Lithium Prescribing during Pregnancy: A UK Primary Care Database Study

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

Incidence and prevalence of diabetes and cost of illness analysis of polycystic ovary syndrome: a Bayesian modelling study

STUDY QUESTION: What is the incidence/prevalence of type 2 diabetes in women with polycystic ovary syndrome (PCOS) and the economic burden associated with PCOS in the UK? SUMMARY ANSWER: The incidence and prevalence of type 2 diabetes in women with PCOS are 3-33 per 1000 person years and 26.5%, respectively, with an associated annual healthcare burden of at least £237 million in the UK. WHAT IS KNOWN ALREADY: Although observational studies have been designed to assess the incidence of diabetes in women with PCOS, these have been open to criticism because of short periods of follow-up, small sample sizes or invalidated diagnosis of PCOS. Only one study has estimated the healthcare-related economic burden of PCOS, reporting a cost of $4.36 billion per year in the USA. STUDY DESIGN, SIZE, DURATION: This was a modelling study using individual patient data from a UK primary care database between 2004 and 2014 and aggregate data from the literature to obtain conversion rates through disease progression of PCOS. A simulation approach was applied to model the population dynamics of PCOS over a follow-up period of 25 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 14 135 women with PCOS or symptoms indicative of PCOS were selected from the primary care database to estimate the incidence of confirmed diagnosis of PCOS and diagnosis of type 2 diabetes. A 'virtual' cohort including the entire PCOS population (size estimated from the UK census data) was simulated to model the population dynamics of PCOS. The economic and utility analyses were further conducted from a healthcare perspective. MAIN RESULTS AND THE ROLE OF CHANCE: The peak conversion rate from possible to diagnosed PCOS was 121 per 1000 person-year (PY). The maximal incidence of type 2 diabetes was 33 per 1000 PY. The estimated prevalence of diabetes in the PCOS population was 26.5% (95% interval: 25.4-27.8%) during a 25-year follow-up. The annual healthcare burden of PCOS based on our conservative estimate is at least £237 million for the follow-up period examined. LIMITATIONS, REASONS FOR CAUTION: Due to lack of data, a full economic evaluation including healthcare costs of all the comorbidities associated with PCOS was not possible. Simplification of the real-world situation represented by the model may be a concern. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that a large number of women with symptoms indicative of PCOS never receive a definitive diagnosis yet can suffer from a rapid conversion to diabetes. This significantly reduces the quality of life for individual patients and incurs high costs for healthcare providers. As the risk of diabetes in women with PCOS is similar to that seen in populations at high risks of diabetes, it is possible that including them in national screening programmes may be cost effective. STUDY FUNDING/COMPETING INTEREST(S): There was no funding for the current study. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable

Diagnosis and management of polycystic ovary syndrome in the UK (2004-2014): a retrospective cohort study.

OBJECTIVE: To estimate the incidence and prevalence of polycystic ovary syndrome (PCOS) in UK primary care and investigate prescribing patterns before and after a PCOS diagnosis. DESIGN: Retrospective cohort study. SETTING: UK primary care (2004-2014). PARTICIPANTS: Women aged 15-45 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The incidence and prevalence of diagnosed PCOS and probable PCOS (ie, those without a confirmed diagnosis but with at least 2 PCOS features recorded within 3 years). Among women with diagnosed or probable PCOS, the prevalence of prescribing of drugs typically used to treat PCOS was calculated prior to and in the 24 months after the diagnosis of PCOS. RESULTS: We identified 7233 women with PCOS diagnoses and 7057 women with records suggestive of probable PCOS, corresponding to incidence rates of 0.93 and 0.91 per 1000 person-years at risk (PYAR) and an overall rate of 1.84 per 1000 PYAR. Women aged 20-24 years and women living in deprived areas had the highest incidence of PCOS. The prevalence of PCOS in 2014 was ∼2%. The proportion of women with a prescription in the 24 months after their PCOS index date varied by drug type: 10.2% metformin, 15.2% combined oral contraceptives, 18.8% acne-related treatments, 1.93% clomiphene, 1.0% spironolactone, 0.28% cyproterone and 3.11% eflornithine. Acne-related treatments were more commonly used to treat probable (28.3%) than diagnosed (12.3%) cases, while metformin was prescribed much more commonly in diagnosed cases. CONCLUSIONS: In conclusion, compared to rates estimated in community samples, the incidence and prevalence of women presenting in primary care with PCOS diagnoses and features are low, indicating that PCOS is an under-recognised condition. Although considerable variation is observed in treatments prescribed to women with PCOS, the treatments initiated following a confirmed diagnosis generally reflect the long-term prognostic concerns raised in PCOS consensuses

