Objective: Dynamic Optimal Timing (Dot) is a smartphone
application (app) that estimates the menstrual cycle fertile window based on the
user's menstrual period start dates. Dot uses machine learning ...to adapt to cycles over
time and informs users of 'low' and 'high' fertility days. We
investigated Dot's effectiveness, calculating perfect- and typical-use failure
rates.
Methods: This prospective, 13 cycle observational study
(ClinicalTrials.gov NCT02833922) followed 718 women who were using Dot to prevent
pregnancy. Participants contributed 6616 cycles between February 2017 and October 2018,
providing data on menstrual period start dates, daily sexual activity and prospective intent to
prevent pregnancy. We determined pregnancy through participant-administered urine pregnancy
tests and/or written or verbal confirmation. We calculated perfect- and typical-use failure
rates using multi-censoring, single-decrement life-table analysis, and conducted sensitivity,
attrition and survival analyses.
Results: The perfect-use failure rate was calculated to be 1.0%
(95% confidence interval CI: 0.9%, 2.9%) and the
typical-use failure rate was 5.8% (95% CI: 3.57%, 8.09%) for women aged 18-39
(n = 718). Survival analyses identified no
significant differences among age or racial/ethnic groups or women in different types of
relationships. Attrition analyses revealed no significant sociodemographic differences, except
in age, between women completing 13 cycles and those exiting the study earlier.
Conclusion: Dot's effectiveness is within the range of other
user-initiated contraceptive methods.
Trial registration:
ClinicalTrials.gov identifier: NCT02833922.
Next generation sequencing (NGS) is a trending new standard for genotypic HIV-1 drug resistance (HIVDR) testing. Many NGS HIVDR data analysis pipelines have been independently developed, each with ...variable outputs and data management protocols. Standardization of such analytical methods and comparison of available pipelines are lacking, yet may impact subsequent HIVDR interpretation and other downstream applications. Here we compared the performance of five NGS HIVDR pipelines using proficiency panel samples from NIAID Virology Quality Assurance (VQA) program. Ten VQA panel specimens were genotyped by each of six international laboratories using their own in-house NGS assays. Raw NGS data were then processed using each of the five different pipelines including HyDRA, MiCall, PASeq, Hivmmer and DEEPGEN. All pipelines detected amino acid variants (AAVs) at full range of frequencies (1~100%) and demonstrated good linearity as compared to the reference frequency values. While the sensitivity in detecting low abundance AAVs, with frequencies between 1~20%, is less a concern for all pipelines, their specificity dramatically decreased at AAV frequencies <2%, suggesting that 2% threshold may be a more reliable reporting threshold for ensured specificity in AAV calling and reporting. More variations were observed among the pipelines when low abundance AAVs are concerned, likely due to differences in their NGS read quality control strategies. Findings from this study highlight the need for standardized strategies for NGS HIVDR data analysis, especially for the detection of minority HIVDR variants.
Abstract
Background
Fatigue is one of the most important symptoms among patients receiving dialysis and is nominated as a core outcome to be reported in all clinical trials in this setting. However, ...few trials of interventions targeting fatigue have been conducted. Patients historically have rarely been involved in the design of interventions, which can limit acceptability and uptake. When asked, they have indicated a preference for lifestyle interventions, such as exercise, to improve fatigue. While some research has focussed on intradialytic exercise for patients receiving haemodialysis, patients have also indicated a preference for a convenient method of exercising with guidance, but on their own time outside of dialysis hours. In response to this, a mobile phone application was proposed as the method of delivery for a home-based exercise intervention targeting fatigue.
Methods
We convened a workshop with five breakout group sessions in Australia, with 24 patients on dialysis (16 haemodialysis and 8 peritoneal dialysis) and 8 caregivers to identify, prioritize and discuss exercise interventions for fatigue in patients receiving dialysis and the delivery of this through a mobile application.
Results
Of the 21 types of exercise identified, the top-ranked were walking outdoors, walking on a treadmill and cardio and resistance training. Six themes were identified: (i) ‘an expectation of tangible gains from exercise’, including strengthening and protecting against bodily deterioration related to dialysis; (ii) ‘overcoming physical limitations’, meaning that comorbidities, baseline fatigue and fluctuating health needed to be addressed to engage in exercise; (iii) ‘fear of risks’, which reinforced the importance of safety and compatibility of exercise with dialysis; (iv) ‘realistic and achievable’ exercise, which would ensure initial readiness for uptake; (v) ‘enhancing motivation and interest’ , which expected to support sustained use of the exercise intervention and (vi) ‘ensuring usability of the mobile application’ , which would require simplicity, convenience and comprehensibility.
