Effectiveness and Safety of the European Society of Cardiology 0-/1-h Troponin Rule-Out Protocol: The Design of the ESC-TROP Multicenter Implementation Study.

Chest pain is one of the most common complaints at the emergency department (ED), and it is commonly the perceived likelihood of acute coronary syndrome (ACS) that drives management. Guidelines from the European Society of Cardiology (ESC) recommend the use of a 0-/1-h high-sensitivity cardiac troponin T (hs-cTnT) protocol to rule out or in ACS, but this is mostly based on observational studies. The aim of the ESC-TROP trial is to determine the safety and effectiveness of the ESC 0-/1-h hs-cTnT protocol when implemented in routine care. Adult chest pain patients at 5 EDs in the Skåne Region, Sweden, are included in the trial. The 0-/1-h hs-cTnT ESC protocol supplemented with clinical assessment and electrocardiography (ECG) is implemented at 3 EDs, and the other 2 EDs act as concurrent controls. Outcomes will be evaluated during the 10 months after the implementation and the corresponding 10 months of the previous year. The 2 co-primary outcomes are (a) acute myocardial infarction (AMI) and all-cause death within 30 days in patients discharged from the ED, and (b) ED length of stay of the same patients. Secondary outcomes include the proportion of chest pain patients discharged from the ED and the number of ruled-out patients undergoing objective testing within 30 days. The ESC-TROP trial will determine the performance and applicability of the 0-/1-h hs-cTnT ESC protocol supplemented with clinical assessment and ECG when implemented in routine ED care. It will provide evidence whether 0-/1-h hs-cTnT testing is safe, effective, and feasible, and whether widespread implementation as recommended by ESC guidelines should be supported.

Cancer chromosome breakpoints cluster in gene-rich genomic regions.

Cancer cells are characterized by chromosome abnormalities, of which some, in particular balanced rearrangements, are associated with distinct tumor entities and/or with specific gene rearrangements that represent important steps in the carcinogenic process. However, the vast majority of cytogenetically detectable structural aberrations in cancer cells have not been characterized at the nucleotide level; hence, their importance and functional consequences are unknown. By ascertaining the chromosomal breakpoints in 22 344 different clonal structural chromosome abnormalities identified in the karyotypes of 49 626 cases of neoplastic disorders we here show that the distribution of breakpoints is strongly associated (P < 0.0001) with gene content within the affected chromosomal bands. This association also remains highly significant in separate analyses of recurrent and nonrecurrent chromosome abnormalities as well as of specific subtypes of cancer (P < 0.0001 for all comparisons). In contrast, the impact of band length was negligible. The breakpoint distribution is thus not stochastic-gene-rich regions are preferentially affected. Several genomic features relating to transcription, replication, and chromatin organization have been found to enhance chromosome breakage frequencies; this indicates that gene-rich regions may be more break-prone. The salient finding in the present study is that a substantial fraction of all structural chromosome abnormalities, not only those specifically associated with certain tumor types, may affect genes that are pathogenetically important. If this interpretation is correct, then the prevailing view that the great majority of cancer chromosome aberrations is cytogenetic noise can be seriously questioned.

Most gene fusions in cancer are stochastic events.

Cancer-associated gene fusions resulting in chimeric proteins or aberrant expression of one or both partner genes are pathogenetically and clinically important in several hematologic malignancies and solid tumors. Since the advent of different types of massively parallel sequencing (MPS), the number of identified gene fusions has increased dramatically, prompting the question whether they all have a biologic impact. By ascertaining the chromosomal locations of 8934 genes involved in 10 861 gene fusions reported in the literature, we here show that there is a highly significant association between gene content of chromosomes and chromosome bands and number of genes involved in fusions. This strongly suggests that a clear majority of gene fusions detected by MPS are stochastic events associated with the number of genes available to participate in fusions and that most reported gene fusions are passengers without any pathogenetic importance.

Increasing colorectal cancer incidence in individuals aged < 50 years-a population-based study.

