The risk of acute infections in new users of antidepressants: An observational cohort study.

BACKGROUND: Preclinical studies suggested that drugs that functionally inhibit acid sphingomyelinase (FIASMA)may enhance immune cell longevity and potentially offer protection against infections. Many antidepressants have shown FIASMA activity. METHODS: We conducted a cohort study using primary-care data from the UK-based Clinical Practice Research Datalink (2000-2021). We assessed the association of composite diagnosed acute infections in new users of fluoxetine, sertraline, paroxetine, or venlafaxine aged 18-80 years compared to citalopram. We compared SARS-CoV-2 infections between groups in a secondary analysis. We estimated incidence rates (IR) and IR ratios (IRR) of acute infections in four pairwise comparisons using negative binomial regression. We applied propensity score (PS) fine stratification to control for confounding. RESULTS: In the PS-weighted cohorts, we included 353,138 fluoxetine, 222,463 sertraline, 69,963 paroxetine, 32,608 venlafaxine, and between 515,996 and 516,583 new citalopram users. PS-weighted IRs ranged between 76.8 acute infections /1000 person-years (py) (sertraline) and 98.9 infections/1000 py (citalopram). We observed PS-weighted IRRs around unity for paroxetine (0.97, 95 % CI, 0.95-1.00), fluoxetine (0.94, 95 % CI, 0.92-0.95), and venlafaxine (0.90, 95 % CI, 0.87-0.94) vs citalopram. Reduced IRR for sertraline vs citalopram (0.84, 95 % CI, 0.82-0.85), became null within subgroups by cohort entry date. In the analysis of SARS-CoV-2 infection, no statistically relevant risk reduction was seen. LIMITATIONS: Analysis not limited to patients with diagnosed depression, possible underestimation of infection incidence, and unclear FIASMA activity of citalopram. CONCLUSIONS: Fluoxetine, sertraline, paroxetine, and venlafaxine were not associated with a reduced risk of acute infection when compared with the presumably weak FIASMA citalopram.

Risk of skin cancer in new users of thiazides and thiazide-like diuretics: a cohort study using an active comparator group.

BACKGROUND: Case-control studies report a dose-dependent increased risk of skin cancer in users of hydrochlorothiazide (HCTZ) vs. nonusers. The degree to which other thiazides and thiazide-like diuretics (TZs) are associated with skin cancer is less certain. OBJECTIVES: To assess the risk of skin cancer in new users of different TZs compared with new users of calcium channel blockers (CCBs). METHODS: We conducted a cohort study using a UK primary-care database (1998-2017), including 271 154 new TZ users [87·6% bendroflumethiazide (BFT), 5·8% indapamide and 3·6% HCTZ] and 275 263 CCB users. The outcomes were basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous malignant melanoma (CMM). We estimated incidence rates (IRs) and IR ratios (IRRs) in short-term (< 20 prescriptions) and long-term (≥ 20 prescriptions) users of TZs and CCBs using negative binomial regression, and calculated rate differences (RDs) for selected results. We used fine stratification on the propensity score (PS) to control for 23 baseline covariates. RESULTS: Long-term use of HCTZ increased absolute and relative risks of SCC [PS-weighted IRR 1·95; 95% confidence interval (CI) 1·87-2·02; RD per 100 000 person-years 87.4], but not of BCC or CMM. Long-term use of indapamide was associated with an increased incidence of CMM (IRR 1·43; 95% CI 1·35-1·50). BFT was not meaningfully associated with the risk of any type of skin cancer. CONCLUSIONS: Our results corroborate the previously reported increased risk of SCC (but not of BCC or CMM) for long-term use of HCTZ. BFT may be a safer alternative for patients at increased risk of skin cancer.

Incident depression in patients diagnosed with multiple sclerosis: a multi-database study.

BACKGROUND AND PURPOSE: Data on rates of newly diagnosed depression after multiple sclerosis (MS) diagnosis are sparse. Here, incident, treated depression in MS patients after diagnosis compared with matched non-MS patients is described. METHODS: A matched cohort study was conducted in two separate electronic medical databases: the US Department of Defense (US-DOD) military healthcare system and the UK's Clinical Practice Research Datalink GOLD (UK-CPRD). The study population included all patients with a first recorded diagnosis of MS and matched non-MS patients. Patients with a history of treated depression were excluded. Incidence rates and incidence rate ratios with 95% confidence intervals for treated depression after MS diagnosis/matched date were estimated. RESULTS: Incidence rate ratios of treated depression amongst MS patients compared with non-MS patients were 3.20 (95% confidence interval 3.05-3.35) in the US-DOD and 1.90 (95% confidence interval 1.74-2.06) in the UK-CPRD. Incidence rate ratios were elevated across age and sex. Rates were higher in females than males but, compared to non-MS patients, males with MS had a higher relative risk than females with MS. CONCLUSIONS: Multiple sclerosis patients in the UK and the USA have a two- to three-fold increased risk of new, treated depression compared to matched non-MS patients.

