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Background: Research has questioned the safety of delaying or withholding antibiotics for suspected urinary tract infection (UTI) in older patients. We evaluated the association between antibiotic treatment for lower UTI and risk of bloodstream infection (BSI) in adults aged ≥65 years in primary care., Methods and Findings: We analyzed primary care records from patients aged ≥65 years in England with community-onset UTI using the Clinical Practice Research Datalink (2007-2015) linked to Hospital Episode Statistics and census data. The primary outcome was BSI within 60 days, comparing patients treated immediately with antibiotics and those not treated immediately. Crude and adjusted associations between exposure and outcome were estimated using generalized estimating equations. A total of 147,334 patients were included representing 280,462 episodes of lower UTI. BSI occurred in 0.4% (1,025/244,963) of UTI episodes with immediate antibiotics versus 0.6% (228/35,499) of episodes without immediate antibiotics. After adjusting for patient demographics, year of consultation, comorbidities, smoking status, recent hospitalizations, recent accident and emergency (A&E) attendances, recent antibiotic prescribing, and home visits, the odds of BSI were equivalent in patients who were not treated with antibiotics immediately and those who were treated on the date of their UTI consultation (adjusted odds ratio [aOR] 1.13, 95% CI 0.97-1.32, p-value = 0.105). Delaying or withholding antibiotics was associated with increased odds of death in the subsequent 60 days (aOR 1.17, 95% CI 1.09-1.26, p-value < 0.001), but there was limited evidence that increased deaths were attributable to urinary-source BSI. Limitations include overlap between the categories of immediate and delayed antibiotic prescribing, residual confounding underlying differences between patients who were/were not treated with antibiotics, and lack of microbiological diagnosis for BSI., Conclusions: In this study, we observed that delaying or withholding antibiotics in older adults with suspected UTI did not increase patients' risk of BSI, in contrast with a previous study that analyzed the same dataset, but mortality was increased. Our findings highlight uncertainty around the risks of delaying or withholding antibiotic treatment, which is exacerbated by systematic differences between patients who were and were not treated immediately with antibiotics. Overall, our findings emphasize the need for improved diagnostic/risk prediction strategies to guide antibiotic prescribing for suspected UTI in older adults., Competing Interests: The authors have declared that no competing interests exist.

Background: The predictD intervention, a multicomponent intervention delivered by family physicians (FPs), reduced the incidence of major depression by 21% versus the control group and was cost-effective. A qualitative methodology was proposed to identify the mechanisms of action of these complex interventions., Purpose: To seek the opinions of these FPs on the potential successful components of the predictD intervention for the primary prevention of depression in primary care and to identify areas for improvement., Method: Qualitative study with FPs who delivered the predictD intervention at 35 urban primary care centres in seven Spanish cities. Face-to-face semi-structured interviews adopting a phenomenological approach. The data was triangulated by three investigators using thematic analysis and respondent validation was carried out., Results: Sixty-seven FPs were interviewed and they indicated strategies used to perform the predictD intervention, including specific communication skills such as empathy and the activation of patient resources. They perceived barriers such as lack of time and facilitators such as prior acquaintance with patients. FPs recognized the positive consequences of the intervention for FPs, patients and the doctor-patient relationship. They also identified strategies for future versions and implementations of the predictD intervention., Conclusions: The FPs who carried out the predictD intervention identified factors potentially associated with successful prevention using this program and others that could be improved. Their opinions about the predictD intervention will enable development of a more effective and acceptable version and its implementation in different primary health care settings., Competing Interests: The authors have declared that no competing interests exist.

