Symptom content analysis of OSA questionnaires: time to identify and improve relevance of diversity of OSA symptoms?

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a heterogeneous condition covering many clinical phenotypes in terms of the diversity of symptoms. Patient-based OSA screening questionnaires used in routine practice contain significantly varying contents that can impact the reliability and validity of the screening. We investigated to what extent common patient-based OSA screening questionnaires differ or overlap in their item content by conducting a rigorous, methodical, and quantified content overlap analysis. METHODS: We conducted an item content analysis of 11 OSA screening questionnaires validated in adult populations and characterized their overlap using a 4-step approach: (1) selection of OSA screening questionnaires, (2) item extraction and selection, (3) extraction of symptoms from items, and (4) assessment of content overlap with the Jaccard index (from 0, no overlap, to 1, full overlap). RESULTS: We extracted 72 items that provided 25 distinct symptoms from 11 selected OSA questionnaires. The overlap between them was weak (mean Jaccard index: 0.224; ranging from 0.138 to 0.329). All questionnaires contained symptoms of the "OSA symptom" dimension (eg, snoring or witnessed apneas). The STOP-BANG (0.329) and the Berlin (0.280) questionnaires exhibited the highest overlap content. Ten symptoms (40%) were investigated in only 1 questionnaire. CONCLUSIONS: The heterogeneity of content and the low overlap across these questionnaires reflect the challenges of screening OSA. The different OSA questionnaires potentially capture varying aspects of the disorder, with the risk of biased results in studies. Suggestions are made for better OSA screening and refinement of clinical OSA phenotypes. CITATION: Gauld C, Baillieul S, Martin VP, et al. Symptom content analysis of OSA questionnaires: time to identify and improve relevance of diversity of OSA symptoms? J Clin Sleep Med. 2024;20(7):1105-1117.

Prevalence of Select New Symptoms and Conditions Among Persons Aged Younger Than 20 Years and 20 Years or Older at 31 to 150 Days After Testing Positive or Negative for SARS-CoV-2.

Importance: New symptoms and conditions can develop following SARS-CoV-2 infection. Whether they occur more frequently among persons with SARS-CoV-2 infection compared with those without is unclear. Objective: To compare the prevalence of new diagnoses of select symptoms and conditions between 31 and 150 days after testing among persons who tested positive vs negative for SARS-CoV-2. Design, Setting, and Participants: This cohort study analyzed aggregated electronic health record data from 40 health care systems, including 338 024 persons younger than 20 years and 1 790 886 persons aged 20 years or older who were tested for SARS-CoV-2 during March to December 2020 and who had medical encounters between 31 and 150 days after testing. Main Outcomes and Measures: International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes were used to capture new symptoms and conditions that were recorded 31 to 150 days after a SARS-CoV-2 test but absent in the 18 months to 7 days prior to testing. The prevalence of new symptoms and conditions was compared between persons with positive and negative SARS-CoV-2 tests stratified by age (20 years or older and young than 20 years) and care setting (nonhospitalized, hospitalized, or hospitalized and ventilated). Results: A total of 168 701 persons aged 20 years or older and 26 665 younger than 20 years tested positive for SARS-CoV-2, and 1 622 185 persons aged 20 years or older and 311 359 younger than 20 years tested negative. Shortness of breath was more common among persons with a positive vs negative test result among hospitalized patients (≥20 years: prevalence ratio [PR], 1.89 [99% CI, 1.79-2.01]; <20 years: PR, 1.72 [99% CI, 1.17-2.51]). Shortness of breath was also more common among nonhospitalized patients aged 20 years or older with a positive vs negative test result (PR, 1.09 [99% CI, 1.05-1.13]). Among hospitalized persons aged 20 years or older, the prevalence of new fatigue (PR, 1.35 [99% CI, 1.27-1.44]) and type 2 diabetes (PR, 2.03 [99% CI, 1.87-2.19]) was higher among those with a positive vs a negative test result. Among hospitalized persons younger than 20 years, the prevalence of type 2 diabetes (PR, 2.14 [99% CI, 1.13-4.06]) was higher among those with a positive vs a negative test result; however, the prevalence difference was less than 1%. Conclusions and Relevance: In this cohort study, among persons hospitalized after a positive SARS-CoV-2 test result, diagnoses of certain symptoms and conditions were higher than among those with a negative test result. Health care professionals should be aware of symptoms and conditions that may develop after SARS-CoV-2 infection, particularly among those hospitalized after diagnosis.

