Tag: pubmed

J Glaucoma. 2021 Nov 12. doi: 10.1097/IJG.0000000000001965. Online ahead of print.

ABSTRACT

PRECIS: Patient education and dosing self-efficacy are important factors related to ongoing adherence to glaucoma topical treatment, and patients view their disease management as a shared effort with their provider.

PURPOSE: Glaucoma affects nearly 3 million Americans and medication adherence has been reported to be as low as 20% in this patient population; however, key limitations to our understanding of this behavior in adults with glaucoma exist.

PATIENT AND METHODS: This research used an electronic survey including validated concepts related to topical medication use and an in-person interview to investigate the influencers of and solutions for challenges to medication adherence in adults with glaucoma. Patient eligibility was determined upon arrival to a regularly-scheduled visit to the Vanderbilt Eye Institute during which they were asked for consent to complete the survey. Responses were captured by tablet and assessed using descriptive and inferential statistics. The primary focus was instrument correlations with the Adherence to Refills and Medications Scale (ARMS) score, and were run between ARMS and the totaled score for each individual questionnaire as well as individual items. Recorded interviews were thematically assessed by multiple study team members.

RESULTS: Survey results of adults with glaucoma suggested that self-efficacy, forgetfulness, fear of side effects, and dosing ability were all related to self-reported medication adherence. Despite most having glaucoma for several years, discrepancies in disease knowledge were observed. Patient interviews uncovered three overall themes related to glaucoma treatment: (1) glaucoma management as a shared responsibility; (2) the importance of patient education; and (3) specific adherence facilitators and barriers.

CONCLUSION: Glaucoma medication adherence interventions may benefit from focusing on developing patient medication-taking self-efficacy, disease-related education, and engagement with their provider.

PMID:34772874 | DOI:10.1097/IJG.0000000000001965

JAAPA. 2021 Nov 10. doi: 10.1097/01.JAA.0000800260.99283.d3. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effect of an arthritis center on patient care and operational throughput.

METHODS: A single-institution, retrospective review was conducted of patients with hip or knee osteoarthritis from January 2016 to October 2019. Our physician assistant (PA) led arthritis center opened in November 2017, and manages nonoperative treatment of osteoarthritis by formulating individualized treatment plans. Descriptive and inferential statistics comparing operational measures, treatment patterns, and patient satisfaction pre- and postcenter opening were performed.

RESULTS: Overall patient volume, new patient volume, and the proportion of new patients seen increased after the arthritis center opened. Encounters per patient and clinicians seen per patient decreased, while the rate of injections and surgery increased. Patient satisfaction improved after opening of the arthritis center.

CONCLUSIONS: The establishment of a dedicated PA-led arthritis center is associated with improved access to care, operational efficiency, and patient satisfaction in patients with hip and knee osteoarthritis.

PMID:34772855 | DOI:10.1097/01.JAA.0000800260.99283.d3

Am J Surg Pathol. 2021 Nov 15. doi: 10.1097/PAS.0000000000001840. Online ahead of print.

ABSTRACT

The separation of benign from malignant mesothelial proliferations is often a difficult pathologic problem. UHRF1 (ubiquitin-like with plant homeodomain and ring finger domains-1) is a regulator of DNA methylation and an epigenetic driver of various human cancers. It has recently been reported that UHRF1 is overexpressed in mesotheliomas. We asked whether UHRF1 immunohistochemistry could be used to separate benign from malignant mesothelial proliferations. Initial studies showed that UHRF1 stained mesothelial cells but also endothelial and other non-neoplastic cells, so that accurate counting of positive mesothelial cells was difficult. Therefore, we ran dual UHRF1-AE1/AE3 stains on 2 tissue microarrays containing 40 reactive mesothelial proliferations and 61 mesotheliomas and only counted UHRF1 staining in keratin-positive cells. On average 10.3±8.6% (mean±SD; range: 0% to 36, median: 6.8%) of epithelioid mesothelioma cells stained compared with 5.3±4.8% (range: 0% to 15%, median: 4.1%) of reactive epithelial mesothelial cells. This difference was statistically significant but there was too much overlap to use diagnostically. In contrast, 37±26% (range: 2.5% to 95%, median: 31%) of cells in sarcomatoid mesotheliomas compared with 1.2±1.2% (range: 0% to 3.0%, median: 1.0%) of cells in reactive spindle cell mesothelial proliferations stained. To confirm this difference we stained whole sections of 21 sarcomatoid mesotheliomas and 19 cases of organizing pleuritis. Staining of mesothelial cells was seen in 2.1±2.4% (range: 0% to 6.8%, median: 1.0%) of organizing pleuritis cases and 44±22% (range: 14% to 90%, median: 41%) of sarcomatoid mesotheliomas. We conclude that dual UHRF1-AE1/AE3 immunohistochemistry is very useful for separating benign spindle cell mesothelial proliferations from sarcomatoid mesotheliomas.