Conclusion
Exercise interventions that are expected by patients to improve health outcomes and that are safe, realistic and easy to adopt may be more acceptable to patients on dialysis.
Florbetapir F 18 PET can image amyloid-β (Aβ) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting Aβ pathology using florbetapir PET in ...subjects at risk for progressive cognitive decline.
A total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (Aβ+) or negative (Aβ-) for pathologic levels of β-amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined from the baseline PET images. Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status. Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline.
In both MCI and CN, baseline Aβ+ scans were associated with greater clinical worsening on the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog (p < 0.01) and Clinical Dementia Rating-sum of boxes (CDR-SB) (p < 0.02). In MCI Aβ+ scans were also associated with greater decline in memory, Digit Symbol Substitution (DSS), and Mini-Mental State Examination (MMSE) (p < 0.05). In MCI, higher baseline SUVr similarly correlated with greater subsequent decline on the ADAS-Cog (p < 0.01), CDR-SB (p < 0.03), a memory measure, DSS, and MMSE (p < 0.05). Aβ+ MCI tended to convert to AD dementia at a higher rate than Aβ- subjects (p < 0.10).
Florbetapir PET may help identify individuals at increased risk for progressive cognitive decline.
This study was designed to evaluate whether subjects with amyloid beta (Aβ) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than ...subjects without Aβ pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aβ+) or negative (Aβ-), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aβ+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aβ+ MCI subjects demonstrated greater worsening compared with Aβ- subjects on the ADAS-Cog over 36 months (5.66 ± 1.47 vs -0.71 ± 1.09, P = 0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal fluency test (P < 0.05). Similar to MCI subjects, Aβ+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aβ+ AD patients showed greater declines in verbal fluency and the MMSE (P < 0.05). Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aβ+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ- subjects do.
UWALK is a multi-strategy, multi-sector, theory-informed, community-wide approach using e and mHealth to promote physical activity in Alberta, Canada. The aim of UWALK is to promote physical ...activity, primarily via the accumulation of steps and flights of stairs, through a single over-arching brand. This paper describes the development of the UWALK program. A social ecological model and the social cognitive theory guided the development of key strategies, including the marketing and communication activities, establishing partnerships with key stakeholders, and e and mHealth programs. The program promotes the use of physical activity monitoring devices to self-monitor physical activity. This includes pedometers, electronic devices, and smartphone applications. In addition to entering physical activity data manually, the e and mHealth program provides the function for objective data to be automatically uploaded from select electronic devices (Fitbit®, Garmin and the smartphone application Moves) The RE-AIM framework is used to guide the evaluation of UWALK. Funding for the program commenced in February 2013. The UWALK brand was introduced on April 12, 2013 with the official launch, including the UWALK website on September 20, 2013. This paper describes the development and evaluation framework of a physical activity promotion program. This program has the potential for population level dissemination and uptake of an ecologically valid physical activity promotion program that is evidence-based and theoretically framed.
Observational studies have shown beneficial relationships between exercise and cognitive function. Some clinical trials have also demonstrated improvements in cognitive function in response to ...moderate-high intensity aerobic exercise; however, these have been limited by relatively small sample sizes and short durations. The Lifestyle Interventions and Independence for Elders (LIFE) Study is the largest and longest randomized controlled clinical trial of physical activity with cognitive outcomes, in older sedentary adults at increased risk for incident mobility disability. One LIFE Study objective is to evaluate the effects of a structured physical activity program on changes in cognitive function and incident all-cause mild cognitive impairment or dementia. Here, we present the design and baseline cognitive data. At baseline, participants completed the modified Mini Mental Status Examination, Hopkins Verbal Learning Test, Digit Symbol Coding, Modified Rey-Osterrieth Complex Figure, and a computerized battery, selected to be sensitive to changes in speed of processing and executive functioning. During follow up, participants completed the same battery, along with the Category Fluency for Animals, Boston Naming, and Trail Making tests. The description of the mild cognitive impairment/dementia adjudication process is presented here. Participants with worse baseline Short Physical Performance Battery scores (prespecified at ≤ 7) had significantly lower median cognitive test scores compared with those having scores of 8 or 9 with modified Mini Mental Status Examination score of 91 versus (vs) 93, Hopkins Verbal Learning Test delayed recall score of 7.4 vs 7.9, and Digit Symbol Coding score of 45 vs 48, respectively (all P<0.001). The LIFE Study will contribute important information on the effects of a structured physical activity program on cognitive outcomes in sedentary older adults at particular risk for mobility impairment. In addition to its importance in the area of prevention of cognitive decline, the LIFE Study will also likely serve as a model for exercise and other behavioral intervention trials in older adults.