Pediatric antiphospholipid syndrome: clinical features and therapeutic interventions in a single center retrospective case series.

BACKGROUND/PURPOSE: Pediatric antiphospholipid syndrome (APS) is a thromboinflammatory disease characterized by the presence of circulating antiphospholipid antibodies and either thrombotic events or pregnancy morbidity. The objective of this study was to review a large institution's experience to better understand the characteristics of children with APS. METHODS: We conducted a retrospective review of pediatric APS at a tertiary referral center. The electronic medical record system was queried from 2000 through 2019, and 21 cases were included based on meeting the revised Sapporo Classification criteria by age 18 or younger. Comparisons between primary and secondary APS patients were made with two-tailed t-tests. RESULTS: Twenty-one patients were included with a median age at diagnosis of 16 years and median follow-up of 5.8 years. Secondary APS was slightly more common than primary APS (11 vs. 10 cases) and was primarily diagnosed in the context of systemic lupus erythematosus. Two thirds of patients (67%) also had "non-criteria" manifestations of APS including thrombocytopenia, autoimmune hemolytic anemia, and livedo reticularis/racemosa. Almost half of patients (43%) had recurrent thrombosis, typically when patients were subtherapeutic or non-adherent with anticoagulation. Damage Index in Patients with Thrombotic APS (DIAPS) scores indicated a chronic burden of disease in both primary and secondary APS patients. CONCLUSION: This case series of pediatric APS provides important context regarding disease phenotypes displayed by children with APS. High prevalence of non-criteria clinical manifestations highlights the need to consider these characteristics when developing pediatric-specific classification criteria and when considering this relatively rare diagnosis in pediatric practice.

Long-term outcomes of Holmium laser enucleation of prostate and predictive model for symptom recurrence.

INTRODUCTION AND OBJECTIVES: Holmium laser enucleation of prostate (HoLEP) represents one of the most studied surgical techniques for benign prostatic hyperplasia (BPH). Its efficacy in symptom relief has been widely depicted. However, few evidence is available regarding the possible predictors of symptom recurrence. We aimed to evaluate long-term outcomes, symptom recurrence rate, and predictors in patients that underwent HoLEP. MATERIALS AND METHODS: We retrospectively analyzed data from patients that consecutively underwent HoLEP for BPH from 2012 to 2015 at two tertiary referral centers. Functional outcomes were evaluated by uroflowmetry parameters and International Prostate Symptom Score (IPSS) questionnaire administration at follow-up visits at 12, 24, and 60 months. The primary outcome was the symptomatic patients' rate presenting lower urinary tract symptoms (LUTS) after 60 months from surgery, defined as in case of one or more of the following: IPSS more than 7, post voidal residue (PVR) more than 20 ml, need for medical therapy for LUTS or redo surgery for bladder outlet obstruction. Multivariable logistic regression analyses evaluated predictors for being symptomatic at follow-up. Covariates consisted of: preoperative peak flow rate (PFR), PVR, and IPSS, prostate volume, age (all as continuous), and surgical technique. RESULTS: A total of 567 patients were available for our analyses. Median prostate volume was 80cc, with a median PFR of 8 ml/s and median PVR of 100cc. One hundred and twenty-five (22%) patients were found to be symptomatic at follow-up. Redo surgery was needed for 25 (4.4%) patients. After adjusting for possible confounders, an increase in preoperative PVR (odds ratio [OR] 1.005) and IPSS (OR 1.12) resulted as independent predictors for symptom recurrence (all p < 0.001). CONCLUSIONS: HoLEP can provide durable symptom relief regardless of the chosen technique. Patients with an important preoperative symptom burden or a high PVR should be carefully counseled on the risk of symptom recurrence.

Effect of Metabolic Syndrome on Anatomy and Function of the Lower Urinary Tract Assessed on MRI.

