Variation in Rates of Post-Mastectomy Radiotherapy Among Women with Early Invasive Breast Cancer in England and Wales: A Population-Based Cohort Study.

AIMS: This study examined whether patterns of post-mastectomy radiotherapy (PMRT) among women with early invasive breast cancer (EIBC) varied within England and Wales and explored the role of different patient factors in explaining any variation. MATERIALS AND METHODS: The study used national cancer data on women aged ≥50 years diagnosed with EIBC (stage I-IIIa) in England and Wales between January 2014 and December 2018 who had a mastectomy within 12 months of diagnosis. A multilevel mixed-effects logistic regression model was used to calculate risk-adjusted rates of PMRT for geographical regions and National Health Service acute care organisations. The study examined the variation in these rates within subgroups of women with different risks of recurrence (low: T1-2N0; intermediate: T3N0/T1-2N1; high: T1-2N2/T3N1-2) and investigated whether the variation was linked to patient case-mix within regions and organisations. RESULTS: Among 26 228 women, use of PMRT increased with greater recurrence risk (low: 15.0%; intermediate: 59.4%; high: 85.1%). In all risk groups, use of PMRT was more common among women who had received chemotherapy and decreased among women aged ≥80 years. There was weak or no evidence of an association between use of PMRT and comorbidity or frailty, for each risk group. In women with an intermediate risk, unadjusted rates of PMRT varied substantially between geographical regions (range 40.3-77.3%), but varied less for the high-risk (range 77.1-91.6%) and low-risk groups (range 4.1-32.9%). Adjusting for patient case-mix reduced the variation in regional and organisational PMRT rates to a small degree. CONCLUSIONS: Rates of PMRT are consistently high across England and Wales among women with high-risk EIBC, but variation exists across regions and organisations for women with intermediate-risk EIBC. Effort is required to reduce unwarranted variation in practice for intermediate-risk EIBC.

The Association Between Survival and Receipt of Post-mastectomy Radiotherapy According to Age at Diagnosis Among Women With Early Invasive Breast Cancer: A Population-Based Cohort Study.

AIMS: Clinical trials of post-mastectomy radiotherapy (PMRT) for early invasive breast cancer (EIBC) have included few older women. This study examined whether the association between overall survival or breast cancer-specific survival (BCSS) and receipt of PMRT for EIBC altered with age. MATERIALS AND METHODS: The study used patient-level linked cancer registration, routine hospital and radiotherapy data for England and Wales. It included 31 243 women aged ≥50 years diagnosed between 2014 and 2018 with low- (T1-2N0), intermediate- (T3N0/T1-2N1) or high-risk (T1-2N2/T3N1-2) EIBC who received a mastectomy within 12 months from diagnosis. Patterns of survival were analysed using a landmark approach. Associations between overall survival/BCSS and PMRT in each risk group were analysed with flexible parametric survival models, which included patient and tumour factors; whether the association between PMRT and overall survival/BCSS varied by age was assessed using interaction terms. RESULTS: Among 4711 women with high-risk EIBC, 86% had PMRT. Five-year overall survival was 70.5% and BCSS was 79.3%. Receipt of PMRT was associated with improved overall survival [adjusted hazard ratio (aHR) 0.75, 95% confidence interval 0.64-0.87] and BCSS (aHR 0.78, 95% confidence interval 0.65-0.95) compared with women who did not have PMRT; associations did not vary by age (overall survival, P-value for interaction term = 0.141; BCSS, P = 0.077). Among 10 814 women with intermediate-risk EIBC, 59% had PMRT; 5-year overall survival was 78.4% and BCSS was 88.0%. No association was found between overall survival (aHR 1.01, 95% confidence interval 0.92-1.11) or BCSS (aHR 1.16, 95% confidence interval 1.01-1.32) and PMRT. There was statistical evidence of a small change in the association with age for overall survival (P = 0.007), although differences in relative survival were minimal, but not for BCSS (P = 0.362). CONCLUSIONS: The association between PMRT and overall survival/BCSS does not appear to be modified by age among women with high- or intermediate-risk EIBC and, thus, treatment recommendations should not be modified on the basis of age alone.