Background: Little is known about the relative risk of common bacterial, viral, fungal, and parasitic infections in the general population of individuals exposed to systemic glucocorticoids, or about the impact of glucocorticoid exposure duration and predisposing factors on this risk., Methods and Findings: The hazard ratios of various common infections were assessed in 275,072 adults prescribed glucocorticoids orally for ≥15 d (women: 57.8%, median age: 63 [interquartile range 48-73] y) in comparison to those not prescribed glucocorticoids. For each infection, incidence rate ratios were calculated for five durations of exposure (ranging from 15-30 d to >12 mo), and risk factors were assessed. Data were extracted from The Health Improvement Network (THIN) primary care database. When compared to those with the same underlying disease but not exposed to glucocorticoids, the adjusted hazard ratios for infections with significantly higher risk in the glucocorticoid-exposed population ranged from 2.01 (95% CI 1.83-2.19; p < 0.001) for cutaneous cellulitis to 5.84 (95% CI 5.61-6.08; p < 0.001) for lower respiratory tract infection (LRTI). There was no difference in the risk of scabies, dermatophytosis and varicella. The relative increase in risk was stable over the durations of exposure, except for LRTI and local candidiasis, for which it was much higher during the first weeks of exposure. The risks of infection increased with age and were higher in those with diabetes, in those prescribed higher glucocorticoid doses, and in those with lower plasma albumin level. Most associations were also dependent on the underlying disease. A sensitivity analysis conducted on all individuals except those with asthma or chronic obstructive pulmonary disease produced similar results. Another sensitivity analysis assessing the impact of potential unmeasured confounders such as disease severity or concomitant prescription of chemotherapy suggested that it was unlikely that adjusting for these potential confounders would have radically changed the findings. Limitations of our study include the use of electronic medical records, which could have resulted in some degree of misclassification of the infectious outcomes; a possible reporting bias, as general practitioners could be more prone to record an infection in those exposed to glucocorticoids; and a low number of events for some outcomes such as scabies or varicella, which may have led to limited statistical power., Conclusions: The relative risk of LRTI and local candidiasis is very high during the first weeks of glucocorticoid exposure. Further studies are needed to assess whether low albumin level is a risk factor for infection by itself (e.g., by being associated with a higher free glucocorticoid fraction) or whether it reflects other underlying causes of general debilitation.

Background: Illicit drug use is a multifaceted public-health problem with potentially serious impacts. The United Kingdom has one of the highest prevalence of illegal drug use in Europe. Reduction of overall illegal drug use in England and Wales has decreased from 11% to 8.2% (2012/13) over the past 10 years. People who use drugs often seek help from their family doctors., Aims: To investigate General Practitioners (family doctors) first recording of drug use and opioid substitute treatment in primary care settings., Design: A descriptive study design. Males and females (16-64 years old) were extracted from The Health Improvement Network (THIN) database., Setting: England and Wales primary care., Method: The first recording of drug use and opioid substitution treatment in primary care was estimated for the period (1994-2012). Poisson regressions were conducted to estimate incidence risk ratios (IRR)., Results: We identified 33,508 first recordings of drug use and 10,869 individuals with prescriptions for opioid substitute treatment. Overall, males (IRR 2.02, 95% CI:1.97-2.07), people in the age-group; 16-24 (IRR 6.7, 95% CI:6.4-6.9) compared to those over 25 years and the most deprived (IRR 4.2, 95% CI:3.9-4.4) were more likely to have a recording of drug use. Males (IRR 1.2 95% CI:1.2-1.3), in the age-group; 25-34 (IRR 1.8 95% CI:1.7-1.9) and the most deprived (IRR 3.9 95% CI:3.6-4.3) were the groups more likely to have a opioid substitute treatment prescription., Conclusion: It is evident from this study that there is little recording of drug use and opioid substitute treatment in primary care. Most drug users do not receive treatment in primary care.

