Tag: nevin manimala

Am J Public Health. 2023 Sep 21:e1-e9. doi: 10.2105/AJPH.2023.307381. Online ahead of print.

ABSTRACT

Data System. The UK Department of Health and Social Care funded the REal-time Assessment of Community Transmission-2 (REACT-2) study to estimate community prevalence of SARS-CoV-2 IgG (immunoglobulin G) antibodies in England. Data Collection/Processing. We obtained random cross-sectional samples of adults from the National Health Service (NHS) patient list (near-universal coverage). We sent participants a lateral flow immunoassay (LFIA) self-test, and they reported the result online. Overall, 905 991 tests were performed (28.9% response) over 6 rounds of data collection (June 2020-May 2021). Data Analysis/Dissemination. We produced weighted estimates of LFIA test positivity (validated against neutralizing antibodies), adjusted for test performance, at local, regional, and national levels and by age, sex, and ethnic group and area-level deprivation score. In each round, fieldwork occurred over 2 weeks, with results reported to policymakers the following week. We disseminated results as preprints and peer-reviewed journal publications. Public Health Implications. REACT-2 estimated the scale and variation in antibody prevalence over time. Community self-testing and -reporting produced rapid insights into the changing course of the pandemic and the impact of vaccine rollout, with implications for future surveillance. (Am J Public Health. Published online ahead of print September 21, 2023:e1-e9. https://doi.org/10.2105/AJPH.2023.307381).

PMID:37733993 | DOI:10.2105/AJPH.2023.307381

JCO Oncol Pract. 2023 Sep 21:OP2300038. doi: 10.1200/OP.23.00038. Online ahead of print.

ABSTRACT

PURPOSE: Treatment-associated symptoms drive early discontinuation of adjuvant endocrine therapy (ET) for breast cancer. We hypothesized that symptom monitoring with electronic patient-reported outcomes (ePROs) during adjuvant ET will enhance symptom detection, symptom management, and persistence.

METHODS: Eligible patients were initiating ET for stage 0-III breast cancer. Participants completed ePRO surveys via smartphone at baseline and 1, 3, 6, and 12 months. Measures included Patient-Reported Outcomes Measurement Information System Anxiety, Depression, Fatigue, and Vaginal Discomfort; plus Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items assessing joint pain, hot flashes, vaginal dryness, concentration problems, and memory problems. Scores surpassing prespecified thresholds triggered alerts, and recommended symptom management pathways were provided to clinicians. The primary objective was to evaluate feasibility, assessed by survey completion rates, with targets of >65% for the baseline survey and ≥1 follow-up survey during the first 6 months. Secondary objectives included 12-month ET discontinuation rate (target: ≤15%), describing symptoms and evaluating pathway implementation.

RESULTS: Among 250 participants, 73.2% completed the baseline survey and 69.6% completed ≥1 follow-up survey during the first 6 months. Thirty-one percent of participants had ≥1 symptom alert at baseline and 74% had ≥1 symptom alert during follow-up. The proportions of participants for whom pathway-concordant symptom management was documented at each time point ranged from 12.8% to 36.6%. Twenty-eight participants (11.2%) discontinued ET by 12 months.

CONCLUSION: Symptom monitoring with ePROs during adjuvant ET is feasible. Despite infrequent documentation of pathway-concordant symptom management after symptom alerts, ePROs were associated with favorable short-term ET persistence.

PMID:37733984 | DOI:10.1200/OP.23.00038

JCO Oncol Pract. 2023 Sep 21:OP2300007. doi: 10.1200/OP.23.00007. Online ahead of print.

ABSTRACT

PURPOSE: Germline genetic testing (GT) is recommended for men with prostate cancer (PC), but testing through traditional models is limited. The ProGen study examined a novel model aimed at providing access to GT while promoting education and informed consent.

METHODS: Men with potentially lethal PC (metastatic, localized with a Gleason score of ≥8, persistent prostate-specific antigen after local therapy), diagnosis age ≤55 years, previous malignancy, and family history suggestive of a pathogenic variant (PV) and/or at oncologist’s discretion were randomly assigned 3:1 to video education (VE) or in-person genetic counseling (GC). Participants had 67 genes analyzed (Ambry), with results disclosed via telephone by a genetic counselor. Outcomes included GT consent, GT completion, PV prevalence, and survey measures of satisfaction, psychological impact, genetics knowledge, and family communication. Two-sided Fisher’s exact tests were used for between-arm comparisons.