The prevalence of polycystic ovary syndrome in reproductive-aged women of different ethnicity: a systematic review and meta-analysis

The prevalence of PCOS was investigated in many studies in different continents. However, there is no established prevalence of PCOS for distinct ethnic groups. In the current analysis, we conducted searches in PubMed, The Cochrane Library, EMBASE, CINAHL up to Jan. 2017 to identify studies reporting prevalence of PCOS in the general female population. Forty-two studies were identified, with 13 eligible for evidence synthesis. The prevalence among different ethnicity was estimated using random effect modelling. Our results suggested the lowest prevalence in Chinese women(2003 Rotterdam criterion: 5.6% 95% interval: 4.4–7.3%), and then in an ascending order for Caucasians (1990 NIH criterion: 5.5% 95% interval: 4.8–6.3%), Middle Eastern (1990 NIH 6.1% 95% interval: 5.3–7.1%; 2003 Rotterdam 16.0% 95% interval: 13.8–18.6%; 2006 AES 12.6% 95% interval: 11.3–14.2%), and Black women (1990 NIH: 6.1% 95% interval: 5.3–7.1%).There is variation in prevalence of PCOS under different diagnostic criteria and across ethnic groups. This emphasises the need for ethnicity-specific guidelines for PCOS to prevent under- or over-diagnosis of the condition given that under-diagnosis may lead to rapid conversion of metabolic disorders for patients whereas over-diagnosis may exert negative psychological effects on patients which worsens the major symptoms of PCOS

Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad

Antiepileptic drugs prescribed in pregnancy and prevalence of major congenital malformations: comparative prevalence studies.

OBJECTIVE: The aim of this study was to examine the prevalence of major congenital malformations associated with antiepileptic drug (AED) treatment in pregnancy. PATIENTS AND METHODS: Using data from The Health Improvement Network, we identified women who have given live birth and their offspring. Four subgroups were selected based on the AED treatment in early pregnancy, valproate, carbamazepine, lamotrigine and women not receiving AED treatment. We compared the prevalence of major congenital malformations within children of these four groups and estimated prevalence ratios (PRs) using Poisson regression adjusted for maternal age, sex of child, quintiles of Townsend deprivation score and indication for treatment. RESULTS: In total, 240,071 women were included in the study. A total of 229 women were prescribed valproate in pregnancy, 357 were prescribed lamotrigine and 334 were prescribed carbamazepine and 239,151 women were not prescribed AEDs. Fifteen out of 229 (6.6%) women prescribed valproate gave birth to a child with a major congenital malformation. The figures for lamotrigine, carbamazepine and women not prescribed AEDs were 2.7%, 3.3% and 2.2%, respectively. The prevalence of major congenital malformation was similar for women prescribed lamotrigine or carbamazepine compared to women with no AED treatment in pregnancy. For women prescribed valproate in polytherapy, the prevalence was fourfold higher. After adjustments, the effect of estimates attenuated, but the prevalence remained two- to threefold higher in women prescribed valproate. CONCLUSION: The results of our study suggest that lamotrigine and carbamazepine are safer treatment options than valproate in pregnancy and should be considered as alternative treatment options for women of childbearing potential and in pregnancy

Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records.

