Explore the vast range of titles available.

The prognostic value of cardiopulmonary exercise testing (CPET) for survival in cystic fibrosis (CF) in the context of current clinical management, when controlling for other known prognostic factors, is unclear. To determine the prognostic value of CPET-derived measures beyond peak oxygen uptake ( o peak) following rigorous adjustment for other predictors. Data from 10 CF centers in Australia, Europe, and North America were collected retrospectively. A total of 510 patients completed a cycle CPET between January 2000 and December 2007, of which 433 fulfilled the criteria for a maximal effort. Time to death/lung transplantation was analyzed using Cox proportional hazards regression. In addition, phenotyping using hierarchical Ward clustering was performed to characterize high-risk subgroups. Cox regression showed, even after adjustment for sex, FEV % predicted, body mass index (z-score), age at CPET, Pseudomonas aeruginosa status, and CF-related diabetes as covariates in the model, that o peak in % predicted (hazard ratio [HR], 0.964; 95% confidence interval [CI], 0.944-0.986), peak work rate (% predicted; HR, 0.969; 95% CI, 0.951-0.988), ventilatory equivalent for oxygen (HR, 1.085; 95% CI, 1.041-1.132), and carbon dioxide (HR, 1.060; 95% CI, 1.007-1.115) (all P < 0.05) were significant predictors of death or lung transplantation at 10-year follow-up. Phenotyping revealed that CPET-derived measures were important for clustering. We identified a high-risk cluster characterized by poor lung function, nutritional status, and exercise capacity. CPET provides additional prognostic information to established predictors of death/lung transplantation in CF. High-risk patients may especially benefit from regular monitoring of exercise capacity and exercise counseling.

Purpose Potentially inappropriate prescriptions (PIPs) criteria are widely used for evaluating the quality of prescribing in elderly. However, there is limited evidence on their association with adverse drug reactions (ADRs) across healthcare settings. The study aimed to determine the prevalence of PIPs, defined by the Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) criteria, in the Swedish elderly general population and to investigate the association between PIPs and occurrence of ADRs. Method Persons ≥65 years old were identified from a random sample of 5025 adults drawn from the Swedish Total Population Register. A retrospective cohort study was conducted among 813 elderly with healthcare encounters in primary and specialised healthcare settings during a 3-month period in 2008. PIPs were identified from the Swedish Prescribed Drug Register, medical records and health administrative data. ADRs were independently identified by expert reviewers in a stepwise manner using the Howard criteria. Multivariable logistic regression examined the association between PIPs and ADRs. Results Overall, 374 (46.0 %) persons had ≥1 PIPs and 159 (19.5 %) experienced ≥1 ADRs during the study period. In total, 29.8 % of all ADRs was considered caused by PIPs. Persons prescribed with PIPs had more than twofold increased odds of experiencing ADRs (OR 2.47; 95 % CI 1.65–3.69). PIPs were considered the cause of 60 % of ADRs affecting the vascular system, 50 % of ADRs affecting the nervous system and 62.5 % of ADRs resulting in falls. Conclusion PIPs are common among the Swedish elderly and are associated with increased odds of experiencing ADRs. Thus, interventions to decrease PIPs may contribute to preventing ADRs, in particular ADRs associated with nervous and vascular disorders and falls.

Background: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. Methods: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. Results: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. Conclusion: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.

Difficulty of asthma ascertainment and its associated methodologic heterogeneity have created significant barriers to asthma care and research. We evaluated the validity of an existing natural language processing (NLP) algorithm for asthma criteria to enable an automated chart review using electronic medical records (EMRs). The study was designed as a retrospective birth cohort study using a random sample of 500 subjects from the 1997-2007 Mayo Birth Cohort who were born at Mayo Clinic and enrolled in primary pediatric care at Mayo Clinic Rochester. Performance of NLP-based asthma ascertainment using predetermined asthma criteria was assessed by determining both criterion validity (chart review of EMRs by abstractor as a gold standard) and construct validity (association with known risk factors for asthma, such as allergic rhinitis). After excluding three subjects whose respiratory symptoms could be attributed to other conditions (e.g., tracheomalacia), among the remaining eligible 497 subjects, 51% were male, 77% white persons, and the median age at last follow-up date was 11.5 years. The asthma prevalence was 31% in the study cohort. Sensitivity, specificity, positive predictive value, and negative predictive value for NLP algorithm in predicting asthma status were 97%, 95%, 90%, and 98%, respectively. The risk factors for asthma (e.g., allergic rhinitis) that were identified either by NLP or the abstractor were the same. Asthma ascertainment through NLP should be considered in the era of EMRs because it can enable large-scale clinical studies in a more time-efficient manner and improve the recognition and care of childhood asthma in practice.