Infections in patients diagnosed with multiple sclerosis: A multi-database study.

BACKGROUND: Recent data on the rates of infections among patients with multiple sclerosis (MS) are sparse. The objective of this study was to quantify incidence of infections in patients with MS compared with a matched sample of patients without MS (non-MS). METHODS: This study was conducted in two separate electronic medical databases: the United States Department of Defense (US-DOD) military health care system and the United Kingdom's Clinical Practice Research Datalink GOLD (UK-CPRD). We identified patients with a first recorded diagnosis of MS between 2001 and 2016 (UK-CPRD) or 2004 and 2017 (US-DOD) and matched non-MS patients. We identified infections recorded after the MS diagnosis date (or the matched date in non-MS patients) and calculated incidence rates (IRs) and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) by infection site and type. RESULTS: Relative to non-MS patients, MS patients had higher rates of any infection (US-DOD IRR 1.76; 95% CI 1.72-1.80 and UK-CPRD IRR 1.25; 95% CI 1.21-1.29) and a two-fold higher rate of hospitalized infections (US-DOD IRR 2.43; 95% CI 2.23-2.63 and UK-CPRD IRR 2.00; 95% CI 1.84-2.17). IRs of any infection were higher in females compared with males in both MS and non-MS patients, while IRs of hospitalized infections were similar between sexes in both MS and non-MS patients. The IR of first urinary tract or kidney infection was nearly two-fold higher in MS compared with non-MS patients (US-DOD IRR 1.88; 95% CI 1.81-1.95 and UK-CPRD IRR 1.97; 95% CI 1.86-2.09) with higher rates in females compared with males. IRs for any opportunistic infection, candidiasis and any herpes virus were increased between 20 and 52% among MS patients compared with non-MS patients. IRs of meningitis, tuberculosis, hepatitis B and C were all low. CONCLUSION: MS patients have an increased risk of infection, notably infections of the renal tract, and a two-fold increased risk of hospitalized infections compared with non-MS patients.

The risk of treated anxiety and treated depression among patients with psoriasis and psoriatic arthritis treated with apremilast compared to biologics, DMARDs and corticosteroids: a cohort study in the United States MarketScan database.

BACKGROUND: Anxiety and depression are common among psoriasis and psoriatic arthritis (PsA) patients, but rates may differ by treatment. OBJECTIVE: To quantify the risk of incident treated anxiety, depression and mixed anxiety + depression in users of apremilast compared with users of other treatments for psoriasis and PsA. METHODS: We conducted two separate cohort studies of psoriasis and PsA patients treated with apremilast, tumour necrosis factor inhibitor biologics, interleukin-17, -23 or -12/23 inhibitor biologics, conventional DMARDs or systemic corticosteroids in the United States MarketScan database. Cohort entry was date of first study drug after 21 March 2014. We identified cases who had a depression and/or anxiety diagnosis with a prescription for antidepressant/antianxiety medication within 30 days of the diagnosis code. We calculated incidence rates (IRs) and incidence rate ratios with 95% confidence intervals (CIs) for treated anxiety, treated depression and treated anxiety + depression per 1000 patient-years (PY) among patients. RESULTS: Among the psoriasis cohort, IRs for each outcome were similar between exposure categories and highest among users of systemic corticosteroids alone. IRs (95% CI) for apremilast alone were 9.2 (6.6-12.5), 4.6 (2.8-7.1) and 4.6 (2.8-7.1) per 1000 PY for treated anxiety, treated depression and treated anxiety + depression, respectively. In the PsA cohort, the rate of anxiety was highest among users of apremilast alone; rates of depression and anxiety + depression were similar for apremilast compared with other PsA treatments. IRs for each outcome were also high for users of corticosteroids in both the psoriasis and PsA cohorts. CONCLUSIONS: Among patients with psoriasis, users of apremilast had similar rates of anxiety and depression as users of other non-corticosteroid systemic psoriasis treatments. Among PsA patients, users of apremilast had similar rates of depression and anxiety + depression compared with users of other systemic non-corticosteroid PsA drugs; however, the rate of anxiety was slightly higher.

