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Birth weight of a child is an important indicator of its vulnerability for childhood illness and chances of survival. A large number of infant deaths can be averted by appropriate management of low birth weight babies and prevention of factors associated with low birth weight. The prevalence of low birth weight babies in Nepal is estimated to be about 12-32%.Our study aimed at identifying major determinants of low birth weight among term babies in Nepal. A hospital-based retrospective case control study was conducted in maternity ward of Tribhuvan University Teaching Hospital from February to July 2011. A total of 155 LBW babies and 310 controls were included in the study. Mothers admitted to maternity ward during the study period were interviewed, medical records were assessed and anthropometric measurements were done. Risk factors, broadly classified into proximal and distal factors, were assessed for any association with birth of low-birth weight babies. Regression analysis revealed that a history of premature delivery (adjusted odds ratio; aOR5.24, CI 1.05-26.28), hard physical work during pregnancy (aOR1.48, CI 0.97-2.26), younger age of mother (aOR1.98, CI 1.15-3.41), mothers with haemoglobin level less than 11gm/dl (aOR0.51, CI0.24-1.07) and lack of consumption of nutritious food during pregnancy (aOR1.99, CI 1.28-3.10) were significantly associated with the birth of LBW babies. These factors should be addressed with appropriate measures so as to decrease the prevalence of low birth weight among term babies in Nepal.

Data on the efficacy and safety of interferon (IFN)-α for the treatment of essential thrombocythemia (ET) and polycythemia vera (PV) are inconsistent. We conducted a systematic review and meta-analysis and searched MEDLINE and EMBASE via Ovid, Scopus, COCHRANE registry of clinical trials, and Web of Science from inception through 03/2019 for studies of pegylated IFN (peg-IFN) and non-pegylated IFN (non-peg-IFN) in PV and ET patients. Random-effects models were used to pool response rates for the primary outcome of overall response rate (ORR) defined as a composite of complete response, partial response, complete hematologic response (CHR) and partial hematologic response. Peg-IFN and non-peg-IFN were compared by meta-regression analyses. In total, 44 studies with 1359 patients (730 ET, 629 PV) were included. ORR were 80.6% (95% confidence interval: 76.6–84.1%, CHR: 59.0% [51.5%–66.1%]) and 76.7% (67.4–84.0%; CHR: 48.5% [37.8–59.4%]) for ET and PV patients, respectively. In meta-regression analyses results did not differ significantly for non-peg-IFN vs. peg-IFN. Annualized rates of thromboembolic complications and treatment discontinuation due to adverse events were low at 1.2% and 8.8% for ET and 0.5% and 6.5% for PV patients, respectively. Both peg-IFN and non-peg-IFN can be effective and safe long-term treatments for ET and PV.

Introduction: Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare entity with no standard of care and high mortality, despite the use of plasma exchange. Methods: Using specific search terms, all cases having TA-TMA treated with eculizumab and indexed in MEDLINE (English language only) by November 2014 were reviewed. Results: A total of 26 cases, 53% men, had a median age of 33 years (range 2-61). Transplant-associated thrombotic microangiopathy occurred after stem-cell transplant (35%) or solid-organ transplant (65%), frequently associated with the use of cyclosporine or tacrolimus (96%). A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS 13) level was always >10%. After TA-TMA diagnosis, the following drug adjustments were made: discontinuation of cyclosporine or tacrolimus in 45%, dose reduction in another 27%, continuation of the drugs in 23%, and switch from cyclosporine to tacrolimus in remaining 5%. Plasma exchange was performed in ∼43%. The median interval between transplant and initiation of eculizumab was 63 days (range 11-512). A median of 5.5 doses (range 2-21) of eculizumab was utilized with 92% response occurring after a median of 2 doses (range 1-18). At a median follow-up of 52 weeks (range 3-113), the survivors (92%) were doing well. Conclusion: Within the limits of this retrospective analysis, our study demonstrates that eculizumab use may result in high response rate and 1-year survival in patients with TA-TMA refractory to discontinuation of calcineurin inhibitor and plasma exchange.

PARP inhibitors target BRCA mutations and defective homologous recombination repair (HRR) for the treatment of epithelial ovarian cancer (EOC). However, the treatment of HRR-proficient EOC with PARP inhibitors remains challenging. The objective of this study was to determine whether the combination of triapine (ribonucleotide reductase inhibitor), cediranib (vascular endothelial growth factor receptor tyrosine kinase inhibitor), and the PARP inhibitor olaparib synergized against BRCA wild-type and HRR-proficient EOC in xenograft mouse models. In addition, the mechanisms by which cediranib augmented the efficacy of triapine and olaparib were investigated. BRCA-wild type and PARP inhibitor-resistant EOC cell lines were implanted subcutaneously (s.c.) into nude mice or injected intraperitoneally (i.p.) into SCID-Beige mice. Mice were then treated i.p. with olaparib, cediranib, triapine, various double and triple combinations. The volume of s.c tumor in nude mice and the abdominal circumference of SCID-Beige mice were measured to evaluate the effectiveness of the treatment to delay tumor growth and prolong the survival time of mice. In both xenograft mouse models, the combination of triapine, olaparib and cediranib resulted in marked suppression of BRCA-wild type EOC growth and significant prolongation of the survival time of mice, with efficacy greater than any double combinations and single drugs. Furthermore, we identified that cediranib abrogated pro-survival and anti-apoptotic AKT signaling, thereby enhancing the efficacy of triapine and olaparib against BRCA-wild type EOC cells. Taken together, our results demonstrate a proof-of-principle approach and the combination regiment holds promise in treating BRCA-wild type and PARP inhibitor-resistant EOC.