Background: Women taking lithium must decide whether to continue the medication if they conceive or plan to conceive. Little is known about the extent of prescribing of lithium during pregnancy., Aims: To determine: 1) the prevalence of lithium prescribing during pregnancy and 2) to assess whether pregnancy is associated with discontinuation of lithium., Method: First, we identified women receiving any lithium prescriptions before and during pregnancy using The Health Improvement Network (THIN) primary care database. Subsequently, we used a Kaplan-Meier plot to compare time to last prescription in women prescribed lithium continuously three months before pregnancy and a comparison group of non-pregnant women. Finally, we described the characteristics of the women prescribed lithium in pregnancy., Results: Very few women were prescribed lithium during pregnancy; out of 458,761 pregnancies, we identified 47 (0.01%) in which lithium was prescribed after the 6th week of pregnancy (when the pregnancy was likely to be known). In our study of discontinuation, we found pregnant women were more likely to stop lithium than those who were not pregnant. Of the 52 women who were being continuously prescribed lithium three months before pregnancy, only 17 (33%) continued receiving prescriptions beyond the 6th week of pregnancy. However, most of these 17 women continued treatment throughout pregnancy., Conclusions: Pregnancy was strongly associated with discontinuation of lithium. Further evidence on the risks of lithium is needed so that women can weight these against the risk of a deterioration in maternal mental health.

Background: There are no risk algorithms for the onset of anxiety syndromes at 12 months in primary care. We aimed to develop and validate internally a risk algorithm to predict the onset of anxiety syndromes at 12 months., Methods: A prospective cohort study with evaluations at baseline, 6 and 12 months. We measured 39 known risk factors and used multilevel logistic regression and inverse probability weighting to build the risk algorithm. Our main outcome was generalized anxiety, panic and other non-specific anxiety syndromes as measured by the Primary Care Evaluation of Mental Disorders, Patient Health Questionnaire (PRIME-MD-PHQ). We recruited 3,564 adult primary care attendees without anxiety syndromes from 174 family physicians and 32 health centers in 6 Spanish provinces., Results: The cumulative 12-month incidence of anxiety syndromes was 12.2%. The predictA-Spain risk algorithm included the following predictors of anxiety syndromes: province; sex (female); younger age; taking medicines for anxiety, depression or stress; worse physical and mental quality of life (SF-12); dissatisfaction with paid and unpaid work; perception of financial strain; and the interactions sex*age, sex*perception of financial strain, and age*dissatisfaction with paid work. The C-index was 0.80 (95% confidence interval=0.78-0.83) and the Hedges' g=1.17 (95% confidence interval=1.04-1.29). The Copas shrinkage factor was 0.98 and calibration plots showed an accurate goodness of fit., Conclusions: The predictA-Spain risk algorithm is valid to predict anxiety syndromes at 12 months. Although external validation is required, the predictA-Spain is available for use as a predictive tool in the prevention of anxiety syndromes in primary care.

Objective: To explore whether there are gender differences in the number of GP recorded cases, the probability of survival and consulting pattern prior to diagnosis amongst patients with three non-sex-specific cancers., Design: Cross sectional study., Setting: UK primary care., Subjects: 12,189 patients aged 16 years or over diagnosed with colorectal cancer (CRC), 11,081 patients with lung cancer and 4,352 patients with malignant melanoma, with first record of cancer diagnosis during 1997-2006., Main Outcome Measures: Cancer cases recorded in primary care; probability of survival following diagnosis; and number of GP contacts within the 24 months preceding diagnosis., Results: From 1997-2006, overall rates of GP recorded CRC and lung cancer cases recorded were higher in men than in women, but rates of malignant melanoma were higher in women than in men. Gender differences in survival were small; 49% of men and 53% of women survived at least 5 years following CRC diagnosis; 9% of men and 12% of women with lung cancer, and 77% of men and 86% of women with malignant melanoma. The adjusted male to female relative hazard ratio of death in all patients was 1.20 (95%CI 1.13-1.30), 1.24 (95%CI 1.16-1.33) and 1.73 (95%CI 1.51-2.00) for CRC, lung cancer and malignant melanoma respectively. However, gender differences in the relative risk were much smaller amongst those who died during follow-up. For each cancer, there was little evidence of gender difference in the percentage who consulted and the number of GP contacts made within 24 months prior to diagnosis., Conclusions: This study found that patterns of consulting prior to cancer diagnosis differed little between two genders, providing no support for the hypothesis that gender differences in survival are explained by gender differences in consultation for more serious illness, and suggests the need for a more critical view of gender and consultation.

