Familial confounding of internalising symptoms and obesity in adolescents and young adults; a co-twin analysis.

BACKGROUND: Obesity and internalising disorders, including depression and anxiety, often co-occur. There is evidence that familial confounding contributes to the co-occurrence of internalising disorders and obesity in adults. However, its impact on this association among young people is unclear. Our study investigated the extent to which familial factors confound the association between internalising disorders and obesity in adolescents and young adults. SUBJECTS/METHODS: We used a matched co-twin design to investigate the impact of confounding by familial factors on associations between internalising symptoms and obesity in a sample of 4018 twins aged 16 to 27 years. RESULTS: High levels of internalising symptoms compared to low levels increased the odds of obesity for the whole cohort (adjusted odds ratio [AOR] = 3.1, 95% confidence interval [CI]: 1.5, 6.8), and in females (AOR = 4.1, 95% CI 1.5, 11.1), but not in males (AOR = 2.8 95% CI 0.8, 10.0). We found evidence that internalising symptoms were associated with an increased between-pair odds of obesity (AOR 6.2, 95% CI 1.7, 22.8), using the paired analysis but not using a within-pair association, which controls for familial confounding. Sex-stratified analyses indicated high internalising symptoms were associated with increased between-pair odds of obesity for females (AOR 12.9, 95% CI 2.2, 76.8), but this attenuated to the null using within-pair analysis. We found no evidence of between or within-pair associations for males and weak evidence that sex modified the association between internalising symptoms and obesity (likelihood ratio test p = 0.051). CONCLUSIONS: Some familial factors shared by twins confound the association between internalising symptoms and obesity in adolescent and young adult females. Internalising symptoms and obesity were not associated for adolescent and young adult males. Therefore, prevention and treatment efforts should especially address familial shared determinants of obesity, particularly targeted at female adolescents and young adults with internalising symptoms and those with a family history of these disorders.

Fecal microbiota transplantation for recurrent C. difficile infection in patients with inflammatory bowel disease: A systematic review and meta-analysis.

Fecal microbiota transplantation (FMT) is known to be highly effective in patients with recurrent Clostridioides difficile infection (rCDI), but its role in patients who also suffer from inflammatory bowel disease (IBD) is unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of FMT for the treatment of rCDI in patients with IBD. We searched the available literature until November 22, 2022 to identify studies that included patients with IBD treated with FMT for rCDI, reporting efficacy outcomes after at least 8 weeks of follow-up. The proportional effect of FMT was summarized with a generalized linear mixed-effect model fitting a logistic regression accounting for different intercepts among studies. We identified 15 eligible studies, containing 777 patients. Overall, FMT achieved high cure rates of rCDI, 81% for single FMT, based on all included studies and patients, and 92% for overall FMT, based on nine studies with 354 patients, respectively. We found a significant advantage of overall FMT over single FMT in improving cure rates of rCDI (from 80% to 92%, p = 0.0015). Serious adverse events were observed in 91 patients (12% of the overall population), with the most common being hospitalisation, IBD-related surgery, or IBD flare. In conclusion, in our meta-analysis FMT achieved high cure rates of rCDI in patients with IBD, with a significant advantage of overall FMT over single FMT, similar to data observed in patients without IBD. Our findings support the use of FMT as a treatment for rCDI in patients with IBD.

Primary abandon of hernia sac for inguinoscrotal hernias: a safe way to cut corners.

