Tag: nevin manimala

Int J Epidemiol. 2021 Mar 23:dyab036. doi: 10.1093/ije/dyab036. Online ahead of print.

ABSTRACT

BACKGROUND: Rigorous evaluation of the calibration and discrimination of breast-cancer risk-prediction models in prospective cohorts is critical for applications under clinical guidelines. We comprehensively evaluated an integrated model incorporating classical risk factors and a 313-variant polygenic risk score (PRS) to predict breast-cancer risk.

METHODS: Fifteen prospective cohorts from six countries with 239 340 women (7646 incident breast-cancer cases) of European ancestry aged 19-75 years were included. Calibration of 5-year risk was assessed by comparing expected and observed proportions of cases overall and within risk categories. Risk stratification for women of European ancestry aged 50-70 years in those countries was evaluated by the proportion of women and future cases crossing clinically relevant risk thresholds.

RESULTS: Among women <50 years old, the median (range) expected-to-observed ratio for the integrated model across 15 cohorts was 0.9 (0.7-1.0) overall and 0.9 (0.7-1.4) at the highest-risk decile; among women ≥50 years old, these were 1.0 (0.7-1.3) and 1.2 (0.7-1.6), respectively. The proportion of women identified above a 3% 5-year risk threshold (used for recommending risk-reducing medications in the USA) ranged from 7.0% in Germany (∼841 000 of 12 million) to 17.7% in the USA (∼5.3 of 30 million). At this threshold, 14.7% of US women were reclassified by adding the PRS to classical risk factors, with identification of 12.2% of additional future cases.

CONCLUSION: Integrating a 313-variant PRS with classical risk factors can improve the identification of European-ancestry women at elevated risk who could benefit from targeted risk-reducing strategies under current clinical guidelines.

PMID:33755131 | DOI:10.1093/ije/dyab036

Europace. 2021 Mar 23:euab028. doi: 10.1093/europace/euab028. Online ahead of print.

ABSTRACT

AIM: The Prevention of Arrhythmia Device Infection Trial (PADIT) infection risk score, developed based on a large prospectively collected data set, identified five independent predictors of cardiac implantable electronic device (CIED) infection. We performed an independent validation of the risk score in a data set extracted from U.S. healthcare claims.

METHODS AND RESULTS: Retrospective identification of index CIED procedures among patients aged ≥18 years with at least one record of a CIED procedure between January 2011 and September 2014 in a U.S health claims database. PADIT risk factors and major CIED infections (with system removal, invasive procedure without system removal, or infection-attributable death) were identified through diagnosis and procedure codes. The data set was randomized by PADIT score into Data Set A (60%) and Data Set B (40%). A frailty model allowing multiple procedures per patient was fit using Data Set A, with PADIT score as the only predictor, excluding patients with prior CIED infection. A data set of 54 042 index procedures among 51 623 patients with 574 infections was extracted. Among patients with no history of prior CIED infection, a 1 unit increase in the PADIT score was associated with a relative 28% increase in infection risk. Prior CIED infection was associated with significant incremental predictive value (HR 5.66, P < 0.0001) after adjusting for PADIT score. A Harrell’s C-statistic for the PADIT score and history of prior CIED infection was 0.76.

CONCLUSION: The PADIT risk score predicts increased CIED infection risk, identifying higher risk patients that could potentially benefit from targeted interventions to reduce the risk of CIED infection. Prior CIED infection confers incremental predictive value to the PADIT score.

PMID:33755136 | DOI:10.1093/europace/euab028

Eur J Prev Cardiol. 2021 Mar 23;28(1):8-17. doi: 10.1177/2047487320939217.

ABSTRACT

AIMS: To evaluate the effect of linagliptin on left ventricular systolic function beyond glycaemic control in type 2 diabetes mellitus.

