Borderline Evidence Research Articles

Mean nocturnal baseline impedance: Influencing factors and diagnostic value in gastroesophageal reflux disease.

At present, there are few studies related to mean nocturnal baseline impedance (MNBI), esophageal dynamic reflux monitoring, high-resolution esophageal manometry (HRM) parameter indexes, and its diagnostic value in gastroesophageal reflux disease (GERD). To analyze the factors influencing MNBI and examine the diagnostic value of MNBI in GERD. A retrospective analysis on 434 patients with typical reflux symptoms who underwent gastroscopy, 24-hour multichannel intraluminal impedance and pH monitoring (MII/pH) and HRM. They were divided into the conclusive evidence group (103 cases), borderline evidence group (229 cases), and exclusion evidence group (102 cases) according to the level of diagnostic evidence of GERD based on the Lyon Consensus. We analyzed the differences in MNBI, esophagitis grade, MII/pH and HRM index among the groups; the correlation between MNBI and the above indexes and its influence on MNBI; and to evaluate the diagnostic value of MNBI in GERD. There were significant differences in MNBI, Acid Exposure Time (AET) 4%, DeMeester score, and total reflux episodes among the three groups (P< 0.001). EGJ contractile integral (EGJ-CI) of the conclusive evidence group and the borderline evidence group was significantly lower than that in the exclusion evidence group (P< 0.001). MNBI was significantly and negatively correlated with age, BMI, AET 4%, DeMeester score, total reflux episodes, EGJ classification, esophageal motility abnormalities, and esophagitis grade (all P< 0.05), and significantly and positively correlated with EGJ-CI (P< 0.001). Age, BMI, AET 4%, EGJ classification, EGJ-CI, and esophagitis grade had significant effects on MNBI (P< 0.05); MNBI was used to diagnose GERD with a diagnostic cutoff of 2061 Ω, and AUC was 0.792 (sensitivity 74.9%, specificity 67.4%); MNBI was used to diagnose exclusion evidence group with a diagnostic cutoff of 2432 Ω, AUC was 0.774 (sensitivity 67.6%, specificity 72%). AET, EGJ-CI, and esophagitis grade are the most important influence factors of MNBI. MNBI has good diagnostic value in identifying conclusive GERD.

Mast Cells in Kidney Transplant Biopsies With Borderline T Cell-mediated Rejection and Their Relation to Chronicity.

Fourty-seven KTx biopsies (2009-2018) with borderline pathological evidence for T cell-mediated rejection according to the Banff'17 Update were retrospectively included and corresponding clinical data was collected. Immunohistochemistry for tryptase was performed on formalin-fixed paraffin-embedded sections. Cortical MCs were counted and corrected for area (MC/mm²). Interstitial fibrosis was assessed by Sirius Red staining and quantified using digital image analysis (QuPath). Increased MC number was correlated to donor age (spearman's r = 0.35, P = 0.022), deceased donor kidneys (mean difference = 0.74, t [32.5] = 2.21, P = 0.035), and delayed graft function (MD = 0.78, t [33.9] = 2.43, P = 0.020). Increased MC number was also correlated to the amount of interstitial fibrosis (r = 0.42, P = 0.003) but did not correlate with transplant function over time (r = -0.14, P = 0.36). Additionally, transplant survival 2 y post-biopsy was not correlated to MC number (mean difference = -0.02, t [15.36] = -0.06, P = 0.96). MC number in suspicious (borderline) for acute T cell-mediated rejection is correlated to interstitial fibrosis and time post-transplantation, suggesting MCs to be a marker for cumulative burden of tissue injury. There was no association between MCs and transplant function over time or transplant survival 2 y post-biopsy. It remains unclear whether MCs are just a bystander or have pro-inflammatory or anti-inflammatory effects in the KTx with minimal lesions.

