Tag: statistics

JMIR Res Protoc. 2022 Sep 22;11(9):e38788. doi: 10.2196/38788.

ABSTRACT

BACKGROUND: Chronic pain and access to care are identified as critical needs of the Veterans Health Administration. Music imagery and music listening interventions have shown promise as effective nonpharmacological options for pain management. However, most studies have focused on acute pain, passive music experiences, and in-person delivery.

OBJECTIVE: In this study, we aimed to examine the feasibility and acceptability of 2 music interventions delivered through telehealth for chronic musculoskeletal pain, trial design, and theoretical model before conducting a fully powered efficacy or comparative effectiveness trial.

METHODS: FAMILIA (Feasibility and Acceptability of Music Imagery and Listening Interventions for Analgesia) is a 3-arm, parallel group, pilot trial. A total of 60 veterans will be randomized to one of the three conditions: music imagery, music listening, or usual care. Aim 1 is to test the feasibility and acceptability of a multicomponent, interactive music imagery intervention (8-weekly, individual sessions) and a single-component, minimally interactive music learning intervention (independent music listening). Feasibility metrics related to recruitment, retention, engagement, and completion of the treatment protocol and questionnaires will be assessed. Up to 20 qualitative interviews will be conducted to assess veteran experiences with both interventions, including perceived benefits, acceptability, barriers, and facilitators. Interview transcripts will be coded and analyzed for emergent themes. Aim 2 is to explore the effects of music imagery and music listening versus usual care on pain and associated patient-centered outcomes. These outcomes and potential mediators will be explored through changes from baseline to follow-up assessments at 1, 3, and 4 months. Descriptive statistics will be used to describe outcomes; this pilot study is not powered to detect differences in outcomes.

RESULTS: Recruitment for FAMILIA began in March 2022, and as of July 2022, 16 participants have been enrolled. We anticipate that enrollment will be completed by May 2023. We expect that music imagery and music listening will prove acceptable to veterans and that feasibility benchmarks will be reached. We hypothesize that music imagery and music listening will be more effective than usual care on pain and related outcomes.

CONCLUSIONS: FAMILIA addresses four limitations in music intervention research for chronic pain: limited studies in veterans, evaluation of a multicomponent music intervention, methodological rigor, and internet-based delivery. Findings from FAMILIA will inform a fully powered trial to identify putative mechanisms and test efficacy.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05426941; https://tinyurl.com/3jdhx28u.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38788.

PMID:36136377 | DOI:10.2196/38788

Hum Vaccin Immunother. 2022 Sep 22:2122379. doi: 10.1080/21645515.2022.2122379. Online ahead of print.

ABSTRACT

Influenza causes significant mortality and morbidity in the United States (US). Employees are exposed to influenza at work and can spread it to others. The influenza vaccine is safe, effective, and prevents severe outcomes; however, coverage among US adults (50.2%) is below Healthy People 2030 target of 70%. These highlights need for more effective vaccination promotion interventions. Understanding predictors of vaccination acceptance could inform vaccine promotion messages, improve coverage, and reduce illness-related work absences. We aimed to identify factors influencing influenza vaccination among US non-healthcare workers. Using mixed-methods approach, we evaluated factors influencing influenza vaccination among employees in three US companies during April-June 2020. Survey questions were adapted from the WHO seasonal influenza survey. Most respondents (n = 454) were women (272, 59.9%), 20-39 years old (n = 250, 55.1%); white (n = 254, 56.0%); had a college degree (n = 431, 95.0%); and reported receiving influenza vaccine in preceding influenza season (n = 297, 65.4%). Logistic regression model was statistically significant, X (16, N = 450) = 31.6, p = .01. Education [(OR) = 0.3, 95%CI = 0.1-0.6)] and race (OR = 0.4, 95%CI = 0.2-0.8) were significant predictors of influenza vaccine acceptance among participants. The majority had favorable attitudes toward influenza vaccination and reported that physician recommendation would influence their vaccination decisions. Seven themes were identified in qualitative analysis: “Protecting others” (109, 24.0%), “Protecting self” (105, 23.1%), “Vaccine accessibility” (94, 20.7%), “Education/messaging” (71, 15.6%), “Policies/requirements” (15, 3.3%), “Reminders” (9, 2.0%), and “Incentives” (3, 0.7%). Our findings could facilitate the development of effective influenza vaccination promotion messages and programs for employers, and workplace vaccination programs for other diseases such as COVID-19, by public health authorities.