Background: The predictD study developed and validated a risk algorithm for predicting the onset of major depression in primary care. We aimed to explore the opinion of patients about knowing their risk for depression and the values and criteria upon which these opinions are based., Methods: A maximum variation sample of patients was taken, stratified by city, age, gender, immigrant status, socio-economic status and lifetime depression. The study participants were 52 patients belonging to 13 urban health centres in seven different cities around Spain. Seven Focus Groups (FGs) were given held with primary care patients, one for each of the seven participating cities., Results: The results showed that patients generally welcomed knowing their risk for depression. Furthermore, in light of available evidence several patients proposed potential changes in their lifestyles to prevent depression. Patients generally preferred to ask their General Practitioners (GPs) for advice, though mental health specialists were also mentioned. They suggested that GPs undertake interventions tailored to each patient, from a "patient-centred" approach, with certain communication skills, and giving advice to help patients cope with the knowledge that they are at risk of becoming depressed., Conclusions: Patients are pleased to be informed about their risk for depression. We detected certain beliefs, attitudes, values, expectations and behaviour among the patients that were potentially useful for future primary prevention programmes on depression.

Background: There is increasing emphasis on primary care services for individuals with severe mental illnesses (SMI), including schizophrenia, bipolar disorder, and other non-organic psychotic disorders. However we lack information on how many people receive these different diagnoses in primary care. Primary care databases offer an opportunity to explore the recording of new SMI diagnoses in representative general practices., Methods: We used data from The UK Health Improvement Network (THIN) primary care database including longitudinal patient records for individuals aged over 16 years from 437 general practices. We determined the annual GP recorded rate of first diagnosis of SMI by age, gender, social deprivation and urbanicity between 2000 and 2010., Results: We identified 10,520 individuals with a first record of schizophrenia, bipolar disorder or other non-organic psychosis among 4,164,794 patients. This corresponded to a rate of first diagnosis of 46.4 per 100,000 person years at risk (PYAR) (95% CI 45.4 to 47.4) in the 16-65 age group. The rate of first record of schizophrenia was 9.2 per 100,000 PYAR (95% CI 8.7 to 9.6) in this age group, bipolar disorder was 15.0 per 100,000 PYAR (95% CI 14.4 to 15.5) and other non-organic psychotic disorder was 22.3 per 100,000 PYAR (95% CI 21.6 to 23.0)., Conclusions: The rates of GP recorded SMI in primary care records were broadly comparable to incidence rates from previous epidemiological studies of SMI and show similar patterns by socio-demographic characteristics. However there were some differences by specific diagnoses. GPs may be recording rates that are higher than those used to commission services.

Bereaved spouses or partners are thought to be at increased risk of morbidity and mortality. However, there are few large prospective studies and results are inconsistent. We estimated the relative mortality, prescription of psychotropic medication and use of primary medical care services in adults whose cohabitee died of cancer. To do this, we undertook a cohort study using The Health Improvement Network (THIN) UK primary care database. Participants were 1) people aged over 40, who were registered with general practices and had been exposed to the death of a cohabitee from cancer; and 2) a comparison cohort frequency matched on five year age bands and sex who were cohabiting with a living partner. The baseline was chosen as six months before the date of the cancer death for the exposed group and a random date for the unexposed group. Incidence rate ratios (IRR) with 95% confidence intervals (CI) were estimated using random effects Poisson regression to account for clustering within general practices and adjusting for other key variables. 92,129 patients were studied for a median follow up of 4 years. Cohabitees of patients who died of cancer were less likely to die of any cause (IRR 0.71, CI 0.68-0.74) after adjustment for age, gender, number of non-psychotropic prescriptions 6 months before the cancer death/index date, use of psychotropic medication 6 months before the cancer death/index date, smoking, alcohol and area deprivation score. Exposed patients were more likely to receive a prescription for antidepressant or hypnotic medication and to attend their GP both before and after the death of the cohabitee. In conclusion, we did not confirm increased mortality in cohabitees of people dying from cancer.