Chronic pain is a common condition which causes patients much suffering and is very costly to society. Factors known to be associated with chronic pain include female gender, acute pain, depression, and anxiety. This study investigated whether stress, sleep disturbance, and physical inactivity were risk factors for developing chronic pain among young adults, and whether there were any interactions between these. This retrospective longitudinal study was based on an existing database from a cohort study on IT use and health, called Health 24 Years. A questionnaire was sent to students aged 19-24 in Sweden for five consecutive years, containing questions on pain, stress, sleep, physical activity, technology use, health, and more. In logistic regressions, stress, sleep, and physical activity at baseline were potential predictors of chronic pain one and four years later. In addition, a new variable including all possible interactions between potential predictors was created to test for effect modification between risk factors. At the one-year follow-up, stress, non-restorative sleep, and physical inactivity showed odds ratios of 1.6 (95% CI: 1.0-2.4), 1.5 (95% CI: 1.0-2.3), and 1.8 (95% CI: 1.1-3.0) respectively after adjusting for confounders, the reference being non-stressed, having restorative sleep and being active. At the four-year follow-up, stress showed an adjusted odds ratio of 1.9 (95% CI: 1.3-2.9), while non-restorative sleep and physical inactivity were statistically insignificant. At the one-year follow-up, the interaction between risk factors were significant. The most clear example of this effect modification was to be inactive and not have -restorative sleep, compared to individuals who were active and had restorative sleep, showing an adjusted odds ratio of 6.9 (95% CI: 2.5-19.2) for developing chronic pain one year after baseline. This in comparison of odds ratios for only inactive respectively only non-restorative sleep being 1.7 (95% CI: 0.6-5.3) respectively 1.6 (95% CI: 0.7-3.5). Stress, non-restorative sleep, and physical inactivity were risk factors for developing chronic pain one year after baseline, and stress were also a risk factor four years after baseline. These findings suggest that non-restorative sleep and inactivity are risk factors in the short term while stress is a risk factor in both the short and the long term. In addition to the independent effects of non-restorative sleep and inactivity, their combination seems to further increase the odds of chronic pain.

PurposeTo examine the live birth and other outcomes reported with and without preimplantation genetic testing for aneuploidy (PGT-A) in the United Kingdom (UK) Human Embryology and Fertilization Authority (HFEA) data collection.MethodsA retrospective cohort analysis was conducted following freedom of information (FoI) requests to the HFEA for the PGT-A and non-PGT-A cycle outcomes for 2016–2018. Statistical analysis of differences between PGT-A and non-PGT-A cycles was performed. Other than grouping by maternal age, no further confounders were controlled for; fresh and frozen transfers were included.ResultsOutcomes collected between 2016 and 2018 included total number of cycles, cycles with no embryo transfer, total number of embryos transferred, live birth rate (LBR) per embryo transferred and live birth rate per treatment cycle. Data was available for 2464 PGT-A out of a total 190,010 cycles. LBR per embryo transferred and LBR per treatment cycle (including cycles with no transfer) were significantly higher for all PGT-A vs non-PGT-A age groups (including under 35), with nearly all single embryo transfers (SET) after PGT-A (significantly more in non-PGT-A) and a reduced number of transfers per live birth particularly for cycles with maternal age over 40 years.ConclusionThe retrospective study provides strong evidence for the benefits of PGT-A in terms of live births per embryo transferred and per cycle started but is limited in terms of matching PGT-A and non-PGT-A cohorts (e.g. in future studies, other confounders could be controlled for). This data challenges the HFEA “red traffic light” guidance that states there is “no evidence that PGT-A is effective or safe” and hence suggests the statement be revisited in the light of this and other new data.

Tuberculosis (TB) remains a significant public health concern, particularly in low-resource settings. The treatment outcome is a crucial indicator of the effectiveness of TB treatment programs. Assessing the current treatment outcome and its associated factors is essential for improving patient care and reducing the spread of TB. Therefore, this study aimed to assess TB treatment outcomes and their associated factors among TB patients who received treatment at public healthcare facilities in Motta Town, Northwest Ethiopia. A facility-based retrospective cross-sectional study design was employed in two TB treatment centers in Motta town from January 2017 to December 2021. The study participants were all patients diagnosed with TB who received treatment. A p -value of 0.05 with a 95% confidence interval (CI) was used to determine statistical significance. A total of 362 TB patients were included in the study. The overall treatment success rate was 88.4% (95% CI 85.1, 91.7). Male gender (AOR = 2.40, 95% CI 1.16, 4.98), normal nutritional status (AOR = 3.11, 95% CI 1.33, 7.25), HIV negative status (AOR = 3.35, 95% CI 1.31, 8.60), and non-presumptive drug resistance to TB (AOR = 3.72, 95% CI 1.74, 7.98) were significantly associated with successful TB treatment outcomes ( p  < 0.05). In the current study, nine out of ten study participants had successful TB treatment outcome rates. Male gender, normal nutritional status, non-presumed drug resistance to TB, and HIV-negative status were significantly associated with successful TB treatment outcomes. By taking risk factors associated with poor treatment outcomes like those found in this study into account, patient management and treatment can be optimized. Sufficient TB control measures for populations are imperative and could significantly reduce the nation's total TB burden.