BACKGROUND: Although many women treated with psychotropic medication become pregnant, no psychotropic medication has been licensed for use in pregnancy. This leaves women and their health-care professionals in a treatment dilemma, as they need to balance the health of the woman with that of the unborn child. The aim of this project was to investigate the risks and benefits of psychotropic medication in women treated for psychosis who become pregnant. OBJECTIVE(S): (1) To provide a descriptive account of psychotropic medication prescribed before pregnancy, during pregnancy and up to 15 months after delivery in UK primary care from 1995 to 2012; (2) to identify risk factors predictive of discontinuation and restarting of lithium (multiple manufacturers), anticonvulsant mood stabilisers and antipsychotic medication; (3) to examine the extent to which pregnancy is a determinant for discontinuation of psychotropic medication; (4) to examine prevalence of records suggestive of adverse mental health, deterioration or relapse 18 months before and during pregnancy, and up to 15 months after delivery; and (5) to estimate absolute and relative risks of adverse maternal and child outcomes of psychotropic treatment in pregnancy. DESIGN: Retrospective cohort studies. SETTING: Primary care. PARTICIPANTS: Women treated for psychosis who became pregnant, and their children. INTERVENTIONS: Treatment with antipsychotics, lithium or anticonvulsant mood stabilisers. MAIN OUTCOME MEASURES: Discontinuation and restarting of treatment; worsening of mental health; acute pre-eclampsia/gestational hypertension; gestational diabetes; caesarean section; perinatal death; major congenital malformations; poor birth outcome (low birthweight, preterm birth, small for gestational age, low Apgar score); transient poor birth outcomes (tremor, agitation, breathing and muscle tone problems); and neurodevelopmental and behavioural disorders. DATA SOURCES: Clinical Practice Research Datalink database and The Health Improvement Network primary care database. RESULTS: Prescribing of psychotropic medication was relatively constant before pregnancy, decreased sharply in early pregnancy and peaked after delivery. Antipsychotic and anticonvulsant treatment increased over the study period. The recording of markers of worsening mental health peaked after delivery. Pregnancy was a strong determinant for discontinuation of psychotropic medication. However, between 40% and 76% of women who discontinued psychotropic medication before or in early pregnancy restarted treatment by 15 months after delivery. The risk of major congenital malformations, and neurodevelopmental and behavioural outcomes in valproate (multiple manufacturers) users was twice that in users of other anticonvulsants. The risks of adverse maternal and child outcomes in women who continued antipsychotic use in pregnancy were not greater than in those who discontinued treatment before pregnancy. LIMITATIONS: A few women would have received parts of their care outside primary care, which may not be captured in this analysis. Likewise, the analyses were based on prescribing data, which may differ from usage. CONCLUSIONS: Psychotropic medication is prescribed before, during and after pregnancy. Many women discontinue treatment before or during early pregnancy and then restart again in late pregnancy or after delivery. Our results support previous associations between valproate and adverse child outcomes but we found no evidence of such an association for antipsychotics. FUTURE WORK: Future research should focus on (1) curtailing the use of sodium valproate; (2) estimating the benefits of psychotropic drug use in pregnancy; and (3) investigating the risks associated with lifestyle choices that are more prevalent among women using psychotropic drugs. FUNDING DETAILS: The National Institute for Health Research Health Technology Assessment programme

Topological Surface States Protected From Backscattering by Chiral Spin Texture

Topological insulators are a new class of insulators in which a bulk gap for electronic excitations is generated by strong spin orbit coupling. These novel materials are distinguished from ordinary insulators by the presence of gapless metallic boundary states, akin to the chiral edge modes in quantum Hall systems, but with unconventional spin textures. Recently, experiments and theoretical efforts have provided strong evidence for both two- and three-dimensional topological insulators and their novel edge and surface states in semiconductor quantum well structures and several Bi-based compounds. A key characteristic of these spin-textured boundary states is their insensitivity to spin-independent scattering, which protects them from backscattering and localization. These chiral states are potentially useful for spin-based electronics, in which long spin coherence is critical, and also for quantum computing applications, where topological protection can enable fault-tolerant information processing. Here we use a scanning tunneling microscope (STM) to visualize the gapless surface states of the three-dimensional topological insulator BiSb and to examine their scattering behavior from disorder caused by random alloying in this compound. Combining STM and angle-resolved photoemission spectroscopy, we show that despite strong atomic scale disorder, backscattering between states of opposite momentum and opposite spin is absent. Our observation of spin-selective scattering demonstrates that the chiral nature of these states protects the spin of the carriers; they therefore have the potential to be used for coherent spin transport in spintronic devices.Comment: to be appear in Nature on August 9, 200

Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular system

Primary headaches such as migraine are among the most prevalent neurological disorders, affecting up to one-fifth of the adult population. The scientific work in the last decade has unraveled much of the pathophysiological background of migraine, which is now considered to be a neurovascular disorder. It has been discovered that the trigemino-cerebrovascular system plays a key role in migraine headache pathophysiology by releasing the potent vasodilator calcitonin gene-related peptide (CGRP). This neuropeptide is released in parallel with the pain and its concentration correlates well with the intensity of the headache. The development of drugs of the triptan class has provided relief for the acute attacks but at the cost of, mainly cardiovascular, side effects. Thus, the intention to improve treatment led to the development of small CGRP receptor antagonists such as olcegepant (BIBN4096BS) and MK-0974 that alleviate the acute migraine attack without acute side events. The purpose of this review is to give a short overview of the pathological background of migraine headache and to illustrate the mechanisms behind the actions of triptans and the promising CGRP receptor blockers