OBJECTIVES: To update previous guidelines to score the Cumulative Illness Rating Scale (CIRS) and test their usefulness in hospitalized elderly patients.
DESIGN: The CIRS was scored retrospectively ...in a cohort of elderly patients followed for 18 months.
SETTING: An acute internal medicine ward in an academic tertiary care hospital.
PARTICIPANTS: Three hundred eighty‐seven patients aged 65 and older.
MEASUREMENTS: The CIRS was retrospectively scored for the enrolled patients. Intrarater and interrater reliability were calculated. Two illness severity indices (total score (TSC) and severity (SV)) and one comorbidity index (CM) were obtained. Clinical features and comprehensive geriatric assessment (CGA) variables were also used. All patients underwent an 18‐month follow‐up for mortality and rehospitalization.
RESULTS: Intrarater and interrater reliability of the CIRS scored following the guidelines was good (intraclass correlation coefficients of 0.83 and 0.81, respectively). The TSC, SV, and CM correlated with clinical features (laboratory values, medication usage, and length of in‐hospital stay) and CGA variables (cognitive impairment, depression and disability). All three indices were able to predict 18‐month mortality and rehospitalization rates.
CONCLUSION: This study confirmed the validity of the CIRS as an indicator of health status and demonstrated its ability to predict 18‐month mortality and rehospitalization in hospitalized elderly patients. The availability of detailed guidelines for scoring the CIRS can improve its usefulness and facilitate more‐widespread use for research and clinical aims.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Translocations are being increasingly proposed as a way of conserving biodiversity, particularly in the management of threatened and keystone species, with the aims of maintaining biodiversity and ...ecosystem function under the combined pressures of habitat fragmentation and climate change. Evolutionary genetic considerations should be an important part of translocation strategies, but there is often confusion about concepts and goals. Here, we provide a classification of translocations based on specific genetic goals for both threatened species and ecological restoration, separating targets based on ‘genetic rescue’ of current population fitness from those focused on maintaining adaptive potential. We then provide a framework for assessing the genetic benefits and risks associated with translocations and provide guidelines for managers focused on conserving biodiversity and evolutionary processes. Case studies are developed to illustrate the framework.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract Background Cisplatin-based neoadjuvant chemotherapy (NAC) before cystectomy is the standard of care for muscle-invasive bladder cancer (MIBC), with 25–50% of patients expected to achieve a ...pathologic response. Validated biomarkers predictive of response are currently lacking. Objective To discover and validate biomarkers predictive of response to NAC for MIBC. Design, setting, and participants Pretreatment MIBC samples prospectively collected from patients treated in two separate clinical trials of cisplatin-based NAC provided the discovery and validation sets. DNA from pretreatment tumor tissue was sequenced for all coding exons of 287 cancer-related genes and was analyzed for base substitutions, indels, copy number alterations, and selected rearrangements in a Clinical Laboratory Improvements Amendments–certified laboratory. Outcome measurements and statistical analysis The mean number of variants and variant status for each gene were correlated with response. Variant data from the discovery cohort were used to create a classification tree to discriminate responders from nonresponders. The resulting decision rule was then tested in the independent validation set. Results and limitations Patients with a pathologic complete response had more alterations than those with residual tumor in both the discovery ( p = 0.024) and validation ( p = 0.018) sets. In the discovery set, alteration in one or more of the three DNA repair genes ATM , RB1 , and FANCC predicted pathologic response ( p < 0.001; 87% sensitivity, 100% specificity) and better overall survival ( p = 0.007). This test remained predictive for pathologic response in the validation set ( p = 0.033), with a trend towards better overall survival ( p = 0.055). These results require further validation in additional sample sets. Conclusions Genomic alterations in the DNA repair-associated genes ATM , RB1 , and FANCC predict response and clinical benefit after cisplatin-based chemotherapy for MIBC. The results suggest that defective DNA repair renders tumors sensitive to cisplatin. Patient summary Chemotherapy given before bladder removal (cystectomy) improves the chance of cure for some but not all patients with muscle-invasive bladder cancer. We found a set of genetic mutations that when present in tumor tissue predict benefit from neoadjuvant chemotherapy, suggesting that testing before chemotherapy may help in selecting patients for whom this approach is recommended.