Change in the Use of Fractionation in Radiotherapy Used for Early Breast Cancer at the Start of the COVID-19 Pandemic: A Population-Based Cohort Study of Older Women in England and Wales.

AIMS: Adjuvant radiotherapy is recommended for most patients with early breast cancer (EBC) receiving breast-conserving surgery and those at moderate/high risk of recurrence treated by mastectomy. During the first wave of COVID-19 in England and Wales, there was rapid dissemination of randomised controlled trial-based evidence showing non-inferiority for five-fraction ultra-hypofractionated radiotherapy (HFRT) regimens compared with standard moderate-HFRT, with guidance recommending the use of five-fraction HFRT for eligible patients. We evaluated the uptake of this recommendation in clinical practice as part of the National Audit of Breast Cancer in Older Patients (NABCOP). MATERIALS AND METHODS: Women aged ≥50 years who underwent surgery for EBC from January 2019 to July 2020 were identified from the Rapid Cancer Registration Dataset for England and from Wales Cancer Network data. Radiotherapy details were from linked national Radiotherapy Datasets. Multivariate mixed-effects logistic regression models were used to assess characteristics influential in the use of ultra-HFRT. RESULTS: Among 35 561 women having surgery for EBC, 71% received postoperative radiotherapy. Receipt of 26 Gy in five fractions (26Gy5F) increased from <1% in February 2020 to 70% in April 2020. Regional variation in the use of 26Gy5F during April to July 2020 was similar by age, ranging from 49 to 87% among women aged ≥70 years. Use of 26Gy5F was characterised by no known nodal involvement, no comorbidities and initial breast-conserving surgery. Of those patients receiving radiotherapy to the breast/chest wall, 85% had 26Gy5F; 23% had 26Gy5F if radiotherapy included regional nodes. Among 5139 women receiving postoperative radiotherapy from April to July 2020, nodal involvement, overall stage, type of surgery, time from diagnosis to start of radiotherapy were independently associated with fractionation choice. CONCLUSIONS: There was a striking increase in the use of 26Gy5F dose fractionation regimens for EBC, among women aged ≥50 years, within a month of guidance published at the start of the COVID-19 pandemic in England and Wales.

Synthesis, characterization and evaluation of azobenzene nanogels for their antibacterial properties in adhesive dentistry.

The presence of cariogenic bacteria within the prepared tooth cavity at the adhesive resin-dentin interface is detrimental to the long-term stability and function of composite restorations. Here, we report the synthesis and incorporation of methacrylated azobenzene nanogels within bisphenol A-glycidyl methacrylate/hydroxyethyl methacrylate/ethanol (B/H/E) adhesive resins and evaluate their ability to reduce the bacterial invasion of cariogenic Streptococcus mutans biofilms while preserving the mechanical strength and structural integrity of the critical interfacial connection between the restoration and the tooth. The azobenzene nanogel, with a hydrodynamic radius of < 2 nm and a molecular weight of 12,000 Da, was polymerized within B/H/E adhesive formulations at concentrations of 0.5 wt.%, 1.5 wt.%, and 2.5 wt.%. While the double-bond conversion, cytocompatibility, water solubility, and sorption of the adhesive networks were comparable, azobenzene nanogel networks showed improved hydrophobicity with a ≥ 25° increase in water contact angle. The polymerized adhesive surfaces formulated with azobenzene nanogels showed a 66% reduction in bacterial biofilms relative to the control while maintaining the mechanical properties and micro-tensile bond strength of the adhesive networks. The increased hydrophobicity and antibacterial activity are promising indicators that azobenzene nanogel additives have the potential to increase the durability and longevity of adhesive resins.