PURPOSE: Data on the incidence of colorectal cancer (CRC) is conflicting, and it is unknown if the incidence is constant, declining, or increasing. Proximal colon cancer is considered to be more common among older individuals, but recent data have shown that rectal cancer and distal colon cancer have been increasing in the younger population. The aim of this study was to determine the trends regarding CRC incidence and tumour location in Sweden. METHODS: CRC statistics from the National Board of Health and Welfare 1995-2015 were used. CRC incidence rates by age group (< 50 years, 50-79 years, ≥ 80 years), sex, and tumour localisation (proximal colon, distal colon, or rectum) were calculated and analysed using Poisson regression. RESULTS: The age-standardised incidence of CRC increased in Sweden during the study period. This increase was significant (P < 0.0001) for colon cancer during the study period for all age groups regardless of tumour localisation. The greatest increase (27-52% per decade) in the colon cancer incidence rate was seen among men and women < 50 years of age. The incidence rate for rectal cancer increased for men < 50 years (P < 0.0001), decreased for both men and women aged ≥ 80 years (P < 0.005), and did not change for the remaining groups. CONCLUSIONS: The CRC incidence in Sweden, in particular colon cancer, is increasing regardless of tumour localisation for individuals < 50 years of age. This paper supports the implementation of population-based colorectal cancer screening. A diagnostic workup should be performed in symptomatic individuals < 50 years of age.

Midlife development of type 2 diabetes and hypertension in women by history of hypertensive disorders of pregnancy.

BACKGROUND: Women with history of hypertensive disorders of pregnancy (HDP) are at increased risk of early onset cardiovascular disease and type 2 diabetes (T2D). We aimed to investigate the extent to which HDP is also associated with midlife development of T2D and hypertension above and beyond established risk factors. METHODS: We included parous women who attended population-based structured clinical visits at age 50 and 60 years in Sweden 1991-2013 (N = 6587). Women with prior diabetes mellitus, stroke, or ischemic heart disease at age 50 years were excluded. Data on reproductive history were collected from registries. To study the association between history of HDP and the between-visits development of T2D, hypertension, and clinical risk factors of cardiometabolic disease (body mass index (BMI), blood pressure, and total cholesterol), we utilized multivariable adjusted regression models (logistic, log binomial, and linear regression, respectively). Models included data on outcome risk factors at age 50 years, e.g. BMI, 75 g 2 h oral glucose tolerance test result, and mean arterial pressure, respectively. RESULTS: Between ages 50 and 60 years, 5.8% of initially disease-free women developed T2D and 31.6% developed hypertension. History of HDP was associated with increased risk of developing T2D between age 50 and 60 years even when adjusting for risk factors, including BMI, at age 50 years (odds ratio (OR) 1.96, 95% confidence interval (CI) 1.29-2.98). By contrast, the higher risk of developing hypertension observed in women with history of HDP (relative risk (RR) 1.47, 95% CI 1.22-1.78) was attenuated when adjusted for risk factors (RR 1.09, 95% CI 0.94-1.25). Participants with a history of HDP had higher mean BMI and blood pressure at age 50 years, with levels roughly corresponding to those observed at age 60 years in unaffected women. CONCLUSIONS: Women with history of HDP are not only at higher risk of cardiometabolic disease during their reproductive years, but HDP is also associated with midlife T2D development above and beyond established risk factors.

The value of pregnancy complication history for 10-year cardiovascular disease risk prediction in middle-aged women.

Women with a history of hypertensive disorders of pregnancy (HDP; preeclampsia and gestational hypertension) or delivering low birth weight offspring (LBW; < 2500 g) have twice the risk of cardiovascular disease (CVD). We aimed to study the extent to which history of these pregnancy complications improves CVD risk prediction above and beyond conventional predictors. Parous women attended standardized clinical visits in Sweden. Data were linked to registries of deliveries and CVD. Participants were followed for a first CVD event within 10 years from age 50 (n = 7552) and/or 60 years (n = 5360) and the predictive value of each pregnancy complication above and beyond conventional predictors was investigated. History of LBW offspring was associated with increased risk of CVD when added to conventional predictors in women 50 years of age [Hazard ratio 1.68, 95% Confidence interval (CI) 1.19, 2.37] but not at age 60 (age interaction p = 0.04). However, at age 50 years CVD prediction was not further improved by information on LBW offspring, except that a greater proportion of the women who developed CVD were assigned to a higher risk category (categorical net reclassification improvement for events 0.038, 95% CI 0.003, 0.074). History of HDP was not associated with CVD when adjusted for reference model predictors. In conclusion, a history of pregnancy complications can identify women with increased risk of CVD midlife. However, considered with conventional risk factors, history of HDP or having delivered LBW offspring did not meaningfully improve 10-year CVD risk prediction in women age 50 years or older.

