Risk of fibromyalgia following antibiotic prescriptions: A population-based case-control study.

BACKGROUND: The health of the gut microbiome is now recognized to be an important component of the gut-brain axis which itself appears to be implicated in pain perception. Antibiotics are known to create dysbiosis in the microbiome, so whether fibromyalgia is more commonly diagnosed after antibiotic prescriptions provides a means of exploring the role of the microbiome in the experience of chronic pain. METHODS: A case-control study was carried out using electronic health records collected in the UK's Clinical Practice Research Datalink (CPRD), a comprehensive database of primary care consultations. For each case of diagnosed fibromyalgia, three controls were identified and matched by age, gender and GP practice. The exposure variable was the number and timing of antibiotic prescriptions over previous years. The analysis involved adjusting for a wide range of co-variates that might be possible confounders. RESULTS: A total of 44,674 cases of fibromyalgia were identified together with 133,513 controls. After adjusting for co-variates, it was found that both the total number of prescriptions and their timing was associated with an FM diagnosis. For example, the quartile with the highest number of prescriptions and that with the longest exposure had a greater than three-fold increase in FM diagnoses (number of prescriptions: odds ratio 3.92; 95% CIs: 3.71-4.13; exposure odds ratio 3.28; CIs: 3.13-3.43). Some antibiotics (such as tetracyclines and metronidazole) seemed to confer greater risk than others. CONCLUSIONS: The results lend support for prior antibiotics being an important risk factor for a diagnosis of FM. SIGNIFICANCE: This study shows an association between the volume as well as timing of prior antibiotic prescriptions and of a subsequent diagnosis of fibromyalgia in primary care.

Depressive symptoms during early adulthood and the development of physical multimorbidity in the UK: an observational cohort study.

BACKGROUND: An understanding of whether early-life depression is associated with physical multimorbidity could be instrumental for the development of preventive measures and the integrated management of depression. We therefore aimed to map out the cumulative incidence of physical multimorbidity over adulthood, and to determine the association between the presence of depressive symptoms during early adulthood and the development of physical multimorbidity in middle age. METHODS: In this observational cohort study, we used pooled data from the 1958 National Child Development Study (NCDS) and the 1970 British Cohort Study (BCS). Cohort waves were pooled in each decade of adult life available (when cohort members were aged 26 years in the BCS and 23 years in the NCDS [baseline]; 34 years in the BCS and 33 years in the NCDS [age 34 BCS/33 NCDS]; 42 years in the BCS and NCDS [age 42 BCS/NCDS]; and 46 years in the BCS and 50 years in the NCDS [age 46 BCS/50 NCDS]). We included participants who had completed the nine-item Malaise Inventory at baseline, and did not have a history of physical multimorbidity, any physical multimorbidity at baseline, or the presence of depressive symptoms before the development of physical multimorbidity. The presence of depressive symptoms was determined using the nine-item Malaise Inventory (cutoff score ≥4). Physical multimorbidity was defined as having at least two measures of any of the following ten self-reported groups of long-term conditions: asthma or bronchitis; backache; bladder or kidney conditions; cancer; cardiovascular conditions; convulsions or epilepsy; diabetes; hearing conditions; migraine; and stomach, bowel, or gall conditions. Cumulative incidence (with 95% CI) of physical multimorbidity was calculated for each decade considered after baseline, with physical multimorbidity being assessed as both a dichotomous and categorical variable. The association between depressive symptoms and the development of physical multimorbidity was assessed using adjusted relative risk ratios (with 95% CIs). FINDINGS: Analyses included 15 845 participants, of whom 4001 (25·25%; 95% CI 24·57-25·93) had depressive symptoms at baseline and 11 844 (74·75%; 74·07-75·42) did not. The cumulative incidence of physical multimorbidity (dichotomous) ranged over the study period from 2263 (18·44%; 95% CI 17·75-18·14) of 12 273 participants at age 34 BCS/33 NCDS, to 4496 (42·90%; 41·95-43·85) of 10 481 participants at age 46 BCS/50 NCDS, and was consistently higher in participants with depressive symptoms at baseline. The adjusted relative risk of physical multimorbidity was higher in participants with depressive symptoms than in those without and remained stable over the study period (adjusted relative rate ratio 1·67, 95% CI 1·50-1·87, at age 34 BCS/33 NCDS; 1·63, 1·48-1·79, at age 42 BCS/NCDS; and 1·58, 1·43-1·73, at age 46 BCS/50 NCDS). INTERPRETATION: The presence of depressive symptoms during early adulthood is associated with an increased risk of the development of physical multimorbidity in middle age. Although further research about the drivers of this relationship is needed, these results could help to enhance the integrated management of individuals with depressive symptoms and the development of preventive strategies to reduce the effect and burden of physical multimorbidity. FUNDING: UK Medical Research Council and Guy's Charity.

