Nevin Manimala

Phys Ther. 2021 Apr 5:pzab109. doi: 10.1093/ptj/pzab109. Online ahead of print.

ABSTRACT

OBJECTIVES: Physical therapy intervention studies can be deemed ineffective when, in fact, they may not have been delivered as intended. Measurement of treatment fidelity (TF) can address this issue. The purpose was to describe TF of a home-based intervention, identify factors associated with TF, and examine whether components of TF were associated with the outcome of change in 6-minute walk distance (∆6MWD).

METHODS: This is a secondary analysis of community-dwelling hip fracture participants who completed standard therapy and were randomized to the active intervention (Push). Push was 16-weeks of lower extremity strengthening, function and endurance training. TF was defined as delivery (attendance rate, exercise duration) and receipt (progression in training load, heart rate reserve (HRR) during endurance training, and exercise position (exercise on floor). The outcome was ∆6MWD. Independent variables included baseline (demographic and clinical) measures. Descriptive statistics were calculated; linear and logistic regressions were performed.

RESULTS: 89 participants were included in this analysis; 59 (66%) had attendance ≥75%. Participants walked for ≥20 minutes for 78% of sessions. The average training load increased by 22%; the mean HRR was 35%; and 61 (69%) participants exercised on the floor ≥75% of sessions. Regression analyses showed that a higher body mass index (BMI) and greater baseline 6MWD were related to components of TF; and four out of 5 components of TF were significantly related to ∆6MWD. The strongest TF relationship showed that those who exercised on the floor improved by 62 meters (95% CI: 31, 93) more than those who did not get on the floor.

CONCLUSIONS: Measures of TF should extend beyond attendance rate. This analysis demonstrates how measures of TF, including program attendance, progression in training load, endurance duration and exercising on the floor were significantly related to improvement in 6MWD in participants post hip fracture.

IMPACT: This careful analysis of treatment fidelity assured that the intervention was delivered and received as intended. Analysis of data from a large trial with participants after hip fracture showed that regular attendance, frequent endurance training for 20 minutes, increases in lower extremity training loads, and exercising on the floor were associated with improvements in the outcome of 6-minute-walk distance. The strongest association with improvement was exercising on the floor.

PMID:33823028 | DOI:10.1093/ptj/pzab109

J Natl Cancer Inst. 2021 Apr 5:djab053. doi: 10.1093/jnci/djab053. Online ahead of print.

ABSTRACT

BACKGROUND: Breast cancer survivors are at increased risk for developing second primary cancers compared to the general population. Little is known about whether body mass index (BMI) increases this risk. We examined the association between BMI and second cancers among women with incident invasive breast cancer.

METHODS: This retrospective cohort included 6,481 patients from Kaiser Permanente Colorado and Washington of whom 822 (12.7%) developed a second cancer (mean follow-up was 88.0 months). BMI at the first cancer was extracted from the medical record. Outcomes included: 1) all second cancers, 2) obesity-related second cancers, 3) any second breast cancer, and 4) estrogen receptor (ER)-positive second breast cancers. Multivariable Poisson regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI) for second cancers associated with BMI adjusted for site, diagnosis year, treatment, demographic, and tumor characteristics.

RESULTS: The mean age at initial breast cancer diagnosis was 61.2 (standard deviation = 11.8) years. Most cases were overweight (33.4%) or obese (33.8%) and diagnosed at stage I (62.0%). In multivariable models, for every 5 kg/m2 increase in BMI, the risk of any second cancer diagnosis increased by 7% (RR = 1.07, 95% CI = 1.01 to 1.14); 13% (RR = 1.13, 95% CI = 1.05 to 1.21) for obesity-related cancers; 11% (RR = 1.11, 95% CI = 1.02 to 1.21) for a second breast cancer, and 15% (RR = 1.15, 95% CI = 1.04 to 1.27) for a second ER-positive breast cancer.

CONCLUSION: We observed a statistically significant increased risk of second cancers associated with increasing BMI. These findings have important public health implications given the prevalence of overweight and obesity in breast cancer survivors and underscore the need for effective prevention strategies.

PMID:33823007 | DOI:10.1093/jnci/djab053

J Radiat Res. 2021 Apr 5:rraa056. doi: 10.1093/jrr/rraa056. Online ahead of print.

ABSTRACT

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions.