Background: Most research on frequent attendance has been cross-sectional and restricted to one year attendance rates. A few longitudinal studies suggest that frequent attendance is self-limiting. Frequent attenders are more likely to have social and psychiatric problems, medically unexplained physical symptoms, chronic somatic diseases (especially diabetes) and are prescribed more psychotropic medication and analgesics., Research Question: To describe the attendance rates in a longitudinal study and to test if depression, panic syndrome, other anxiety syndrome, alcohol misuse and general quality of life are associated with frequent attendance in next two consecutive years., Methods: 1118 consecutive family practice attendees, aged 18 to 75 years from randomly selected family medicine practices were recruited at baseline and followed up at 12 and 24 months. We identified frequent attenders in the top 10 centile within one year. Using a multivariate model, we ascertained if presence of common mental disorders and quality of life assessed at baseline in 2003 predict frequent attendance in 2004 and 2005., Results: 40% of frequent attenders continue to be frequent attenders in the following year and 20% of the frequent attenders were so for the 24 month period. Lower physical scores on the SF-12 questionnaire were strongly associated with future frequent attendance at 12 and 24 months. There was a trend for people with greater than elementary school education to be less likely to become frequent attenders at both 12 and 24 months. For other variables these effects were less consistent. Presence of major depression, panic syndrome, other anxiety syndrome and alcohol misuse were not predictive of frequent attendance in the following two years., Conclusion: Low physical quality of life is strongly predictive of higher frequent attendance and similar finding was observed for people with lower educational level but further confirmatory research is required to establish this association.

Background: Anxiety is common, with significant morbidity, but little is known about presentations and recording of anxiety diagnoses and symptoms in primary care. This study aimed to determine trends in incidence and socio-demographic variation in General Practitioner (GP) recorded diagnoses of anxiety, mixed anxiety/depression, panic and anxiety symptoms., Methodology/principal Findings: Annual incidence rates of anxiety diagnoses and symptoms were calculated from 361 UK general practices contributing to The Health Improvement Network (THIN) database between 1998 and 2008, adjusted for year of diagnosis, gender, age, and deprivation. Incidence of GP recorded anxiety diagnosis fell from 7.9 to 4.9/1000PYAR from 1998 to 2008, while incidence of anxiety symptoms rose from 3.9 to 5.8/1000PYAR. Incidence of mixed anxiety/depression fell from 4.0 to 2.2/1000PYAR, and incidence of panic disorder fell from 0.9/1000PYAR in 1998 to 0.5/1000PYAR in 2008. All these entries were approximately twice as common in women and more common in deprived areas. GP-recorded anxiety diagnoses, symptoms and mixed anxiety/depression were commonest aged 45-64 years, whilst panic disorder/attacks were more common in those 16-44 years. GPs predominately use broad non-specific codes to record anxiety problems in the UK., Conclusions/significance: GP recording of anxiety diagnoses has fallen whilst recording of anxiety symptoms has increased over time. The incidence of GP recorded diagnoses of anxiety diagnoses was lower than in screened populations in primary care. The reasons for this apparent under-recording and whether it represents under-detection in those being seen, a reluctance to report anxiety to their GP, or a reluctance amongst GPs to label people with anxiety requires investigation.

