Nevin Manimala

Br J Haematol. 2021 Aug 2. doi: 10.1111/bjh.17691. Online ahead of print.

ABSTRACT

Patients with asymptomatic/smouldering Waldenström macroglobulinaemia (SWM) have a variable risk of progression to active WM. Our study evaluated 143 patients with SWM consecutively seen between January 1996 and December 2013. With a median [95% confidence interval (CI)] follow-up of 9·5 [8·1-11·5] years, the cumulative rate of progression was 11% at 1 year, 38% at 3 years and 55% at 5 years. On multivariate analysis, haemoglobin (Hb) ≤123 g/l [risk ratio (RR) 2·08; P = 0·009] and β₂ -microglobulin (β₂ M) ≥2·7 µg/ml (RR 2·0; P = 0·01) were independent predictors of a shorter time-to-progression (TTP) to active WM. Patients with myeloid differentiation factor 88 wild type (MYD88^WT ) genotype (n = 11) demonstrated a trend toward shorter TTP [median (95% CI) 1·7 (0·7-8·7) vs. 4·7 (2·4-7·7) years for the MYD88^L265P cohort, n = 42; P = 0·11]. The presence of C-X-C chemokine receptor type 4 (CXCR4) mutation (n = 29) did not impact the TTP (median: 3 years for CXCR4^WT vs. 5·6 years for CXCR4^MUT , P = 0·34). The overall survival (OS) for patients with SWM (median: 18·1 years) was comparable to an age-, sex- and calendar year-matched USA population (median: 20·3 years, P = 0·502). In conclusion, Hb and β₂ M at diagnosis represent independent predictors of progression to active WM. Comparable survival of SWM and a matched USA population argues against pre-emptive intervention in this patient population.

PMID:34340248 | DOI:10.1111/bjh.17691

Stat Med. 2021 Aug 2. doi: 10.1002/sim.9151. Online ahead of print.

ABSTRACT

In the statistical literature, a number of methods have been proposed to ensure valid inference about marginal effects of variables on a longitudinal outcome in settings with irregular monitoring times. However, the potential biases due to covariate-driven monitoring times and confounding have rarely been considered simultaneously, and never in a setting with an ordinal outcome and a continuous exposure. In this work, we propose and demonstrate a methodology for causal inference in such a setting, relying on a proportional odds model to study the effect of the exposure on the outcome. Irregular observation times are considered via a proportional rate model, and a generalization of inverse probability of treatment weights is used to account for the continuous exposure. We motivate our methodology by the estimation of the marginal (causal) effect of the time spent on video or computer games on suicide attempts in the Add Health study, a longitudinal study in the United States. Although in the Add Health data, observation times are prespecified, our proposed approach is applicable even in more general settings such as when analyzing data from electronic health records where observations are highly irregular. In simulation studies, we let observation times vary across individuals and demonstrate that not accounting for biasing imbalances due to the monitoring and the exposure schemes can bias the estimate for the marginal odds ratio of exposure.

PMID:34340246 | DOI:10.1002/sim.9151

Nature. 2021 Aug 2. doi: 10.1038/s41586-021-03843-2. Online ahead of print.

ABSTRACT

Enhancing vaccine uptake is a critical public health challenge¹. Overcoming vaccine hesitancy^2,3 and failure to follow-through on vaccination intentions³ requires effective communication strategies^3,4. We present two sequential randomized controlled trials (RCTs) to test the impact of behavioral interventions on COVID-19 vaccine uptake. We designed text-based reminders that make vaccination salient and easy, and delivered them to patients of a healthcare system one day (first RCT; N=93,354, clinicaltrials #NCT04800965) and eight days (second RCT; N=67,092, NCT04801524) after they received notification of vaccine eligibility. The first reminder boosted appointments and vaccination rates within the healthcare system by 6.07 (84%) and 3.57 (26%) percentage points, respectively; the second reminder increased those outcomes by 1.65 and 1.06 percentage points, respectively. The first reminder was more impactful when it made patients feel the vaccine was already theirs. However, we find no evidence that combining it with an information intervention addressing vaccine hesitancy heightened its effect. Online studies (N=3,181) examining vaccination intentions reveal divergent patterns from the first RCT, underscoring the importance of pilot-testing interventions in the field. These findings inform the design of behavioral nudges for promoting health decisions⁵, highlighting the value of making vaccination easy and inducing feelings of ownership.

PMID:34340242 | DOI:10.1038/s41586-021-03843-2

Gerontology. 2021 Aug 2:1-14. doi: 10.1159/000517659. Online ahead of print.