Long-term persistence of antibodies after diphtheria/tetanus vaccination in immunosuppressed patients with inflammatory rheumatic diseases and healthy controls

Many vaccines demonstrate high effectiveness for years. This prospective multicentre study was conducted in Switzerland to assess the long-term persistence of antibodies to the diphtheria/tetanus (dT)-vaccine in adult patients with rheumatic diseases (PRDs). 163 PRDs and 169 controls were included in the study. The median age of all participants was 50 years (range: 18–83 years) and 56% were female. After a median time interval of 16 years after vaccination, the median anti-vaccine antibody concentrations were lower in PRDs than in controls for tetanus (1.68 vs 2.01; p = 0.049) and diphtheria (0.05 vs 0.22; p = 0.002). Based on the currently accepted seroprotection threshold (antibody concentration ≥ 0.1 IU/ml), PRDs had lower proportions of short-term tetanus and diphtheria protection as demonstrated by crude odds ratios (OR) of 0.30 (p = 0.017) and OR: 0.52 (p = 0.004), respectively. After adjusting for ‘age’ and ‘time since last dT vaccination’, the strength of associations became weaker; for tetanus, borderline evidence remained for a true difference between PRDs and controls (OR: 0.36 [p = 0.098]), however, not for diphtheria (OR: 0.86 [p = 0.58]). We hypothesize that in the presence of rheumatic diseases and its immunosuppressive treatment, vaccine-specific long-lived plasma cells (LLPCs) may be diminished or competitively displaced by rheumatism-specific LLPCs, a process which may decrease the persistence of vaccine-specific antibodies. Novel studies should be designed by incorporating methodologies allowing to determine the attributable fraction of immunosuppressive/immunomodulatory medications and rheumatic disease itself on long-lasting vaccine-specific antibody persistence, as well as, further study the role of LLPCs.

Gender Interaction in Association of Perceived Social Support and Health-Related Quality of Life Among Iranian Older People: A Cross-sectional Survey.

Background: The purpose of this study was to examine the relationship between perceived social support (PSS) and dimensions of health-related quality of life (HRQoL) and to examine possible gender interaction in the mentioned associations. Methods: A community-based cross-sectional study conducted among 644 participants over the age of 60 years old in Tehran. The data were collected through face-to-face interviews conducted in their own homes, by using a structured multi-sectional questionnaire. The version 1 of the SF-12 scale was used to measure the HRQoL, consisting of two summary measures; PCS (Physical Component Score) and MCS (Mental Component Score). The Persian version of the Social Provisions Scale (SPS) was used to measure PSS. Four multilevel mixed-effects logistic regression models were used to examine the associations. Results: Older people with poor SPS score were 1.8 times more likely to be in the worst quartile of the MCS distribution (CI=1.11-2.93, P =0.021), and twice as likely to be in the worst quartile of the PCS distribution (CI=1.18-3.54, P =0.011). We found strong evidence to support the hypothesis of gender interaction in the association between economic status and PCS [Men: OR 0.28, CI (0.11-0.71); Women: OR 1.00, CI (0.53-1.88); P of Interaction 0.021], and a borderline evidence for gender interaction in the association between physical activity and PCS [Men: OR 5.32, CI (2.14-13.20); Women: OR 1.80, CI (0.82-3.93); P of Interaction 0.051]. Conclusions: Social support could be regarded as one of the main social determinants affecting HRQoL among older people. Men with poor economic status and poor physical activity, compared to women, are more likely to suffer from poor quality of life, thus men should be prioritized in financial support and life style and physical activity interventions.

Resistant Maltodextrin Consumption in a Double-Blind, Randomized, Crossover Clinical Trial Induces Specific Changes in Potentially Beneficial Gut Bacteria.