Objectives: To assess whether people with learning disability in the UK have poorer access to cancer screening., Design: Four cohort studies comparing people with and without learning disability, within the recommended age ranges for cancer screening in the UK. We used Poisson regression to determine relative incidence rates of cancer screening., Setting: The Health Improvement Network, a UK primary care database with over 450 General practices., Participants: Individuals with a recorded diagnosis of learning disability including general diagnostic terms, specific syndromes, chromosomal abnormalities and autism in their General Practitioner computerised notes. For each type of cancer screening, a comparison cohort of up to six people without learning disability was selected for each person with a learning disability, using stratified sampling on age within GP practice., Main Outcome Measures: Incidence rate ratios for receiving 1) a cervical smear test, 2) a mammogram, 3) a faecal occult blood test and 4) a prostate specific antigen test., Results: Relative rates of screening for all four cancers were significantly lower for people with learning disability. The adjusted incidence rate ratios (95% confidence intervals) were Cervical smears: Number eligible with learning disability = 6,254; IRR = 0.54 (0.52-0.56). Mammograms: Number eligible with learning disability = 2,956; IRR = 0.76 (0.72-0.81); Prostate Specific Antigen: Number eligible = 3,520; IRR = 0.87 (0.80-0.96) and Faecal Occult Blood Number eligible = 6,566; 0.86 (0.78-0.94). Differences in screening rates were less pronounced in more socially deprived areas. Disparities in cervical screening rates narrowed over time, but were 45% lower in 2008/9, those for breast cancer screening appeared to widen and were 35% lower in 2009., Conclusion: Despite recent incentives, people with learning disability in the UK are significantly less likely to receive screening tests for cancer that those without learning disability. Other methods for reducing inequalities in access to cancer screening should be considered.

Background: In 2003, the Committee on Safety of Medicines (CSM) advised against treatment with selective serotonin reuptake inhibitors (SSRIs) other than fluoxetine in children, due to a possible increased risk of suicidal behaviour. This study examined the effects of this safety warning on general practitioners' depression diagnosing and prescription behaviour in children., Methods and Findings: We identified a cohort of 1,502,753 children (<18 y; registered with GP for >6 m) in The Health Improvement Network (THIN) UK primary care database. Trends in incidence of depression diagnoses, symptoms and antidepressant prescribing were examined 1995-2009, accounting for deprivation, age and gender. We used segmented regression analysis to assess changes in prescription rates. Overall, 45,723 (3%) children had ≥ 1 depression-related entry in their clinical records. SSRIs were prescribed to 16,925 (1%) of children. SSRI prescription rates decreased from 3.2 (95%CI:3.0,3.3) per 1,000 person-years at risk (PYAR) in 2002 to 1.7 (95%CI:1.7,1.8) per 1,000 PYAR in 2005, but have since risen to 2.7 (95%CI:2.6,2.8) per 1,000 PYAR in 2009. Prescription rates for CSM-contraindicated SSRIs citalopram, sertraline and especially paroxetine dropped dramatically after 2002, while rates for fluoxetine and amitriptyline remained stable. After 2005 rates for all antidepressants, except paroxetine and imipramine, started to rise again. Rates for depression diagnoses dropped from 3.0 (95%CI:2.8,3.1) per 1,000 PYAR in 2002 to 2.0 (95%CI:1.9,2.1) per 1,000 PYAR in 2005 and have been stable since. Recording of symptoms saw a steady increase from 1.0 (95%CI:0.8,1.2) per 1,000 PYAR in 1995 to 4.7 (95%CI:4.5,4.8) per 1,000 PYAR in 2009., Conclusions: The rates of depression diagnoses and SSRI prescriptions showed a significant drop around the time of the CSM advice, which was not present in the recording of symptoms. This could indicate caution on the part of GPs in making depression diagnoses and prescribing antidepressants following the CSM advice.