RESULTS: Over a 2-year period, 662 participants at three sites were randomly assigned and pretest VE (n = 498) or GC (n = 164) was completed by 604 participants (VE, 93.1%; GC, 88.8%), of whom 596 participants (VE, 98.9%; GC, 97.9%) consented to GT and 591 participants completed GT (VE, 99.3%; GC, 98.6%). These differences were not statistically significant although subtle differences in satisfaction and psychological impact were. Notably, 84 PVs were identified in 78 participants (13.2%), with BRCA1/2 PV comprising 32% of participants with a positive result (BRCA2 n = 21, BRCA1 n = 4).

CONCLUSION: Both VE and traditional GC yielded high GT uptake without significant differences in outcome measures of completion, GT uptake, genetics knowledge, and family communication. The increased demand for GT with limited genetics resources supports consideration of pretest VE for patients with PC.

PMID:37733980 | DOI:10.1200/OP.23.00007

JCO Oncol Pract. 2023 Sep 21:OP2300117. doi: 10.1200/OP.23.00117. Online ahead of print.

ABSTRACT

PURPOSE: Evidence supporting social media-based recruitment of cancer survivors is limited. This paper describes how we used Facebook during the COVID-19 pandemic to augment our recruitment of breast cancer survivors for our two-site telephone-based randomized clinical trial (RCT) at Dartmouth-Hitchcock Medical Center and the University of Alabama at Birmingham.

METHODS: Originally a two-site RCT of a telephone-delivered breast cancer survivorship intervention, we extended our clinic-based recruitment to Facebook. Participant characteristics, geographic reach, and baseline outcomes were compared across recruitment sources (ie, two clinics and Facebook) using descriptive statistics and effect sizes.

RESULTS: Enrollment rates (20%-29%) were comparable across recruitment sources. The 21-month Facebook marketing campaign accounted for 59% (n = 179/303) of our total sample and had the greatest geographic reach, recruiting women from 24 states. The Facebook campaign reached a total of 51,787 unique individuals and cost $88.44 in US dollars (USD) per enrolled participant. Clinic samples had a greater proportion of women who were widowed (8% v 1%; P = .03) and Facebook had a higher proportion of women with a household income over $40,000 USD (83% v 71%; P = .02). There were no statistically significant differences between Facebook and the two clinics on baseline survey scores.

CONCLUSION: Augmenting traditional recruitment with Facebook increased our RCT’s geographic and sociodemographic reach and supported meeting recruitment goals in a timely way. In the wake of the COVID-19 pandemic, cancer survivorship researchers should consider using social media as a recruitment strategy while weighing the advantages and potential biases introduced through such strategies.

PMID:37733975 | DOI:10.1200/OP.23.00117

Otol Neurotol. 2023 Sep 15. doi: 10.1097/MAO.0000000000004014. Online ahead of print.

ABSTRACT

OBJECTIVE: Investigate the relationship between Vestibular Migraine Patient Assessment Tool and Handicap Inventory (VM-PATHI) scores and daily dizziness symptoms.

STUDY DESIGN: Prospective cohort analysis of 52 patients with vestibular migraine (VM).

SETTING: Tertiary referral center.

PATIENTS: Fifty-two patients diagnosed with VM or probable VM according to Barany Society criteria.

INTERVENTIONS: Subjects reported their dizzy symptoms (on a scale of 0 [no symptoms], 1 [mild], 2 [moderate], and 3 [severe]) every day for 1 month via automated text messaging linked to a cloud-based research database. Subjects completed VM-PATHI and Dizziness Handicap Inventory (DHI) scores at the end of the month. We examined the correlation between a composite of daily dizziness scores with VM-PATHI and DHI scores through linear regression and correlation analysis.

MAIN OUTCOME MEASURES: Pearson correlation coefficient, R2 value.

RESULTS: VM-PATHI showed a moderate correlation with daily dizziness symptoms (correlation coefficient, 0.51). DHI showed a lower correlation with daily dizziness (correlation coefficient, 0.38). VM-PATHI score was a strong predictor of daily dizziness with univariate linear regression (R2 = 0.26, p = 0.001). In a multiple linear regression model with age, history of anxiety and/or depression, and VM-PATHI, the VM-PATHI score was the only statistically significant predictor of daily dizziness (p < 0.001).