Acrylated Hydroxyazobenzene Copolymers in Composite-Resin Matrix Inhibits Streptococcus mutans Biofilms In Vitro.

Purpose: The purpose of this study was to evaluate the effect of acrylated hydroxyazobenzene (AHA) copolymers in a composite-resin matrix on Streptococcus mutans (SM) biofilms. Methods: The AHA was synthesized and polymerized within a bisphenol A-glycidyl methacrylate and triethylene glycol dimethacrylate (bisGMA:TEGDMA) matrix while bisGMA:TEGDMA discs served as controls. The cytotoxicity of AHA was determined using a cell viability assay. Sucrose-dependent SM biofilms were grown on the AHA and control substrates. At 24 hours and after mechanical toothbrushing (equivalent to six months), the number of live SM was quantified on the substrates and in the surrounding media. Microscopic images of the substrates were captured after live-dead staining. Results: The AHA substrates were as biocompatible as bisGMA: TEGDMA substrates. The microscopic images and quantification demonstrated no live SM on the AHA substrates and in the surrounding media as compared to the controls. The inhibitory efficacy of AHA substrates on SM biofilm was intact even after mechanical toothbrushing. Conclusions: Acrylated hydroxyazobenzene in a composite-resin matrix completely inhibits SM proliferation growth and demonstrates a zone of SM inhibition. The antibacterial propertyof AHA could be harnessed for caries prevention in high caries-risk children by incorporating AHA into the restorative and sealant materials.

Surgical decisions in older women with early breast cancer: patient and disease factors.

BACKGROUND: Studies reporting lower rates of surgery for older women with early invasive breast cancer have focused on women with oestrogen receptor (ER)-positive tumours. This study examined the factors that influence receipt of breast surgery in older women with ER-positive and ER-negative early invasive breast cancer . METHODS: Women aged 50 years or above with unilateral stage 1-3A early invasive breast cancer diagnosed in 2014-2017 were identified from linked English and Welsh cancer registration and routine hospital data sets. Logistic regression analysis was used to evaluate the influence of tumour and patient factors on receipt of surgery. RESULTS: Among 83 188 women, 86.8 per cent had ER-positive and 13.2 per cent had ER-negative early invasive breast cancer. These proportions were unaffected by age at diagnosis. Compared with women with ER-negative breast cancer, a higher proportion of women with ER-positive breast cancer presented with low risk tumour characteristics: G1 (20.0 versus 1.5 per cent), T1 (60.8 versus 44.2 per cent) and N0 (73.9 versus 68.8 per cent). The proportions of women with any recorded co-morbidity (13.7 versus 14.3 per cent) or degree of frailty (25 versus 25.8 per cent) were similar among women with ER-positive and ER-negative disease respectively. In women with ER-positive early invasive breast cancer aged 70-74, 75-79 and 80 years or above, the rate of no surgery was 5.6, 11.0 and 41.9 per cent respectively. Among women with ER-negative early invasive breast cancer, the corresponding rates were 3.8, 3.7 and 12.3 per cent. The relatively lower rate of surgery for ER-positive breast cancer persisted in women with good fitness. CONCLUSION: The reasons for the observer differences should be further explored to ensure consistency in treatment decisions.

Prevalence of Adverse Childhood Experiences of Parenting Women in Drug Treatment for Opioid Use Disorder.

Descriptive adverse childhood experience (ACE) prevalence data on parenting women seeking treatment for opioid use disorder (OUD) is limited, despite this group being one of the fastest growing sub-populations of the opioid epidemic. The aim of this study was to: (1) determine prevalence of ACEs) in a population of parenting women in treatment for OUD, (2) characterize ACEs, and (3) compare study ACE data to Pennsylvania Behavioral Risk Factor Surveillance System (PA BRFSS) to normalize study results. Between 2014 and 2018, ACEs were collected from parenting women (N = 152) enrolled in treatment for OUDs. Results showed on average women were 30.3 years of age (SD 4.6, range 22-41 years) non-Hispanic (87.0%), white (74.0%), and held a high school education or less (76.0%). The mean total ACE score was 4.3 (SD 2.3; range 0-8). Most women reported 4 ≥ ACEs (65.0%), while only 5.0% reported 0 ACEs. The current sample had higher mean ACE score (4.3 PSMDT vs. 1.4 PA BRFSS Data) than PA BRFSS Data. The burden of ACEs in parenting women in treatment for OUD is significant. Understanding the trauma parenting women in drug treatment have experienced, may support efforts to reduce stigma of this population. Public health intervention and policy work that is trauma proactive is needed to address this growing epidemic.