PMID:36136345 | DOI:10.1080/21645515.2022.2122379

JAMA Netw Open. 2022 Sep 1;5(9):e2231930. doi: 10.1001/jamanetworkopen.2022.31930.

ABSTRACT

IMPORTANCE: Approximately 50% of all patients with cancer have an indication for radiotherapy, and approximately 50% of radiotherapy is delivered with palliative intent, with the aim of alleviating symptoms. Symptoms are best assessed by patient-reported outcomes (PROs), yet their reliable interpretation requires adequate reporting in publications.

OBJECTIVE: To investigate the use and reporting of PROs in clinical trials of palliative radiotherapy.

EVIDENCE REVIEW: This preregistered systematic review searched PubMed/Medline, EMBASE, and the Cochrane Center Register of Controlled Trials for clinical trials of palliative radiotherapy published from 1990 to 2020. Key eligibility criteria were palliative setting, palliative radiotherapy as treatment modality, and clinical trial design (per National Institutes of Health definition). Two authors independently assessed eligibility. Trial characteristics were extracted and standard of PRO reporting was assessed in adherence to the Consolidated Standards of Reporting Trials (CONSORT) PRO extension. The association of the year of publication with the use of PROs was assessed by logistic regression. Factors associated with higher CONSORT-PRO adherence were analyzed by multiple regression. This study is reported following the PRISMA guidelines.

FINDINGS: Among 7377 records screened, 225 published clinical trials representing 24 281 patients were eligible. Of these, 45 trials (20%) used a PRO as a primary end point and 71 trials (31%) used a PRO as a secondary end point. The most prevalent PRO measures were the Numeric Rating Scale/Visual Analogue Scale (38 trials), European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (32 trials), and trial-specific unvalidated measures (25 trials). A more recent year of publication was significantly associated with a higher chance of PROs as a secondary end point (odds ratio [OR], 1.04 [95% CI, 1.00-1.07]; P = .03) but not as primary end point. Adherence to CONSORT-PRO was poor or moderate for most items. Mean (SD) adherence to the extension adherence score was 46.2% (19.6%) for trials with PROs as primary end point and 31.8% (19.8%) for trials with PROs as a secondary end point. PROs as a primary end point (regression coefficient, 9.755 [95% CI, 2.270-17.240]; P = .01), brachytherapy as radiotherapy modality (regression coefficient, 16.795 [95% CI, 5.840-27.751]; P = .003), and larger sample size (regression coefficient, 0.028 [95% CI, 0.006-0.049]; P = .01) were significantly associated with better PRO reporting per extension adherence score.

CONCLUSIONS AND RELEVANCE: In this systematic review of palliative radiotherapy trials, the use and reporting of PROs had room for improvement for future trials, preferably with PROs as a primary end point.

PMID:36136335 | DOI:10.1001/jamanetworkopen.2022.31930

JAMA Netw Open. 2022 Sep 1;5(9):e2232576. doi: 10.1001/jamanetworkopen.2022.32576.

ABSTRACT

IMPORTANCE: Obtaining follow-up blood cultures (FUBCs) in patients with Staphylococcus aureus bloodstream infection (BSI) is standard practice, although its utility in patients with gram-negative bacterial BSI (GN-BSI) is unclear.

OBJECTIVE: To examine whether obtaining FUBCs is associated with decreased mortality (key question [KQ] 1) and whether positive vs negative FUBCs are associated with increased mortality (KQ2).

DATA SOURCES: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and gray literature were searched from inception to March 11, 2022.