ABSTRACT

Youth, working age and the elderly: On a timeline, chronological age (CA) and biological age (BA) may dissociate; nosological entities manifest themselves at different BAs. In determining which disease corresponds to a given age decade, statistical registries of causes of death are unreliable and this does not change with SARS CoV-2 infection. Beyond adolescence, ageing metrics involve estimations of changes in fitness, including prediction models to estimate the number of remaining years left to live. A substantial disparity in biomarker levels and health status of ageing can be observed: the difference in CA and BA in the large cohorts under consideration is glaring. Here, we focus more closely on ageing and senescence metrics in order to make information available for risk analysis non the least with COVID-19, including the most recent risk factors of ABO blood type and 3p21.31 chromosome cluster impacting on C5a and SC5b-9 plasma levels. From the multitude of routine medical laboratory assays, a potentially meaningful set of assays aimed to best reflect the stage of individual senescence; hence risk factors the observational prospective SENIORLABOR study of 1,467 healthy elderly performed since 2009 and similar approaches since 1958 can be instantiated as a network to combine a set of elementary laboratory assays quantifying senescence.

PMID:34340235 | DOI:10.1159/000517659

Oncology. 2021 Aug 2:1-7. doi: 10.1159/000517738. Online ahead of print.

ABSTRACT

INTRODUCTION: Heterogeneous tumor response has been reported in cancer patients treated with immune checkpoint inhibitors (ICIs). This study investigated whether the tumor site is associated with the response to ICIs in patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC).

METHODS: Patients with ESCC who had measurable tumors in the liver, lung, or lymph node (LN) according to the response evaluation criteria in solid tumors (RECIST) 1.1 and received ICIs at 2 medical centers in Taiwan were enrolled. In addition to RECIST 1.1, tumor responses were determined per individual organ basis according to organ-specific criteria modified from RECIST 1.1. Fisher test or χ2 test was used for statistical analysis.

RESULTS: In total, 37 patients were enrolled. The overall response rate per RECIST 1.1 was 13.5%. Measurable tumors in the LN, lung, and liver were observed in 26, 17, and 13 patients, respectively. The organ-specific response rates were 26.9%, 29.4%, and 15.4% for the LN, lung, and liver tumors, respectively (p = 0.05). The organ-specific disease control rates were 69.2%, 52.9%, and 21.1% for the LN, lung, and liver tumors, respectively (p = 0.024). Five (27.8%) among 18 patients harboring at least 2 involved organs had heterogeneous tumor response.

CONCLUSION: The response and disease control to ICIs may differ in ESCC tumors located at different metastatic sites, with a lesser likelihood of response and disease control in metastatic liver tumors than in tumors located at the LNs and lung.

PMID:34340231 | DOI:10.1159/000517738

J Neural Eng. 2021 Aug 2. doi: 10.1088/1741-2552/ac19d3. Online ahead of print.

ABSTRACT

OBJECTIVE: Impaired trunk stability is frequent in spinal cord injury (SCI), but there is a lack of quantitative measures for assessing trunk function. Our objectives were to: 1) evaluate trunk muscle activity and movement patterns during a reaching task in SCI patients, 2) compare the impact of cervical (cSCI) and thoracic (tSCI) injuries in trunk function, and 3) investigate the effects of a startling acoustic stimulus (SAS) in these patients.

APPROACH: Electromyographic (EMG) and smartphone accelerometer data were recorded from 15 cSCI patients, 9 tSCI patients, and 24 healthy controls, during a reaching task requiring trunk tilting. We calculated the response time (RespT) until pressing a target button, EMG onset latencies and amplitudes, and trunk tilt, lateral deviation, and other movement features from accelerometry. Statistical analysis was applied to analyze the effects of group (cSCI, tSCI, control) and condition (SAS, non-SAS) in each outcome measure.

MAIN RESULTS: SCI patients, especially those with cSCI, presented significantly longer RespT and EMG onset latencies than controls. Moreover, in SCI patients, forward trunk tilt was accompanied by significant lateral deviation. RespT and EMG latencies were remarkably shortened by the SAS (the so-called StartReact effect) in tSCI patients and controls, but not in cSCI patients, who also showed higher variability.

SIGNIFICANCE: The combination of EMG and smartphone accelerometer data can provide quantitative measures for the assessment of trunk function in SCI. Our results show deficits in postural control and compensatory strategies employed by SCI patients, including delayed responses and higher lateral deviations, possibly to improve sitting balance. This is the first study investigating the StartReact responses in trunk muscles in SCI patients and shows that the SAS significantly accelerates RespT in tSCI, but not in cSCI, suggesting an increased cortical control exerted by these patients.

PMID:34340222 | DOI:10.1088/1741-2552/ac19d3

J Natl Compr Canc Netw. 2021 Jul;19(7):xliii. doi: 10.6004/jnccn.2021.7063.

NO ABSTRACT

PMID:34340213 | DOI:10.6004/jnccn.2021.7063

Nurse Educ Today. 2021 Jul 24;106:105080. doi: 10.1016/j.nedt.2021.105080. Online ahead of print.