Improving suicide surveillance systems through the use of the Patient Health Questionnaire-9.

Suicide is a major public health problem worldwide and continues to be one of the main causes of death. Implementing surveillance strategies for suicidal thoughts and behaviours would make it possible to identify individuals at high risk of ending their lives by suicide. While a universal screening would be controversial, the increasing use of the 9-item version of the Patient Health Questionnaire (PHQ-9) in different healthcare settings, such as primary care or hospital emergency departments, offers an opportunity for testing its performance for suicide surveillance. Beyond being a screening of depression, the PHQ-9 has shown merit as a marker of suicidal thinking, thoughts of self-harm, and suicide. Implementing systematic surveillance strategies for suicide in different healthcare settings including data from the PHQ-9 might be an effective way to improve case detection. This could help to enhance the identification of highest risk population groups and, consequently, to avoid potentially preventable suicides.

The association between colorectal cancer and prior antibiotic prescriptions: case control study.

BACKGROUND: Antibiotic use over several decades is believed to be associated with colorectal adenomas. There is little evidence, however, for the effect of more recent antibiotic use on frequency of colorectal cancers. METHODS: A case control study used the RCGP's Research and Surveillance Centre cohort of patients drawn from NHS England. In all, 35,214 patients with a new diagnosis of colorectal cancer between 1 January 2008 and 31 December 2018 were identified in the database and were matched with 60,348 controls. Conditional logistic regression was used to examine the association between antibiotic prescriptions and colorectal cancer. RESULTS: A dose-response association between colorectal cancers and prior antibiotic prescriptions was observed. The risk was related to the number and recency of prescriptions with a high number of antibiotic prescriptions over a long period carrying the highest risk. For example, patients prescribed antibiotics in up to 15 years preceding diagnosis were associated with a higher risk of colorectal cancer (odds ratio (OR) = 1.90, 95% confidence intervals (CI), 1.61-2.19, p < 0.001). CONCLUSIONS: Antibiotic use over previous years is associated with subsequent colorectal cancer. While the study design cannot determine causality, the findings suggest another reason for caution in prescribing antibiotics, especially in high volumes and over many years.

Drug Utilization and Inappropriate Prescribing in Centenarians.

OBJECTIVES: To use primary care electronic health records (EHRs) to evaluate prescriptions and inappropriate prescribing in men and women at age 100. DESIGN: Population-based cohort study. SETTING: Primary care database in the United Kingdom, 1990 to 2013. PARTICIPANTS: Individuals reaching the age of 100 between 1990 and 2013 (N = 11,084; n = 8,982 women, n = 2,102 men). MEASUREMENTS: Main drug classes prescribed and potentially inappropriate prescribing according to the 2012 American Geriatrics Society Beers Criteria. RESULTS: At the age of 100, 73% of individuals (79% of women, 54% of men) had received one or more prescription drugs, with a median of 7 (interquartile range 0-12) prescription items. The most frequently prescribed drug classes were cardiovascular (53%), central nervous system (CNS) (53%), and gastrointestinal (47%). Overall, 32% of participants (28% of men, 32% of women) who received drug prescriptions may have received one or more potentially inappropriate prescriptions, with temazepam and amitriptyline being the most frequent. CNS prescriptions were potentially inappropriate in 23% of individuals, and anticholinergic prescriptions were potentially inappropriate in 18% of individuals. CONCLUSION: The majority of centenarians are prescribed one or more drug therapies, and the prescription may be inappropriate for up to one-third of these individuals. Research using EHRs offers opportunities to understand prescribing trends and improve pharmacological care of the oldest adults.

Incidence and mortality of relapsing polychondritis in the UK: a population-based cohort study.

OBJECTIVE: Relapsing polychondritis is a rare disease characterized by cartilage inflammation. Our aim was to estimate the incidence, prevalence and mortality of relapsing polychondritis and describe the clinical features of relapsing polychondritis in a large population. METHODS: All participants diagnosed with relapsing polychondritis were sampled from the Clinical Practice Research Datalink. Prevalence and incidence rates for 1990-2012 were estimated. Relative mortality rates were estimated in a time-to-event framework using reference UK life tables. A questionnaire validation study assessed diagnostic accuracy. RESULTS: There were 117 participants with relapsing polychondritis ever recorded. Fifty (82%) of 61 cases were validated by a physician and unconfirmed cases were excluded. The analysis included 106 participants (42 men, 64 women) diagnosed with relapsing polychondritis. The mean age (range) at diagnosis in men was 55 (range 17-81) years and in women 51 (range 11-79) years. The median interval from first symptom to diagnosis was 1.9 years. The incidence of relapsing polychondritis between 1990 and 2012 was 0.71 (95% CI 0.55, 0.91) per million population per year. There were 19 deaths from any cause. There were 16 observed deaths eligible for survival analysis and 7.4 deaths expected for the UK population of the same age, sex and period. The standardized mortality ratio was 2.16 (95% CI 1.24, 3.51), P < 0.01. Respiratory disease, cardiac conditions and cancer were the most frequent causes of death. CONCLUSION: The incidence of relapsing polychondritis may be lower than previously estimated, and diagnostic misclassification and delay are common. Mortality in relapsing polychondritis is more than twice that of the general population.