PMID:34772842 | DOI:10.1097/PAS.0000000000001840

AIDS. 2021 Nov 11. doi: 10.1097/QAD.0000000000003131. Online ahead of print.

ABSTRACT

OBJECTIVE: To propose a unified continuum-of-care (CoC) analysis combining cross-sectional and longitudinal elements, incorporating time spent between stages.

DESIGN: The established 90-90-90 target follows a cross-sectional 4-stage CoC analysis, lacking information on timing of diagnosis, antiretroviral therapy (ART) initiation and viral suppression (VS) durability.

METHODS: Data were derived from the Athens Multicenter AIDS Cohort Study (AMACS). In the cross-sectional CoC, we added stratification of diagnosed people living with HIV (PLHIV) by estimated time from infection to diagnosis; of those who ever initiated ΑRT or achieved VS by corresponding current status (in 2018); and cumulative incidence function (CIF) of ART initiation and VS, treating loss-to-follow-up (LTFU) as competing event. VS was defined as viral load (VL)<500 copies/ml. VS durability was assessed by the CIF of VL rebound.

FINDINGS: 89.1% of PLHIV in 2018 were diagnosed (range of diagnoses: 1980-2018). Median time to diagnosis was 3.5 years (IQR:1.1-7.0). Among diagnosed 89.1% were ever treated, of whom 86.7% remained on ART. CIF of ART initiation and LTFU before ART initiation were 80.9% and 6.0% at 5 years since diagnosis, respectively. Among treated, 89.4% achieved VS, of whom 87.4% were currently virally suppressed. The CIF of VL rebound was 24.2% at 5 years since first VS but substantially reduced in more recent years.

INTERPRETATION: The proposed analysis highlights time gaps in CoC not evident by the standard cross-sectional approach. Our analysis highlights the need for early diagnosis and identifies late presenters as a key population for interventions that could decrease gaps in the CoC.

PMID:34772850 | DOI:10.1097/QAD.0000000000003131

Proc Natl Acad Sci U S A. 2021 Nov 16;118(46):e2109307118. doi: 10.1073/pnas.2109307118.

ABSTRACT

Extra or missing chromosomes-a phenomenon termed aneuploidy-frequently arise during human meiosis and embryonic mitosis and are the leading cause of pregnancy loss, including in the context of in vitro fertilization (IVF). While meiotic aneuploidies affect all cells and are deleterious, mitotic errors generate mosaicism, which may be compatible with healthy live birth. Large-scale abnormalities such as triploidy and haploidy also contribute to adverse pregnancy outcomes, but remain hidden from standard sequencing-based approaches to preimplantation genetic testing for aneuploidy (PGT-A). The ability to reliably distinguish meiotic and mitotic aneuploidies, as well as abnormalities in genome-wide ploidy, may thus prove valuable for enhancing IVF outcomes. Here, we describe a statistical method for distinguishing these forms of aneuploidy based on analysis of low-coverage whole-genome sequencing data, which is the current standard in the field. Our approach overcomes the sparse nature of the data by leveraging allele frequencies and linkage disequilibrium (LD) measured in a population reference panel. The method, which we term LD-informed PGT-A (LD-PGTA), retains high accuracy down to coverage as low as 0.05 × and at higher coverage can also distinguish between meiosis I and meiosis II errors based on signatures spanning the centromeres. LD-PGTA provides fundamental insight into the origins of human chromosome abnormalities, as well as a practical tool with the potential to improve genetic testing during IVF.

PMID:34772814 | DOI:10.1073/pnas.2109307118

Proc Natl Acad Sci U S A. 2021 Nov 16;118(46):e2117968118. doi: 10.1073/pnas.2117968118.