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We report the first large-scale exome-wide analysis of the combined germline-somatic landscape in ovarian cancer. Here we analyse germline and somatic alterations in 429 ovarian carcinoma cases and ...557 controls. We identify 3,635 high confidence, rare truncation and 22,953 missense variants with predicted functional impact. We find germline truncation variants and large deletions across Fanconi pathway genes in 20% of cases. Enrichment of rare truncations is shown in BRCA1, BRCA2 and PALB2. In addition, we observe germline truncation variants in genes not previously associated with ovarian cancer susceptibility (NF1, MAP3K4, CDKN2B and MLL3). Evidence for loss of heterozygosity was found in 100 and 76% of cases with germline BRCA1 and BRCA2 truncations, respectively. Germline-somatic interaction analysis combined with extensive bioinformatics annotation identifies 222 candidate functional germline truncation and missense variants, including two pathogenic BRCA1 and 1 TP53 deleterious variants. Finally, integrated analyses of germline and somatic variants identify significantly altered pathways, including the Fanconi, MAPK and MLL pathways.
Abstract The use of a “clock-face” to describe the anterior cruciate ligament femoral tunnel position is fraught with difficulties. Much work has been done to promote “anatomic” anterior cruciate ...ligament femoral tunnel positioning, and more research and clinical follow-up studies are necessary to further clarify this concept.
IMPORTANCE: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a spectrum of severe mucocutaneous drug reaction associated with significant morbidity and mortality. A previously ...developed SJS/TEN-specific severity-of-illness model (Score of Toxic Epidermal Necrolysis SCORTEN) has been reported to overestimate and underestimate SJS/TEN-related in-hospital mortality in various populations. OBJECTIVE: To derive a risk prediction model for in-hospital mortality among patients with SJS/TEN and to compare prognostic accuracy with the SCORTEN model in a multi-institutional cohort of patients in the United States. DESIGN, SETTING, AND PARTICIPANTS: Data from a multicenter cohort of patients 18 years and older treated for SJS/TEN between January 1, 2000, and June 1, 2015, were obtained from inpatient consult databases and electronic medical record systems at 18 medical centers in the United States as part of the Society for Dermatology Hospitalists. A risk model was derived based on data from 370 of these patients. Model discrimination (calculated as area under the receiver operating characteristic curve AUC) and calibration (calculated as predicted vs observed mortality, and examined using the Hosmer-Lemeshow goodness-of-fit statistic) were assessed, and the predictive accuracy was compared with that of SCORTEN. All analysis took place between December 2016 and April 2018. MAIN OUTCOMES AND MEASURES: In-hospital mortality. RESULTS: Among 370 patients (mean SD age 49.0 19.1 years; 195 52.7% women), 54 (15.14%) did not survive to hospital discharge. Five covariates, measured at the time of admission, were independent predictors of in-hospital mortality: age in years (odds ratio OR, 1.05; 95% CI, 1.02-1.07), body surface area (BSA) in percentage of epidermal detachment (OR, 1.02; 95% CI, 1.01-1.04), serum bicarbonate level below 20 mmol/L (OR, 2.90; 95% CI, 1.43-5.88), active cancer (OR, 4.40; 95% CI, 1.82-10.61), and dialysis prior to admission (OR, 15.94; 95% CI, 3.38-66.30). A severity-of-illness score was calculated by taking the sum of 1 point each for age 50 years or older, epidermal detachment greater than 10% of BSA, and serum bicarbonate level below 20 mmol/L; 2 points for the presence of active cancer; and 3 points for dialysis prior to admission. The score was named ABCD-10 (age, bicarbonate, cancer, dialysis, 10% BSA). The ABCD-10 model showed good discrimination (AUC, 0.816; 95% CI, 0.759-0.872) and calibration (Hosmer-Lemeshow goodness of fit test, P = .30). For SCORTEN, on admission, the AUC was 0.827 (95% CI, 0.774-0.879) and was not significantly different from that of the ABCD-10 model (P = .72). CONCLUSIONS AND RELEVANCE: In this cohort of patients with SJS/TEN, ABCD-10 accurately predicted in-hospital mortality, with discrimination that was not significantly different from SCORTEN. Additional research is needed to validate ABCD-10 in other populations. Future use of a new mortality prediction model may provide improved prognostic information for contemporary patients, including those enrolled in observational studies and therapeutic trials.
