Nevin Manimala

JMIR Public Health Surveill. 2023 Oct 17;9:e40149. doi: 10.2196/40149.

ABSTRACT

BACKGROUND: With population aging, the prevalence of both cancer and atrial fibrillation (AF) have increased. However, there is scarce epidemiological data concerning the comorbid state of cancer and AF in low- and middle-income countries, including China.

OBJECTIVE: We aimed to evaluate the site-, sex-, and age-specific profiles of cancer and AF comorbidities in Chinese populations.

METHODS: Data from the Shanghai Municipal Health Commission database between 2015 and 2020 were screened, covering all medical records of Shanghai residents with medical insurance. Site-specific cancer profiles were evaluated for the population with AF relative to the age- and sex-adjusted population of residents without AF. The sex distribution and peak age of cancer diagnosis were also assessed.

RESULTS: A total of 25,964,447 adult patients were screened. Among them, 22,185 patients presented cancers comorbid with AF (median 77, IQR 67-82 years of age; men: n=13,631, 61.44%), while 839,864 presented cancers without AF (median 67, IQR 57-72 years of age; men: n=419,020, 49.89%), thus yielding a higher cancer prevalence among residents with AF (8.27%) than among those without AF (6.05%; P<.001). In the population with AF, the most prevalent cancer type was lung cancer, followed by colorectal, male genital organ, stomach, breast, liver, bladder, thyroid, leukemia, and esophageal cancers. AF was associated with an average of nearly 1.4-fold (prevalence ratio [PR] 1.37, 95% CI 1.35-1.38) increased prevalence of cancer after adjusting for age and sex. For site-specific analyses, an increased prevalence of cancer in the population with AF was observed in 20 of 21 cancer sites. This increased prevalence was most prominent for nonsolid tumors, including multiple myeloma (PR 2.56, 95% CI 2.28-2.87), leukemia (PR 1.73, 95% CI 1.57-1.90), and non-Hodgkin lymphoma (PR 1.59, 95% CI 1.43-1.77); intrathoracic malignancies, including mediastinum (PR 2.34, 95% CI 1.89-2.90), lung (PR 1.64, 95% CI 1.59-1.69), and esophageal cancers (PR 1.41, 95% CI 1.28-1.56); bone and soft tissue neoplasms (PR 1.56, 95% CI 1.37-1.77); and kidney cancer (PR 1.53, 95% CI 1.36-1.72). Cancer prevalence in the population with AF relative to that in the population without AF was higher in men than in women in 14 of 18 cancer sites, and female predominance was only observed for thyroid cancer. The peak age of index cancer diagnosis was lower in the population with AF (age group: 70-74 years) than in that without AF (age group: 75-79 years), especially for specific cancer types, including thyroid, central nervous system, mediastinum, esophageal, bladder, and biliary cancers.

CONCLUSIONS: Patients with AF are associated with increased prevalence, heightened male predominance, and younger peak age of cancer. Further studies are needed to determine whether early screening of specific cancers is cost-effective and beneficial for patients with AF.

PMID:37847541 | DOI:10.2196/40149

JMIR Form Res. 2023 Oct 17;7:e51019. doi: 10.2196/51019.

ABSTRACT

BACKGROUND: Lower urinary tract symptoms affect a large number of people of all ages and sexes. The clinical assessment typically involves a bladder diary and uroflowmetry test. Conventional paper-based diaries are affected by low patient compliance, whereas in-clinic uroflowmetry measurement face challenges such as patient stress and inconvenience factors. Home uroflowmetry and automated bladder diaries are believed to overcome these limitations.

OBJECTIVE: In this study, we present our first-year experience of managing urological patients using Minze homeflow, which combines home uroflowmetry and automated bladder diaries. Our objective was 2-fold: first, to provide a description of the reasons for using homeflow and second, to compare the data obtained from homeflow with the data obtained from in-clinic uroflowmetry (hospiflow).