METHODS AND RESULTS: A multicentre, randomised, double-blind, placebo controlled, parallel-group study, was performed (the DYDA 2 trial). Individuals with type 2 diabetes mellitus and asymptomatic impaired left ventricular systolic function were randomly allocated in a 1:1 ratio to receive for 48 weeks either linagliptin 5 mg daily or placebo, in addition to their diabetes therapy. Eligibility criteria were age 40 years and older, haemoglobin A1c 8.0% or less (≤64 mmol/mol), no history of cardiac disease, concentric left ventricular geometry (relative wall thickness ≥0.42), impaired left ventricular systolic function defined as midwall fractional shortening 15% or less at baseline echocardiography. The primary end point was the modification of midwall fractional shortening over time. The main secondary objectives were changes in diastolic and/or in longitudinal left ventricular systolic function as measured by tissue Doppler echocardiography. One hundred and eighty-eight patients were enrolled, predominantly men with typical insulin-resistance comorbidities. At baseline, mean midwall fractional shortening was 13.3%±2.5. At final evaluation, 88 linagliptin patients and 86 placebo patients were compared: midwall fractional shortening increased from 13.29 to 13.82 (+4.1%) in the linagliptin group, from 13.58 to 13.84 in the placebo group (+1.8%, analysis of covariance P = 0.86), corresponding to a 2.3-fold higher increase in linagliptin than the placebo group, although non-statistically significant. Also, changes in diastolic and longitudinal left ventricular systolic function did not differ between the groups. Serious adverse events or linagliptin/placebo permanent discontinuation occurred in very few cases and in the same percentage between the groups.

CONCLUSIONS: In the DYDA 2 patients the addition of linagliptin to stable diabetes therapy was safe and provided a modest non-significant increase in left ventricular systolic function measured as midwall fractional shortening.

TRIAL REGISTRATION NUMBER: ClinicalTrial.gov (ID NCT02851745).

PMID:33755143 | DOI:10.1177/2047487320939217

Am J Epidemiol. 2021 Mar 23:kwab077. doi: 10.1093/aje/kwab077. Online ahead of print.

ABSTRACT

Severe maternal morbidity (SMM) is a composite outcome measure that indicates serious, potentially life-threatening maternal health problems. There is great interest in defining SMM using administrative data for surveillance and research. In the US, one common way of defining SMM at the population level is an index developed by the Centers for Disease Control and Prevention. Modifications have been proposed to this index (e.g., excluding maternal transfusion); some research defines SMM using an index introduced by Bateman et al. Birth certificate data are also increasingly being used to define SMM. We compared commonly used US definitions of SMM to each other among all California births, 2007-2012, using the Kappa statistic and other measures. We also evaluated agreement between maternal morbidity fields on the birth certificate compared to claims data. Concordance was generally low between the 7 definitions of SMM analyzed (i.e., κ < 0.4 for 13 of 21 two-way comparisons), Low concordance was particularly driven by presence/absence of transfusion and claims data versus birth certificate definitions. Low agreement between administrative data-based definitions of SMM highlights that results can be expected to differ between them. Further research is needed on validity of SMM definitions, using more fine-grained data sources.

PMID:33755046 | DOI:10.1093/aje/kwab077

Br J Surg. 2021 Mar 23:znaa121. doi: 10.1093/bjs/znaa121. Online ahead of print.

ABSTRACT

BACKGROUND: Although both neoadjuvant chemoradiotherapy (nCRT) and chemotherapy (nCT) are used as neoadjuvant treatment for oesophageal cancer, it is unknown whether one provides a survival advantage over the other, particularly with respect to histological subtype. This study aimed to compare prognosis after nCRT and nCT in patients undergoing oesophagectomy for oesophageal adenocarcinoma (OAC) or squamous cell carcinoma (OSCC).

METHODS: Data from the National Cancer Database (2006-2015) were used to identify patients with OAC and OSCC. Propensity score matching and Cox multivariable analyses were used to account for treatment selection biases.

RESULTS: The study included 11 167 patients with OAC (nCRT 9972, 89.3 per cent; nCT 1195, 10.7 per cent) and 2367 with OSCC (nCRT 2155, 91.0 per cent; nCT 212, 9.0 per cent). In the matched OAC cohort, nCRT provided higher rates of complete pathological response (35.1 versus 21.0 per cent; P < 0.001) and margin-negative resections (90.1 versus 85.9 per cent; P < 0.001). However, patients who had nCRT had similar survival to those who received nCT (hazard ratio (HR) 1.04, 95 per cent c.i. 0.95 to 1.14). Five-year survival rates for patients who had nCRT and nCT were 36 and 37 per cent respectively (P = 0.123). For OSCC, nCRT had higher rates of complete pathological response (50.9 versus 30.4 per cent; P < 0.001) and margin-negative resections (92.8 versus 82.4 per cent; P < 0.001). A statistically significant overall survival benefit was evident for nCRT (HR 0.78, 0.62 to 0.97). Five-year survival rates for patients who had nCRT and nCT were 45.0 and 38.0 per cent respectively (P = 0.026).

CONCLUSION: Despite pathological benefits, including primary tumour response to nCRT, there was no prognostic benefit of nCRT compared with nCT for OAC suggesting that these two modalities are equally acceptable. However, for OSCC, nCRT followed by surgery appears to remain the optimal treatment approach.