Choosing the best method to utilise single positron emission computed tomography (SPECT) scans in the management of unilateral condylar hyperplasia.

Facial asymmetry secondary to unilateral condylar hyperplasia can be a diagnostic challenge to oral and maxillofacial surgeons. Single positron emission computed tomography (SPECT) scans provide a useful adjunct. We report a brief summary of the evidence describing the effectiveness of different methods of analysing SPECT scans and compare it with the results of a 10-year study at Sunderland Royal Hospital. Overall, both the evidence base and our study strongly favour use of the condyle:condyle ratio over the condyle:reference bone ratio, suggesting that no further comparisons are needed.

Optically Responsive, Smart Anti-Bacterial Coatings via the Photofluidization of Azobenzenes.

Antibacterial strategies sans antibiotic drugs have recently garnered much interest as a mechanism by which to inhibit biofilm formation and growth on surfaces due to the rise of antibiotic-resistant bacteria. Based on the photofluidization of azobenzenes, we demonstrate for the first time the ability achieve up to a 4 log reduction in bacterial biofilms by opto-mechanically activating the disruption and dispersion of biofilms. This unique strategy with which to enable biofilm removal offers a novel paradigm with which to combat antibiotic resistance.

Gestational diabetes exacerbates maternal immune activation effects in the developing brain.

Maternal inflammation and diabetes increase the risk for psychiatric disorders in offspring. We hypothesized that these co-occurring risk factors may potentiate each other. To test this, we maternally exposed developing mice in utero to gestational diabetes mellitus (GDM) and/or maternal immune activation (MIA). Fetal mouse brains were exposed to either vehicle, GDM, MIA or GDM+MIA. At gestational day (GD) 12.5, GDM produced a hyperglycemic, hyperleptinemic maternal state, whereas MIA produced significant increases in proinflammatory cytokines and chemokines. Each condition alone resulted in an altered, inflammatory and neurodevelopmental transcriptome profile. In addition, GDM+MIA heightened the maternal inflammatory state and gave rise to a new, specific transcriptional response. This exacerbated response was associated with pathways implicated in psychiatric disorders, including dopamine neuron differentiation and innate immune response. Based on these data, we hypothesize that children born to GDM mothers and exposed to midgestation infections have an increased vulnerability to psychiatric disorder later in life, and this should be tested in follow-up epidemiological studies.

Abuse-related effects of synthetic cathinones:importance of DAT/SERT relationships / 中国药理学与毒理学杂志