STUDY SELECTION: Two investigators used predefined eligibility criteria to independently screen titles, abstracts, and relevant full texts. Randomized clinical trials or observational studies that matched or statistically adjusted for differences in, at minimum, level of acute illness between patients in the intervention (eg, FUBCs obtained) and control (eg, FUBCs not obtained) groups were included in primary analyses. Articles published in languages other than English were excluded.

DATA EXTRACTION AND SYNTHESIS: Data abstraction and quality assessments were performed by one investigator and verified by a second investigator. Risk of bias was assessed with the Newcastle-Ottawa Scale. Effect sizes were pooled using random-effects models. The study followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline.

MAIN OUTCOMES AND MEASURES: Mortality before hospital discharge or up to 30 days from the index blood culture.

RESULTS: From 3495 studies, 15 were included (all nonrandomized). In the 5 studies (n = 4378 patients) that met criteria for the KQ1 primary analysis, obtaining FUBCs was associated with decreased mortality (hazard ratio, 0.56; 95% CI, 0.45-0.71). For KQ2, 2 studies met criteria for the primary analysis (ie, matched or statistically adjusted for differences in patients with positive vs negative FUBCs), so an exploratory meta-analysis of all 9 studies that investigated KQ2 (n = 3243 patients) was performed. Positive FUBCs were associated with increased mortality relative to negative blood cultures (odds ratio, 2.27; 95% CI, 1.54-3.34). Limitations of the literature included a lack of randomized studies and few patient subgroup analyses.

CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, obtaining FUBCs in patients with GN-BSI was associated with decreased mortality. The benefit of FUBCs may stem from identification of patients with positive FUBCs, which was a poor prognostic marker.

PMID:36136334 | DOI:10.1001/jamanetworkopen.2022.32576

JAMA Netw Open. 2022 Sep 1;5(9):e2232787. doi: 10.1001/jamanetworkopen.2022.32787.

ABSTRACT

IMPORTANCE: National Comprehensive Cancer Network guidelines currently recommend germline testing for high-risk genes in selected patients with breast cancer. The clinical utility of recommending testing all patients with breast cancer with multigene panels is currently under consideration.

OBJECTIVE: To examine the implications of universal testing of patients with breast cancer with respect to clinical decision-making.

DESIGN, SETTING, AND PARTICIPANTS: Patients from a previously reported cohort were assessed as in-criteria or out-of-criteria according to the 2017 guidelines and underwent testing with a multigene germline panel between 2017 to 2018. Patients were women and men aged 18 to 90 years, with a new and/or previous diagnosis of breast cancer who had not undergone either single or multigene testing. Clinicians from 20 community and academic sites documented patient clinical information and changes to clinical recommendations made according to test findings. Association between prevalence of pathogenic or likely pathogenic germline variants and previously unreported clinical features, including scores generated by the BRCAPRO statistical model, was determined. Data were analyzed from April 2020 to May 2022.

EXPOSURE: New and/or previous diagnosis of breast cancer.

MAIN OUTCOMES AND MEASURES: Disease management recommendations that were changed as a result of genetic testing results are reported.

RESULTS: Clinicians were asked to assess changes to clinical management as a result of germline genetic testing for 952 patients. Informative clinician-reported recommendations were provided for 939 (467 in-criteria and 472 out-of-criteria) of the patients with breast cancer (936 [99.7%] female; 702 [74.8%] White; mean [SD] age at initial diagnosis, 57.6 [11.5] years). One or more changes were reported for 31 of 37 (83.8%) in-criteria patients and 23 of 34 (67.6%) out-of-criteria patients with a pathogenic or likely pathogenic variant. Recommendations were changed as a result of testing results for 14 of 22 (63.6%) out-of-criteria patients who had a variant in a breast cancer predisposition gene. Clinicians considered testing beneficial for two-thirds of patients with pathogenic or likely pathogenic variants and for one-third of patients with either negative results or variants of uncertain significance. There was no difference in variant rate between patients meeting the BRCAPRO threshold (≥10%) and those who did not (P = .86, Fisher exact test). No changes to clinical recommendations were made for most patients with negative results (345 of 349 patients [98.9%]) or variants of uncertain significance (492 of 509 patients [96.7%]).