CONCLUSIONS: Daily dizziness symptoms are better correlated with VM-PATHI score than the DHI, providing further validation of VM-PATHI as a disease-specific outcome measure for patients with VM.

PMID:37733970 | DOI:10.1097/MAO.0000000000004014

J Bone Joint Surg Am. 2023 Sep 21. doi: 10.2106/JBJS.22.01302. Online ahead of print.

ABSTRACT

BACKGROUND: Periprosthetic fractures are rare but devastating complications of knee replacement, often requiring complex surgery with substantial morbidity and mortality. It is not known how the fracture rates after total knee replacement (TKR) and unicompartmental knee replacement (UKR) compare. We performed the first matched study comparing TKR and UKR periprosthetic fracture rates.

METHODS: This study involved 54,215 UKRs and 54,215 TKRs, identified in the National Joint Registry and Hospital Episodes Statistics database, which were propensity score-matched on patient and surgical factors. The International Classification of Diseases, Tenth Revision, (ICD-10) code M96.6 was used to identify periprosthetic fractures at ≤3 and >3 months postoperatively, as well as estimate rates at up to 10 years. Subgroup analyses were performed in different age groups (<55, 55 to 64, 65 to 74, and ≥75 years), body mass index (BMI) categories (normal, 18.5 to <25 kg/m2; overweight, 25 to <30 kg/m2; obese, 30 to <40 kg/m2; and morbidly obese, ≥40 kg/m2), and sexes.

RESULTS: The 3-month fracture rate was 0.09% (n = 50) in the UKR group and 0.05% (n = 25) in the TKR group, with this difference being significant (odds ratio [OR], 2.0; p = 0.004). The rate of fractures occurring at >3 months was 0.32% (n = 171) in the UKR group and 0.61% (n = 329) in the TKR group (OR, 0.51; p < 0.001). At 10 years, the cumulative incidence of fractures was 0.6% after UKR versus 1% after TKR (OR, 0.68; p < 0.001). Fracture rates increased with increasing age, decreasing BMI, and female sex for both UKRs and TKRs.

CONCLUSIONS: The fracture risk was small after both UKR and TKR, with small absolute differences between implant types. During the first 3 postoperative months, the fracture rate after UKR was 0.1% and was about twice as high as that after TKR. However, over the first 10 years, the cumulative fracture rate after TKR was 1% and was almost twice as high as that after UKR. Fracture rates after both UKR and TKR were higher in women, patients ≥75 years of age, and patients with normal weight.

LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

PMID:37733918 | DOI:10.2106/JBJS.22.01302

J Bone Joint Surg Am. 2023 Sep 21. doi: 10.2106/JBJS.23.00252. Online ahead of print.

ABSTRACT

BACKGROUND: Despite the fact that many synovial fluid biomarkers have found application in the routine diagnosis of periprosthetic joint infection (PJI), this process still remains a challenge for orthopaedic surgeons. To simplify this process, fast point-of-care (POC) tests can be used during ambulatory visits and in operating room conditions. However, before such tests can be routinely used in clinical practice, they require validation. The purpose of the present study was to evaluate the diagnostic accuracy of different fast POC tests for detecting C-reactive protein (CRP) in synovial fluid for the diagnosis of PJI.

METHODS: Synovial fluid samples were collected from 120 consecutive patients who underwent revision total joint arthroplasty (TJA). The patients were divided into 2 groups. The first group included 76 patients who underwent revision for reasons other than infection (the aseptic revision TJA [arTJA] group), and the second group included 44 patients who underwent revision because of periprosthetic joint infection (PJI). The diagnosis of infection was made according to the International Consensus Meeting (ICM) 2018 criteria. All patients were operatively treated at a single orthopaedic center from January 2022 to February 2023. Four fast CRP tests with different cutoff values (1 and 3 mg/L, ≥8 mg/L, ≥10 mg/L [cassette], ≥10 mg/L [strip]) were used off-label for synovial fluid testing. Tests were performed on the same synovial fluid samples, and the results of these tests were compared with those obtained with the laboratory method.