Background: We have previously reported that the addition of resistant maltodextrin (RMD), a fermentable functional fiber, to the diet increases fecal weight as well as the amount of fecal bifidobacteria. Here, we report on the targeted analysis of changes in potentially beneficial gut bacteria associated with the intervention. Objective: The primary objective of this study was to determine the effect of adding 0, 15 and 25 g RMD to the diets of healthy free-living adults on potentially beneficial gut bacteria. Methods: We expanded on our previously reported microbiota analysis in a double-blind, placebo-controlled feeding study (NCT02733263) by performing additional qPCR analyses targeting fecal lactic acid bacteria (LAB), Akkermansia muciniphila, Faecalibacterium prausnitzii and Fusicatenibacter saccharivorans in samples from 49 participants. Results: RMD resulted in an approximately two-fold increase in fecal Fusicatenibacter saccharivorans (p = 0.024 for 15 g/day RMD and p = 0.017 for 25 g/day RMD). For Akkermansia muciniphila and Faecalibacterium prausnitzii, we obtained borderline evidence that showed increased amounts in participants that had low baseline levels of these bacteria (p < 0.1 for 25 g/day RMD). We did not detect any effects of RMD on LAB. Conclusions: RMD supplementation in healthy individuals increases Fusicatenibacter saccharivorans. Albeit to a lesser extent, RMD at the higher intake level may also increase Akkermansia muciniphila and Faecalibacterium prausnitzii in individuals with low baseline levels of those two species. Potential benefits associated with these microbiota changes remain to be established in studies with quantifiable health-related endpoints.

Adenoma characteristics associated with post-polypectomy proximal colon cancer incidence: a retrospective cohort study

BackgroundColorectal cancer (CRC) screening is less effective at reducing cancer incidence in the proximal colon compared to the distal colorectum. We aimed to identify adenoma characteristics associated with proximal colon cancer (PCC).MethodsEndoscopy and pathology data for patients with ≥1 adenoma detected at baseline colonoscopy were obtained from 17 UK hospitals between 2001 and 2010. Multivariable Cox regression models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for PCC, and, for comparison, distal CRC incidence, by adenoma characteristics.ResultsAmong 18,431 patients, 152 and 105 developed PCC and distal CRC, respectively, over a median follow-up of 9.8 years. Baseline adenoma characteristics positively associated with PCC incidence included number (≥3 vs. < 3: aHR 2.10, 95% CI: 1.42–3.09), histology (tubulovillous/villous vs. tubular: aHR 1.61, 95% CI: 1.10–2.35) and location (any proximal vs. distal only: aHR 1.70, 95% CI: 1.20–2.42), for which there was borderline evidence of heterogeneity by subsite (p = 0.055). Adenoma dysplasia (high vs. low grade) was associated with distal CRC (aHR 2.42, 95% CI: 1.44–4.04), but not PCC (p-heterogeneity = 0.023).ConclusionsBaseline adenoma number, histology and proximal location were independently associated with PCC and may be important to identify patients at higher risk for post-polypectomy PCC.

Role of the Mean Nocturnal Baseline Impedance in Identifying Evidence Against Pathologic Reflux in Patients With Refractory Gastroesophageal Reflux Disease Symptoms as Classified by the Lyon Consensus.

Background/AimsMean nocturnal baseline impedance (MNBI) is a new reflux metric for mucosal integrity. It remains unclear whether MNBI can help identify evidence against pathological reflux by the Lyon Consensus in patients with refractory gastroesophageal reflux disease (GERD) symptoms.MethodsThree hundred and forty-nine patients with refractory GERD symptoms enrolled in this study were subjected to high-resolution manometry, 24-hour multichannel intraluminal impedance-pH (MII-pH) monitoring, and endoscopy. Conventional indexes (ie, reflux events and acid exposure time) and the novel index (MNBI) of MII-pH monitoring were extracted and analyzed. The value of MNBI in diagnosing patients with evidence against pathologic reflux was evaluated by receiver-operating-characteristic analysis.ResultsThere were 102 (29.2%) patients with evidence against pathologic reflux, 149 (42.7%) with inconclusive or borderline evidence and 98 (28.1%) with conclusive evidence for pathologic reflux. The MNBI was significantly higher while the proportion of pathological MNBI was significantly lower in subjects with evidence against pathologic reflux than in patients with inconclusive or borderline evidence and in patients with conclusive evidence for pathologic reflux (2444.3 [1977.9-2997.4] vs 1992.8 [1615.5-2253.6] and vs 1772.3 [758.6-2161.3], both P < 0.001; 42.2% vs 79.7% and vs 80.0%, both P < 0.05). When identifying evidence against pathologic reflux in patients with refractory GERD symptoms, the MNBI yielded an area under the curve of 0.749 (P < 0.001) at a cut-off value of 1941.8 Ω.ConclusionsThe MNBI has a good diagnostic value for evidence against pathological reflux in patients with refractory GERD symptoms. For its simplicity and reproducibility, we believe that MNBI should be referred to in reports of impedance-pH tracings by physicians.