INTRODUCTION: Inguinoscrotal hernias (ISH) pose a challenge to surgeons with consistently higher rates of postoperative complications and recurrence rates. The aim of this study is to report our initial experience and early results with a new technique for inguinoscrotal hernia repair. METHODS: A review of a prospectively maintained multi-center database was conducted in patients who underwent minimally invasive repair using the "primary abandon-of-the-sac" (PAS) technique for inguinoscrotal hernias from March 2021 to July 2022. Demographics and outcomes were analyzed. Univariate analysis and multivariate logistic regression were performed. RESULTS: A total of 76 minimally invasive inguinal hernia repairs were performed. In 70 patients (92%) C-PAS was used as the technique to abandon the sac while in the remaining 6 patients, "pirate-eye-patch" technique was used. Median hernia ring was 3 (IQR 2.5-3.5) cm and median hernia sac was 9.5 (8-10.8) cm. Median operative time was 70 min (IQR 56-96). Seroma was present in 22 (28.9%) patients 7 days after surgery. Most had seroma only in the inguinal area (n = 19; 25%). Thirty days after surgery, 12 (15.8%) patients still had seroma in the inguinal area and 6 (7.9%) in the inguinoscrotal area. Ninety days after surgery, four (5.3%) patients had inguinal seroma, 2 (2.6%) scrotal seromas and 3 (3.9%) inguinoscrotal seromas. The size of the hernia sac was not associated with seroma formation 7 days after surgery (OR 1.06; 95% CI 0.89-1.2; P = 0.461) in the multivariate logistic regression. BMI was also not associated with seroma formation (OR 0.8; 95% CI 0.74-1.06; P = 0.2). CONCLUSIONS: Planned abandon of the hernia sac is an interesting alternative and is associated with a low rate of complications and acceptable seroma formation rates.

Global prevalence of Barrett's oesophagus and oesophageal cancer in individuals with gastro-oesophageal reflux: a systematic review and meta-analysis.

OBJECTIVES: Chronic gastro-oesophageal reflux might lead to the development of Barrett's oesophagus (BO) or even oesophageal adenocarcinoma. There has been no definitive systematic review and meta-analysis of data to estimate global prevalence of BO or oesophageal adenocarcinoma in individuals with gastro-oesophageal reflux. DESIGN: We searched MEDLINE, Embase and Embase Classic to identify cross-sectional surveys that reported prevalence of BO or oesophageal adenocarcinoma in adults with gastro-oesophageal reflux. We extracted prevalence for all studies, both for endoscopically suspected and histologically confirmed cases. We calculated pooled prevalence according to study location, symptom frequency and sex, as well as ORs with 95% CIs. RESULTS: Of the 4963 citations evaluated, 44 reported prevalence of endoscopically suspected and/or histologically confirmed BO. Prevalence of BO among individuals with gastro-oesophageal reflux varied according to different geographical regions ranging from 3% to 14% for histologically confirmed BO with a pooled prevalence of 7.2% (95% CI 5.4% to 9.3%), whereas pooled prevalence for endoscopically suspected BO was 12.0% (95% CI 5.5% to 20.3%). There was heterogeneity in many of our analyses. Prevalence of BO was significantly higher in men, both for endoscopically suspected (OR=2.1; 95% CI 1.6 to 2.8) and histologically confirmed BO (OR=2.3; 95% CI 1.7 to 3.2). Dysplasia was present in 13.9% (95% CI 8.9% to 19.8%) of cases of histologically confirmed BO, 80.7% of which was low-grade. CONCLUSION: The prevalence of Barrett's oesophagus among individuals with gastro-oesophageal reflux varied strikingly among countries, broadly resembling the geographical distribution of gastro-oesophageal reflux itself. Prevalence of BO was significantly higher in men.

Comparison of Protocols to Reduce Diabetic Ketoacidosis in Patients With Type 1 Diabetes Prescribed a Sodium-Glucose Cotransporter 2 Inhibitor.

OBJECTIVE | Sodium-glucose cotransporter 2 (SGLT2) inhibitors are approved for type 1 diabetes in Europe and Japan, with off-label use in type 1 diabetes in the United States. Although there were no consistent approaches to risk mitigation in clinical trials of these agents, protocols have been developed to try to reduce the risk of diabetic ketoacidosis (DKA). However, a validated risk mitigation strategy does not exist. We reviewed available DKA risk mitigation protocols to better understand the various strategies currently in use. METHODS | We conducted a search of the published medical literature and other medical information sources, including conference presentations, for protocols. We then categorized the information provided into guidance on patient selection, initiation of SGLT2 inhibitors, ketone monitoring, necessary patient action in the event of ketosis or DKA, and inpatient treatment of ketosis or DKA. RESULTS | Patient selection is generally similar among the protocols, although some require a minimum BMI and insulin dose. All protocols advocate routine measurement of ketones, although some insist on blood ketone tests. Although action steps for ketosis varies, all protocols advocate rapid patient intervention. The importance of evaluating ketones and acid-base balance even in the absence of hyperglycemia is emphasized by all protocols, as is the need to continue administering insulin until ketosis has resolved. CONCLUSION | DKA risk mitigation must be pursued systematically in individuals with type 1 diabetes, although the best strategy remains to be determined. Given the ongoing need for adjunctive therapies in type 1 diabetes and current use of SGLT2 inhibitors for this purpose, additional education and research are crucial, especially in the hospital environment, where DKA may not be diagnosed promptly and treated appropriately.