CONCLUSIONS AND RELEVANCE: In this cohort study, germline genetic testing was used by clinicians to direct treatment for most out-of-criteria patients with breast cancer with pathogenic or likely pathogenic germline variants, including those with moderate-risk variants. Universal germline testing informs clinical decision-making and provides access to targeted treatments and clinical trials for all patients with breast cancer.

PMID:36136330 | DOI:10.1001/jamanetworkopen.2022.32787

JAMA Otolaryngol Head Neck Surg. 2022 Sep 22. doi: 10.1001/jamaoto.2022.2840. Online ahead of print.

ABSTRACT

IMPORTANCE: Intraoperative margin assessment is an important technique for ensuring complete tumor resection in malignant cancers. However, in patients undergoing transoral robotic surgery (TORS) for oropharyngeal carcinomas, tissue artifact may provide pathologic uncertainty.

OBJECTIVE: To assess the benefit of providing frozen section control samples (“positive tumor biopsies”) for use during intraoperative margin assessment for patients undergoing TORS for human papillomavirus (HPV)-16-positive oropharyngeal squamous cell carcinoma (OPSCC).

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, patients receiving curative-intent TORS for biopsy-proven HPV-16-positive OPSCC performed by a single attending surgeon (A.H.M.) at Ronald Reagan UCLA Medical Center from 2017 to 2021 were included in a retrospective data analysis. Exclusion criteria included HPV-negative status, participation in clinical trials, and tumors of unknown primary origin.

MAIN OUTCOMES AND MEASURES: Survival outcomes investigated included overall and disease-free survival. Adverse pathologic outcomes measured included occurrence of nondiagnostic margins and margin reversal from frozen to fixed pathology.

RESULTS: Of the 170 patients included (mean [SD] age, 61.8 [9.9] years; 140 [82%] male), 50% of patients (n = 85) received a frozen section control. Use of a frozen section control was associated with statistically significantly improved sensitivity of intraoperative margin assessment, from 82.8% to 88.9% (difference, 6.1%; 95% CI, 3.9%-8.3%). Eleven percent (n = 18) of all tumors evaluated exhibited at least 1 nondiagnostic intraoperative margin, and 11% (n = 18) experienced margin reversal from frozen to fixed pathology. In patients with nondiagnostic margins, use of frozen section controls was associated with statistically significantly reduced time spent in the operating room (Cohen d, 1.14; 95% CI, 0.12-2.14).

CONCLUSIONS AND RELEVANCE: In this cohort study, frozen intraoperative margins assessed during TORS resections of HPV-16-positive OPSCC were diagnostically challenging. Adverse pathologic outcomes, such as margin status reversal from positive on frozen pathology to negative on formal analysis, were common. Providing intraoperative frozen section control biopsies may offer clarity in cases with nondiagnostic margins, reducing the need for additional sampling and time spent in the operating room.

PMID:36136328 | DOI:10.1001/jamaoto.2022.2840

JAMA Ophthalmol. 2022 Sep 22. doi: 10.1001/jamaophthalmol.2022.3667. Online ahead of print.

ABSTRACT

IMPORTANCE: A bayesian network meta-analysis (NMA) can help compare the various types of multifocal and monofocal intraocular lenses (IOLs) used in clinical practice.

OBJECTIVE: To compare outcomes of presbyopia-correcting IOLs frequently recommended in clinical practice through a bayesian NMA based on a systematic review.

DATA SOURCES: Medline (PubMed) and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched on May 15, 2021, from inception.

STUDY SELECTION: Based on the research question, randomized clinical trials assessing multifocal IOLs in patients who underwent bilateral cataract extraction were searched. Nonrandomized studies, studies in patients with unilateral or contralateral cataract extractions, duplicated studies, conference abstracts, and nonpeer-reviewed articles were excluded.