NO ABSTRACT

PMID:34772821 | DOI:10.1073/pnas.2117968118

Proc Natl Acad Sci U S A. 2021 Nov 16;118(46):e2108031118. doi: 10.1073/pnas.2108031118.

ABSTRACT

We generalize Taylor’s law for the variance of light-tailed distributions to many sample statistics of heavy-tailed distributions with tail index α in (0, 1), which have infinite mean. We show that, as the sample size increases, the sample upper and lower semivariances, the sample higher moments, the skewness, and the kurtosis of a random sample from such a law increase asymptotically in direct proportion to a power of the sample mean. Specifically, the lower sample semivariance asymptotically scales in proportion to the sample mean raised to the power 2, while the upper sample semivariance asymptotically scales in proportion to the sample mean raised to the power [Formula: see text] The local upper sample semivariance (counting only observations that exceed the sample mean) asymptotically scales in proportion to the sample mean raised to the power [Formula: see text] These and additional scaling laws characterize the asymptotic behavior of commonly used measures of the risk-adjusted performance of investments, such as the Sortino ratio, the Sharpe ratio, the Omega index, the upside potential ratio, and the Farinelli-Tibiletti ratio, when returns follow a heavy-tailed nonnegative distribution. Such power-law scaling relationships are known in ecology as Taylor’s law and in physics as fluctuation scaling. We find the asymptotic distribution and moments of the number of observations exceeding the sample mean. We propose estimators of α based on these scaling laws and the number of observations exceeding the sample mean and compare these estimators with some prior estimators of α.

PMID:34772810 | DOI:10.1073/pnas.2108031118

J Nucl Med. 2021 Nov 12:jnumed.121.263006. doi: 10.2967/jnumed.121.263006. Online ahead of print.

ABSTRACT

Aim: We aimed to evaluate the role of Positron Emission Tomography (PET) targeting the Prostate-Specific Membrane Antigen (PSMA) for response assessment in metastatic prostate cancer (mPCa) patients treated with taxane-based chemotherapy (docetaxel or cabazitaxel) and its predictive value on patient outcome. Methods: We retrospectively evaluated 37 patients with metastatic hormone-sensitive or castration-resistant prostate cancer (mHSPC or mCRPC) who underwent ⁶⁸Ga-PSMA-11 PET/CT at baseline and after the last cycle of taxane-based chemotherapy (docetaxel or cabazitaxel) without treatment modification between scans. Biochemical response (BR) was defined as an undetectable or decreased prostate-specific antigen (PSA) by ≥50% compared to baseline. Association between BR and different PET parameters were tested. A cut-off of ≥30% change in PSMA total tumor volume (PSMA-TV) was used to define PSMA responders (PSMA-R) vs PSMA non-responders (PSMA-NR). Correlation between PSMA-PET/CT response and BR was evaluated using the Phi coefficient. Association between PET-response and overall survival (OS) was performed using Cox regression and Kaplan-Meier method. Results: Our cohort was composed of 8 (22%) mHSPC and 29 (78%) mCRPC patients. Twenty-one patients received docetaxel, and 16 received cabazitaxel treatment (median: 6 cycles, interquartile (IQR):5-8). BR was found in 18/37 patients. Using PSMA-TV, PSMA-PET/CT response was concordant with BR in 35/37 patients (Phi=0.89, p<0.0001). There were 18/37 PSMA-R (6 complete response and 12 partial response) and 19/37 PSMA-NR (17 progressive disease and 2 stable disease). After a median follow-up of 23 months there was a statistically significant longer overall survival (OS) for PSMA-R compared to PSMA-NR (median OS not reached vs 12 months, respectively, HR 0.10; 95%CI: 0.03-0.39, P = 0.001) for the entire population. Among the mCRPC subgroup, differences in OS were also observed (median 22 vs 12 months respectively, HR 0.22, 95%CI: 0.06-0.82, P = 0.023) with a 12-month OS rate of 100% for PSMA-R and 52% for PSMA-NR (P = 0.011). Conclusion: This retrospective analysis suggests that ⁶⁸Ga-PSMA-11 PET/CT is a promising imaging modality for assessing response to taxane-based chemotherapy in mPCa. PSMA-expression changes might be used as a predictive biomarker for OS which might help tailor individual therapy and select eligible patients for clinical trials.