PMID:33822986 | DOI:10.1093/jrr/rraa056

J Antimicrob Chemother. 2021 Apr 5:dkab096. doi: 10.1093/jac/dkab096. Online ahead of print.

ABSTRACT

BACKGROUND: Bacteraemia data are often used as a general measure of resistance prevalence but may poorly represent other infection types. We compared resistance prevalence between bloodstream infection (BSI) and lower respiratory tract infection (LRTI) isolates collected by the BSAC Resistance Surveillance Programme.

METHODS: BSI isolates (n = 8912) were collected during 2014-18 inclusive and LRTI isolates (n = 6280) between October 2013 to September 2018 from participating laboratories in the UK and Ireland, to a fixed annual quota per species group. LRTI isolates, but not BSI, were selected by onset: community for Streptococcus pneumoniae; hospital for Staphylococcus aureus, Pseudomonas aeruginosa and Enterobacterales. MICs were determined centrally by agar dilution; statistical modelling adjusted for ICU location and possible clustering by collection centre.

RESULTS: Resistance was more prevalent among the LRTI isolates, even after adjusting for a larger proportion of ICU patients. LRTI P. aeruginosa and S. pneumoniae were more often resistant than BSI isolates for most antibiotics, and the proportion of MRSA was higher in LRTI. For S. pneumoniae, the observation reflected different serotype distributions in LRTI and BSI. Relationships between LRTI and resistance were less marked for Enterobacterales, but LRTI E. coli were more often resistant to β-lactams, particularly penicillin/β-lactamase inhibitor combinations, and LRTI K. pneumoniae to piperacillin/tazobactam. For E. cloacae there was a weak association between LRTI, production of AmpC enzymes and cephalosporin resistance.

CONCLUSIONS: Estimates of resistance prevalence based upon bloodstream isolates underestimate the extent of the problem in respiratory isolates, particularly for P. aeruginosa, S. pneumoniae, S. aureus and, less so, for Enterobacterales.

PMID:33822968 | DOI:10.1093/jac/dkab096

Gigascience. 2021 Apr 5;10(4):giab023. doi: 10.1093/gigascience/giab023.

ABSTRACT

BACKGROUND: The role of synonymous single-nucleotide variants in human health and disease is poorly understood, yet evidence suggests that this class of “silent” genetic variation plays multiple regulatory roles in both transcription and translation. One mechanism by which synonymous codons direct and modulate the translational process is through alteration of the elaborate structure formed by single-stranded mRNA molecules. While tools to computationally predict the effect of non-synonymous variants on protein structure are plentiful, analogous tools to systematically assess how synonymous variants might disrupt mRNA structure are lacking.

RESULTS: We developed novel software using a parallel processing framework for large-scale generation of secondary RNA structures and folding statistics for the transcriptome of any species. Focusing our analysis on the human transcriptome, we calculated 5 billion RNA-folding statistics for 469 million single-nucleotide variants in 45,800 transcripts. By considering the impact of all possible synonymous variants globally, we discover that synonymous variants predicted to disrupt mRNA structure have significantly lower rates of incidence in the human population.

CONCLUSIONS: These findings support the hypothesis that synonymous variants may play a role in genetic disorders due to their effects on mRNA structure. To evaluate the potential pathogenic impact of synonymous variants, we provide RNA stability, edge distance, and diversity metrics for every nucleotide in the human transcriptome and introduce a “Structural Predictivity Index” (SPI) to quantify structural constraint operating on any synonymous variant. Because no single RNA-folding metric can capture the diversity of mechanisms by which a variant could alter secondary mRNA structure, we generated a SUmmarized RNA Folding (SURF) metric to provide a single measurement to predict the impact of secondary structure altering variants in human genetic studies.

PMID:33822938 | DOI:10.1093/gigascience/giab023

Int J Qual Health Care. 2021 Apr 5:mzab062. doi: 10.1093/intqhc/mzab062. Online ahead of print.

ABSTRACT

BACKGROUND: At the end of December 2019, the world in general and Wuhan, the industrial hub of China, in particular, experienced the COVID-19 pandemic. Massive increment of cases and deaths occurred in China and 209 countries in Europe, America, Australia, Asia, and Pakistan. Pakistan was first hit by COVID-19 when a case was reported in Karachi on 26 February 2020. Several methods were presented to model the death rate due to the COVID-19 pandemic and to forecast the pinnacle of reported deaths. Still, these methods were not used in identifying the first day when Pakistan enters or exits the early exponential growth phase.