OBJECTIVE: To investigate the relationship between metabolic syndrome (MetS) and lower urinary tract symptoms (LUTS) with functional and anatomic changes of the lower urinary tract with MRI. MATERIALS AND METHODS: The bladder and prostate of 95 subjects (56M, 39F) were segmented on T2-weighted pelvic MRI using Materialize Mimics 3D software. Bladder wall volume (BWV), post-void residual (PVR) and prostate volume (PV) were quantified from the 3D renderings. LUTS were quantified using validated questionnaires administered at the time of MRI. Wilcoxin rank sum, win ratio and chi-square tests were used to correlate symptom scores, BWV, PVR and PV in patients 1) without vs with MetS, 2) with mild (IPSS or UDI-6: 0-7) vs moderate-severe (IPSS: 8-35 or UDI-6: ≥8) and 3) normal vs enlarged prostates (>40cm3). Multivariate linear regression was used to determine predictors for BWV, PVR and PV. RESULTS: Men with MetS had increased BWV (66.8 vs 51.1cm3, P = .003), higher PVR (69.1 vs 50.5cc, P= .05) and increased PV (67.2 vs 40.1cm3, P= .01). Women without and with MetS had similar BWV, PVR and LUTS (P= .3-.78). There was no difference in prevalence of MetS, BWV, PVR or PV in men or women with mild vs moderate-severe LUTS (P = .26-.97). Men with enlarged prostates were more likely to have MetS (P = .003). There was no difference in BWV, PVR and LUTS for men with normal vs enlarged prostates (P= .44-.94). In men, BWV was highly correlated with MetS (P = .005) on regression analysis. CONCLUSION: MetS leads to detrusor hypertrophy and may contribute to impaired bladder function, likely related to the effect on the prostate.

Consequences of the first and second COVID-19 wave on kidney transplant recipients at a large Indian transplant centre.

BACKGROUND: There is a scarcity of data comparing the consequences of first and second COVID-19 waves on kidney transplant recipients (KTRs) in India. METHODS: We conducted a single-centre retrospective study of 259 KTRs with COVID-19 to compare first wave (March 15-December 31 2020, n = 157) and second wave (April 1-May 31 2021, n = 102). RESULTS: KTRs during second wave were younger (43 vs. 40 years; p-value .04) and also included paediatric patients (0 vs. 5.9%; p-value .003). Symptoms were milder during the second wave (45 vs. 62.7%; p-value .007); COVID-19 positive patients had less frequent cough (32 vs. 13.8%; p-value .001), fever was less frequent (58 vs. 37%; p-value .001), and we observed fewer co-morbidities (11 vs. 20.6%; p-value .04). The percentages of neutrophils (77 vs. 83%; p-value .001) and serum ferritin (439 vs. 688; p-value .0006) were higher during second wave, while lymphocyte counts were reduced (20 vs. 14%; p-value .0001). Hydroxychloroquine (11 vs. 0%; p-value .0001) and tocilizumab (7 vs. 0%; p-value .004) were more frequently prescribed during first wave, while utilization of dexamethasone (6 vs. 27%; p-value .0001) and remdesivir (47 vs. 65%; p-value .03) increased during the second wave. Mucormycosis (1.3 vs. 10%; p-value .01) and ICU admissions (20 vs. 37.2%; p-value .002) were more frequent during second wave. The 28-day mortality rate (9.6 vs. 10%; p-value 1) was not different. CONCLUSIONS: There has been a different clinical spectrum of COVID-19 amongst KTR with similar mortality between the two waves at a large Indian transplant centre.

Perceived Disease Activity in Rheumatoid Arthritis: When the Physician's Gender Matters.

BACKGROUND: In rheumatoid arthritis (RA), females usually have a worse prognosis. To date, the influence of physician gender in the evaluation of RA activity is still largely unknown. OBJECTIVES: To investigate the discrepancy in RA disease activity assessment between male and female physicians and to compare patient and evaluator perception of disease activity and global health (GH) status. METHODS: One female and one male rheumatologist evaluated 154 RA patients recording tender and swollen joint count, GH, evaluator global assessment (EGA), and patient global assessment (PGA) disease activity. A third rheumatologist calculated DAS28, CDAI, and SDAI. Difference was evaluated by Wilcoxon test. Physician-patient agreement was assessed by intraclass correlation coefficient. RESULTS: GH, PGA, and DAS28 were higher when recorded by the female examiner. Male EGA was higher than female. Among male patients, PGA was higher when collected by the female examiner. The probability of being judged as having an active disease did not rely on physician gender. The agreement with the physician's evaluation of disease activity was high. PGA values were higher than EGA in both examiners. The physician-patient agreement was moderate for the male examiner and good for the female. The female physician had a higher agreement with both genders. CONCLUSIONS: Subjective measure of disease activity differs between female and male rheumatologists, contributing to a different evaluation of disease activity. Patients have a higher perception of disease activity compared to physicians. The stronger agreement between female physicians and patients may be related to a more emphatic setting established by the female physician.