Estimating the yield of NHS Health Checks in England: a population-based cohort study.

BACKGROUND: This study aimed to evaluate the yield of the NHS Health Checks programme. METHODS: A cohort study, conducted in the Clinical Practice Research Datalink in England. Electronic health records were analysed for patients aged 40-74 receiving an NHS Health Check between 2010 and 2013. RESULTS: There were 65 324 men and 75 032 women receiving a health check. For every 1000 men assessed, there were 205 smokers (95% confidence interval 195-215), 355 (340-369) with hypertension (≥140/90 mmHg) and 633 (607-658) with elevated cholesterol (≥5 mmol/l). Among 1000 women, there were 161 (151-171) smokers, 247 (238-257) with hypertension and 668 (646-689) with elevated cholesterol. In the 12 months following the check, statins were prescribed to 18% of men and 21% of women with ≥20% cardiovascular risk and antihypertensive drugs to 11% of men and 16% of women with ≥20% cardiovascular risk. Slight reductions in risk factor values were observed in the minority of participants with follow-up values recorded in the 15 months following the check. CONCLUSIONS: A universal primary prevention programme identifies substantial risk factor burden in a population without known cardiovascular disease. Research is needed to monitor interventions, and intermediate- and long-term outcomes, in those identified at high risk.

Incidence of type 2 diabetes after bariatric surgery: population-based matched cohort study.

BACKGROUND: The effect of currently used bariatric surgical procedures on the development of diabetes in obese people is not well defined. We aimed to assess the effect of bariatric surgery on development of type 2 diabetes in a large population of obese individuals. METHODS: We did a matched cohort study of adults (age 20­100 years) identified from a UK-wide database of family practices, who were obese (BMI ≥30 kg/m2) and did not have diabetes. We enrolled 2167 patients who had undergone bariatric surgery between Jan 1, 2002, and April 30, 2014, and matched them--according to BMI, age, sex, index year, and HbA1c--with 2167 controls who had not had surgery. Procedures included laparoscopic gastric banding (n=1053), gastric bypass (795), and sleeve gastrectomy (317), with two procedures undefined. The primary outcome was development of clinical diabetes, which we extracted from electronic health records. Analyses were adjusted for matching variables, comorbidity, cardiovascular risk factors, and use of antihypertensive and lipid-lowering drugs. FINDINGS: During a maximum of 7 years of follow-up (median 2·8 years [IQR 1·3­4·5]), 38 new diagnoses of diabetes were made in bariatric surgery patients and 177 were made in controls. By the end of 7 years of follow-up, 4·3% (95% CI 2·9­6·5) of bariatric surgery patients and 16·2% (13·3­19·6) of matched controls had developed diabetes. The incidence of diabetes diagnosis was 28·2 (95% CI 24·4­32·7) per 1000 person-years in controls and 5·7 (4·2­7·8) per 1000 person-years in bariatric surgery patients; the adjusted hazard ratio was 0·20 (95% CI 0·13­0·30, p<0·0001). This estimate was robust after varying the comparison group in sensitivity analyses, excluding gestational diabetes, or allowing for competing mortality risk. INTERPRETATION: Bariatric surgery is associated with reduced incidence of clinical diabetes in obese participants without diabetes at baseline for up to 7 years after the procedure. FUNDING: UK National Institute for Health Research.

Are alarm symptoms predictive of cancer survival?: population-based cohort study.