OBJECTIVE Wide spread abuse of synthetic cathinones found in bath salts preparations has resulted in regulation of some cathinones internationally. Chemists skirt these laws by altering the chemical structures of first-generation cathinones (ie, MDPV, methylone, and mephedrone), resulting in second-generation cathinones (eg, α-PVP, α-PPP, MDPPP, and MDPBP). Although MDPV is a more effective reinforcer than cocaine, little is known about the reinforcing effectiveness of second-generation cathinones. To test the hypothesis that synthetic cathinones with higher selectivity for DAT relative to SERT are more effective reinforcers. METHODS Monoamine transporter inhibition was determined using synaptosomes prepared from rat brains. The relative reinforcing effectiveness of intravenously self-administered MDPV, MDPBP, MDPPP, α-PVP, α-PPP, and cocaine were directly compared through evaluations of ① dose- response curves under a progressive ratio (PR) schedule of reinforcement and ② demand curves obtained for each drug in male Sprague-Dawley rats. RESULTS Rank order selectivity for DAT/SERT was α-PVP>MDPV>α-PPP≈MDPBP>MDPPP>cocaine. Comparisons of the maximum number of infusions obtained under a PR schedule of reinforcement (α-PVP>MDPV>α-PPP>MDPBP≈MDPPP>cocaine) and the essential value obtained for each drug in demand analyses (α-PVP>MDPV>α-PPP≈MDPBP≈MDPPP>cocaine) suggest relative reinforcing effectiveness is related to DAT/SERT selectivity. CONCLUSION These data provide evidence that DAT/SERT selectivity accounts for select synthetic cathinones functioning as more effective reinforcers than cocaine and may predict the abuse-related effects of novel synthetic cathinones in humans.

Unintended consequences of policy change to watchful waiting for asymptomatic inguinal hernias.

INTRODUCTION: In 2009 the Department of Health instructed McKinsey & Company to provide advice on how commissioners might achieve world class National Health Service productivity. Asymptomatic inguinal hernia repair was identified as a potentially cosmetic procedure, with limited clinical benefit. The Birmingham and Solihull primary care trust cluster introduced a policy of watchful waiting for asymptomatic inguinal hernia, which was implemented across the health economy in December 2010. This retrospective cohort study aimed to examine the effect of a change in clinical commissioning policy concerning elective surgical repair of asymptomatic inguinal hernias. METHODS: A total of 1,032 patients undergoing inguinal hernia repair in the 16 months after the policy change were compared with 978 patients in the 16 months before. The main outcome measure was relative proportion of emergency repair in groups before and after the policy change. Multivariate binary logistic regression was used to adjust the main outcome for age, sex and hernia type. RESULTS: The period after the policy change was associated with 59% higher odds of emergency repair (3.6% vs 5.5%, adjusted odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.03-2.47). In turn, emergency repair was associated with higher odds of adverse events (4.7% vs 18.5%, adjusted OR: 3.68, 95% CI: 2.04-6.63) and mortality (0.1% vs 5.4%, p<0.001, Fisher's exact test). CONCLUSIONS: Introduction of a watchful waiting policy for asymptomatic inguinal hernias was associated with a significant increase in need for emergency repair, which was in turn associated with an increased risk of adverse events. Current policies may be placing patients at risk.

Hysterectomy, endometrial ablation and Mirena® for heavy menstrual bleeding: a systematic review of clinical effectiveness and cost-effectiveness analysis.