Iron supplementation in Switzerland - A bi-national, descriptive and observational study.

BACKGROUND: Iron deficiency is the most common nutritional disorder in the world, and it is the only common nutrient deficiency in industrialised nations. It is thought to be the most common cause of anaemia. Use of iron supplementation in Switzerland has not been previously quantified in detail. OBJECTIVES: We quantified use of iron supplementation from Swiss data and compared it with data from the UK. We assessed the frequency of serum ferritin and haemoglobin tests prior to newly started iron therapy to see whether use was based on documented low iron levels or blood parameters, especially in the case of parenteral iron supplementation. METHODS: We conducted a retrospective descriptive study of prescription iron supplementation use, and compared use of oral or parenteral iron drugs between Switzerland (CH) and the UK. We retrieved Swiss data from the Swiss Health Insurance Helsana Group, and UK data were from the Clinical Practice Research Datalink (CPRD). The study period was 2012 to 2014. RESULTS: The 3-year prevalence of iron supplementation was 9.4% in Switzerland and 4.4% in the UK. Iron use increased slightly between 2012 and 2014 in both countries (CH +0.3%, UK +0.2%). Recorded parenteral iron administration was roughly a thousand times higher in Switzerland (1.9%) than in the UK in 2014. In Switzerland, iron supplements were mostly given to patients aged 20 to 49 years or older than of 80 years. In the UK, iron supplementation was less frequent in younger people, but more prevalent in the elderly. Prior to a first iron prescription, ferritin tests were done more frequently in Switzerland (oral 67.2%, parenteral 86.6%) than in the UK (oral 43.3%, parenteral 65.5%). Haemoglobin was measured before a new parenteral iron therapy rarely in Switzerland (oral 14.9%, parenteral 11.7%), but frequently in the UK (oral 77.4%, parenteral 85.6%). CONCLUSIONS: Iron supplementation is more common in Switzerland than in the UK, particularly parenteral iron supplementation. Haemoglobin measurements prior to a new parenteral iron therapy are relatively infrequent in Switzerland despite the required documentation of haemoglobin prior to therapy.

Hyperlipidaemia and incident osteoarthritis of the hand: a population-based case-control study.

OBJECTIVE: Preclinical evidence suggests that increased cholesterol levels might be involved in the pathophysiology of osteoarthritis of the hand (HOA), but evidence from observational studies remains scarce. We aimed to analyse the association between hyperlipidaemia and incident HOA. DESIGN: We conducted a matched (1:1) case-control study using the UK-based Clinical Practice Research Datalink (CPRD). Cases were patients aged 30-89 years with an incident diagnosis of HOA between 1995 and 2014. In multivariable conditional logistic regression analyses, we calculated odds ratios (OR) for incident HOA in patients with hyperlipidaemia, categorized by gender, age, previous duration of hyperlipidaemia, and recent statin treatment. RESULTS: Among 19,590 cases and 19,590 controls, we observed an increased risk of HOA in patients with hyperlipidaemia (OR 1.37, 95% confidence intervals (CI) 1.28-1.47), when compared to patients without hyperlipidaemia. Thus, of all HOA cases in our study population, 3.6% may have been attributable to the presence of hyperlipidaemia (population attributable risk). Most patients with HOA were elderly, but the strength of the association between HOA and hyperlipidaemia inversely correlated with increasing age, with the highest OR of 1.72 (95% CI 1.24-2.38) in patients aged 29-49 years. Categorization by previous hyperlipidaemia duration, as well as sub-classification of patients with hyperlipidaemia into those with and without recent statin use did not meaningfully change the effect estimate. CONCLUSIONS: Our results suggest that hyperlipidaemia may be an independent risk factor for new onset HOA.

Metformin use and risk of lactic acidosis in people with diabetes with and without renal impairment: a cohort study in Denmark and the UK.