Background: Severe mental illness is a serious and potentially life changing set of conditions. This paper describes and analyses patient characteristics and service usage over one year of a representative cohort of people with a diagnosis of severe mental illness across England, including contacts with primary and secondary care and continuity of care., Methods and Findings: Data were collected from primary care patient notes (n = 1150) by trained nurses from 64 practices in England, covering all service contacts from 1(st) April 2008 to 31st March 2009. The estimated national rate of patients seen only in primary care in the period was 31.1% (95% C.I. 27.2% to 35.3%) and the rates of schizophrenia and bipolar disorder were 56.8% (95% C.I. 52.3% to 61.2%) and 37.9% (95% C.I. 33.7% to 42.2%). In total, patients had 7,961 consultations within primary care and 1,993 contacts with mental health services (20% of the total). Unemployed individuals diagnosed more recently were more likely to have contact with secondary care. Of those seen in secondary care, 61% had at most two secondary care contacts in the period. Median annual consultation rates with GPs were lower than have been reported for previous years and were only slightly above the general population. Relational continuity in primary care was poor for 21% of patients (Modified Modified Continuity Index = <0.5), and for almost a third of new referrals to mental health services the primary care record contained no information on the referral outcome., Conclusions: Primary care is centrally involved in the care of people with serious mental illness, but primary care and cross-boundary continuity is poor for a substantial proportion. Research is needed to determine the impact of poor continuity on patient outcomes, and above all, the impact of new collaborative ways of working at the primary/secondary care interface.

Objective: Antiepileptic drugs (AEDs) are commonly prescribed for epilepsy and bipolar disorder but little is known about their use in pregnancy. We examined secular trends in AED prescribing in pregnancy and pregnancy as a determinant for stopping AED prescribing., Methods: We identified 174,055 pregnancies from The Health Improvement Network UK primary care database. Secular trends in AED prescribing during pregnancy were examined between 1994 and 2009. We used Cox's regression analyses to compare time to discontinuation of AED prescriptions between pregnant and non-pregnant women and to identify predictors of discontinuation of AEDs in pregnancy., Results: Prescribing of carbamazepine and sodium valproate have declined since 1994 despite being the most commonly prescribed AEDs in pregnancy up to 2004. Prescribing of lamotrigine in pregnancy has steadily increased and has been the most popular AED prescribed in pregnancy since 2004. Pregnant women with epilepsy were twice as likely to stop receiving AEDs (Hazard Ratio (HR) 2.00, 95% Confidence Interval (CI) 1.62-2.47) when compared to non-pregnant women and for women with bipolar disorder this was even higher (HR 3.07, 95% CI 2.04-4.62). For pregnant women with epilepsy, those receiving AEDs less regularly before pregnancy were more likely to stop receiving AEDs in pregnancy., Conclusions: Lamotrigine has been increasingly prescribed in pregnancy over older AEDs namely carbamazepine and sodium valproate. Pregnancy is a strong determinant for the discontinuation of AED prescribing particularly for women with bipolar disorder.

Background: Little is known about the risk of progression to hazardous alcohol use in people currently drinking at safe limits. We aimed to develop a prediction model (predictAL) for the development of hazardous drinking in safe drinkers., Methods: A prospective cohort study of adult general practice attendees in six European countries and Chile followed up over 6 months. We recruited 10,045 attendees between April 2003 to February 2005. 6193 European and 2462 Chilean attendees recorded AUDIT scores below 8 in men and 5 in women at recruitment and were used in modelling risk. 38 risk factors were measured to construct a risk model for the development of hazardous drinking using stepwise logistic regression. The model was corrected for over fitting and tested in an external population. The main outcome was hazardous drinking defined by an AUDIT score ≥8 in men and ≥5 in women., Results: 69.0% of attendees were recruited, of whom 89.5% participated again after six months. The risk factors in the final predictAL model were sex, age, country, baseline AUDIT score, panic syndrome and lifetime alcohol problem. The predictAL model's average c-index across all six European countries was 0.839 (95% CI 0.805, 0.873). The Hedge's g effect size for the difference in log odds of predicted probability between safe drinkers in Europe who subsequently developed hazardous alcohol use and those who did not was 1.38 (95% CI 1.25, 1.51). External validation of the algorithm in Chilean safe drinkers resulted in a c-index of 0.781 (95% CI 0.717, 0.846) and Hedge's g of 0.68 (95% CI 0.57, 0.78)., Conclusions: The predictAL risk model for development of hazardous consumption in safe drinkers compares favourably with risk algorithms for disorders in other medical settings and can be a useful first step in prevention of alcohol misuse.

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.