OBJECTIVE: The aim of this project was to determine the clinical effectiveness and cost-effectiveness of hysterectomy, first- and second-generation endometrial ablation (EA), and Mirena® (Bayer Healthcare Pharmaceuticals, Pittsburgh, PA, USA) for the treatment of heavy menstrual bleeding. DESIGN: Individual patient data (IPD) meta-analysis of existing randomised controlled trials to determine the short- to medium-term effects of hysterectomy, EA and Mirena. A population-based retrospective cohort study based on record linkage to investigate the long-term effects of ablative techniques and hysterectomy in terms of failure rates and complications. Cost-effectiveness analysis of hysterectomy versus first- and second-generation ablative techniques and Mirena. SETTING: Data from women treated for heavy menstrual bleeding were obtained from national and international trials. Scottish national data were obtained from the Scottish Information Services Division. PARTICIPANTS: Women who were undergoing treatment for heavy menstrual bleeding were included. INTERVENTIONS: Hysterectomy, first- and second-generation EA, and Mirena. MAIN OUTCOME MEASURES: Satisfaction, recurrence of symptoms, further surgery and costs. RESULTS: Data from randomised trials indicated that at 12 months more women were dissatisfied with first-generation EA than hysterectomy [odds ratio (OR): 2.46, 95% confidence interval (CI) 1.54 to 3.93; p = 0.0002), but hospital stay [WMD (weighted mean difference) 3.0 days, 95% CI 2.9 to 3.1 days; p < 0.00001] and time to resumption of normal activities (WMD 5.2 days, 95% CI 4.7 to 5.7 days; p < 0.00001) were longer for hysterectomy. Unsatisfactory outcomes associated with first- and second-generation techniques were comparable [12.2% (123/1006) vs 10.6% (110/1034); OR 1.20, 95% CI 0.88 to 1.62; p = 0.2). Rates of dissatisfaction with Mirena and second-generation EA were similar [18.1% (17/94) vs 22.5% (23/102); OR 0.76, 95% CI 0.38 to 1.53; p = 0.4]. Indirect estimates suggested that hysterectomy was also preferable to second-generation EA (OR 2.32, 95% CI 1.27 to 4.24; p = 0.006) in terms of patient dissatisfaction. The evidence to suggest that hysterectomy is preferable to Mirena was weaker (OR 2.22, 95% CI 0.94 to 5.29; p = 0.07). In women treated by EA or hysterectomy and followed up for a median [interquartile range (IQR)] duration of 6.2 (2.7-10.8) and 11.6 (7.9-14.8) years, respectively, 962/11,299 (8.5%) women originally treated by EA underwent further gynaecological surgery. While the risk of adnexal surgery was similar in both groups [adjusted hazards ratio 0.80 (95% CI 0.56 to 1.15)], women who had undergone ablation were less likely to need pelvic floor repair [adjusted hazards ratio 0.62 (95% CI 0.50 to 0.77)] and tension-free vaginal tape surgery for stress urinary incontinence [adjusted hazards ratio 0.55 (95% CI 0.41 to 0.74)]. Abdominal hysterectomy led to a lower chance of pelvic floor repair surgery [hazards ratio 0.54 (95% CI 0.45 to 0.64)] than vaginal hysterectomy. The incidence of endometrial cancer following EA was 0.02%. Hysterectomy was the most cost-effective treatment. It dominated first-generation EA and, although more expensive, produced more quality-adjusted life-years (QALYs) than second-generation EA and Mirena. The incremental cost-effectiveness ratios for hysterectomy compared with Mirena and hysterectomy compared with second-generation ablation were £1440 per additional QALY and £970 per additional QALY, respectively. CONCLUSIONS: Despite longer hospital stay and time to resumption of normal activities, more women were satisfied after hysterectomy than after EA. The few data available suggest that Mirena is potentially cheaper and more effective than first-generation ablation techniques, with rates of satisfaction that are similar to second-generation techniques. Owing to a paucity of trials, there is limited evidence to suggest that hysterectomy is preferable to Mirena. The risk of pelvic floor surgery is higher in women treated by hysterectomy than by ablation. Although the most cost-effective strategy, hysterectomy may not be considered an initial option owing to its invasive nature and higher risk of complications. Future research should focus on evaluation of the clinical effectivesness and cost-effectiveness of the best second-generation EA technique under local anaesthetic versus Mirena and types of hysterectomy such as laparoscopic supracervical hysterectomy versus conventional hysterectomy and second-generation EA. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Hysterectomy, endometrial destruction, and levonorgestrel releasing intrauterine system (Mirena) for heavy menstrual bleeding: systematic review and meta-analysis of data from individual patients.