COVID-19 Seropositive Rates between the Waves, Israel.

BACKGROUND: Israel has experienced three waves of coronavirus disease-2019 (COVID-19) infection since late February 2020, with lockdown and other measures employed to contain infection rates. In cooperation with the Israel Ministry of Health, serological testing was conducted by all four health maintenance organizations (HMO) in order to estimate national infection rates and the proportion of previously undetected disease. OBJECTIVES: To estimate the proportion of the population that was seropositive, identify factors associated with seropositive outcome, and approximate the proportion of residents that were asymptomatic. METHODS: Seroconversion rates (IgG) were measured in a representative sample of over 17,000 members of Maccabi Healthcare Services. Direct standardization was used to estimate the seropositive rates for COVID-19 infection for members of the HMO. Rates were adjusted for sensitivity and specificity of the testing products used. In addition to blood sampling, respondents were asked to complete a digital survey regarding potential exposures and symptoms experienced. RESULTS: It was estimated that 1.9% of the adult HMO population was seropositive 4 months after the first infected person was identified in the country. Seroconversion was associated with travel abroad and exposure to infected individuals. Loss of smell and taste, fever, cough, and fatigue are associated with infection. Of those found to be seropositive for COVID-19, 160 (59%) had a prior negative polymerase chain reaction (PCR) or no PCR test at all. CONCLUSIONS: Adult seropositive rates of infection were low relative to other countries. The findings suggest that early initiatives to limit infection entry and spread were effective.

How much time is needed in clinical practice to reach a diagnosis of clinically established Parkinson's disease?

INTRODUCTION: The implementation of accepted clinical diagnostic criteria has improved the accuracy of a clinical diagnosis of Parkinson's disease (PD). Time frames of 3-10 years have been empirically proposed to reach a diagnosis of clinically established PD. METHODS: We explored the time to a Final Clinical Diagnosis (FCD) and the factors that predict faster diagnoses in patients presenting with parkinsonism and/or tremor between 2009 and 2015 at our tertiary center. All patients underwent a standardized workout process to reach a FCD, which included an acute levodopa challenge (LDC) after the first visit. RESULTS: Among the 326 patients included, 215 (66%) received a FCD within the first six months after the LDC. A FCD was reached in 95% and 100% of patients in 33 and 108 months, respectively. PD was the FCD in 196 patients (60.1%). The FCD was reached faster in patients with a positive response to levodopa and when the FCD was PD. CONCLUSION: The time needed to reach a final diagnosis in the clinical setting was 2.75 years in 95% of patients presenting initially with parkinsonism and/or tremor. Patients with positive responses to levodopa at the LDC, benefited from shorter delays until the FCD.

Exploring the clinical meaningfulness of the Scale for the Assessment and Rating of Ataxia: A comparison of patient and physician perspectives at the item level.

BACKGROUND: The Scale for the Assessment and Rating of Ataxia (SARA) is commonly used as the primary outcome measure in therapeutic trials. Driven by spontaneous comments from ataxia patients participating in a trial, we aimed to examine the clinical meaningfulness of the SARA from their perspective. METHODS: Twenty mildly to moderately affected individuals with spinocerebellar ataxia type 3 (SARA score 11.3 ± 4.1) completed a custom-designed survey. SARA item scores were compared with self-reported complaints in everyday life. Discrepancies between SARA ratings and patients' daily life experiences were reported as "overestimation" (i.e., a SARA item score more than 0, but no corresponding complaints) or "underestimation" (i.e., a SARA item score of 0, yet accompanying complaints). RESULTS: Patient-physician discrepancies were present in essentially all SARA items except for gait. The mean number of overestimated SARA points per patient was 3.1 ± 2.1. Underestimation occurred less frequently, but was relatively common in stance and fast alternating hand movements. Three quarters of patients marked gait as the most valuable SARA item, while the remaining 25% selected stance. CONCLUSION: On average, a quarter of total SARA score does not reflect meaningful impairments from a patient's perspective. Our data suggest that it is doubtful whether potential improvements at some of the items will be perceived as comparably important by mildly to moderately affected ataxia patients. These observations question the utility of delta SARA score as the most appropriate primary endpoint in clinical trials and call for the addition of outcome measures, such as the Patient Global Impression of Change scale and validated ataxia-specific patient-reported outcome measures.