METHODS: A descriptive retrospective analysis was conducted using Minze homeflow between July 2019 and July 2020 at a tertiary university hospital. The device comprises a Bluetooth-connected gravimetric uroflowmeter, a patient smartphone app, and a cloud-based clinician portal. Descriptive statistics, Bland-Altman plots, the McNemar test, and the Wilcoxon signed rank test were used for data analysis.

RESULTS: The device was offered to 166 patients, including 91 pediatric and 75 adult patients. In total, 3214 homeflows and 129 hospiflows were recorded. Homeflow proved valuable for diagnosis, particularly in cases where hospiflow was unreliable or unsuccessful, especially in young children. It confirmed or excluded abnormal hospiflow results and provided comprehensive data with multiple measurements taken at various bladder volumes, urge levels, and times of the day. As a result, we found that approximately one-fourth of the patients with abnormal flow curves in the clinic had normal bell-shaped flow curves at home. Furthermore, homeflow offers the advantage of providing an individual’s plot of maximum flow rate (Q-max) versus voided volume as well as an average or median result. Our findings revealed that a considerable percentage of patients (22/76, 29% for pediatric patients and 24/50, 48% for adult patients) had a Q-max measurement from hospiflow falling outside the range of homeflow measurements. This discrepancy may be attributed to the unnatural nature of the hospiflow test, resulting in nonrepresentative uroflow curves and an underestimation of Q-max, as confirmed by the Bland-Altman plot analysis. The mean difference for Q-max was -3.1 mL/s (with an upper limit of agreement of 13 mL/s and a lower limit of agreement of -19.2 mL/s), which was statistically significant (Wilcoxon signed rank test: V=2019.5; P<.001). Given its enhanced reliability, homeflow serves as a valuable tool not only for diagnosis but also for follow-up, allowing for the evaluation of treatment effectiveness and home monitoring of postoperative and recurrent interventions.

CONCLUSIONS: Our first-year experience with Minze homeflow demonstrated its feasibility and usefulness in the diagnosis and follow-up of various patient categories. Homeflow provided more reliable and comprehensive voiding data compared with hospiflow.

PMID:37847531 | DOI:10.2196/51019

Clin J Am Soc Nephrol. 2023 Oct 17. doi: 10.2215/CJN.0000000000000328. Online ahead of print.

ABSTRACT

BACKGROUND: There is a lack of randomized controlled trial data regarding differences in immunogenicity of varying COVID-19 mRNA vaccine regimens in chronic kidney disease (CKD) populations.

METHODS: We conducted a randomized controlled trial at three kidney centres in Toronto, Ontario, Canada evaluating the SARS-CoV-2 antibody response following third dose vaccination. Participants (n=273) with CKD not on dialysis or receiving dialysis were randomized 1:1 to third dose 30µg BNT162b2 (Pfizer-BioNTech) or 100µg mRNA-1273 (Moderna). The primary outcome of this study was SARS-CoV-2 IgG binding antibodies to the receptor binding domain (anti-RBD). Spike protein (anti-spike), nucleocapsid protein, and vaccine reactogenicity were also evaluated. Serology was measured prior to third dose, 1 month, 3 months, and 6 months following third dose. A subset of participants (n=100) were randomly selected to assess viral pseudovirus neutralization against wild-type D614G, B.1.617.2 (Delta), and B.1.1.529 (Omicron BA.1).

RESULTS: Among 273 participants randomized, 94% were receiving maintenance dialysis and 59% received BNT162b2 for initial two dose COVID-19 vaccination. Third dose of mRNA-1273 was associated with higher mean anti-RBD levels (1871 BAU/mL; 95% CI 829, 2988) over a 6-month period in comparison to third dose BNT162b2 (1332 BAU/mL; 95% CI 367, 2402) with a difference of 539 BAU/mL (95% CI 139, 910; p=0.009). Neither anti-spike levels nor neutralizing antibodies to wild-type, Delta, Omicron BA.1 pseudoviruses were statistically different. COVID-19 infection occurred in 10% of participants:15 (11%) receiving mRNA-1273 and 11 (8%) receiving BNT162b2. Third dose BNT162b2 was not associated with a significant different risk for COVID-19 in comparison to mRNA-1273 (HR 0.78; 95% CI 0.27, 2.2, p=0.63).

