleukin-6 (IL-6) were assessed in 1991-1993 and 1997-1999. We used reduced rank regression methods to determine a dietary pattern associated with elevated IL-6. Cognitive tests were performed in 1997-1999 and repeated in 2002-2004 and 2007-2009. The association between dietary pattern and cognitive decline between ages 45 and 79 was assessed using linear mixed models. RESULTS: We identified an inflammatory dietary pattern characterized by higher intake of red meat, processed meat, peas and legumes, and fried food, and lower intake of whole grains which correlated with elevated IL-6 both in 1991-1993 and 1997-1999. A greater decline in reasoning was seen in participants in the highest tertile of adherence to the inflammatory dietary pattern (-0.37 SD; 95% confidence interval [CI] -0.40, -0.34) compared to those in the lowest tertile (-0.31; 95% CI -0.34, -0.28) after adjustment for age, sex, ethnicity, occupational status, education, and total energy intake (p for interaction across tertiles = 0.01). This association remained significant after multivariable adjustment. Similarly for global cognition, the inflammatory dietary pattern was associated with faster cognitive decline after multivariable adjustment (p for interaction across tertiles = 0.04). Associations were stronger in younger participants (<56 years), reducing the possibility of reverse causation. CONCLUSIONS: Our study found that a dietary pattern characterized as higher intake of red and processed meat, peas, legumes and fried food, and lower intake of whole grains was associated with higher inflammatory markers and accelerated cognitive decline at older ages. This supports the case for further research.

Midlife and Late-Life Smoking and Risk of Dementia in the Community: The Hisayama Study.

OBJECTIVES: To clarify the association between midlife and late-life smoking and risk of dementia. DESIGN: Prospective cohort study. SETTING: The Hisayama Study, Japan. PARTICIPANTS: Japanese community-dwellers without dementia aged 65 to 84 (mean age 72) followed for 17 years (1988-2005) (N = 754), 619 of whom had participated in a health examination conducted in 1973-74 (mean age, 57) and were included in the midlife analysis. MEASUREMENTS: The risk estimates of smoking status on the development of dementia were computed using a Cox proportional hazards model. RESULTS: During follow-up, 252 subjects developed all-cause dementia; 143 had Alzheimer's disease (AD), and 76 had vascular dementia (VaD). In late life, the multivariable-adjusted risk of all-cause dementia was significantly greater in current smokers than in never smokers; similar associations were seen for all-cause dementia, AD, and VaD in midlife current smokers. Meanwhile, no significant association was observed between past smoking and risk of any type of dementia in late or midlife. Multivariable analysis showed that smokers in midlife and late life had significantly greater risks than lifelong nonsmokers of all-cause dementia (adjusted hazard ratio (aHR) = 2.28, 95% confidence interval (CI) = 1.49-3.49), AD (aHR = 1.98, 95% CI = 1.09-3.61), and VaD (aHR = 2.88, 95% CI = 1.34-6.20). Such associations were not observed for midlife smokers who quit smoking in late life. CONCLUSION: Persistent smoking from mid- to late life is a significant risk factor for dementia and its subtypes in the general Japanese population.

Factors related to starting and continuing smoking among senior high school boys in Fukuoka, Japan.

The purpose of this study was to identify factors that influence starting and quitting smoking among Japanese male adolescents aged 15-18. Two thousand and twelve senior high school boys in Fukuoka City, Japan, answered unsigned self-administrated anonymous questionnaires in July 2001. Odds ratios (ORs) and their 95 % confidence intervals (CIs) were computed to assess the strength of associations between students' smoking status and alcohol consumption habits. Additionally, the link between a students' smoking status and parental influence (parental smoking) was also assessed. Approximately 90% of the students, both current and ex-smokers, had ever smoked prior to senior high school while 77% of the students (smokers and non-smokers) had the experience of drinking alcohol prior to admission to senior high school. After adjustment for school year (i.e., freshman, sophomore, junior, senior), academic education level, after-school club activities, time of first drinking experience and the frequency of drinking, there was a significant increased risk to become a smoker when one parent was a smoker (OR = 1.67, 95% CI = 1.18-2.37) or when both parents were smokers (OR = 2.94, 95% CI = 1.66-5.18) compared to both parents being non-smokers. The consumption of alcohol prior to entering senior high school was significantly associated with more than 2.5-fold greater risk for the onset of smoking when compared to the risk of becoming a smoker when alcohol consumption started after entering senior high school. An increased frequency of drinking was also associated with starting smoking (OR =14.00, 95% CI = 8.08-24.26; 2-3 times/week vs. never). Similarly, an increase in drinking frequency resulted in less likelihood of smoking cessation. For instance, the data showed that, the subjects were 1/3 less likely to quit smoking. Paternal smoking had a significant impact on whether or not a child would quit smoking (OR = 0.55, 95% CI = 0.38-0.81) as compared to a child that had paternal and maternal non-smokers. This study suggested that drinking habits started earlier than smoking habits among adolescents. Many students had already experienced drinking before admission to senior high school, while the experience of smoking mostly typically started after admission to high school. These data show the urgency of developing anti-smoking educational programs that could be developed and introduced prior to admission to high school.