ABSTRACT

BACKGROUND: Patient deterioration should be detected early and responded appropriately for patient safety. It is necessary to strengthen situational awareness regarding patient deterioration. Inattentional blindness is a major factor that hinders situational awareness about patient deterioration in the clinical setting.

OBJECTIVES: To analyze the impact of patient deterioration simulation using inattentional blindness (PDS-IB) on situational awareness and patient safety competency-attitude among final year nursing students.

DESIGN: A randomized controlled trial.

PARTICIPANTS: Final year nursing students at a university in South Korea.

METHODS: Students were randomly assigned to an experimental or control group. The experimental group (n = 47) was given a PDS-IB. The control group (n = 44) received a simple patient deterioration simulation. Situational awareness and patient safety competency-attitude were measured at baseline, post intervention, and at 2 weeks follow-up. Data were analyzed using a two-way repeated measures ANOVA.

RESULTS: There were statistically significant group effects, time effects, and group and time interaction effects in situational awareness and patient safety competency-attitude.

CONCLUSION: PDS-IB is an effective educational strategy that increases situational awareness and patient safety competency-attitude in final year nursing students.

PMID:34340194 | DOI:10.1016/j.nedt.2021.105080

J Anxiety Disord. 2021 Jul 9;83:102450. doi: 10.1016/j.janxdis.2021.102450. Online ahead of print.

ABSTRACT

Individuals with dental anxiety show biased attentional processing of threat- and dental-related information. Disgust sensitivity and anxiety sensitivity are both associated with dental fears and attentional biases. Whereas disgust sensitivity is generally associated with attentional avoidance (Armstrong et al., 2014), anxiety sensitivity may be associated with attentional engagement (Keogh et al., 2001a). Elucidating the role of these constructs in dental anxiety-relevant attentional biases could inform theoretical models and/or intervention recommendations. Participants (N = 51) with high dental anxiety completed a Posner paradigm to assess attentional biases to dental versus neutral stimuli. We examined whether disgust sensitivity and anxiety sensitivity moderated degree of attentional bias. Results indicated that both disgust sensitivity (mutilation subscale) and anxiety sensitivity (physical concerns subscale) statistically moderated degree of attentional bias at trend level, and in opposite directions. Simple effects analyses further indicated that disgust sensitivity regarding mutilation was associated with less attentional bias toward dental relative to neutral stimuli, potentially indicating attentional avoidance, and remained so when adjusting for anxiety sensitivity. In contrast, simple effects analysis indicated that anxiety sensitivity regarding physical concerns was not associated with magnitude of attentional bias. If replicated, findings highlight the potential role of disgust in dental anxiety.

PMID:34340171 | DOI:10.1016/j.janxdis.2021.102450

Int J Drug Policy. 2021 Jul 30;98:103383. doi: 10.1016/j.drugpo.2021.103383. Online ahead of print.

ABSTRACT

BACKGROUND: Naloxone distribution, a key global strategy to prevent fatal opioid overdose, has been a recent target of legislation in the U.S., but there is insufficient empirical evidence from causal inference methods to identify which components of these policies successfully reduce opioid-related harms. This study aimed to examine expert consensus on the effectiveness and implementability of various state-level naloxone policies.

METHODS: We used the online ExpertLens platform to conduct a three-round modified-Delphi process with a purposive sample of 46 key stakeholders (advocates, healthcare providers, human/social service practitioners, policymakers, and researchers) with naloxone policy expertise. The Effectiveness Panel (n = 24) rated average effects of 15 types of policies on naloxone pharmacy distribution, opioid use disorder (OUD) prevalence, nonfatal opioid-related overdoses, and opioid-related overdose mortality. The Implementation Panel (n = 22) rated the same policies on acceptability, feasibility, affordability, and equitability. We compared ratings across policies using medians and inter-percentile ranges, with consensus measured using the RAND/UCLA Appropriateness Method Inter-Percentile Range Adjusted for Symmetry technique.

RESULTS: Experts reached consensus on all items. Except for liability protections and required provision of education or training, experts perceived all policies to generate moderate-to-large increases in naloxone pharmacy distribution. However, only three policies were expected to yield substantive decreases on fatal overdose: statewide standing/protocol order, over-the-counter supply, and statewide “free naloxone.” Of these, experts rated only statewide standing/protocol orders as highly affordable and equitable, and unlikely to generate meaningful population-level effects on OUD or nonfatal opioid-related overdose. Across all policies, experts rated naloxone prescribing mandates relatively lower in acceptability, feasibility, affordability, and equitability.

CONCLUSION: Experts believe statewide standing/protocol orders are an effective, implementable, and equitable policy for addressing opioid-related overdose mortality. While experts believe many other broad policies are effective in reducing opioid-related harms, they also believe these policies face implementation challenges related to cost and reaching vulnerable populations.

PMID:34340167 | DOI:10.1016/j.drugpo.2021.103383