AIMS: To assess risk of lactic acidosis among metformin users compared with other glucose-lowering agent users, according to renal function. METHODS: Using routine registries and databases, we conducted a cohort study. Of 43 580 metformin and 37 788 other glucose-lowering agent users in northern Denmark and 102 688 metformin and 28 788 other glucose-lowering agent users in the UK during 2001-2011, we identified lactic acidosis using diagnostic codes. We calculated the incidence rates of lactic acidosis in metformin and other glucose-lowering agent users overall and according to baseline estimated GFR (eGFR) levels. RESULTS: In Denmark, the incidence rates of lactic acidosis were 11.6 (95% CI 7.0-18.1) and 1.8 (95% CI 0.4-5.4) per 100 000 person-years of metformin use and of other glucose-lowering agent use, respectively. In the UK, the corresponding lactic acidosis incidence rates were 6.8 (95% CI 4.6-9.6) and 1.0 (95% CI 0.01-5.7) per 100 000 person-years of metformin use and of other glucose-lowering agent use. The incidence rates increased with decreasing baseline eGFR in both countries. Of the metformin-exposed people with lactic acidosis, 37% in Denmark and 34% in the UK experienced a decline in renal function in the year before the diagnosis. CONCLUSIONS: Risk of lactic acidosis was higher in metformin users than in other glucose-lowering agent users, and increased with decreasing eGFR, although this could be attributable to surveillance bias; however, diagnosed lactic acidosis was rare and can occur regardless of renal function.

Antibiotic use during pregnancy and asthma in preschool children: the influence of confounding.

BACKGROUND: A recent study suggested that early-life intestinal microbiota may play an important role in the development of childhood asthma, indicating that antibiotics taken during early life or in late pregnancy may be associated with childhood asthma. OBJECTIVE: This study aims to assess the association between prenatal antibiotic use and asthma in preschool children using data from the prescription database IADB.nl. To assess the influence of potential confounding, we conducted both a case-sibling and a case-control study and compared the results. METHODS: We conducted a case-sibling study in which 1228 children with asthma were compared to 1228 siblings without asthma, using data from the prescription database IADB.nl. In addition, a case-control study was conducted. Asthma in preschool children was defined as ≥ 3 prescriptions for anti-asthma medication within a year before the fifth birthday. Conditional logistic regression was used to estimate crude and adjusted odds ratios (aORs). RESULTS: In both the case-sibling and case-control analysis, the use of antibiotics in the third trimester of pregnancy was associated with an increased risk of asthma in preschool children (aOR 1.37; 95% CI 1.02-1.83 and aOR 1.40; 95% CI 1.15-1.47). Time-trend analyses showed that results were not influenced by a time trend in antibiotic exposure. A significant association between exposure to antibiotics in any trimester of pregnancy and the development of asthma in preschool children was observed in the case-control analysis only (aOR 1.46; 95% CI 1.34-1.59). CONCLUSION: Antibiotic use in the third trimester of pregnancy was associated with a small increased risk of asthma in preschool children. This association was robust to time-invariant confounding or exposure time trends, further supporting the important role for early-life intestinal microbiota in the development of childhood asthma.

Type II diabetes mellitus and incident osteoarthritis of the hand: a population-based case-control analysis.

OBJECTIVES: Emerging evidence suggests that diabetes may be a risk factor for osteoarthritis (OA). However, previous results on the association between diabetes and all OA were conflicting. We aimed to comprehensively analyse the association between type II diabetes mellitus (T2DM) and osteoarthritis of the hand (HOA) specifically. METHODS: We conducted a matched (1:1) case-control study using the UK-based Clinical Practice Research Datalink (CPRD) of cases aged 30-90 years with an incident diagnosis of HOA from 1995 to 2013. In multivariable conditional logistic regression analyses, we calculated odds ratios (OR) for incident HOA in patients with T2DM, categorized by T2DM severity (HbA1C), duration, and pharmacological treatment. We further performed sensitivity analyses in patients with and without other metabolic diseases (hypertension (HT), hyperlipidaemia (HL), obesity). RESULTS: Among 13,500 cases and 13,500 controls, we observed no statistically significant association between T2DM and HOA (OR 0.95, 95% confidence interval (CI) 0.87-1.04), regardless of T2DM severity, duration, or pharmacological treatment. Having HT did not change the OR. Although we observed slightly increased ORs in overweight T2DM patients with co-occurring HL with or without coexisting HT, none of these ORs were statistically significant. CONCLUSIONS: Our results provide evidence that T2DM is not an independent risk factor for HOA. Concurrence of T2DM with HT, HL, and/or obesity did not change this association significantly.

Intrauterine device use and the risk of pre-eclampsia: a case-control study.