Sperm DNA fragmentation index and cumulative live birth rate in a cohort of 2,713 couples undergoing assisted reproduction treatment.

OBJECTIVE: To study how the choice of the first assisted reproductive technology treatment type affects the cumulative live birth rate (CLBR) in couples with high sperm DNA fragmentation index (DFI). DESIGN: Longitudinal cohort study. SETTING: University-affiliated fertility clinic. PATIENT(S): A total of 2,713 infertile couples who underwent assisted reproductive technology treatment between 2007 and 2017 were included in the study. All in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments (up to three fresh treatments and all associated frozen-thawed embryo transfers) offered to the couples by the public health care system were included, in total 5,422 cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was the CLBR. The secondary outcomes were the fertilization rate and the miscarriage rate. The IVF and ICSI groups were defined according to the method applied in the first treatment cycle. RESULT(S): In the IVF group, the CLBR values were higher for couples with normal DFI compared with those for couples with high DFI (≥20%) (48.1% vs. 41.6% for conservative CLBR estimate and 55.6% vs. 51.4% for optimal CLBR estimate after adjustment for female age, respectively). No DFI-dependent difference was seen in the ICSI group. CONCLUSION(S): Our results demonstrated that a high DFI predicts a statistically significantly lower CLBR if IVF and not ICSI is applied in the first cycle of assisted reproduction.

Low-Dose Oral Ketamine for Procedural Analgesia in Pediatric Cancer Patients Undergoing Lumbar Puncture at a Resource-Limited Cancer Hospital in India.

Aim: The aim of this study was to evaluate the therapeutic efficacy and safety profile of orally administered low-dose ketamine for procedural pain management in pediatric cancer patients undergoing lumbar puncture (LP) in a resource-limited hospital setting. Methods: Patients between 4 and 15 years of age, with leukemia, undergoing LP were asked to participate. The study was designed as a two-armed blinded placebo-controlled trial where 0.8 mg/kg (bodyweight) of ketamine mixed in juice was given 30 minutes before the procedure to Group K (ketamine) compared with placebo, only juice, to Group P (placebo). In addition, topical analgesia (EMLA®) was given according to established standard of care. Patients and caregivers assessed the pain using the Wong-Baker Faces Pain Rating Scale. Results: A total number of 52 patients, equally distributed between Group K and Group P, were included in the study. The placebo-controlled group had significantly higher self-reported pain score than the group receiving ketamine (p = 0.046), as well as in caregiver-assessed pain (p = 0.033). Only three incidents of mild adverse effects were reported. Conclusion: Low-dose oral ketamine can be safely administered for procedural analgesia in pediatric cancer patients undergoing LP in a resource-limited hospital setting and have significant pain-reducing effect compared with placebo.

A potential benefit from infectious disease specialist and stationary ward in rational antibiotic therapy of complicated skin and skin structure infections.

BACKGROUND: Management practices of complicated skin and skin structure infections (cSSSI) were compared between two areas with similar healthcare structure and low prevalence of antimicrobial resistance. METHODS: The high affinity to public health-care in the Nordic countries enabled population-based approach used in this retrospective study. The study population (n = 460) consisted of all adult residents from Helsinki (Finland) and Gothenburg (Sweden) treated in hospital due to cSSSI during 2008-2011. RESULTS: The majority of patients in Helsinki (57%) visited more than one ward during their hospital stay while in Gothenburg the majority of patients (85%) were treated in one ward only. Background and disease characteristics were largely similar in both cities but patients in Helsinki were younger [mean(SD) 59(18) versus 63(19) years, p = .0117], and greater proportions had diabetes (50% versus 32%, p < .0001) and polymicrobial infections (34% versus 13%, p < .0001). Patients in Helsinki received antimicrobials with Gram-negative coverage (in initial therapy 96%) more frequently than in Gothenburg (47%, p < .0001), had more treatment modifications (mean 4.3 versus 2.7 antibiotic agents used per patient, p < .0001), and longer median duration of antimicrobial therapy (29 versus 12 days, p < .0001) and median length of hospital stay (17 versus 11 days, p < .0001). CONCLUSIONS: This real-life study revealed remarkable differences in the management of cSSSI between the two Nordic cities. Compared to mainly Infectious Disease Specialist guided treatment in Gothenburg, the more frequent transfer from one ward to another in Helsinki was linked to longer antimicrobial therapy and hospital stay and to more frequent changes in antimicrobial treatment.