Sociodemographic features and mortality of individuals on haemodialysis treatment who test positive for SARS-CoV-2: A UK Renal Registry data analysis.

Kidney disease is a recognised risk factor for poor COVID-19 outcomes. Up to 30 June 2020, the UK Renal Registry (UKRR) collected data for 2,385 in-centre haemodialysis (ICHD) patients with COVID-19 in England and Wales. Overall unadjusted survival at 1 week after date of positive COVID-19 test was 87.5% (95% CI 86.1-88.8%); mortality increased with age, treatment vintage and there was borderline evidence of Asian ethnicity (HR 1.16, 95% CI 0.94-1.44) being associated with higher mortality. Compared to the general population, the relative risk of mortality for ICHD patients with COVID-19 was 45.4 and highest in younger adults. This retrospective cohort study based on UKRR data supports efforts to protect this vulnerable patient group.

Investigating the Effect of Prompt Treatment on Malaria Prevalence in Children Aged below Five Years in Zambia: A Nested Case-Control Study in a Cross-Sectional Survey

Background. In a highly malaria endemic country like Zambia, prompt treatment of cases is known to reduce morbidity and mortality; however, it is not known whether it has a role as an effective prevention strategy because of the presence of asymptomatic chronic carriers who do not seek treatment and maintain the reservoirs of infection in the population. This study investigated the role of treatment of malaria cases as a prevention strategy in low, moderate, and high endemic settings. Methods. A nested case-control design was employed using datasets from a large countrywide national Malaria Indicator Survey of 2015. Self-reported malaria cases (n = 209) who took treatment in the two weeks preceding the survey were matched with controls (n = 511) who did not report malaria and did not take treatment during the same period using nearest neighbour propensity score matching for age, sex, and district. The data were analysed using conditional logistic regression in STATA version 15.1. Results. The malaria cases were more likely to be from rural areas (p=0.001), poorest households (p=0.049), and who lived in improvised housing structures (p=0.004) compared with the controls. Data from low and moderate malaria endemic areas did not have sufficient cases for the analysis to proceed; however, data from high endemic areas showed borderline evidence (p=0.054) that prompt treatment reduces the risk of malaria by almost half in the short-term aOR 0.057 (95% CI 0.32–1.01). Conclusion. We found borderline evidence which suggests that prompt treatment of malaria cases even in high endemic areas has potential to reduce the risk of malaria by almost half in the short term.

Depression and risk of gestational diabetes: A meta-analysis of cohort studies

AimsTo systematically assess the association between depression and risk of gestational diabetes by a meta-analysis of cohort studies. MethodsWe searched multiple electronic databases for cohort studies investigating depression and risk of gestational diabetes before December 31th, 2018. Pooled odds ratios (ORs) and confidence intervals (CIs) of the included articles were calculated using a fixed- or random-effect model. Publication bias was detected using the Egger’s and Begg’s tests. ResultsWe obtained 5 cohort studies with a total number of 122,197 women. Women with a history of depression compared with those without it had a significantly increased risk of gestational diabetes (pooled OR = 1.20, 95% CI: 1.09, 1.33) but borderline significant evidence of heterogeneity was observed (I2 = 45.1%, P for heterogeneity = 0.12). Subgroup analysis by study design showed a stronger association in prospective cohort studies than that in retrospective cohort studies (pooled OR: 1.61 [1.17, 2.21] vs. 1.16 [1.05, 1.29]), though the difference was not statistically significant (P for interaction = 0.26). We observed some evidence of publication bias; however, correction for such bias using “trim-and-fill” analysis yielded similar results. ConclusionWomen with a history of depression may be at an increased risk of gestational diabetes. Future prospective studies of high quality are needed to confirm our findings.