RESULTS: The cassette test with a minimum cutoff value of ≥8 mg/L demonstrated the best accuracy for the diagnosis of chronic PJI, with a sensitivity and specificity of 90.9% and 90.8%, respectively. For the cassette test with a cutoff value of >3 mg/L, the sensitivity and specificity were 68.2% and 77.6%, respectively. For the tests with a minimum cutoff value of ≥10 mg/L, the sensitivity and specificity were 77.3% and 94.7%, respectively, for the cassette test and 77.3% and 96.1%, respectively, for the strip test. The laboratory method with the statistically calculated threshold (2.7 mg/L) revealed the highest AUC (area under the receiver operating characteristic curve) value (0.95), with 90.9% sensitivity and 94.7% specificity.

CONCLUSIONS: The cassette POC test with the minimum cutoff value of ≥8 mg/L had very good accuracy for the diagnosis of chronic PJI. This test had comparable sensitivity and slightly lower specificity in comparison with the laboratory method with the calculated threshold of 2.7 mg/L.

LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

PMID:37733911 | DOI:10.2106/JBJS.23.00252

Science. 2023 Sep 22;381(6664):eadg7492. doi: 10.1126/science.adg7492. Epub 2023 Sep 22.

ABSTRACT

The vast majority of missense variants observed in the human genome are of unknown clinical significance. We present AlphaMissense, an adaptation of AlphaFold fine-tuned on human and primate variant population frequency databases to predict missense variant pathogenicity. By combining structural context and evolutionary conservation, our model achieves state-of-the-art results across a wide range of genetic and experimental benchmarks, all without explicitly training on such data. The average pathogenicity score of genes is also predictive for their cell essentiality, capable of identifying short essential genes that existing statistical approaches are underpowered to detect. As a resource to the community, we provide a database of predictions for all possible human single amino acid substitutions and classify 89% of missense variants as either likely benign or likely pathogenic.

PMID:37733863 | DOI:10.1126/science.adg7492

Science. 2023 Sep 22;381(6664):eadd1250. doi: 10.1126/science.add1250. Epub 2023 Sep 22.

ABSTRACT

Short tandem repeats (STRs) are enriched in eukaryotic cis-regulatory elements and alter gene expression, yet how they regulate transcription remains unknown. We found that STRs modulate transcription factor (TF)-DNA affinities and apparent on-rates by about 70-fold by directly binding TF DNA-binding domains, with energetic impacts exceeding many consensus motif mutations. STRs maximize the number of weakly preferred microstates near target sites, thereby increasing TF density, with impacts well predicted by statistical mechanics. Confirming that STRs also affect TF binding in cells, neural networks trained only on in vivo occupancies predicted effects identical to those observed in vitro. Approximately 90% of TFs preferentially bound STRs that need not resemble known motifs, providing a cis-regulatory mechanism to target TFs to genomic sites.

PMID:37733848 | DOI:10.1126/science.add1250

PLoS Comput Biol. 2023 Sep 21;19(9):e1011396. doi: 10.1371/journal.pcbi.1011396. Online ahead of print.

ABSTRACT

Personalized prediction of chronic diseases is crucial for reducing the disease burden. However, previous studies on chronic diseases have not adequately considered the relationship between chronic diseases. To explore the patient-wise risk of multiple chronic diseases, we developed a multitask learning Cox (MTL-Cox) model for personalized prediction of nine typical chronic diseases on the UK Biobank dataset. MTL-Cox employs a multitask learning framework to train semiparametric multivariable Cox models. To comprehensively estimate the performance of the MTL-Cox model, we measured it via five commonly used survival analysis metrics: concordance index, area under the curve (AUC), specificity, sensitivity, and Youden index. In addition, we verified the validity of the MTL-Cox model framework in the Weihai physical examination dataset, from Shandong province, China. The MTL-Cox model achieved a statistically significant (p<0.05) improvement in results compared with competing methods in the evaluation metrics of the concordance index, AUC, sensitivity, and Youden index using the paired-sample Wilcoxon signed-rank test. In particular, the MTL-Cox model improved prediction accuracy by up to 12% compared to other models. We also applied the MTL-Cox model to rank the absolute risk of nine chronic diseases in patients on the UK Biobank dataset. This was the first known study to use the multitask learning-based Cox model to predict the personalized risk of the nine chronic diseases. The study can contribute to early screening, personalized risk ranking, and diagnosing of chronic diseases.

PMID:37733837 | DOI:10.1371/journal.pcbi.1011396