Background Computed tomography (CT) scans are routinely obtained in oncology and provide measures of muscle and adipose tissue predictive of morbidity and mortality. Automated segmentation of CT has advanced past single slices to multi‐slice measurements, but the concordance of these approaches and their associations with mortality after cancer diagnosis have not been compared. Methods A total of 2871 patients with colorectal cancer diagnosed during 2012–2017 at Kaiser Permanente Northern California underwent abdominal CT scans as part of routine clinical care from which mid‐L3 cross‐sectional areas and multi‐slice T12–L5 volumes of skeletal muscle (SKM), subcutaneous adipose (SAT), visceral adipose (VAT) and intermuscular adipose (IMAT) tissues were assessed using Data Analysis Facilitation Suite, an automated multi‐slice segmentation platform. To facilitate comparison between single‐slice and multi‐slice measurements, sex‐specific z‐scores were calculated. Pearson correlation coefficients and Bland–Altman analysis were used to quantify agreement. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for death adjusting for age, sex, race/ethnicity, height, and tumour site and stage. Results Single‐slice area and multi‐slice abdominal volumes were highly correlated for all tissues (SKM R = 0.92, P < 0.001; SAT R = 0.97, P < 0.001; VAT R = 0.98, P < 0.001; IMAT R = 0.89, P < 0.001). Bland–Altman plots had a bias of 0 (SE: 0.00), indicating high average agreement between measures. The limits of agreement were narrowest for VAT ( ± 0.42 SD) and SAT ( ± 0.44 SD), and widest for SKM ( ± 0.78 SD) and IMAT ( ± 0.92 SD). The HRs had overlapping CIs, and similar magnitudes and direction of effects; for example, a 1‐SD increase in SKM area was associated with an 18% decreased risk of death (HR = 0.82; 95% CI: 0.72–0.92), versus 15% for volume from T12 to L5 (HR = 0.85; 95% CI: 0.75–0.96). Conclusions Single‐slice L3 areas and multi‐slice T12–L5 abdominal volumes of SKM, VAT, SAT and IMAT are highly correlated. Associations between area and volume measures with all‐cause mortality were similar, suggesting that they are equivalent tools for population studies if body composition is assessed at a single timepoint. Future research should examine longitudinal changes in multi‐slice tissues to improve individual risk prediction.

Background The European Working Group on Sarcopenia in Older People (EWGSOP) recommends SARC‐F as a tool for identifying sarcopenia among older adults. However, the role of SARC‐F among older adults with cancer remains unexplored. We aimed to evaluate the diagnostic utility of SARC‐F to identify those with sarcopenia, or low muscle mass (using skeletal muscle index [SMI]), and myosteatosis (using skeletal muscle density [SMD]) from computed tomography (CT) imaging and the association of SARC‐F with all‐cause mortality. Methods Older adults (≥60 years) presenting for initial consultation at UAB medical oncology clinic who underwent geriatric assessment were enrolled in a prospective cohort study. We identified study participants who completed SARC‐F screening and had available CT imaging within 60 days of study enrollment. Using single‐slice CT images at the L3 vertebral level, we computed SMI and SMD using published methods. Sarcopenia and myosteatosis were defined using published cutpoints. We calculated the sensitivity and specificity of SARC‐F for detecting low muscle mass and low muscle density using published thresholds. Finally, we computed the impact of SARC‐F and CT measures on overall survival using Kaplan–Meier curves and Cox regression models, after adjusting for age, sex, cancer type, and cancer stage. Results We identified 212 older adults with a median age of 68.8 years; with 60.8% males, 76.6% whites, and pancreatic cancer (21.2%) being the most common malignancy. In the overall cohort, 30.7% had abnormal SARC‐F using published cutpoints. SARC‐F ≥ 4 had a sensitivity of 35% and a specificity of 76% to identify low muscle mass. SARC‐F ≥ 4 had a sensitivity of 38% and a specificity of 74% to identify low muscle density. Those with SARC‐F ≥ 4 and low SMI/SMD had worse survival compared to those with low SMI/SMD alone. Incorporating SARC‐F improved survival prognostication beyond SMI and SMD (HR = 3.1; p < 0.001; Harrel's C from 0.73 to 0.76). Conclusions SARC‐F as a screening tool has limited diagnostic utility for identifying older adults with low muscle mass and/or density. However, SARC‐F retains prognostic value independent of CT‐based muscle measures in predicting mortality among older adults with cancer. Patient‐reported measures such as SARC‐F have been used to identify sarcopenia in community‐dwelling adults, but the utility of SARC‐F to identify sarcopenia and myosteatosis among older adults with cancer remains unknown. Herein, we show that SARC‐F and computed tomography analysis identify distinct populations, and they can be used together to better predict overall survival among older adults with cancer.