CONCLUSIONS: In patients with CKD third dose COVID-19 mRNA vaccination with mRNA-1273 elicited higher SARS-CoV-2 anti-RBD levels in comparison to BNT162b2 over a 6-month period.

PMID:37847518 | DOI:10.2215/CJN.0000000000000328

JAMA Netw Open. 2023 Oct 2;6(10):e2337494. doi: 10.1001/jamanetworkopen.2023.37494.

ABSTRACT

IMPORTANCE: Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer.

OBJECTIVE: To determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, prospective, double-blinded, placebo-controlled, 2 × 2 factorial randomized clinical trial included patients with newly diagnosed NMIBC recruited from 10 secondary or tertiary care hospitals in the UK. A total of 755 patients were screened for inclusion; 484 did not meet the inclusion criteria, and 1 declined to participate. A total of 270 patients were randomly assigned to 4 groups (selenium plus placebo, vitamin E plus placebo, selenium plus vitamin E, and placebo plus placebo) in a double-blind fashion between July 17, 2007, and October 10, 2011. Eligibility included initial diagnosis of NMIBC (stages Ta, T1, or Tis); randomization within 12 months of first transurethral resection was required.

INTERVENTIONS: Oral selenium (200 μg/d of high-selenium yeast) and matched vitamin E placebo, vitamin E (200 IU/d of d-alfa-tocopherol) and matched selenium placebo, selenium and vitamin E, or placebo and placebo.

MAIN OUTCOME AND MEASURES: Recurrence-free interval (RFI) on an intention-to-treat basis (analyses completed on November 28, 2022).

RESULTS: The study randomized 270 patients (mean [SD] age, 68.9 [10.4] years; median [IQR] age, 69 [63-77] years; 202 male [75%]), with 65 receiving selenium and vitamin E placebo, 71 receiving vitamin E and selenium placebo, 69 receiving selenium and vitamin E, and 65 receiving both placebos. Median overall follow-up was 5.5 years (IQR, 5.1-6.1 years); 228 patients (84%) were followed up for more than 5 years. Median treatment duration was 1.5 years (IQR, 0.9-2.5 years). The study was halted because of slow accrual. For selenium (n = 134) vs no selenium (n = 136), there was no difference in RFI (hazard ratio, 0.92; 95% CI, 0.65-1.31; P = .65). For vitamin E (n = 140) vs no vitamin E (n = 130), there was a statistically significant detriment to RFI (hazard ratio, 1.46; 95% CI, 1.02-2.09; P = .04). No significant differences were observed for progression-free interval or overall survival time with either supplement. Results were unchanged after Cox proportional hazards regression modeling to adjust for known prognostic factors. In total, 1957 adverse events were reported; 85 were serious adverse events, and all were considered unrelated to trial treatment.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of selenium and vitamin E, selenium supplementation did not reduce the risk of recurrence in patients with NMIBC, but vitamin E supplementation was associated with an increased risk of recurrence. Neither selenium nor vitamin E influenced progression or overall survival. Vitamin E supplementation may be harmful to patients with NMIBC, and elucidation of the underlying biology is required.

TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN13889738.

PMID:37847504 | DOI:10.1001/jamanetworkopen.2023.37494

JAMA Netw Open. 2023 Oct 2;6(10):e2338060. doi: 10.1001/jamanetworkopen.2023.38060.

ABSTRACT

IMPORTANCE: The clinical significance of hemodynamic reactivity to mental stress in the population with coronary artery disease (CAD) is unclear.

OBJECTIVE: To investigate the association between hemodynamic reactivity to mental stress and the risk of adverse cardiovascular events in patients with stable CAD.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included individuals with stable CAD from 2 prospective studies from a university-based hospital network: the Mental Stress Ischemia Prognosis Study (MIPS) and the Myocardial Infarction and Mental Stress Study 2 (MIMS2). Participants were enrolled between June 2011 and March 2016 and followed up for a median of 6.0 (IQR, 5.6-6.0) years in MIPS and 4.6 (IQR, 3.8-5.3) years in MIMS2. Data were analyzed from December 1, 2022, to February 15, 2023.