Impact and sustainability of centralising acute stroke services in English metropolitan areas: retrospective analysis of hospital episode statistics and stroke national audit data

ObjectivesTo investigate whether further centralisation of acute stroke services in Greater Manchester in 2015 was associated with changes in outcomes and whether the effects of centralisation of acute stroke services...

Associations of TRAF1/C5 rs10818488 and rs3761847 polymorphisms with genetic susceptibility to rheumatoid arthritis: a case-control study and updated meta-analysis.

The results on associations of tumor necrosis factor (TNF)-receptor associated factor 1/complement component 5 (TRAF1/C5) rs10818488 and rs3761847 polymorphisms with rheumatoid arthritis (RA) are controversial, thus this study was performed to examine whether the aforementioned polymorphisms were associated with RA in a Chinese population. Furthermore, an updated meta-analysis was conducted. The polymorphisms were genotyped in 328 Chinese RA patients and 449 healthy controls. Studies examining the association of TRAF1/C5 rs10818488 and/or rs3761847 polymorphism with RA were exhaustively searched. No significant difference in either genotype or allele distribution between RA patients and controls was found. The updated meta-analysis was conducted based on 19 articles including the present study. A significant association of RA with TRAF1/C5 rs10818488 polymorphism G allele in Europeans (OR = 0.843, 95% CI = 0.730-0.975, p = 0.021) and in Asians (OR = 1.070, 95% CI = 1.009-1.136, p = 0.024) was found. Additionally, a significant association of RA with TRAF1/C5 rs10818488 polymorphism G allele under the recessive model in Asians (OR = 1.129, 95% CI = 1.023-1.246, p = 0.016) and in Africans (OR = 0.657, 95% CI = 0.507-0.851, p = 0.001) was found. Only a borderline significant association of RA with TRAF1/C5 rs3761847 polymorphism A allele was found in Europeans. Non-significant associations of RA with TRAF1/C5 rs10818488 and rs3761847 polymorphisms were found in our study. The updated meta-analysis results demonstrate that TRAF1/C5 rs10818488 polymorphism is associated with RA in Europeans, Asians and Africans, and TRAF1/C5 rs3761847 polymorphism is associated with RA in Europeans with borderline significant evidence.

Is dementia incidence declining in high-income countries? A systematic review and meta-analysis.

PurposeTo perform a systematic review and quantitative synthesis of studies on recent trends in dementia incidence in high-income countries (HIC), considering study quality.MethodsPubMed and Web of Science were searched for eligible studies, that is, population-based/community-based prospective cohort studies investigating dementia incidence with similar methods over time, published after 1990. Study selection, data extraction, and quality assessment were performed independently by two investigators. Random-effect meta-analysis and meta-regression were used to estimate incidence change (IC) and to explore associations with study attributes. PRISMA standards were followed.ResultsThe systematic review included seven studies (42,485 individuals), and the meta-analysis included five studies of sufficient quality. Relating dementia incidence of later cohorts to earlier cohorts (reference) yielded a nonsignificant decrease across HIC (IC =0.82; 95% CI 0.51–1.33), with high heterogeneity (I2=94.9%, P<0.001) and without publication bias (Egger’s t=–1.77; P=0.18). Excluding the Japanese Hisayama study, the only study suggesting an increase, indicated borderline evidence for a decrease across Western HIC (IC =0.69; 95% CI 0.47–1.00; I2=88.1%, P<0.001; Egger’s t=–0.34, P=0.77), again with high heterogeneity. Meta-regression did not reveal an association of incidence rate with calendar year or study attributes; however, analyses were low powered.ConclusionThere is evidence of favorable trends in dementia incidence in Western HIC (stabilizing/decreasing). Reverse trends may occur in HIC of other regions, as exemplified by Japan. However, study number was small and heterogeneity was high. Further cohort studies using consistent methods are needed to draw definite conclusions. Our work may inform such future studies.