Helicobacter pylori eradication therapy to prevent gastric cancer: systematic review and meta-analysis.

OBJECTIVES: Gastric cancer is strongly associated with Helicobacter pylori (H. pylori). We conducted a previous systematic review and meta-analysis that suggested eradication therapy reduced future incidence of gastric cancer, but effect size was uncertain, and there was no reduction in gastric cancer-related mortality. We updated this meta-analysis, as more data has accumulated. We also evaluated impact of eradication therapy on future risk of gastric cancer in patients having endoscopic mucosal resection for gastric neoplasia. DESIGN: We searched the medical literature through February 2020 to identify randomised controlled trials (RCTs) examining effect of eradication therapy on subsequent occurrence of gastric cancer in healthy H. pylori-positive adults, and in H. pylori-positive patients with gastric neoplasia undergoing endoscopic mucosal resection. The control arm received placebo or no treatment. Follow-up was for ≥2 years. We estimated the relative risk (RR) number needed to treat (NNT), and evaluated the disability-adjusted life-years (DALYs) gained from screening from the meta-analysis. RESULTS: We identified 10 RCTs, seven recruited 8323 healthy individuals, and three randomised 1841 patients with gastric neoplasia. In healthy individuals, eradication therapy reduced incidence of gastric cancer (RR=0.54; 95% CI 0.40 to 0.72, NNT=72), and reduced mortality from gastric cancer (RR=0.61; 95% CI 0.40 to 0.92, NNT=135), but did not affect all-cause mortality. These data suggest that 8 743 815 DALYs (95% CI 5 646 173 to 11 847 456) would be gained if population screening and treatment was implemented globally. In patients with gastric neoplasia, eradication therapy also reduced incidence of future gastric cancer (RR=0.49; 95% CI 0.34 to 0.70, NNT=21). Adverse events were incompletely reported. CONCLUSION: There is moderate evidence to suggest that H. pylori eradication therapy reduces the incidence of gastric cancer in healthy individuals and patients with gastric neoplasia in East Asian countries. There also appears to be a reduction in gastric cancer-related mortality.

Care-pathways for patients presenting to emergency ambulance services with self-harm: national survey.

BACKGROUND: Self-harm is among the top five causes of acute hospital admissions and ambulance clinicians are often the first point of contact. However, the Emergency Department (ED) may not be the most appropriate place of care and little is known about the existence or nature of alternative pathways available to UK ambulance services. This survey describes the current management pathways used by ambulance services for patients who have self-harmed. METHODS: A structured questionnaire was sent to all UK ambulance services by email and followed up by telephone in 2018. Three independent researchers (two clinical) coded responses which were analysed thematically. RESULTS: All 13 UK ambulance services responded to the survey: nine by email and four by telephone interview. Two services reported a service-wide protocol for managing people presenting with self-harm, with referral to mental health crisis team available as an alternative to conveyance to ED, following on-scene psychosocial assessment. Four services reported local pathways for managing mental health patients which included care of patients who had self-harmed. Four services reported being in the process of developing pathways for managing mental health patients. Six services reported no service-wide nor local pathways for managing self-harm patients. No robust evaluation of new care models was reported. CONCLUSION: Practice in ambulance services in the UK is variable, with a minority having a specific clinical pathway for managing self-harm, with an option to avoid ED. New pathways for patients who have self-harmed must be evaluated in terms of safety, clinical and cost-effectiveness.