ObjectivesSerous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality.DesignRetrospective multinational study including SCN diagnosed between 1990 and 2014.Results2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16–99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2–200)), 9% had resection beyond 1 year of follow-up (3 years (1–20), size at diagnosis: 25 mm (4–140)) and 39% had no surgery (3.6 years (1–23), 25.5 mm (1–200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1).ConclusionsAfter a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN.Trial registration numberIRB 00006477.

Background: Agents targeting programmed death-1 receptor (PD-1) and its ligand (PD-L1) are showing promising results in non-small-cell lung cancer (NSCLC). It is unknown whether PD-1/PD-L1 are differently expressed in oncogene-addicted NSCLC. Methods: We analysed a cohort of 125 NSCLC patients, including 56 EGFR mutated, 29 KRAS mutated, 10 ALK translocated and 30 EGFR/KRAS/ALK wild type. PD-L1 and PD-1 expression were assessed by immunohistochemistry. All cases with moderate or strong staining (2+/3+) in >5% of tumour cells were considered as positive. Results: PD-1 positive (+) was significantly associated with current smoking status ( P =0.02) and with the presence of KRAS mutations ( P =0.006), whereas PD-L1+ was significantly associated to adenocarcinoma histology ( P =0.005) and with presence of EGFR mutations ( P =0.001). In patients treated with EGFR tyrosine kinase inhibitors ( N =95), sensitivity to gefitinib or erlotinib was higher in PD-L1+ vs PD-L1 negative in terms of the response rate (RR: P =0.01) time to progression (TTP: P <0.0001) and survival (OS: P =0.09), with no difference in PD1+ vs PD-1 negative. In the subset of 54 EGFR mutated patients, TTP was significantly longer in PD-L1+ than in PD-L1 negative ( P =0.01). Conclusions: PD-1 and PD-L1 are differentially expressed in oncogene-addicted NSCLC supporting further investigation of specific checkpoint inhibitors in combination with targeted therapies.

Objectives To compare single-energy (SECT) and dual-energy (DECT) abdominal CT examinations in matched patient cohorts regarding differences in radiation dose and image quality performed with second- and third-generation dual-source CT (DSCT). Methods We retrospectively analysed 200 patients (100 male, 100 female; mean age 61.2 ± 13.5 years, mean body mass index 27.5 ± 3.8 kg/m 2 ) equally divided into four groups matched by gender and body mass index, who had undergone portal venous phase abdominal CT with second-generation (group A, 120-kV-SECT; group B, 80/140-kV-DECT) and third-generation DSCT (group C, 100-kV-SECT; group D, 90/150-kV-DECT). The radiation dose was normalised for 40-cm scan length. Dose-independent figure-of-merit (FOM) contrast-to-noise ratios (CNRs) were calculated for various organs and vessels. Subjective overall image quality and reader confidence were assessed. Results The effective normalised radiation dose was significantly lower ( P  < 0.001) in groups C (6.2 ± 2.0 mSv) and D (5.3 ± 1.9 mSv, P  = 0.103) compared to groups A (8.8 ± 2.3 mSv) and B (9.7 ± 2.4 mSv, P  = 0.102). Dose-independent FOM-CNR peaked for liver, kidney, and portal vein measurements (all P  ≤ 0.0285) in group D. Subjective image quality and reader confidence were consistently rated as excellent in all groups (all ≥1.53 out of 5). Conclusions With both DSCT generations, abdominal DECT can be routinely performed without radiation dose penalty compared to SECT, while third-generation DSCT shows improved dose efficiency. Key Points • Dual-source CT (DSCT) allows for single- and dual-energy image acquisition. • Dual-energy acquisition does not increase the radiation dose in abdominal DSCT. • Third-generation DSCT shows improved dose efficiency compared to second-generation DSCT. • Dose-independent figure-of-merit image contrast was highest with third-generation dual-energy DSCT. • Third-generation DSCT shows improved dose efficiency for SECT and DECT.