Vibration thresholds in carpal tunnel syndrome assessed by multiple frequency vibrometry: a case-control study.

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common compression neuropathy, but there is no gold standard for establishing the diagnosis. The ability to feel vibrations in the fingertips is dependent on the function in cutaneous receptors and afferent nerves. Our aim was to investigate vibration perception thresholds (VPTs) in patients with CTS using multi-frequency vibrometry. METHODS: Sixty-six patients (16 men and 50 women) with CTS, diagnosed from clinical signs and by electroneurography, and 66 matched healthy controls were investigated with multi-frequency vibrometry. The VPTs were assessed at seven frequencies (8, 16, 32, 64, 125, 250, and 500 Hz) in the index finger and little finger bilaterally. The severity of the CTS was graded according to Padua and the patient's subjective symptoms were graded according to the Boston carpal tunnel questionnaire. Touch thresholds were assessed using the Semmes-Weinstein monofilaments. RESULTS: Patients with CTS had significantly higher VPTs at all frequencies in the index finger and in 6 out of 7 frequencies in the little finger compared to the controls. However, the VPT was not worse in patients with more severe CTS. Patients with unilateral CTS showed significantly higher VPTs in the affected hand. There were no correlations between VPTs and electrophysiological parameters, subjective symptoms, or touch threshold. CONCLUSIONS: Patients with CTS had impaired VPTs at all frequencies compared to the controls. Since the VPTs are dependent on function in peripheral receptors and their afferent nerves, multi-frequency vibrometry could possibly lead to diagnosis of CTS.

Self-referral psychological treatment centre for young adults: a 2-year observational evaluation of routine practice before and after treatment.

OBJECTIVES: To examine a self-referral psychological service provided to young adults with regard to effects on anxiety, depression and psychological distress and to explore client factors predicting non-adherence and non-response. DESIGN: Observational study over a 2-year period. SETTING: Young Adults Centre providing psychological services by self-referral (preprimary care) to Linköping, Åtvidaberg, and Kinda municipalities (combined population 145,000) in Östergötland county, Sweden. PARTICIPANTS: 607 young adults (16-25 years of age); 71% females (n=429). INTERVENTION: Individually scheduled cognitive behavioural therapy delivered in up to six 45 min sessions structured according to an assessment of the client's mental health problems: anxiety, depression, anxiety and depression combined, or decreased distress without specific anxiety or depression. PRIMARY OUTCOME MEASURES: Pre-post intervention changes in psychological distress (General Health Questionnaire-12, GHQ-12), Hospital Anxiety and Depression Scale Anxiety/Depression (HADS-A/D). RESULTS: 192 clients (32.5%) discontinued the intervention on their own initiative and 39 clients (6.6%) were referred to a psychiatric clinic during the course of the intervention. Intention-to-treat analyses including all clients showed a medium treatment effect size (d=0.64) with regard to psychological distress, and small effect sizes were observed with regard to anxiety (d=0.58) and depression (d=0.57). Restricting the analyses to clients who adhered to the agreed programme, a large effect size (d=1.26) was observed with regard to psychological distress, and medium effect sizes were observed with regard to anxiety (d=1.18) and depression (d=1.19). Lower age and a high initial HADS-A score were the strongest risk factors for non-adherence, and inability to concentrate and thinking of oneself as a worthless person increased the risk for discontinuation. CONCLUSIONS: We conclude that provision of psychological services to young people through a self-referral centre has potential to improve long-term mental health in communities, but management of non-adherence remains a central challenge.