Covid-19 infection in pregnant women in Dubai: a case-control study.

BACKGROUND: Whilst the impact of Covid-19 infection in pregnant women has been examined, there is a scarcity of data on pregnant women in the Middle East. Thus, the aim of this study was to examine the impact of Covid-19 infection on pregnant women in the United Arab Emirates population. METHODS: A case-control study was carried out to compare the clinical course and outcome of pregnancy in 79 pregnant women with Covid-19 and 85 non-pregnant women with Covid-19 admitted to Latifa Hospital in Dubai between March and June 2020. RESULTS: Although Pregnant women presented with fewer symptoms such as fever, cough, sore throat, and shortness of breath compared to non-pregnant women; yet they ran a much more severe course of illness. On admission, 12/79 (15.2%) Vs 2/85 (2.4%) had a chest radiograph score [on a scale 1-6] of ≥3 (p-value = 0.0039). On discharge, 6/79 (7.6%) Vs 1/85 (1.2%) had a score ≥3 (p-value = 0.0438). They also had much higher levels of laboratory indicators of severity with values above reference ranges for C-Reactive Protein [(28 (38.3%) Vs 13 (17.6%)] with p < 0.004; and for D-dimer [32 (50.8%) Vs 3(6%)]; with p < 0.001. They required more ICU admissions: 10/79 (12.6%) Vs 1/85 (1.2%) with p=0.0036; and suffered more complications: 9/79 (11.4%) Vs 1/85 (1.2%) with p=0.0066; of Covid-19 infection, particularly in late pregnancy. CONCLUSIONS: Pregnant women presented with fewer Covid-19 symptoms but ran a much more severe course of illness compared to non-pregnant women with the disease. They had worse chest radiograph scores and much higher levels of laboratory indicators of disease severity. They had more ICU admissions and suffered more complications of Covid-19 infection, such as risk for miscarriage and preterm deliveries. Pregnancy with Covid-19 infection, could, therefore, be categorised as high-risk pregnancy and requires management by an obstetric and medical multidisciplinary team.

Features of "ET plus" correlate with age and tremor duration: "ET plus" may be a disease stage rather than a subtype of essential tremor.

BACKGROUND: Essential tremor (ET) is characterized by considerable clinical heterogeneity. In 2018, the term "ET plus" was introduced to mark a potential stratification point for dividing ET into subtypes - ET vs ET plus (i.e., ET cases with neurological features other than action tremor). However, as ET progresses, patients often develop increasingly severe tremor, spread of tremor, tremor under different activation conditions, and other features. Given this situation, ET plus may represent a disease stage rather than a disease classification or subtype. In theory, if the defining characteristics of a disease subtype fluctuate with age or disease duration, it raises the distinct possibility the "subtype" is a disease stage. METHODS: A cohort of 241 prospectively enrolled ET cases underwent a detailed motor and cognitive assessment in which the features of ET plus including cerebellar signs (intention tremor, tandem gait difficulty), rest tremor, dystonia, and cognitive performance were evaluated. We determined whether these features of ET plus correlated with action tremor duration and age. RESULTS: We demonstrated that numerous ET plus features were significantly correlated with both age and action tremor duration (numerous p values < 0.05). The same relationships were observed in a series of sensitivity analyses. CONCLUSION: We observed that the component parts of ET plus are highly age- and stage-dependent. These features are yearly-changing features conditional on a demographic and disease stage variable. These data support the notion that ET plus may represent a disease stage rather than a distinct disease subtype or disease classification.

Polysymptomatology in Pediatric Patients Receiving Palliative Care Based on Parent-Reported Data.