Withdrawing life-sustaining treatment: a stock-take of the legal and ethical position.

This article, prompted by an extended essay published in the Journal of Medical Ethics by Charles Foster, and the current controversy surrounding the case of Vincent Lambert, analyses the legal and ethical arguments in relation to the withdrawal of life-sustaining treatment from patients with prolonged disorders of consciousness. The article analyses the legal framework through the prism of domestic law, case-law of the European Court of Human Rights and the Convention on the Rights of Persons with Disabilities, and examines the challenge to the ethical consensus made by Foster. It concludes that the right approach remains a version of the approach that has prevailed for the last 25 years since the decision in Airedale NHS Trust v Bland[1993] AC 789, refined to reflect that that there is now, and rightly, a much more limited place for judgments made about the 'burden' of treatment or the quality of life enjoyed by the person made on the basis of assumptions about that person as a category as opposed to investigation of that person as an individual human being.

HIV+ deceased donor referrals: A national survey of organ procurement organizations.

BACKGROUND: HIV-infected (HIV+) donor organs can be transplanted into HIV+ recipients under the HIV Organ Policy Equity (HOPE) Act. Quantifying HIV+ donor referrals received by organ procurement organizations (OPOs) is critical for HOPE Act implementation. METHODS: We surveyed the 58 USA OPOs regarding HIV+ referral records and newly discovered HIV+ donors. Using data from OPOs that provided exact records and CDC HIV prevalence data, we projected a national estimate of HIV+ referrals. RESULTS: Fifty-five (95%) OPOs reported HIV+ referrals ranging from 0 to 276 and newly discovered HIV+ cases ranging from 0 to 10 annually. Six OPOs in areas of high HIV prevalence reported more than 100 HIV+ donor referrals. Twenty-seven (47%) OPOs provided exact HIV+ referral records and 28 (51%) OPOs provided exact records of discovered HIV+ cases, totaling 1450 HIV+ referrals and 39 discovered HIV+ donors in the prior year. These OPOs represented 67% and 59% of prevalent HIV cases in the USA; thus, we estimated 2164 HIV+ referrals and 66 discovered HIV+ cases nationally per year. CONCLUSIONS: OPOs reported a high volume of HIV+ referrals annually, of which a subset will be medically eligible for donation. Particularly in areas of high HIV prevalence, OPOs require ongoing support to implement the HOPE Act.

Self-Harm, Suicidal Behaviours, and Cyberbullying in Children and Young People: Systematic Review.

BACKGROUND: Given the concerns about bullying via electronic communication in children and young people and its possible contribution to self-harm, we have reviewed the evidence for associations between cyberbullying involvement and self-harm or suicidal behaviors (such as suicidal ideation, suicide plans, and suicide attempts) in children and young people. OBJECTIVE: The aim of this study was to systematically review the current evidence examining the association between cyberbullying involvement as victim or perpetrator and self-harm and suicidal behaviors in children and young people (younger than 25 years), and where possible, to meta-analyze data on the associations. METHODS: An electronic literature search was conducted for all studies published between January 1, 1996, and February 3, 2017, across sources, including MEDLINE, Cochrane, and PsycINFO. Articles were included if the study examined any association between cyberbullying involvement and self-harm or suicidal behaviors and reported empirical data in a sample aged under 25 years. Quality of included papers was assessed and data were extracted. Meta-analyses of data were conducted. RESULTS: A total of 33 eligible articles from 26 independent studies were included, covering a population of 156,384 children and young people. A total of 25 articles (20 independent studies, n=115,056) identified associations (negative influences) between cybervictimization and self-harm or suicidal behaviors or between perpetrating cyberbullying and suicidal behaviors. Three additional studies, in which the cyberbullying, self-harm, or suicidal behaviors measures had been combined with other measures (such as traditional bullying and mental health problems), also showed negative influences (n=44,526). A total of 5 studies showed no significant associations (n=5646). Meta-analyses, producing odds ratios (ORs) as a summary measure of effect size (eg, ratio of the odds of cyber victims who have experienced SH vs nonvictims who have experienced SH), showed that, compared with nonvictims, those who have experienced cybervictimization were OR 2.35 (95% CI 1.65-3.34) times as likely to self-harm, OR 2.10 (95% CI 1.73-2.55) times as likely to exhibit suicidal behaviors, OR 2.57 (95% CI 1.69-3.90) times more likely to attempt suicide, and OR 2.15 (95% CI 1.70-2.71) times more likely to have suicidal thoughts. Cyberbullying perpetrators were OR 1.21 (95% CI 1.02-1.44) times more likely to exhibit suicidal behaviors and OR 1.23 (95% CI 1.10-1.37) times more likely to experience suicidal ideation than nonperpetrators. CONCLUSIONS: Victims of cyberbullying are at a greater risk than nonvictims of both self-harm and suicidal behaviors. To a lesser extent, perpetrators of cyberbullying are at risk of suicidal behaviors and suicidal ideation when compared with nonperpetrators. Policy makers and schools should prioritize the inclusion of cyberbullying involvement in programs to prevent traditional bullying. Type of cyberbullying involvement, frequency, and gender should be assessed in future studies.