OBJECTIVE: To evaluate the relative effectiveness of hysterectomy, endometrial destruction (both "first generation" hysteroscopic and "second generation" non-hysteroscopic techniques), and the levonorgestrel releasing intrauterine system (Mirena) in the treatment of heavy menstrual bleeding. DESIGN: Meta-analysis of data from individual patients, with direct and indirect comparisons made on the primary outcome measure of patients' dissatisfaction. DATA SOURCES: Data were sought from the 30 randomised controlled trials identified after a comprehensive search of the Cochrane Library, Medline, Embase, and CINAHL databases, reference lists, and contact with experts. Raw data were available from 2814 women randomised into 17 trials (seven trials including 1359 women for first v second generation endometrial destruction; six trials including 1042 women for hysterectomy v first generation endometrial destruction; one trial including 236 women for hysterectomy v Mirena; three trials including 177 women for second generation endometrial destruction v Mirena). Eligibility criteria for selecting studies Randomised controlled trials comparing hysterectomy, first and second generation endometrial destruction, and Mirena for women with heavy menstrual bleeding unresponsive to other medical treatment. RESULTS: At around 12 months, more women were dissatisfied with outcome with first generation hysteroscopic techniques than with hysterectomy (13% v 5%; odds ratio 2.46, 95% confidence interval 1.54 to 3.9, P<0.001), but hospital stay (weighted mean difference 3.0 days, 2.9 to 3.1 days, P<0.001) and time to resumption of normal activities (5.2 days, 4.7 to 5.7 days, P<0.001) were longer for hysterectomy. Unsatisfactory outcomes were comparable with first and second generation techniques (odds ratio 1.2, 0.9 to 1.6, P=0.2), although second generation techniques were quicker (weighted mean difference 14.5 minutes, 13.7 to 15.3 minutes, P<0.001) and women recovered sooner (0.48 days, 0.20 to 0.75 days, P<0.001), with fewer procedural complications. Indirect comparison suggested more unsatisfactory outcomes with second generation techniques than with hysterectomy (11% v 5%; odds ratio 2.3, 1.3 to 4.2, P=0.006). Similar estimates were seen when Mirena was indirectly compared with hysterectomy (17% v 5%; odds ratio 2.2, 0.9 to 5.3, P=0.07), although this comparison lacked power because of the limited amount of data available for analysis. CONCLUSIONS: More women are dissatisfied after endometrial destruction than after hysterectomy. Dissatisfaction rates are low after all treatments, and hysterectomy is associated with increased length of stay in hospital and a longer recovery period. Definitive evidence on effectiveness of Mirena compared with more invasive procedures is lacking.

High Fat Diet Regulation of ß-Cell Proliferation and ß-Cell Mass.

Type 2 Diabetes (T2D) is characterized by relative insulin insufficiency, caused when peripheral tissues such as liver, muscle, and adipocytes have a decreased response to insulin. One factor that elevates the risk for insulin resistance and T2D is obesity. In obese patients without T2D and initially in people who develop T2D, pancreatic ß-cells are able to compensate for insulin resistance by increasing ß-cell mass, effected by increased proliferation and hypertrophy, as well as increased insulin secretion per ß-cell. In patients that go on to develop T2D, however, this initial period of compensation is followed by ß-cell failure due to decreased proliferation and increased apoptosis. The forkhead box transcription factor FoxM1 is required for ß-cell replication in mice after four weeks of age, during pregnancy, and after partial pancreatectomy. We investigated whether it is also required for ß-cell proliferation due to diet-induced obesity.

The use of metformin as first line treatment in polycystic ovary syndrome.

This study evaluated the use of metformin as first line treatment for patients with polycystic ovary syndrome. A retrospective review of patients' files diagnosed with PCOS over 16 months in Department of obstetrics and gynaecology of a Regional hospital. The outcome was the response to metformin treatment regardless of the main complaint. Treatment response was measured by change in LH/FSH ratio, fasting insulin, testosterone, day 21 progesterone and/or pregnancy. A day 21 progesterone greater than 25.5 nmol/l and/or pregnancy were the parameter of ovulation. Thirty-four patients were diagnosed with PCOS. Twenty-five complained of infertility (14 primary and 11 secondary), six patients had oligomenorrhoea or amenorrhoea and three presented with hirsutism. Seventeen patients received metformin as first line treatment. Eight received it with other treatment (5 clomiphene citrate and 3 ant androgens). Nine patients did not receive metformin. This study justifies the use of metformin as an appropriate first line treatment for PCOS.