PMID:33755097 | DOI:10.1093/bjs/znaa121

J Natl Cancer Inst. 2021 Mar 23:djab049. doi: 10.1093/jnci/djab049. Online ahead of print.

ABSTRACT

Today, there are more than 16.9 million cancer survivors in the United States; this number is projected to grow to 22.2 million by 2030. While much progress has been made in understanding cancer survivors needs and in improving survivorship care since the seminal 2006 Institute of Medicine report From Cancer Patient to Cancer Survivor: Lost in Transition, there is a need to identify evidence gaps and research priorities pertaining to cancer survivorship. Thus, in April 2019, the National Cancer Institute convened grant-funded extramural cancer survivorship researchers, representatives of professional organizations, cancer survivors, and advocates for a one-day in-person meeting. At this meeting, and in a subsequent webinar aimed at soliciting input from the wider survivorship community, evidence gaps and ideas for next steps in the following six areas, identified from the 2006 Institute of Medicine report, were discussed: surveillance for recurrence and new cancers, management of long-term and late physical effects, management of long-term and late psychosocial effects, health promotion, care coordination, and financial hardship. Identified evidence gaps and next steps across the areas included the need to understand and address disparities among cancer survivors, to conduct longitudinal studies as well as longer-term (>5 years post-diagnosis) follow-up studies, to leverage existing data, and to incorporate implementation science strategies to translate findings into practice. Designing studies to address these broad evidence gaps, as well as those identified in each area, will expand our understanding of cancer survivors’ diverse needs, ultimately leading to the development and delivery of more comprehensive evidence-based quality care.

PMID:33755126 | DOI:10.1093/jnci/djab049

Am J Clin Oncol. 2021 Apr 1;44(4):143-149. doi: 10.1097/COC.0000000000000800.

ABSTRACT

OBJECTIVE: The objective of this study was to examine patterns of care and outcomes of female cancer patients treated for sexual and menopausal symptoms following pelvic radiotherapy (PRT) at our institution’s multidisciplinary Sexuality, Intimacy, and Menopause (SIMS) Program.

MATERIALS AND METHODS: We performed a retrospective review of 69 female patients who received PRT for gynecologic or gastrointestinal malignancies and were referred for SIMS Program intervention. Indications for referral and treatment patterns were summarized. Preintervention and postintervention, patients were screened at follow-up visits, and symptoms were recorded. Statistics were performed using Stata 13.1.

RESULTS: Cancer types included cervical (53.6%), endometrial (31.9%), anorectal (5.8%), and vulvar/vaginal (8.7%). The median age was 48 years (interquartile range: 38 to 58 y). Patients were educated on vaginal lubricants, moisturizers, and dilator therapy both before and after PRT. Reasons for SIMS referral included persistent menopausal symptoms (50.7%), dyspareunia (40.6%), vaginal dryness (37.7%), decreased libido (17.4%), intimacy concerns (17.4%), and/or physical examination alterations (27.5%). SIMS interventions included vaginal estrogen (77.3%), nonhormonal climacteric interventions (53%), systemic hormone therapy (31.8%), dehydroepiandrosterone (4.6%), testosterone cream (4.6%), and/or psychological pharmacotherapy or counseling (13.6%). With a median follow-up of 36 months (interquartile range: 18 to 58 mo), sexual symptoms improved or were stable in 83.6%, while menopausal symptoms improved or were stable in 80.5%.

CONCLUSIONS: This study highlights the importance of multidisciplinary care in improving the sexual and menopausal symptoms of women after PRT. Future work examining the impact of intervention timing with respect to PRT and measures of patient satisfaction is warranted.

PMID:33755031 | DOI:10.1097/COC.0000000000000800

Invest Ophthalmol Vis Sci. 2021 Mar 1;62(3):32. doi: 10.1167/iovs.62.3.32.

ABSTRACT

PURPOSE: New lasers with a continuous wave power exceeding 15 W are currently investigated for retinal therapies, promising highly localized effects at and close to the Retinal Pigment Epithelium (RPE). The goal of this work is to evaluate mechanisms and thresholds for RPE cell damage by means of pulse durations up to 50 µs.