Agents of Change: Geriatrics Workforce Programs Addressing Systemic Racism and Health Equity.

Many factors affect how individuals and populations age, including race, ethnicity, and diversity, which can contribute to increased disease risk, less access to quality healthcare, and increased morbidity and mortality. Systemic racism-a set of institutional policies and practices within a society or organization that perpetuate racial inequalities and discrimination-contributes to health inequities of vulnerable populations, particularly older adults. The National Association for Geriatrics Education (NAGE) recognizes the need to address and eliminate racial disparities in healthcare access and outcomes for older adults who are marginalized due to the intersection of race and age. In this paper, we discuss an anti-racist framework that can be used to identify where an organization is on a continuum to becoming anti-racist and to address organizational change. Examples of NAGE member Geriatric Workforce Enhancement Programs (GWEPs) and Geriatrics Academic Career Awards (GACAs) activities to become anti-racist are provided to illustrate the framework and to guide other workforce development programs and healthcare institutions as they embark on the continuum to become anti-racist and improve the care and health of vulnerable older adults.

Health outcomes and service use patterns associated with co-located outpatient mental health care and alcohol and other drug specialist treatment: A systematic review.

ISSUES: Despite long-standing recommendations to integrate mental health care and alcohol and other drug (AOD) treatment, no prior study has synthesised evidence on the impact of physically co-locating these specialist services on health outcomes. APPROACH: We searched Medline, PsycINFO, Embase, Web of Science and CINAHL for studies examining health outcomes associated with co-located outpatient mental health care and AOD specialist treatment for adults with a dual diagnosis of substance use disorder and mental illness. Due to diversity in study designs, patient populations and outcome measures among the included studies, we conducted a narrative synthesis. Risk of bias was assessed using the MASTER scale. KEY FINDINGS: Twenty-eight studies met our inclusion criteria. We found provisional evidence that integrated care that includes co-located mental health care and AOD specialist treatment is associated with reductions in substance use and related harms and mental health symptom severity, improved quality of life, decreased emergency department presentations/hospital admissions and reduced health system expenditure. Many studies had a relatively high risk of bias and it was not possible to disaggregate the independent effect of physical co-location from other common aspects of integrated care models such as care coordination and the integration of service processes. IMPLICATIONS: There are few high-quality, peer-reviewed studies establishing the impact of co-located mental health care and AOD specialist treatment on health outcomes. Further research is required to inform policy, guide implementation and optimise practice. CONCLUSION: Integrated care that includes the co-location of mental health care and AOD specialist treatment may yield health and economic benefits.

Adverse childhood experiences, morbidity, mortality and resilience in socially excluded populations: protocol for a systematic review and meta-analysis.