Importance: Pediatric palliative care treats patients with a wide variety of advanced illness conditions, often with substantial levels of pain and other symptoms. Clinical and research advancements regarding symptom management for these patients are hampered by the scarcity of data on symptoms as well as an overreliance on clinician report. Objective: To provide a detailed description of the symptoms among patients receiving pediatric palliative care based on parental report via a validated, structured symptom assessment measure. Design, Setting, and Participants: Baseline data for this cross-sectional analysis were collected between April 10, 2017, and February 5, 2020, from pediatric palliative care programs in 7 children's hospitals located in Akron, Ohio; Boston, Massachusetts; Birmingham, Alabama; Houston, Texas; Minneapolis, Minnesota; Philadelphia, Pennsylvania; and Seattle, Washington. Data were collected in the hospital, outpatient, and home setting from patients 30 years of age or younger who were receiving pediatric palliative care at 1 of the study sites. Exposures: Analyses were stratified by patients' demographic characteristics, including age, and by whether the patients had received a diagnosis of any of 10 non-mutually exclusive complex chronic condition categories. Main Outcomes and Measures: Twenty symptoms measured via the modified Memorial Symptom Assessment Scale, which scores the frequency and severity of any symptom that is present and provides a total symptom score. Results: Among the first 501 patients enrolled, the median age was 4.1 years (interquartile range, 0.8-12.9 years), 267 (53.3%) were male, and 356 (71.1%) were White. The most prevalent complex chronic conditions included gastrointestinal (357 [71.3%]), neurologic (289 [57.7%]), and cardiovascular (310 [61.9%]) conditions; 438 patients (87.4%) were technology dependent. Parents reported a mean (SD) of 6.7 (3.4) symptoms per patient and a median of 7 symptoms (interquartile range, 4-9 symptoms). A total of 367 patients (73.3%) had 5 or more symptoms. The 5 most prevalent symptoms were pain (319 [63.7%]; 95% CI, 59.4%-67.8%), lack of energy (295 [58.9%]; 95% CI, 54.5%-63.1%), irritability (280 [55.9%]; 95% CI, 51.5%-60.2%), drowsiness (247 [49.3%]; 95% CI, 44.9%-53.7%), and shortness of breath (232 [46.3%]; 95% CI, 41.9%-50.7%). Although older patients were reported by parents as having experienced more symptoms and having higher total symptom scores, variation across condition categories was relatively minor. Patients in the upper 10th percentile of total symptom scores had a median of 12.0 symptoms (interquartile range, 11-13). Conclusions and Relevance: In this cross-sectional study, most children receiving palliative care were experiencing polysymptomatology. An important subgroup of patients frequently experienced numerous severe symptoms. Assessment and management of patients with polysymptomatology are critical aspects of pediatric palliative care.

Evaluation of global and intragenic hypomethylation in colorectal adenomas improves patient stratification and colorectal cancer risk prediction.

BACKGROUND: Aberrant DNA hypomethylation of the long interspersed nuclear elements (LINE-1 or L1) has been recognized as an early event of colorectal transformation. Simultaneous genetic and epigenetic analysis of colorectal adenomas may be an effective and rapid strategy to identify key biological features leading to accelerated colorectal tumorigenesis. In particular, global and/or intragenic LINE-1 hypomethylation of adenomas may represent a helpful tool for improving colorectal cancer (CRC) risk stratification of patients after surgical removal of polyps. To verify this hypothesis, we analyzed a cohort of 102 adenomas derived from 40 high-risk patients (who developed CRC in a post-polypectomy of at least one year) and 43 low-risk patients (who did not develop CRC in a post-polypectomy of at least 5 years) for their main pathological features, the presence of hotspot variants in driver oncogenes (KRAS, NRAS, BRAF and PIK3CA), global (LINE-1) and intragenic (L1-MET) methylation status. RESULTS: In addition to a significantly higher adenoma size and an older patients' age, adenomas from high-risk patients were more hypomethylated than those from low-risk patients for both global and intragenic LINE-1 assays. DNA hypomethylation, measured by pyrosequencing, was independent from other parameters, including the presence of oncogenic hotspot variants detected by mass spectrometry. Combining LINE-1 and L1-MET analyses and profiling the samples according to the presence of at least one hypomethylated assay improved the discrimination between high and low risk lesions (p = 0.005). Remarkably, adenomas with at least one hypomethylated assay identified the patients with a significantly (p < 0.001) higher risk of developing CRC. Multivariable analysis and logistic regression evaluated by the ROC curves proved that methylation status was an independent variable improving cancer risk prediction (p = 0.02). CONCLUSIONS: LINE-1 and L1-MET hypomethylation in colorectal adenomas are associated with a higher risk of developing CRC. DNA global and intragenic hypomethylation are independent markers that could be used in combination to successfully improve the stratification of patients who enter a colonoscopy surveillance program.