METHODS: New approaches are needed that display the death patterns and signal an alarming situation so that corrective actions can be taken before the condition worsens. To meet this purpose, secondary data on daily reported deaths due to the COVID-19 pandemic have been considered, and the c and exponentially weighted moving average (EWMA) control charts are used to monitor variations in deaths and to identify the growth phases such as pre-growth, growth, and post-growth phases in Pakistan due to the COVID-19 pandemic.

RESULTS: The-chart shows that Pakistan switches from the pre-growth to the growth phase on 31 March 2020. The EWMA chart demonstrates that Pakistan remains in the growth-phase from 31 March 2020 to 17 August 2020, with some indications signaling a decrease in deaths. It is found that Pakistan moved to a post-growth phase for a brief period from 27 July 2020 to 28 July 2020. The country encounters a re-growth phase right after this short-term post-growth phase, but the number of deaths is decreasing in that Pakistan may approach the post-growth phase shortly.

CONCLUSION: This novel amalgamation of control charts illustrates a systematic implementation of the charts to government leaders and forefront medical teams to facilitate the rapid detection of daily reported deaths due to COVID-19. Besides government and public health officials, it is also the public’s responsibility to follow the enforced standard operating procedures as a temporary remedy of this pandemic in ensuring public safety while awaiting a suitable vaccine to be discovered.

PMID:33822932 | DOI:10.1093/intqhc/mzab062

Eur J Cardiothorac Surg. 2021 Apr 5:ezab147. doi: 10.1093/ejcts/ezab147. Online ahead of print.

ABSTRACT

OBJECTIVES: The goal of therapy of proximal aortic aneurysms is to prevent an aortic catastrophe, e.g. acute dissection or rupture. The decision to intervene is currently based on maximum aortic diameter complemented by known risk factors like bicuspid aortic valve, positive family history or rapid growth rate. When applying Laplace’s law, wall tension is determined by pressure × radius divided by aortic wall thickness. Because current imaging modalities lack precision, wall thickness is currently neglected. The purpose of our study was therefore to correlate maximum aortic diameter with aortic wall thickness and known indices for adverse aortic events.

METHODS: Aortic samples from 292 patients were collected during cardiac surgery, of whom 158 presented with a bicuspid aortic valve and 134, with a tricuspid aortic valve. Aortic specimens were obtained during the operation and stored in 4% formaldehyde. Histological staining and analysis were performed to determine the thickness of the aortic wall.

RESULTS: Patients were 62 ± 13 years old at the time of the operation; 77% were men. The mean aortic dimensions were 44 mm, 41 mm and 51 mm at the aortic root, sinotubular junction and ascending aorta, respectively. Aortic valve stenosis was the most frequent (49%) valvular dysfunction, followed by aortic valve regurgitation (33%) and combined dysfunction (10%). The maximum aortic diameter at the ascending level did not correlate with the thickness of the media (R = 0.07) or the intima (R = 0.28) at the convex sample site. There was also no correlation of the ascending aortic diameter with age (R = -0.18) or body surface area (R = 0.07). The thickness of the intima (r = 0.31) and the media (R = 0.035) did not correlate with the Svensson index of aortic risk. Similarly, there was a low (R = 0.29) or absent (R = -0.04) correlation between the aortic size index and the intima or media thickness, respectively. There was a similar relationship of median thickness of the intima in the 4 aortic height index risk categories (P < 0.001).

CONCLUSIONS: Aortic diameter and conventional indices of aortic risk do not correlate with aortic wall thickness. Other indices may be required in order to identify patients at high risk for aortic complications.

PMID:33822923 | DOI:10.1093/ejcts/ezab147

J Crohns Colitis. 2021 Apr 5:jjab063. doi: 10.1093/ecco-jcc/jjab063. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Histological healing might be the ultimate therapeutic goal in ulcerative colitis (UC). Our aim was to investigate the association between histological disease activity as measured by a validated index and long-term outcomes in patients with UC.

METHODS: An observational retrospective cohort study was conducted at the Nancy University Hospital between January 2014 and March 2020. All consecutive patients with confirmed UC undergoing colonoscopy with biopsies and available histological reports were eligible for inclusion.