INTRODUCTION: Socially excluded populations, defined by homelessness, substance use disorder, sex work or criminal justice system contact, experience profound health inequity compared with the general population. Cumulative exposure to adverse childhood experiences (ACEs), including neglect, abuse and household dysfunction before age 18, has been found to be independently associated with both an increased risk of social exclusion and adverse health and mortality outcomes in adulthood.Despite this, the impact of ACEs on health and mortality within socially excluded populations is poorly understood. METHODS AND ANALYSIS: We will search MEDLINE, Cumulative Index of Nursing and Allied Health Literature, Educational Resources Information Center, PsycINFO, Applied Social Science Index and Abstracts and Criminal Justice Database for peer-reviewed studies measuring ACEs and their impact on health and mortality in socially excluded populations.Three review questions will guide our data extraction and analysis. First, what is the prevalence of ACEs among people experiencing social exclusion in included studies? Second, what is the relationship between ACEs and health and mortality outcomes among people experiencing social exclusion? Does resilience modify the strength of association between ACEs and health outcomes among people experiencing social exclusion?We will meta-analyse the relationship between ACE exposure and health outcomes classified into six a prior categories: (1) substance use disorders; (2) sexual and reproductive health; (3) communicable diseases; (4) mental illness; (5) non-communicable diseases and (6) violence victimisation, perpetration and injury. If there are insufficient studies for meta-analysis, we will conduct a narrative synthesis. Study quality will be assessed using the MethodologicAl STandards for Epidemiological Research scale. ETHICS AND DISSEMINATION: Our findings will be disseminated in a peer-reviewed journal, in presentations at academic conferences and in a brief report for policy makers and service providers. We do not require ethics approval as this review will use data that have been previously published. PROSPERO REGISTRATION NUMBER: CRD42022357565.

Continuous glucose monitoring and metrics for clinical trials: an international consensus statement.

Randomised controlled trials and other prospective clinical studies for novel medical interventions in people with diabetes have traditionally reported HbA1c as the measure of average blood glucose levels for the 3 months preceding the HbA1c test date. The use of this measure highlights the long-established correlation between HbA1c and relative risk of diabetes complications; the change in the measure, before and after the therapeutic intervention, is used by regulators for the approval of medications for diabetes. However, with the increasing use of continuous glucose monitoring (CGM) in clinical practice, prospective clinical studies are also increasingly using CGM devices to collect data and evaluate glucose profiles among study participants, complementing HbA1c findings, and further assess the effects of therapeutic interventions on HbA1c. Data is collected by CGM devices at 1-5 min intervals, which obtains data on glycaemic excursions and periods of asymptomatic hypoglycaemia or hyperglycaemia (ie, details of glycaemic control that are not provided by HbA1c concentrations alone that are measured continuously and can be analysed in daily, weekly, or monthly timeframes). These CGM-derived metrics are the subject of standardised, internationally agreed reporting formats and should, therefore, be considered for use in all clinical studies in diabetes. The purpose of this consensus statement is to recommend the ways CGM data might be used in prospective clinical studies, either as a specified study endpoint or as supportive complementary glucose metrics, to provide clinical information that can be considered by investigators, regulators, companies, clinicians, and individuals with diabetes who are stakeholders in trial outcomes. In this consensus statement, we provide recommendations on how to optimise CGM-derived glucose data collection in clinical studies, including the specific glucose metrics and specific glucose metrics that should be evaluated. These recommendations have been endorsed by the American Association of Clinical Endocrinologists, the American Diabetes Association, the Association of Diabetes Care and Education Specialists, DiabetesIndia, the European Association for the Study of Diabetes, the International Society for Pediatric and Adolescent Diabetes, the Japanese Diabetes Society, and the Juvenile Diabetes Research Foundation. A standardised approach to CGM data collection and reporting in clinical trials will encourage the use of these metrics and enhance the interpretability of CGM data, which could provide useful information other than HbA1c for informing therapeutic and treatment decisions, particularly related to hypoglycaemia, postprandial hyperglycaemia, and glucose variability.

Tri-mode optical biopsy probe with fluorescence endomicroscopy, Raman spectroscopy, and time-resolved fluorescence spectroscopy.