Post-diagnosis alcohol intake and prostate cancer survival: A population-based cohort study.

Alcohol consumption has been declared a Group 1 carcinogen by the International Agency for Research on Cancer (IARC) and is a potential risk factor for several types of cancer mortality. However, evidence for an association with prostate cancer survival remains inconsistent. We examined how alcohol consumption post-diagnosis was associated with survival after prostate cancer diagnosis. Men diagnosed with prostate cancer (n = 829) in Alberta, Canada between the years 1997 and 2000 were recruited into a population-based case-control study and then followed for up to 19 years for survival outcomes. Pre- and post-diagnosis alcohol consumption, clinical characteristics and lifestyle factors were collected through in-person interviews shortly after diagnosis and again 2-3 years post-diagnosis. Cox proportional hazards were used to examine how post-diagnosis alcohol consumption was associated with all-cause and prostate cancer-specific mortality (competing risk analysis too), in addition to first recurrence/progression or new primary cancer. Most participants reported drinking alcohol (≥once a month for 6 months) post-diagnosis (n = 589, 71.0%). Exceeding Canadian Cancer Society (CCS) alcohol consumption recommendations (≥2 drinks/day) post-diagnosis was associated with prostate cancer-specific mortality relative to non-drinkers (aHR: 1.82, 95% CI: 1.07-3.10) with borderline evidence of a linear trend. Interestingly, those in the highest quartile of drinks/week pre- and post-diagnosis also had a twofold increase for prostate-specific mortality (aHR: 2.67, 95% CI: 1.28-5.56) while controlling for competing risks. Our results support post-diagnosis alcohol consumption was associated with increased mortality after prostate cancer diagnosis, specifically for prostate cancer-related death. Future studies focused on confirming this burden of disease are warranted.

Association Analysis Suggests SOD2 as a Newly Identified Candidate Gene Associated With Leprosy Susceptibility.

Genetic studies have identified several genes and genomic regions contributing to the control of host susceptibility to leprosy. Here, we test variants of the positional and functional candidate gene SOD2 for association with leprosy in 2 independent population samples. Family-based analysis revealed an association between leprosy and allele G of marker rs295340 (P = .042) and borderline evidence of an association between leprosy and alleles C and A of markers rs4880 (P = .077) and rs5746136 (P = .071), respectively. Findings were validated in an independent case-control sample for markers rs295340 (P = .049) and rs4880 (P = .038). These results suggest SOD2 as a newly identified gene conferring susceptibility to leprosy.

A Survey of Same-Sex Sexual Experiences Among Psychiatric Inpatients With and Without Borderline Personality Symptomatology