BACKGROUND: Alarm symptom presentations are predictive of cancer diagnosis but may also be associated with cancer survival. AIM: To evaluate diagnostic time intervals, and consultation patterns after presentation with alarm symptoms, and their association with cancer diagnosis and survival. DESIGN AND SETTING: Cohort study using the Clinical Practice Research Database, with linked Cancer Registry data, in 158 general practices. METHOD: Participants included those with haematuria, haemoptysis, dysphagia, and rectal bleeding or urinary tract cancer, lung cancer, gastro-oesophageal cancer, and colorectal cancer. RESULTS: The median (interquartile range) interval in days from first symptom presentation to the corresponding cancer diagnosis was: haematuria and urinary tract cancer, 59 (28-109); haemoptysis and lung cancer, 35 (18-89); dysphagia and gastro-oesophageal cancer, 25 (12-48); rectal bleeding and colorectal cancer, 49 (20-157). Three or more alarm symptom consultations were associated with increased odds of diagnosis of urinary tract cancer (odds ratio [OR] 1.84, 95% CI = 1.50 to 2.27), lung cancer (OR = 1.76, 95% CI = 1.07 to 2.90) and gastro-oesophageal cancer (OR = 2.17, 95% CI = 1.48 to 3.19). Longer diagnostic intervals were associated with increased mortality only for urinary tract cancer (hazard ratio 2.23, 95% CI = 1.35 to 3.69). Patients with no preceding alarm symptom had shorter survival from diagnosis of urinary tract, lung or colorectal cancer than those presenting with a relevant alarm symptom. CONCLUSION: After alarm symptom presentation, repeat consultations are associated with cancer diagnoses. Longer diagnostic intervals appeared to be associated with a worse prognosis for urinary tract cancer only. Mortality is higher when cancer is diagnosed in the absence of alarm symptoms.

Cardiovascular risk factors and cognitive decline in adults aged 50 and over: a population-based cohort study.

OBJECTIVES: the objective of the present study was to explore the association between cardiovascular risk and cognitive decline in adults aged 50 and over. METHODS: participants were older adults who participated in the English Longitudinal Study of Ageing. Outcome measures included standardised z-scores for global cognition, memory and executive functioning. Associations between cardiovascular risk factors and 10-year Framingham risk scores with cognitive outcomes at 4-year and 8-year follow-ups were estimated. RESULTS: the mean age of participants (n = 8,780) at 2004-05 survey was 66.93 and 55% were females. Participants in the highest quartile of Framingham stroke risk score (FSR) had lower global cognition (b = -0.73,CI: -1.37, -0.10), memory (b = -0.56, CI: -0.99, -0.12) and executive (b = -0.37, CI: -0.74, -0.01) scores at 4-year follow-up compared with those in the lower quartile. Systolic blood pressure ≥160 mmHg at 1998-2001 survey was associated with lower global cognitive (b = -1.26, CI: -2.52, -0.01) and specific memory (b = -1.16, CI: -1.94, -0.37) scores at 8-year follow-up. Smoking was consistently associated with lower performance on all three cognitive outcomes. CONCLUSION: elevated cardiovascular risk may be associated with accelerated decline in cognitive functioning in the elderly. Future intervention studies may be better focused on overall risk rather than individual risk factor levels.

Utility of electronic patient records in primary care for stroke secondary prevention trials.

BACKGROUND: This study aimed to inform the design of a pragmatic trial of stroke prevention in primary care by evaluating data recorded in electronic patient records (EPRs) as potential outcome measures. The study also evaluated achievement of recommended standards of care; variation between family practices; and changes in risk factor values from before to after stroke. METHODS: Data from the UK General Practice Research Database (GPRD) were analysed for 22,730 participants with an index first stroke between 2003 and 2006 from 414 family practices. For each subject, the EPR was evaluated for the 12 months before and after stroke. Measures relevant to stroke secondary prevention were analysed including blood pressure (BP), cholesterol, smoking, alcohol use, body mass index (BMI), atrial fibrillation, utilisation of antihypertensive, antiplatelet and cholesterol lowering drugs. Intraclass correlation coefficients (ICC) were estimated by family practice. Random effects models were fitted to evaluate changes in risk factor values over time. RESULTS: In the 12 months following stroke, BP was recorded for 90%, cholesterol for 70% and body mass index (BMI) for 47%. ICCs by family practice ranged from 0.02 for BP and BMI to 0.05 for LDL and HDL cholesterol. For subjects with records available both before and after stroke, the mean reductions from before to after stroke were: mean systolic BP, 6.02 mm Hg; diastolic BP, 2.78 mm Hg; total cholesterol, 0.60 mmol/l; BMI, 0.34 Kg/m2. There was an absolute reduction in smokers of 5% and heavy drinkers of 4%. The proportion of stroke patients within the recommended guidelines varied from less than a third (29%) for systolic BP, just over half for BMI (54%), and over 90% (92%) on alcohol consumption. CONCLUSIONS: Electronic patient records have potential for evaluation of outcomes in pragmatic trials of stroke secondary prevention. Stroke prevention interventions in primary care remain suboptimal but important reductions in vascular risk factor values were observed following stroke. Better recording of lifestyle factors in the GPRD has the potential to expand the scope of the GPRD for health care research and practice.