OBJECTIVE: To determine the association between intrauterine device (IUD) use, timing of removal prior to pregnancy, and the risk of pre-eclampsia. DESIGN: A case-control study within the Clinical Practice Research Datalink, UK. SETTING: Medical record database in the UK. SAMPLE: Cases of pre-eclampsia (n = 2744) were identified among pregnancies resulting in singleton deliveries from 1993 to 2010. Four controls, or pregnancies unaffected by pre-eclampsia, were matched to each case on maternal age, general practice, and year of delivery. METHODS: Data on IUD use were obtained from patient records. The odds ratios (ORs) for the association between IUD and pre-eclampsia were adjusted for covariates identified a priori, and analyses were stratified by BMI and number of prior deliveries. MAIN OUTCOME MEASURES: Odds ratios (95% confidence intervals, 95% CIs) of pre-eclampsia in pregnancies among women with a history of IUD use, compared with women without a history of IUD use. RESULTS: Prior IUD use was associated with a reduced risk of pre-eclampsia (OR 0.76; 95% CI 0.58-0.98). The timing of removal in relation to the start of pregnancy showed an inverse association, with shorter intervals associated with a larger decrease in risk of pre-eclampsia. IUD removal within a year prior to pregnancy had an OR of 0.68 (95% CI 0.46-1.00). Among women with a prior delivery, the association between IUD use and pre-eclampsia was null. CONCLUSIONS: Intrauterine device use is associated with a small decreased risk of pre-eclampsia, specifically if removed within the year prior to conception. TWEETABLE ABSTRACT: A case-control study of pregnancies in the UK suggests a reduced risk of pre-eclampsia for former IUD users.

Trends in incidence and medical resource utilisation in patients with chronic lymphocytic leukaemia: insights from the UK Clinical Practice Research Datalink (CPRD).

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in European adults. We aimed to evaluate time trends in CLL incidence and medical resource utilisation of CLL patients in the UK. We conducted a retrospective, observational cohort analysis using the UK Clinical Practice Research Datalink (CPRD) comprising mainly primary care data. We included adult patients with newly diagnosed CLL between January 2000 and June 2012. Descriptive and trend analyses of CLL incidence and medical resource utilisation were performed. A total of 2576 patients with CLL met the eligibility criteria. At diagnosis, the majority of patients (71.7 %) were above 65 years of age. The European age-standardised CLL incidence rate in the CPRD was 6.2/100,000 (95 % confidence interval [CI] 6.0, 6.5/100,000) person-years. There was no statistically significant increase over time. The CLL patients had on average 74.6 general practitioner visits during a median follow-up of 3.3 years. Between 2000 and 2012, the average number of recorded hospitalisations and referrals per year corrected for duration of follow-up significantly (p < 0.001) increased by 8.1 % (95 % CI 6.8 %, 9.3 %) and 16.4 % (95 % CI 15.4 %, 17.3 %), respectively. Referrals and hospitalisations in the second year compared to the first year following the CLL diagnosis significantly decreased. CLL incidence rates in the CPRD were stable over the period from 2000 to 2012. Medical resource utilisation in UK primary care was well documented, but further research is needed to describe secondary and tertiary care medical resource utilisation e.g. chemotherapy administration, which is inadequately captured in the CPRD.

Previously diagnosed influenza infections and the risk of developing epilepsy.

Several epidemiological studies suggest a possible involvement of viral infection in the development of epilepsy. While recent research from in vitro studies increasingly supports the role of herpes simplex virus type 1 (HSV-1) in the pathogenesis of epilepsy, little is known about the role of other viral infections such as influenza. Using data from the Clinical Practice Research Datalink (CPRD), we conducted a matched case-control analysis to assess the association between GP-diagnosed influenza infections and the risk of developing an incident diagnosis of epilepsy. During the study period 11 244 incident epilepsy cases and 44 976 matched control patients were identified. Prior exposure to influenza was reported in 7·5% of epilepsy cases and 6·7% of controls [adjusted odds ratio (aOR) 1·12, 95% confidence interval (CI) 1·03-1·22]. Prior history of 'complicated influenza', i.e. influenza associated with a possible super-infection, was associated with a slightly increased epilepsy risk (aOR 1·64, 95% CI 1·10-2·46), particularly if recorded within the 2 months preceding the epilepsy diagnosis (aOR 6·03, 95% CI 1·10-33·2). Our findings suggest that prior influenza exposure does not appear to materially alter the risk of developing epilepsy. By contrast, influenza episodes accompanied by complications were associated with a slightly increased epilepsy risk.