To the Editor: In comparison to the general population, individuals with borderline personality disorder appear to exhibit a higher prevalence of sexual experiences with members of the same sex,1–5 with psychiatric inpatients exhibiting higher rates than psychiatric outpatients, and male psychiatric outpatients exhibiting higher rates than female psychiatric outpatients. In this study, we investigated the prevalence of same-sex sexual experiences among psychiatric inpatients, comparing those with versus without borderline personality disorder symptomatology according to 3 different self-report measures for this disorder. Method. Study candidates were 167 men and women admitted to an urban psychiatric inpatient facility. Exclusion criteria included intellectual, medical, psychiatric, or cognitive impairment of a severity to diminish the individual’s ability to complete a survey. Fourteen individuals were excluded (3 vision problems, 4 intellectually disabled/illiterate, 4 psychotic, 3 malingering). Of those approached, 145 (95%) agreed to participate: 55 men and 89 women (1 participant declined to report gender), with a mean age of 38.06 years (SD = 13.06). The majority self-identified as white (74%), with 16% black. The majority (87%) had at least completed high school. Approximately 41% reported never having been married, with 18% married, 27% divorced, 10% separated, and 3% widowed. At admission, each candidate was invited to complete an anonymous survey that contained the query, “How many same-sex partners have you had in your lifetime?” with response options of ≥ 0–5. The survey also queried about borderline personality disorder using 3 self-report diagnostic measures: the Personality Diagnostic Questionnaire–46 (Cronbach α = 0.74), the McLean Screening Inventory for Borderline Personality Disorder7 (Cronbach α = 0.78), and the screening instrument for the Structured Clinical Interview for DSM-IV Axis II Personality Disorders8 (Cronbach α = 0.86). The elements of informed consent were provided on the cover page of the survey, and completion of the survey was assumed to function as informed consent (stated on the cover page). The project was approved by the sponsoring hospital’s institutional review board. Results. Among participants, 59% reported at least 1 same-sex sexual experience. Using χ2 analyses, we examined participants with versus without borderline personality disorder according to diagnostic cutoffs in terms of this behavior (Table 1). None of these comparisons were statistically significant (all P > .05). Moreover, dimensional scores on the measures of borderline personality disorder also were not statistically significantly correlated with a history of same-sex experiences (see Table 1). Table 1 Associations Between Borderline Personality Disorder Measures and History of Same-Sex Sexual Relationships Stated simply, while inpatients with borderline personality disorder symptomatology appear to have higher rates of same-sex sexual experiences than the general population, surprisingly, these do not appear to exceed the rates encountered among psychiatric inpatients without this personality disorder. To our knowledge, this is a novel finding in the current literature and suggests that mental disorders, in general, may predict higher rates of same-sex sexual experiences. This study has a number of potential limitations, including the small sample size, self-report nature of the data, and use of an urban inpatient psychiatric sample (ie, findings may not generalize to psychiatric inpatients in nonurban settings or psychiatric outpatients). However, findings indicate that while psychiatric inpatients with borderline personality disorder symptomatology evidence higher rates of same-sex sexual experiences than the general population, these rates are not higher than those encountered among psychiatric inpatients without borderline personality disorder symptomatology.

Cytochrome P450 Allele CYP3A7*1C Associates with Adverse Outcomes in Chronic Lymphocytic Leukemia, Breast, and Lung Cancer.

CYP3A enzymes metabolize endogenous hormones and chemotherapeutic agents used to treat cancer, thereby potentially affecting drug effectiveness. Here, we refined the genetic basis underlying the functional effects of a CYP3A haplotype on urinary estrone glucuronide (E1G) levels and tested for an association between CYP3A genotype and outcome in patients with chronic lymphocytic leukemia (CLL), breast, or lung cancers. The most significantly associated SNP was rs45446698, an SNP that tags the CYP3A7*1C allele; this SNP was associated with a 54% decrease in urinary E1G levels. Genotyping this SNP in 1,008 breast cancer, 1,128 lung cancer, and 347 CLL patients, we found that rs45446698 was associated with breast cancer mortality (HR, 1.74; P = 0.03), all-cause mortality in lung cancer patients (HR, 1.43; P = 0.009), and CLL progression (HR, 1.62; P = 0.03). We also found borderline evidence of a statistical interaction between the CYP3A7*1C allele, treatment of patients with a cytotoxic agent that is a CYP3A substrate, and clinical outcome (Pinteraction = 0.06). The CYP3A7*1C allele, which results in adult expression of the fetal CYP3A7 gene, is likely to be the functional allele influencing levels of circulating endogenous sex hormones and outcome in these various malignancies. Further studies confirming these associations and determining the mechanism by which CYP3A7*1C influences outcome are required. One possibility is that standard chemotherapy regimens that include CYP3A substrates may not be optimal for the approximately 8% of cancer patients who are CYP3A7*1C carriers.