PMID:34772793 | DOI:10.2967/jnumed.121.263006

Neurology. 2021 Nov 12:10.1212/WNL.0000000000013049. doi: 10.1212/WNL.0000000000013049. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the association between blood pressure (BP) levels after endovascular thrombectomy (EVT) and the clinical outcomes of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO).

METHODS: A study was eligible if it enrolled AIS patients older than 18 years, with an LVO treated with either successful or unsuccessful EVT, and provided either individual or mean 24-hour systolic BP values after the end of the EVT procedure. Individual patient data from all studies were analyzed using a generalized linear mixed-effects model.

RESULTS: A total of 5874 patients (mean age: 69±14 years, 50% women, median NIHSS on admission: 16) from 7 published studies were included. Increasing mean systolic BP levels per 10 mm Hg during the first 24 hours after the end of the EVT were associated with a lower odds of functional improvement (unadjusted common OR=0.82, 95%CI:0.80-0.85; adjusted common OR=0.88, 95%CI:0.84-0.93) and modified Ranking Scale score≤2 (unadjusted OR=0.82, 95%CI:0.79-0.85; adjusted OR=0.87, 95%CI:0.82-0.93), and a higher odds of all-cause mortality (unadjusted OR=1.18, 95%CI:1.13-1.24; adjusted OR=1.15, 95%CI:1.06-1.23) at 3 months. Higher 24-hour mean systolic BP levels were also associated with an increased likelihood of early neurological deterioration (unadjusted OR=1.14, 95%CI:1.07-1.21; adjusted OR=1.14, 95%CI:1.03-1.24) and a higher odds of symptomatic intracranial hemorrhage (unadjusted OR=1.20, 95%CI:1.09-1.29; adjusted OR=1.20, 95%CI:1.03-1.38) after EVT.

CONCLUSION: Increased mean systolic BP levels in the first 24 hours after EVT are independently associated with a higher odds of symptomatic intracranial hemorrhage, early neurological deterioration, three-month mortality, and worse three-month functional outcomes.

PMID:34772799 | DOI:10.1212/WNL.0000000000013049

BMJ Open. 2021 Nov 12;11(11):e049740. doi: 10.1136/bmjopen-2021-049740.

ABSTRACT

OBJECTIVES: Develop an individualised prognostic risk prediction tool for predicting the probability of adverse COVID-19 outcomes in patients with inflammatory bowel disease (IBD).

DESIGN AND SETTING: This study developed and validated prognostic penalised logistic regression models using reports to the international Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease voluntary registry from March to October 2020. Model development was done using a training data set (85% of cases reported 13 March-15 September 2020), and model validation was conducted using a test data set (the remaining 15% of cases plus all cases reported 16 September-20 October 2020).

PARTICIPANTS: We included 2709 cases from 59 countries (mean age 41.2 years (SD 18), 50.2% male). All submitted cases after removing duplicates were included.

PRIMARY AND SECONDARY OUTCOME MEASURES: COVID-19 related: (1) Hospitalisation+: composite outcome of hospitalisation, ICU admission, mechanical ventilation or death; (2) Intensive Care Unit+ (ICU+): composite outcome of ICU admission, mechanical ventilation or death; (3) Death. We assessed the resulting models’ discrimination using the area under the curve of the receiver operator characteristic curves and reported the corresponding 95% CIs.

RESULTS: Of the submitted cases, a total of 633 (24%) were hospitalised, 137 (5%) were admitted to the ICU or intubated and 69 (3%) died. 2009 patients comprised the training set and 700 the test set. The models demonstrated excellent discrimination, with a test set area under the curve (95% CI) of 0.79 (0.75 to 0.83) for Hospitalisation+, 0.88 (0.82 to 0.95) for ICU+ and 0.94 (0.89 to 0.99) for Death. Age, comorbidities, corticosteroid use and male gender were associated with a higher risk of death, while the use of biological therapies was associated with a lower risk.

CONCLUSIONS: Prognostic models can effectively predict who is at higher risk for COVID-19-related adverse outcomes in a population of patients with IBD. A free online risk calculator (https://covidibd.org/covid-19-risk-calculator/) is available for healthcare providers to facilitate discussion of risks due to COVID-19 with patients with IBD.

PMID:34772750 | DOI:10.1136/bmjopen-2021-049740