Latent Class Analysis of Symptom Burden Among Seriously Ill Adults at the End of Life.

BACKGROUND: Serious illness is characterized by high symptom burden that negatively affects quality of life (QOL). Although palliative care research has highlighted symptom burden in seriously ill adults with cancer, symptom burden among those with noncancer serious illness and multiple chronic conditions has been understudied. Latent class analysis is a statistical method that can be used to better understand the relationship between severity of symptom burden and covariates, such as the presence of multiple chronic conditions. Although latent class analysis has been used to highlight subgroups of seriously ill adults with cancer based on symptom clusters, none have incorporated multiple chronic conditions. OBJECTIVES: The objectives of this study were to (a) describe the demographic and baseline characteristics of seriously ill adults at the end of life in a palliative care cohort, (b) identify latent subgroups of seriously ill individuals based on severity of symptom burden, and (c) examine variables associated with latent subgroup membership, such as QOL, functional status, and the presence of multiple chronic conditions. METHODS: A secondary data analysis of a palliative care clinical trial was conducted. The latent class analysis was based on the Edmonton Symptom Assessment System, which measures nine symptoms on a scale of 0-10 (e.g., pain, fatigue, nausea, depression, anxiousness, drowsiness, appetite, well-being, and shortness of breath). Clinically significant cut-points for symptom severity were used to categorize each symptom item in addition to a categorized total score. RESULTS: Three latent subgroups were identified (e.g., low, moderate, and high symptom burden). Lower overall QOL was associated with membership in the moderate and high symptom burden subgroups. Multiple chronic conditions were associated with statistically significant membership in the high symptom burden latent subgroup. Older adults between 65 and 74 years had a lower likelihood of moderate or high symptom burden subgroup membership compared to the low symptom burden class. DISCUSSION: Lower QOL was associated with high symptom burden. Multiple chronic conditions were associated with high symptom burden, which underlines the clinical complexity of serious illness. Palliative care at the end of life for seriously ill adults with high symptom burden must account for the presence of multiple chronic conditions.

Symptom-based early-stage differentiation between SARS-CoV-2 versus other respiratory tract infections-Upper Silesia pilot study.

In the DECODE project, data were collected from 3,114 surveys filled by symptomatic patients RT-qPCR tested for SARS-CoV-2 in a single university centre in March-September 2020. The population demonstrated balanced sex and age with 759 SARS-CoV-2( +) patients. The most discriminative symptoms in SARS-CoV-2( +) patients at early infection stage were loss of taste/smell (OR = 3.33, p < 0.0001), body temperature above 38℃ (OR = 1.67, p < 0.0001), muscle aches (OR = 1.30, p = 0.0242), headache (OR = 1.27, p = 0.0405), cough (OR = 1.26, p = 0.0477). Dyspnea was more often reported among SARS-CoV-2(-) (OR = 0.55, p < 0.0001). Cough and dyspnea were 3.5 times more frequent among SARS-CoV-2(-) (OR = 0.28, p < 0.0001). Co-occurrence of cough, muscle aches, headache, loss of taste/smell (OR = 4.72, p = 0.0015) appeared significant, although co-occurrence of two symptoms only, cough and loss of smell or taste, means OR = 2.49 (p < 0.0001). Temperature > 38℃ with cough was most frequent in men (20%), while loss of taste/smell with cough in women (17%). For younger people, taste/smell impairment is sufficient to characterise infection, whereas in older patients co-occurrence of fever and cough is necessary. The presented study objectifies the single symptoms and interactions significance in COVID-19 diagnoses and demonstrates diverse symptomatology in patient groups.

Clinical features of autopsy-confirmed multiple system atrophy in the Mayo Clinic Florida brain bank.