Head-to-head comparison of intensive lifestyle intervention (U-TURN) versus conventional multifactorial care in patients with type 2 diabetes: protocol and rationale for an assessor-blinded, parallel group and randomised trial

IntroductionCurrent pharmacological therapies in patients with type 2 diabetes (T2D) are challenged by lack of sustainability and borderline firm evidence of real long-term health benefits. Accordingly, lifestyle intervention remains the...

CT screening for lung cancer: Is the evidence strong enough?

The prevailing questions at this time in both the public mind and the clinical establishment is, do we have sufficient evidence to implement lung cancer Computed Tomography (CT) screening in Europe? If not, what is outstanding? This review addresses the twelve major areas, which are critical to any decision to implement CT screening and where we need to assess whether we have sufficient evidence to proceed to a recommendation for implementation in Europe. The readiness level of these twelve categories in 2015 have been with colour coded, where green indicates we have sufficient evidence, amber is borderline evidence and red requires further evidence. Recruitment from the 'Hard to Reach' community still remains at red, while mortality data, cost effectiveness and screening interval are all categorised as amber. The integration of smoking cessation into CT screening programmes is still considered to be category amber. The US Preventive Services Task Force have recommended that CT screening is implemented in the USA utilising the NLST criteria, apart from continuing screening to 80 years of age. The cost effectiveness of the NLST was calculated to be $81,000/QALY, however, its well recognised that the costs of medical care in the USA, is far higher than that of Europe. Medicare have agreed to cover the cost of screening but have stipulated a number of stringent requirements for inclusion. To date we do not have good CT screening mortality data available in Europe and eagerly await the publication of the NELSON trial data in 2016 and then the pooled UKLS and NELSON data thereafter. However in the meantime we should start planning for implementation in Europe, especially in the areas of the radiological service provision and accreditation, as well as identifying novel mechanisms to recruit from the hardest to reach communities.

Heterogeneous responses of systolic and diastolic left ventricular function to exercise in patients with heart failure and preserved ejection fraction.

AimsThis study aimed to evaluate ventricular diastolic properties using three‐dimensional echocardiography and tissue Doppler imaging at rest and during exercise in heart failure with preserved ejection fraction (HFpEF) patients with borderline evidence of diastolic dysfunction at rest.Methods and resultsResults obtained from 52 HFpEF patients (left ventricular ejection fraction ≥ 50%) identified on the basis of heart failure symptoms and E/E′ values between 8 and 15 were compared with those obtained in 26 control patients with no evidence of cardiovascular disease. Mitral flow patterns, tissue Doppler imaging, and volume analysis obtained by three‐dimensional echocardiography were performed at rest and during bicycle exercise. Diastolic compliance was indexed by the E/E′ ratio and left ventricular end‐diastolic volume [(E/E′)/EDV]. There were no significant differences in end‐diastolic volume (EDV), stroke volume (SV), or ejection fraction at rest between groups. In 27 of the 52 patients, E/E′ increased during exercise (11.2 ± 3.7 to 16.8 ± 10.5), driven by a failure to augment early diastole (E′). This correlated with a fall in SV and was associated with an increase in the diastolic index (E/E′)/EDV as a measure for LV stiffness (0.122 ± 0.038 to 0.217 ± 0.14/mL), indicating that impaired diastolic reserve (designated PEF‐IDR) contributed to exercise intolerance. Of the 52 patients, 25 showed no changes in E/E′ during exercise associated with a significant rise in SV and cardiac output, still inappropriate compared with controls. Despite disturbed early diastole (E′), a blunted increase in estimated systolic LV elastance indicated that impaired systolic reserve and chronotropic incompetence rather than primarily diastolic disturbances contributed to exercise intolerance in this group (designated PEF).ConclusionThree‐dimensional stress echocardiography may allow non‐invasive analysis of changes in cardiac output that can differentiate HFpEF patients with an inappropriate increase or a fall in SV during exercise. Impaired systolic or diastolic reserve can contribute to these haemodynamic abnormalities, which may arise from different underlying pathophysiologic mechanisms.