METHODS: A diode laser with a wavelength of 514 nm, a power of 15 W, and adjustable pulse durations between 2 µs and 50 µs was used. Porcine RPE-choroidal explants (ex vivo) and chinchilla bastard rabbits (in vivo) were irradiated to determine threshold radiant exposures for RPE damage ({bar H_{Cell}}) by calcein vitality staining and fluorescence angiography, respectively. Thresholds for microbubble formation (MBF) ({bar H_{MBF}}) were evaluated by time-resolved optoacoustics. Exemplary histologies support the findings.

RESULTS: ({bar H_{{{MBF}}}}) is significantly higher than ({bar H_{Cell}}) at pulse durations ≥ 5 µs (P < 0.05) ex vivo, while at 2 µs, no statistically significant difference was found. The ratios between ({bar H_{{{MBF}}}}) and ({bar H_{Cell}}) increase with pulse duration from 1.07 to 1.48 ex vivo and 1.1 to 1.6 in vivo, for 5.2 and 50 µs.

CONCLUSIONS: Cellular damage with and without MBF related disintegration are both present and very likely to play a role for pulse durations ≥ 5 µs. With the lower µs pulses, selective RPE disruption might be possible, while higher values allow achieving spatially limited thermal effects without MBF. However, both modi require a very accurate real-time dosing control in order to avoid extended retinal disintegration in this power range.

PMID:33755044 | DOI:10.1167/iovs.62.3.32

Asian J Surg. 2021 Mar 20:S1015-9584(21)00118-4. doi: 10.1016/j.asjsur.2021.02.011. Online ahead of print.

ABSTRACT

BACKGROUND: D3 lymph node dissection is becoming the standard procedure for the treatment of advanced right colon cancer and has shown increasing evidence of its oncologic benefit. However, a clear indication for its application is lacking and data on this topic is unsatisfactory. Thus, the necessity for D3 lymph node dissection in clinical stage I right colon cancer remains controversial.

METHODS: We retrospectively analyzed data from clinical stage I right colon cancer patients who underwent radical surgery at three hospitals of Korea university medical center between January 2015 and June 2018. We compared surgical complications and short-term oncologic outcomes between D2 and D3 lymph node dissections in these patients.

RESULTS: Among 512 patients, 122 (23.8%) were clinical stage I. Of these, 88 and 34 patients received D2 and D3 lymph node dissection, respectively. There were no statistically significant differences in clinicopathologic variables and surgical outcomes between the two groups. Upstaging occurred in 16 patients (47.1%) in the D3 group and 23 patients (26.1%) in the D2 group. There were four recurrences in the D2 group but no recurrence in the D3 group. Log-rank tests showed no statistically significant difference in disease-free survival rates between the two groups (p = 0.210).

CONCLUSION: There was no significant difference in disease-free survival rates between D2 and D3 lymph node dissection in clinical stage I right colon cancer patients. However, recurrence occurred in the D2 group. Efforts to improve the accuracy of clinical staging are required and more studies with better quality are needed.

PMID:33752988 | DOI:10.1016/j.asjsur.2021.02.011

Transfus Apher Sci. 2021 Mar 13:103121. doi: 10.1016/j.transci.2021.103121. Online ahead of print.

ABSTRACT

BACKGROUND: Blood donors are prone to have iron deficiency. The aim of this study was to determine utility of serum hepcidin as an indicator of iron deficiency in blood donors.

METHODS: A total of 200 voluntary, healthy blood donors were included in the study. Donors were categorized into four groups according to the donation frequency. Group I: (n = 50) who donated for the first time, or those who have not donated in the past 2 years (reactivated donors). Group II: (n = 50), who donated blood for the second time and had donated once in the previous 12 months. Group III: (n = 50), who donated blood for third time and had donated twice in the previous 12 months. Group IV: (n = 50) who donated blood for the fourth time and had donated thrice in the previous 12 months. Sera of study participants were evaluated for serum ferritin and serum hepcidin levels based on enzyme linked immunosorbent assay.

RESULTS: Serum hepcidin concentration ranged 2.36-15734 pg/mL. Serum hepcidin and serum ferritin were found to be lowest in group IV donors. When serum ferritin concentration of less than 15 ng/mL was considered as gold standard for diagnosing iron deficiency, AUCROC for serum hepcidin as a diagnostic test of iron deficiency was found to be 0.715. Serum hepcidin showed statistical significant correlation with donation frequency(p = 0 .005) and serum ferritin (p = 0.01). Sensitivity and specificity of serum hepcidin was found to be 77.8 %, 79.6 % respectively.

CONCLUSION: Effectiveness of Serum hepcidin as a diagnostic marker of iron deficiency still needs to be determined.

PMID:33752992 | DOI:10.1016/j.transci.2021.103121