DATA EXTRACTION AND SYNTHESIS: Descriptive statistics and outcomes were extracted. The NMA was conducted to compare different types of IOLs. The mean differences for continuous variables, odds ratios for binary variables, 95% credible intervals (CrIs), and ranks of interventions were estimated.

MAIN OUTCOMES AND MEASURES: The outcomes examined included binocular visual acuities by distance and optical quality, including glare, halos, and spectacle independence.

RESULTS: This NMA included 27 studies comprising 2605 patients. For uncorrected near visual acuity, trifocal IOLs (mean difference, -0.32 [95% CrI, -0.46 to -0.19]) and old bifocal diffractive IOLs (mean difference, -0.33 [95% CrI, -0.50 to -0.14]) afforded better visual acuity than monofocal IOLs. Regarding uncorrected intermediate visual acuity, extended depth-of-focus IOLs provided better visual acuity than monofocal IOLs. However, there were no differences between extended depth-of-focus and trifocal diffractive IOLs in pairwise comparisons. For uncorrected distant visual acuity, all multifocal IOLs were comparable with monofocal IOLs. There were no statistical differences between multifocal and monofocal IOLs regarding contrast sensitivity, glare, or halos.

CONCLUSIONS AND RELEVANCE: For patients considering a multifocal IOL due to presbyopia, bilateral implantation of a trifocal IOL might be an optimal option for patients without compromising distant visual acuity.

PMID:36136323 | DOI:10.1001/jamaophthalmol.2022.3667

JAMA Oncol. 2022 Sep 22. doi: 10.1001/jamaoncol.2022.4071. Online ahead of print.

ABSTRACT

IMPORTANCE: Germline CHEK2 pathogenic variants (PVs) are frequently detected by multigene cancer panel testing (MGPT), but our understanding of PVs beyond c.1100del has been limited.

OBJECTIVE: To compare cancer phenotypes of frequent CHEK2 PVs individually and collectively by variant type.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was carried out in a single diagnostic testing laboratory from 2012 to 2019. Overall, 3783 participants with CHEK2 PVs identified via MGPT were included. Medical histories of cancer in participants with frequent PVs, negative MGPT (wild type), loss-of-function (LOF), and missense were compared.

MAIN OUTCOMES AND MEASURES: Participants were stratified by CHEK2 PV type. Descriptive statistics were summarized including median (IQR) for continuous variables and proportions for categorical characteristics. Differences in age and proportions were assessed with Wilcoxon rank sum and Fisher exact tests, respectively. Frequencies, odds ratios (ORs), 95% confidence intervals were calculated, and P values were corrected for multiple comparisons where appropriate.

RESULTS: Of the 3783 participants with CHEK2 PVs, 3473 (92%) were female and most reported White race. Breast cancer was less frequent in participants with p.I157T (OR, 0.66; 95% CI, 0.56-0.78; P<.001), p.S428F (OR, 0.59; 95% CI. 0.46-0.76; P<.001), and p.T476M (OR, 0.74; 95% CI, 0.56-0.98; P = .04) PVs compared with other PVs and an association with nonbreast cancers was not found. Following the exclusion of p.I157T, p.S428F, and p.T476M, participants with monoallelic CHEK2 PV had a younger age at first cancer diagnosis (P < .001) and were more likely to have breast (OR, 1.83; 95% CI, 1.66-2.02; P < .001), thyroid (OR, 1.63; 95% CI, 1.26-2.08; P < .001), and kidney cancer (OR, 2.57; 95% CI, 1.75-3.68; P < .001) than the wild-type cohort. Participants with a CHEK2 PV were less likely to have a diagnosis of colorectal cancer (OR, 0.62; 95% CI, 0.51-0.76; P < .001) compared with those in the wild-type cohort. There were no significant differences between frequent CHEK2 PVs and c.1100del and no differences between CHEK2 missense and LOF PVs.