Anti-diabetic medications and risk of primary liver cancer in persons with type II diabetes.

BACKGROUND: Type II diabetes increases liver cancer risk but the risk may be mitigated by anti-diabetic medications. However, choice of medications is correlated with diabetes duration and severity, leading to confounding by indication. METHODS: To address this association, we conducted a nested case-control study among persons with type II diabetes in the Clinical Practice Research Datalink. Cases had primary liver cancer and controls were matched on age, sex, practice, calendar time, and number of years in the database. Exposure was classified by type and combination of anti-diabetic prescribed and compared to non-use. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. RESULTS: In 305 cases of liver cancer and 1151 controls, there was no association between liver cancer and anti-diabetic medication use compared to non-use (OR=0.74 (95% CI=0.45-1.20) for metformin-only, 1.10 (95% CI=0.66-1.84) for other oral hypoglycaemic (OH)-only, 0.89 (95% CI=0.58-1.37) for metformin+other OH, 1.11 (95% CI=0.60-2.05) for metformin+insulin, 0.81 (95% CI=0.23-2.85) for other OH+insulin, and 0.72 (95% CI=0.18-2.84) for insulin-only). Stratification by duration of diabetes did not alter the results. CONCLUSIONS: Use of any anti-diabetic medications in patients with type II diabetes was not associated with liver cancer, though there was a suggestion of a small protective effect for metformin.

Metformin and the risk of head and neck cancer: a case-control analysis.

AIMS: Metformin use has been associated with a decreased risk of some cancers, although data on head and neck cancer (HNC) are scarce. We explored the relation between the use of antidiabetic drugs and the risk of HNC. METHODS: We conducted a case-control analysis in the UK-based Clinical Practice Research Datalink (CPRD) of people with incident HNC between 1995 and 2013 below the age of 90 years. Six controls per case were matched on age, sex, calendar time, general practice and number of years of active history in the CPRD prior to the index date. Other potential confounders including body mass index (BMI), smoking, alcohol consumption and comorbidities were also evaluated. The final analyses were adjusted for BMI, smoking and diabetes mellitus (or diabetes duration in a sensitivity analysis). Results are presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Use of metformin was neither associated with a statistically significant altered risk of HNC overall (1-29 prescriptions: adjusted OR 0.87, 95% CI 0.61-1.24 and ≥ 30 prescriptions adjusted OR 0.80, 95% CI 0.53-1.22), nor was long-term use of sulphonylureas (adjusted OR 0.87, 95% CI 0.59-1.30), or any insulin use (adjusted OR 0.92, 95% CI 0.63-1.35). However, we found a (statistically non-significant) decreased risk of laryngeal cancer associated with long-term metformin use (adjusted OR 0.41, 95% CI 0.17-1.03). CONCLUSIONS: In this population-based study, the use of antidiabetic drugs was not associated with a materially altered risk of HNC. Our data suggest a protective effect of long-term metformin use for laryngeal cancer.

Epidemiology of basal cell carcinoma in the United Kingdom: incidence, lifestyle factors, and comorbidities.

BACKGROUND: Little is known about the epidemiology of basal cell carcinoma (BCC). METHODS: Using the Clinical Practice Research Datalink, we calculated annual incidence rates. In a case-control analysis, we examined lifestyle factors and comorbidities. RESULTS: Incidence rose significantly between 2000 and 2011. Basal cell carcinoma risk was increased in alcohol drinkers (slightly) and immunocompromised patients, but reduced in smokers and individuals with abnormal weight. CONCLUSIONS: Basal cell carcinoma places a growing public health burden. Lifestyle factors do not play a major role in pathogenesis, but immunosuppression is important.

Prevalence and management of chronic kidney disease in primary care patients in the UK.