RESULTS: A total of 156 patients were included (53% female with a mean age of 41.3 ± 15.4 years). About a quarter of patients were in histological remission (Nancy index=0) at baseline (n=42, 26.9%). Median follow-up was 30.5 months (range 0-75). Sixteen patients with histological disease activity at baseline (Nancy index ≥ 1) underwent surgery during follow-up compared with no subject in the histological remission group (14.0% vs 0.0%, respectively, p=0.01). Similarly, a higher rate of hospitalization was found in patients with histological disease activity at baseline than in the histological remission group (36.0% vs 7.1%, respectively, p=0,001). The Kaplan Meier analysis showed that patients with histological disease activity at baseline had a 5-year surgery rate of 16.7% (logrank p=0.01) and a 5-year hospitalization rate of 19.7% (logrank p=0.0002). In the multivariate regression model, Nancy index > 0 was independently associated with the risk of hospitalization (hazard ratio 8.88, CI 95% 2.5-31.1, p=0.0007).

CONCLUSION: UC patients with histological disease activity, as measured by the Nancy index, have a greater risk of surgery and hospitalization.

PMID:33822915 | DOI:10.1093/ecco-jcc/jjab063

Zdr Varst. 2021 Mar 18;60(2):82-89. doi: 10.2478/sjph-2021-0013. eCollection 2021 Jun.

ABSTRACT

BACKGROUND: Persons with ID most often have incomplete, contradictory and imprecise knowledge of sexuality and sexual intercourse itself. They are not provided with sufficient information on their own body and sexuality, and are often discouraged from and sanctioned for trying to sexually express themselves. Sexual abuse due to low sexual assertiveness is also common.

AIM: The principal aim of this study was to establish the presence or absence of sexual activity in adults with ID residing in institutional housing, as well as the level and structure of their knowledge of sexuality, their sexual assertiveness and preparedness to react in a sexually dangerous situation.

METHODS: The sample consisted of 100 participants with ID residing in institutional housing. The instruments used included the General Sexual Knowledge Questionnaire, What-if test and Hulbert index of sexual assertiveness. Comparative statistics included coefficient of linear correlation and multiple regression analysis.

RESULTS: The results showed that 82% of the participants are sexually active. Most participants admitted to sometimes having sexual intercourse against their wishes as well as to having difficulty asserting themselves. Their knowledge of pregnancy, contraception and sexually transmitted diseases was very low. Female participants and those that reported having sexual intercourse had more sexual knowledge and were also more sexually assertive.

CONCLUSION: Knowledge of sexuality and sexual assertiveness of persons with ID residing in institutional housing is very low. Additional information on sexuality is necessary, as well as support in learning to express their own desires and to deal with unwanted sexual activity.

PMID:33822835 | PMC:PMC8015653 | DOI:10.2478/sjph-2021-0013

Zdr Varst. 2021 Mar 18;60(2):114-123. doi: 10.2478/sjph-2021-0017. eCollection 2021 Jun.

ABSTRACT

INTRODUCTION: Future nurses should possess the knowledge and competences necessary to ensure patient safety. However, little evidence is available on the way in which students learn patient safety-related principles over time. This study explored the progress of a cohort of Italian undergraduate nursing students as they acquired patient safety knowledge and competences from time of enrolment to graduation.

METHODS: A longitudinal study carried out between 2015 and 2018 enrolled a cohort of 90 nursing students from two Italian Bachelor of Nursing Science Degree Courses at the Udine University, Italy. The students were followed-up on an annual basis and data collection was performed three times: at the end of the 1st, 2nd and 3rd years. The validated Italian version of the Professional Education in Patient Safety Survey tool was used to collect data.

RESULTS: At the end of the 1st year, students reported an average 4.19 out of 5 patient safety knowledge acquired in classrooms (CI 95%, 4.11-4.28), which was stable at the end of the 2nd (4.16; CI 95%, 4.06-4.26) and 3rd years (4.26; CI 95%, 4.16-4.32) and no statistical differences emerged over the years. With regard to the competences acquired in clinical settings, at the end of the 1st year the students reported an average 4.28 out of 5 (CI 95%, 4.20-4.37), which decreased significantly at the end of the 2nd year (4.15; CI 95%, 4.07-4.23; p=0.02) and increased at the end of the 3rd year (4.37; CI 95%, 4.27-4.47; p<0.01).

CONCLUSIONS: Nursing students’ competences in patient safety issues increases over time, while their knowledge remains stable. Students are more vulnerable at the end of the 1st year, when they seem to be overconfident about patient-safety issues.

PMID:33822834 | PMC:PMC8015659 | DOI:10.2478/sjph-2021-0017