BACKGROUND: Multiple system atrophy (MSA) presents with various combinations of autonomic dysfunction, parkinsonism, and cerebellar ataxia. Although clinical diagnostic criteria have been widely used, the sensitivity and specificity are suboptimal. This study aims to provide evidence supporting the revision of the current diagnostic criteria for MSA. METHODS: Medical records of 171 patients with autopsy-confirmed MSA in the Mayo Clinic brain bank were reviewed with regard to their clinical features and diagnoses. Pathologic features, including concomitant pathologies (i.e., Alzheimer-related and Lewy-related pathologies), were also assessed. RESULTS: The cohort included 133 MSA-parkinsonian type, 36 MSA-cerebellar type, and 2 unclassified MSA patients who did not show significant motor symptoms. Twenty-three patients (13%) were not clinically diagnosed with MSA, but instead with progressive supranuclear palsy, Parkinson's disease (PD), PD with dementia (PDD), or dementia with Lewy bodies (DLB). Three patients with PDD and DLB also had concomitant Lewy body pathology. Six patients had late-onset MSA, with an age of onset greater than 75 years. Erectile dysfunction was frequent in male patients (60/63; 95%) in all age ranges. REM sleep behavior disorder (RBD) was present in 82 patients (48%) and was the initial symptom in 13 patients. Cognitive impairment was present in 60 patients (35%), but was an initial symptom in only two patients. CONCLUSIONS: Our findings support the conclusion that late-onset presentation should not exclude MSA. The findings of this large autopsy-based cohort provides valuable insights for improving clinical criteria for MSA.

Comparison of Side Effects and Tolerability Between Intravesical Bacillus Calmette-Guerin, Reduced-Dose BCG and Gemcitabine for Non-Muscle Invasive Bladder Cancer.

OBJECTIVES: To compare patient-reported side effects and tolerability of full-dose Bacillus Calmette-Guérin (BCG), reduced-dose BCG, and gemcitabine one week after administration. METHODS: All patients from July 2019 to November 2020 receiving intravesical therapy (IVT) for non-muscle invasive bladder cancer (NMIBC) at our institution were surveyed before repeat instillation. Survey questions recorded IVT retention times and the duration and severity of the following side effects: bladder symptoms, fatigue, body aches, hematuria, fever, chills, and other. All responses were collected and quantified in a de-identified, password-protected database. Statistical analysis was performed using SAS JMP 13. RESULTS: Of 592 surveys completed, symptoms of any kind were reported on 463 surveys (78%) with the most common symptoms including bladder symptoms (59%), fatigue (52%), body aches (26%), and hematuria (18%). Patients were able to hold full-dose BCG, reduced-dose BCG, and gemcitabine for the protocol-specified duration 87%, 95%, and 71% of the time (P <0.05). The prevalence, severity, and duration of body aches were highest with gemcitabine (P <0.05) while the prevalence and duration of hematuria were higher with BCG (P <0.05). Reduced-dose BCG had the lowest prevalence, severity, and duration of fatigue (P <0.05). CONCLUSION: Significant differences in the side effects and tolerability of full-dose BCG, reduced-dose BCG, and gemcitabine were demonstrated using this novel survey, and these differences are of value for informing IVT selection. Evaluation of IVTs other than gemcitabine and BCG will further inform selection of therapies for NMIBC.

Incidence of Acute Myocardial Infarction in Northern Tanzania: A Modeling Approach Within a Prospective Observational Study.

Background Rigorous incidence data for acute myocardial infarction (AMI) in sub-Saharan Africa are lacking. Consequently, modeling studies based on limited data have suggested that the burden of AMI and AMI-associated mortality in sub-Saharan Africa is lower than in other world regions. Methods and Results We estimated the incidence of AMI in northern Tanzania in 2019 by integrating data from a prospective surveillance study (681 participants) and a community survey of healthcare-seeking behavior (718 participants). In the surveillance study, adults presenting to an emergency department with chest pain or shortness of breath were screened for AMI with ECG and troponin testing. AMI was defined by the Fourth Universal Definition of AMI criteria. Mortality was assessed 30 days following enrollment via in-person or telephone interviews. In the cluster-based community survey, adults in northern Tanzania were asked where they would present for chest pain or shortness of breath. Multipliers were applied to account for AMI cases that would have been missed by our surveillance methods. The estimated annual incidence of AMI was 172 (207 among men and 139 among women) cases per 100 000 people. The age-standardized annual incidence was 211 (263 among men and 170 among women) per 100 000 people. The estimated annual incidence of AMI-associated mortality was 87 deaths per 100 000 people, and the age-standardized annual incidence was 102 deaths per 100 000 people. Conclusions The incidence of AMI and AMI-associated mortality in northern Tanzania is much higher than previously estimated and similar to that observed in high-income countries.