Background Low skeletal muscle mass (LSMM) and/or, function associated with an increased risk of treatment‐related toxicities and inferior overall survival (OS) among adults with solid malignancies. However, the association between LSMM and treatment‐related toxicities among adults with haematologic malignancies remains unclear. Methods Using a pre‐published protocol (CRD42020197814), we searched seven bibliographic databases from inception to 08/2021 for studies reporting the impact of LSMM among adults ≥18 years with a known haematologic malignancy. The primary outcome of interest was OS, and secondary outcomes included progression free survival (PFS) and non‐relapse mortality (NRM). These effect sizes were quantified in terms of hazards ratio (HR) along with 95% confidence interval (CI) and pooled across studies using a DerSimonian–Laird random‐effects model. Heterogeneity was assessed using the Cochran's Q and the I2 statistic. All hypothesis testing was two‐sided with an alpha of 0.05. Results Of 3791 studies screened, we identified 20 studies involving 3468 patients with a mean age of 60 years; 44% were female and the most common malignancy was diffuse large B‐cell lymphoma (42%). Most studies measured muscle mass using single slice computed tomography imaging at the L3 level. The presence of LSMM was associated with worse OS (pooled HR = 1.81, 95% CI = 1.48–2.22, P < 0.001) with moderate heterogeneity (Cochran's Q, I2 = 60.4%), PFS (pooled HR = 1.61, 95% CI = 1.28–2.02, P < 0.001) with moderate heterogeneity (Cochran's Q, I2 = 66.0%). Similarly, LSMM was associated with worse NRM (HR = 1.72, 95% CI = 1.34–2.22, P < 0.001) with little evidence of heterogeneity (Cochran's Q, I2 = 0.0%). Conclusions LSMM is associated with worse survival outcomes among adults with haematologic malignancies. Further research into understanding the underlying mechanism of this association and mitigating the negative effects of LSMM among adults with haematologic malignancies is needed.

Multiple myeloma (MM) is an incurable blood cancer that primarily affects older adults. Several frailty tools have been developed to address the heterogeneity of aging in this population. Uptake of these measures has been variable, leading to a gap in knowledge regarding the proportion of enrolled trial participants considered frail and uncertainty in the treatment-related effects and outcomes among this high-risk population. We performed a systematic review of therapeutic interventional MM clinical trials reporting on frailty. We included 43 clinical trials (24 randomized controlled trials and 19 non-randomized trials) which met eligibility criteria. Frailty was increasingly incorporated in studies in more recent years with 41.9% of included studies being reported in the last two years. Commonly used frailty tools included the International Myeloma Working Group (IMWG) frailty index (41.8%), and the simplified frailty score (39.5%). Frailty status was categorized with 3 levels as (frail, intermediate fit, or fit) in 51.2% of the studies and dichotomized (frail, non-frail) in 18.6% of studies. Frailty prevalence greatly varied across trials ranging from 17.2% to 73.6% of the cohort. Of the included studies, 72.0% conducted subgroup analysis (planned or post-hoc) based on frailty status. Most studies demonstrated a consistent benefit of MM interventions among the frail and non-frail populations, however in general, frail patients had worse outcomes compared to the fit. Although frailty is increasingly being incorporated in MM clinical trials, due to the variation in both the definition and categorization of frailty, there remains heterogeneity in the prevalence of frailty and its potential associated impact on outcomes.

Abstract Background Poor self-rated health (SRH) is a known predictor of frailty and mortality in the general population; however, its role among older adults with cancer is unknown. We evaluated the role of SRH as a potential screening tool to identify frailty and geriatric assessment (GA)-identified impairments. Materials and Methods Adults ≥60 years diagnosed with cancer in the UAB Cancer & Aging Resilience Evaluation (CARE) registry underwent a GA at the time of initial consultation. We measured SRH using a single-item from the Patient-Reported Outcomes Measurement Information System global health scale and dichotomized responses as poor (poor, fair) and good (good, very good, and excellent). We evaluated the diagnostic performance of SRH in measuring frailty, and GA impairment (≥2 deficits among a set of seven GA domains). We examined the impact of SRH with survival using a Cox model adjusting for confounders, exploring the mediating role of frailty. Results Six hundred and three older adults with cancer were included, with a median age of 69 years. Overall, 45% (n = 274) reported poor SRH. Poor SRH demonstrated high sensitivity and specificity for identifying frailty (85% and 78%, respectively) and GA impairment (75% and 78%, respectively). In a Cox regression model, poor SRH was associated with inferior survival (HR = 2.26; 95% CI 1.60-3.18) after adjusting for confounders; frailty mediated 69% of this observed relationship. Conclusion Self-rated health may be used as a screening tool to identify older adults with cancer with frailty and GA impairments. Poor SRH is associated with inferior survival, which is mediated by frailty. This article evaluates the role of self-rated health as a potential screening tool to identify frailty and geriatric assessment-identified impairments.