BACKGROUND: This study aimed to estimate the prevalence of chronic kidney disease (CKD) in the UK in 2010 and to assess prevalence, comorbidities and comedications associated with the disease over time, following inclusion of CKD in the Quality and Outcomes Framework (QOF). METHODS: This was a retrospective, longitudinal study assessing individuals with prevalent or incident CKD (identified using estimated glomerular filtration rate readings and/or Read codes) in the General Practice Research Database (GPRD) in 2010. Individuals were assessed at two time points: in 2010 and at the date of their first classification of CKD in the GPRD. RESULTS: The prevalence of stage 3-5 CKD in 2010 was 5.9%. In patients with stage 3-5 CKD at first classification, their disease remained stable, progressed or improved by 2010 in approximately 50%, 10-15% and 25-30% of patients, respectively. Diagnoses of cardiovascular-related comorbidities (hypertension, hypercholesterolaemia, diabetes and cardiovascular disease), and treatment with antihypertensives and lipid-modifying therapy (LMT), increased with worsening disease severity. When patients were stratified by diagnosis date, the proportion of patients with stage 3-5 CKD and cardiovascular-related comorbidities decreased with time, and the relative use of LMT and antihypertensives among patients with hypercholesterolaemia and hypertension increased with time. CONCLUSIONS: Chronic kidney disease is generally stable or progressive, although more patients improve disease stage than previously assumed. Data suggest that the introduction of CKD into the QOF has increased awareness of CKD among physicians in the UK, allowing for earlier intervention and better control of CKD progression.

Mortality of patients with multiple sclerosis: a cohort study in UK primary care.

We aimed to estimate rates, causes and risk factors of all-cause mortality in a large population-based cohort of multiple sclerosis (MS) patients compared with patients without MS. Using data from the UK General Practice Research Database, we identified MS cases diagnosed during 2001-2006 and validated using patients' original records where possible. We also included MS cases during 1993-2000 identified and validated in an earlier study. Cases were matched to up to ten referents without MS by age, sex, index date (date of first MS diagnosis for cases and equivalent reference date for controls), general practice and length of medical history before first MS diagnosis. Patients were followed up to identify deaths; hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox-proportional regression. MS patients (N = 1,822) had a significantly increased risk of all-cause mortality compared with referents (N = 18,211); adjusted HR 1.7 (95 % CI 1.4-2.1). Compared with referents, female MS patients had a higher but not significantly different HR for death than males; adjusted HR 1.86 (95 % CI 1.46-2.38) vs. HR 1.31 (95 % CI 0.93-1.84), respectively. The most commonly recorded cause of death in MS patients was 'MS' (41 %), with a higher proportion recorded among younger patients. A significantly higher proportion of referents than MS patients had cancer recorded as cause of death (40 vs. 19 %). Patients with MS have a significant 1.7-fold increased risk of all-cause mortality compared with the general population. MS is the most commonly recorded cause of death among MS patients.

Incidence of and risk factors for severe hypoglycaemia in treated type 2 diabetes mellitus patients in the UK--a nested case-control analysis.

AIMS: To assess incidence rates (IRs) of and identify risk factors for incident severe hypoglycaemia in patients with type 2 diabetes newly treated with antidiabetic drugs. METHODS: Using the UK-based General Practice Research Database, we performed a retrospective cohort study between 1994 and 2011 and a nested case-control analysis. Ten controls from the population at risk were matched to each case with a recorded severe hypoglycaemia during follow-up on general practice, years of history in the database and calendar time. Using multivariate conditional logistic regression analyses, we adjusted for potential confounders. RESULTS: Of 130,761 patients with newly treated type 2 diabetes (mean age 61.7 ± 13.0 years), 690 (0.5%) had an incident episode of severe hypoglycaemia recorded [estimated IR 11.97 (95% confidence interval, CI, 11.11-12.90) per 10,000 person-years (PYs)]. The IR was markedly higher in insulin users [49.64 (95% CI, 44.08-55.89) per 10,000 PYs] than in patients not using insulin [8.03 (95% CI, 7.30-8.84) per 10,000 PYs]. Based on results of the nested case-control analysis increasing age [≥ 75 vs. 20-59 years; adjusted odds ratio (OR), 2.27; 95% CI, 1.65-3.12], cognitive impairment/dementia (adjusted OR, 2.00; 95% CI, 1.37-2.91), renal failure (adjusted OR, 1.34; 95% CI, 1.04-1.71), current use of sulphonylureas (adjusted OR, 4.45; 95% CI, 3.53-5.60) and current insulin use (adjusted OR, 11.83; 95% CI, 9.00-15.54) were all associated with an increased risk of severe hypoglycaemia. CONCLUSIONS: Severe hypoglycaemia was recorded in 12 cases per 10,000 PYs. Risk factors for severe hypoglycaemia included increasing age, renal failure, cognitive impairment/dementia, and current use of insulin or sulphonylureas.