CONCLUSIONS AND RELEVANCE: CHEK2 PVs, with few exceptions (p.I157T, p.S428F, and p.T476M), were associated with similar cancer phenotypes irrespective of variant type. CHEK2 PVs were not associated with colorectal cancer, but were associated with breast, kidney, and thyroid cancers. Compared with other CHEK2 PVs, the frequent p.I157T, p.S428F, and p.T476M alleles have an attenuated association with breast cancer and were not associated with nonbreast cancers. These data may inform the genetic counseling and care of individuals with CHEK2 PVs.

PMID:36136322 | DOI:10.1001/jamaoncol.2022.4071

J Appl Lab Med. 2022 Sep 22:jfac069. doi: 10.1093/jalm/jfac069. Online ahead of print.

ABSTRACT

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) is a biomarker used for risk prediction for cardiovascular disease by assessing low concentration of inflammation. Measurements of regular CRP have become very sensitive with a lower detection limit of 0.3 mg/L. This study aimed to compare and explore the association between CRP and hs-CRP.

METHODS: Data from 607 consecutive patients referred for cardiovascular risk assessment with hs-CRP were reviewed retrospectively. In total, 570 patients were included in the analysis and classified into 3 (low-, medium-, and high-risk) groups (hs-CRP cutoff: <1, 1-3, >3 mg/L). Correlation between hs-CRP and CRP was assessed with the kappa statistic and visualized with a Bland-Altman plot. The association between hs-CRP and occurrence of the composite outcome (acute myocardial infarction, stroke, coronary intervention [percutaneous coronary intervention or bypass surgery], or death) was determined with Cox regression analysis and visualized with Kaplan-Meier curves.

RESULTS: A total number reclassification occurred in 8.6% of the cases for CRP risk groups, which demonstrates an agreement of 91.4% (kappa 0.87; P < 0.001). The correlation between CRP and hs-CRP was significant (P < 0.001), Spearman regression R2 = 0.98. A Bland-Altman plot displayed an average difference of 0.19 mg/L (95%CI, 0.17 to 0.23) between the CRP and hs-CRP. Cardiovascular events were more likely to occur in patients who were older, with hs-CRP or CRP >3 mg/L and a history of coronary artery disease.

CONCLUSIONS: The usual laboratory tests for CRP values in the lower range highly correlate with the hs-CRP tests and can therefore replace the costlier hs-CRP measurements.

PMID:36136302 | DOI:10.1093/jalm/jfac069

Int Urol Nephrol. 2022 Sep 22. doi: 10.1007/s11255-022-03368-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Hemodialysis (HD) patients are at increased risk of severe COVID-19 infection but infection rates vary. Our objectives are to describe COVID-19 positive HD patients’ characteristics, infection rates, and factors associated with mortality in HD COVID-19 cases in Kuwait.

METHODS: Data on demographics, comorbidities, and treatments received, as well as mortality for HD patients admitted to hospitals for COVID-19, from 1/March to 31/July 2020, prospectively collected and analyzed.

RESULTS: A total of 141 infected HD patients were admitted (Mean age 58 ± 16.1; Males 56%), representing 7% of the total HD population and 0.2% of all COVID-19 cases during the study period. Of those 141 infected HD patients, 27 (19%) died, and this represents 6% of total COVID-19-related mortality and 27% of the total HD mortality. In contrast, total covid-19-related mortality of all positive cases was only 0.7%, and total HD mortality during the study period was only 5%. COVID-19-positive HD patients who died were older and 59% were males. However, the differences were not statistically significant. Of the 61 infected HD patients who needed to be switched to continuous kidney replacement therapy (CKRT), 34% died, and of the 29 infected HD patients who needed admission to intensive care, 65% died.

CONCLUSION: HD population represents a small fraction of the total population; however, positive HD COVID-19 cases represent a sizable proportion of COVID-19 cases and a significant percentage of total COVID-19-related mortality, and total HD mortality.

PMID:36136260 | DOI:10.1007/s11255-022-03368-1