Autism spectrum disorder (ASD) is categorized by deficits in social communication and interaction, alongside repetitive, restrictive behaviors or interests (RRBIs). Previous research supports the ...efficacy of virtual reality (VR) to train a variety of specific skills (i.e., riding a bus or crossing the street) as well as more complex social skills, such as emotion recognition and functional communication. The present reports the implementation of a VR-based air travel functional communication activity in five children diagnosed with ASD. Using an iPhone X and
device, researchers delivered the VR intervention once per week for 3 weeks to each participant. During these interventions, researchers measured activity completion ability on a 4-point scale. At week 4, all children participated in a real-world air travel rehearsal at the San Diego International Airport. Parents were asked to rate their child's air travel abilities before week 1 and after week 4. All children improved their air travel skills from pre- to postintervention, reflected in both the researchers' and parents' observations. All children navigated the real-world airport under their own power. This preliminary report suggests the efficacy of VR to teach basic air travel skills to young children diagnosed with autism. Clinician observations regarding attention to the VR and strategies for helping participants accept the intervention technique are discussed. Future iterations of this program will require larger sample sizes and more robust clinical measurements-such as communication samples and physiological monitoring.
Asthma has been associated with increased cardiovascular disease (CVD) risk. The authors ascertained the association of asthma with CVD and the roles that sex, concurrent allergy, and asthma ...medications may play in this association. They assembled a cohort of 203,595 Northern California adults with asthma and a parallel asthma-free referent cohort (matched 1:1 on age, sex, and race/ethnicity); both cohorts were followed for incident nonfatal or fatal CVD and all-cause mortality from January 1, 1996, through December 31, 2008. Each cohort was 66% female and 47% white. After adjustment for age, sex, race/ethnicity, cardiac risk factors, and comorbid allergy, asthma was associated with a 1.40-fold (95% confidence interval (CI): 1.35, 1.45) increased hazard of coronary heart disease, a 1.20-fold (95% CI: 1.15, 1.25) hazard of cerebrovascular disease, a 2.14-fold (95% CI: 2.06, 2.22) hazard of heart failure, and a 3.28-fold (95% CI: 3.15, 3.41) hazard of all-cause mortality. Stronger associations were noted among women. Comorbid allergy predicted CVD but did not synergistically increase the CVD risk associated with asthma. Only asthma patients using asthma medications (particularly those on oral corticosteroids alone or in combination) were at enhanced risk of CVD. In conclusion, asthma was prospectively associated with increased risk of major CVD. Modifying effects were noted for sex and asthma medication use but not for comorbid allergy.
Dramatic pigmentation changes have evolved within most vertebrate groups, including fish and humans. Here we use genetic crosses in sticklebacks to investigate the parallel origin of pigmentation ...changes in natural populations. High-resolution mapping and expression experiments show that light gills and light ventrums map to a divergent regulatory allele of the
Kit ligand (
Kitlg) gene. The divergent allele reduces expression in gill and skin tissue and is shared by multiple derived freshwater populations with reduced pigmentation. In humans, Europeans and East Asians also share derived alleles at the
KITLG locus. Strong signatures of selection map to regulatory regions surrounding the gene, and admixture mapping shows that the
KITLG genomic region has a significant effect on human skin color. These experiments suggest that regulatory changes in
Kitlg contribute to natural variation in vertebrate pigmentation, and that similar genetic mechanisms may underlie rapid evolutionary change in fish and humans.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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