We present an endoscopic probe that combines three distinct optical fibre technologies including: A high-resolution imaging fibre for optical endomicroscopy, a multimode fibre for time-resolved fluorescence spectroscopy, and a hollow-core fibre with multimode signal collection cores for Raman spectroscopy. The three fibers are all enclosed within a 1.2 mm diameter clinical grade catheter with a 1.4 mm end cap. To demonstrate the probe's flexibility we provide data acquired with it in loops of radii down to 2 cm. We then use the probe in an anatomically accurate model of adult human airways, showing that it can be navigated to any part of the distal lung using a commercial bronchoscope. Finally, we present data acquired from fresh ex vivo human lung tissue. Our experiments show that this minimally invasive probe can deliver real-time optical biopsies from within the distal lung - simultaneously acquiring co-located high-resolution endomicroscopy and biochemical spectra.

High proportion of fluoroquinolone-resistant Mycobacterium tuberculosis isolates with novel gyrase polymorphisms and a gyrA region associated with fluoroquinolone susceptibility.

Fluoroquinolone resistance in Mycobacterium tuberculosis can be conferred by mutations in gyrA or gyrB. The prevalence of resistance mutations outside the quinolone resistance-determining region (QRDR) of gyrA or gyrB is unclear, since such regions are rarely sequenced. M. tuberculosis isolates from 1,111 patients with newly diagnosed culture-confirmed tuberculosis diagnosed in Tennessee from 2002 to 2009 were screened for phenotypic ofloxacin resistance (>2 µg/ml). For each resistant isolate, two ofloxacin-susceptible isolates were selected: one with antecedent fluoroquinolone exposure and one without. The complete gyrA and gyrB genes were sequenced and compared with M. tuberculosis H37Rv. Of 25 ofloxacin-resistant isolates, 11 (44%) did not have previously reported resistance mutations. Of these, 10 had novel polymorphisms: 3 in the QRDR of gyrA, 1 in the QRDR of gyrB, and 6 outside the QRDR of gyrA or gyrB; 1 did not have any gyrase polymorphisms. Polymorphisms in gyrA codons 1 to 73 were more common in fluoroquinolone-susceptible than in fluoroquinolone-resistant strains (20% versus 0%; P = 0.016). In summary, almost half of fluoroquinolone-resistant M. tuberculosis isolates did not have previously described resistance mutations, which has implications for genotypic diagnostic tests.

Factors associated with initiation of antihyperglycaemic medication in UK patients with newly diagnosed type 2 diabetes.

AIM: To assess the factors associated with antihyperglycaemic medication initiation in UK patients with newly diagnosed type 2 diabetes. METHODS: In a retrospective cohort study, patients with newly diagnosed type 2 diabetes were identified during the index period of 2003-2005. Eligible patients were ≥ 30 years old at the date of the first observed diabetes diagnosis (referred to as index date) and had at least 2 years of follow-up medical history (N = 9,158). Initiation of antihyperglycaemic medication (i.e., treatment) was assessed in the 2-year period following the index date. Adjusted Cox regression models were used to examine the association between time to medication initiation and patient age and other factors. RESULTS: Mean (SD) HbA1c at diagnosis was 8.1% (2.3). Overall, 51% of patients initiated antihyperglycaemic medication within 2 years (65%, 55%, 46% and 40% for patients in the 30- < 45, 45- < 65, 65- < 75, 75+ age groups, respectively). Among the treated patients, median (25th, 75th percentile) time to treatment initiation was 63 (8, 257) days. Of the patients with HbA1c ≥ 7.5% at diagnosis, 87% initiated treatment within 2 years. These patients with a higher HbA1c also had shorter time to treatment initiation (adjusted hazard ratio (HR) = 2.44 [95% confidence interval (CI): 1.61, 3.70]; p < 0.0001). Increasing age (in years) was negatively associated with time to treatment initiation (HR = 0.98 [95% CI: 0.97, 0.99]; p < 0.001). Factors significantly associated with shorter time to treatment initiation included female gender and use of cardiovascular medications at baseline or initiated during follow up. CONCLUSIONS: In this UK cohort of patients with newly diagnosed type 2 diabetes, only 51% had antihyperglycaemic medication initiated over a 2-year period following diagnosis. Older patients were significantly less likely to have been prescribed antihyperglycaemic medications. Elevated HbA1c was the strongest factor associated with initiating antihyperglycaemic medication in these patients.