To assess whether the traditional problem-based learning (PBL) process can be replicated in an online environment, and to identify any barriers and facilitators to learning using a course pilot.
...Eight alumni and one experienced tutor participated in a two-week simulated PBL course comprised of two three-hour synchronous online tutorials. Blackboard Collaborate® software was used to permit audio and visual interaction. The PBL tutorials were recorded and observed by the researchers. Participants completed satisfaction surveys after the pilot, and were invited to take part in a focus group to debrief about their experience.
Once the steep learning curve with the technology was overcome, the quality of the PBL process was similar in the online course as it was in the face-to-face course. Several key factors for success were identified through analysis of the videotaped sessions, and interviews with the participants in the course pilot.
Conducting a course pilot study demonstrated that an online PBL course is feasible, and identified some considerations to facilitate success
Abstract
Introduction
Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially.
Methods
...We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy. Clinical, imaging, and microbiological data were evaluated by multidisciplinary adjudication teams. The primary outcome of interest was grade ≥2 (CTCAEv5) pneumonitis. Clinicopathologic variables, tobacco use, cancer therapies, and preexisting lung disease were assessed for univariate effects using Cox proportional hazards models. We created multivariate Cox proportional hazards models to assess risk factors for pneumonitis and mortality. Pneumonitis, pneumonia, and progression were modeled as time-dependent variables in mortality models.
Results
We evaluated 419 patients between 2013 and 2021. The cumulative incidence of pneumonitis was 9.5% (40/419). In a multivariate model, pneumonitis increased the risk for mortality (HR 1.6, 95% CI, 1.0-2.5), after adjustment for disease progression (HR 1.6, 95% CI, 1.4-1.8) and baseline shortness of breath (HR 1.5, 95% CI, 1.2-2.0). Incomplete resolution was more common with more severe pneumonitis. Interstitial lung disease was associated with higher risk for pneumonitis (HR 5.4, 95% CI, 1.1-26.6), particularly in never smokers (HR 26.9, 95% CI, 2.8-259.0).
Conclusion
Pneumonitis occurred at a high rate and significantly increased mortality. Interstitial lung disease, particularly in never smokers, increased the risk for pneumonitis.
This article examines the predisposing risk factors and incidence of pneumonitis in patients with non-small cell lung cancer undergoing immune checkpoint inhibitor therapy and explores the potential modifying effects of smoking history and preexisting lung disease.
Observational evidence suggests that higher physical activity is associated with slower kidney function decline; however, to our knowledge, no large trial has evaluated whether activity and exercise ...can ameliorate kidney function decline in older adults.
To evaluate whether a moderate-intensity exercise intervention can affect the rate of estimated glomerular filtration rate per cystatin C (eGFRCysC) change in older adults.
This ancillary analysis of the Lifestyle Interventions and Independence For Elders randomized clinical trial enrolled 1199 community-dwelling, sedentary adults aged 70 to 89 years with mobility limitations and available blood specimens. The original trial was conducted across 8 academic centers in the US from February 2010 through December 2013. Data for this study were analyzed from March 29, 2021, to February 28, 2022.
Structured, 2-year, partially supervised, moderate-intensity physical activity and exercise (strength, flexibility) intervention compared with a health education control intervention with 2-year follow-up. Physical activity was measured by step count and minutes of moderate-intensity activity using accelerometers.
The primary outcome was change in eGFRCysC. Rapid eGFRCysC decline was defined by the high tertile threshold of 6.7%/y.
Among the 1199 participants in the analysis, the mean (SD) age was 78.9 (5.2) years, and 800 (66.7%) were women. At baseline, the 2 groups were well balanced by age, comorbidity, and baseline eGFRCysC. The physical activity and exercise intervention resulted in statistically significantly lower decline in eGFRCysC over 2 years compared with the health education arm (mean difference, 0.96 mL/min/1.73 m2; 95% CI, 0.02-1.91 mL/min/1.73 m2) and lower odds of rapid eGFRCysC decline (odds ratio, 0.79; 95% CI, 0.65-0.97).
Results of this ancillary analysis of a randomized clinical trial showed that when compared with health education, a physical activity and exercise intervention slowed the rate of decline in eGFRCysC among community-dwelling sedentary older adults. Clinicians should consider targeted recommendation of physical activity and moderate-intensity exercise for older adults as a treatment to slow decline in eGFRCysC.
ClinicalTrials.gov Identifier: NCT01072500.
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