EXPOSURES: The rate-pressure product (RPP) was calculated as the mean systolic blood pressure times the mean heart rate at rest. Rate-pressure product reactivity was calculated as the maximum RPP during a standardized mental stress test minus the RPP at rest.

MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of cardiovascular death or nonfatal myocardial infarction. The secondary end point additionally included hospitalizations for heart failure.

RESULTS: From the total of 938 individuals from the pooled cohort (mean [SD] age, 60.2 [10.1] years; 611 [65.1%] men), 631 participated in MIPS and 307 in MIMS2. A total of 373 individuals (39.8%) were Black, 519 (55.3%) were White, and 46 (4.9%) were of unknown race or ethnicity. The RPP increased by a mean (SD) of 77.1% (23.1%) during mental stress (mean [SD] absolute change, 5651 [2878]). For every SD decrease in RPP reactivity with mental stress, the adjusted hazard ratios for the primary and secondary end points were 1.30 (95% CI, 1.04-1.72) and 1.30 (95% CI, 1.06-1.56), respectively, in MIPS and 1.41 (95% CI, 1.06-1.97) and 1.21 (95% CI, 1.02-1.60), respectively, in MIMS2. In the pooled sample, when RPP reactivity to mental stress was added to a model including traditional clinical risk characteristics, model discrimination for adverse events improved (increase in C statistic of 5% for the primary end point; P = .009).

CONCLUSIONS AND RELEVANCE: In this cohort study of individuals with stable CAD, a blunted cardiovascular reactivity to mental stress was associated with adverse outcomes. Future studies are needed to assess the clinical utility of mental stress reactivity testing in this population.

PMID:37847500 | DOI:10.1001/jamanetworkopen.2023.38060

JAMA Netw Open. 2023 Oct 2;6(10):e2338088. doi: 10.1001/jamanetworkopen.2023.38088.

ABSTRACT

IMPORTANCE: Evidence that adult attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk of dementia is scarce and inconsistent, and potential sources of bias are untested.

OBJECTIVE: To examine the association between adult ADHD and the risk of dementia.

DESIGN, SETTING, AND PARTICIPANTS: This prospective national cohort study consisted of 109 218 members of a nonprofit Israeli health maintenance organization born between 1933 and 1952 who entered the cohort on January 1, 2003, without an ADHD or dementia diagnosis and were followed up to February 28, 2020. Participants were aged 51 to 70 years in 2003. Statistical analysis was conducted from December 2022 to August 2023.

EXPOSURE: Adult ADHD was a time-varying covariate, classified as present from the age of the first diagnosis (using the International Classification of Diseases, Ninth Revision, and the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision); otherwise, absent.

MAIN OUTCOME AND MEASURES: Cox regression models were fitted to quantify the association between adult ADHD and the risk of incident dementia with hazard ratios (HRs) and their 95% CIs unadjusted and in the primary analysis, using inverse probability weights, adjusted for 18 sources of potential confounding. In 14 complementary analyses, subgroup and sensitivity analyses were implemented.

RESULTS: At the beginning of the follow-up, the sample of 109 218 participants had a mean (SD) age of 57.7 (5.5) years, 56 474 participants (51.7%) were female, and 52 744 (48.3%) were male. During follow-up, 730 participants (0.7%) received a diagnosis of adult ADHD, and 7726 (7.1%) received a diagnosis of dementia. Dementia occurred among 96 of 730 participants (13.2%) with adult ADHD and 7630 of 108 488 participants (7.0%) without adult ADHD. In the primary analysis, compared with the absence of adult ADHD, the presence of adult ADHD was statistically significantly (P < .001) associated with an increased dementia risk (unadjusted HR, 3.62 [95% CI, 2.92-4.49; P < .001]; adjusted HR, 2.77 [95% CI, 2.11-3.63; P < .001]). Twelve of the 14 complementary analyses did not attenuate the conclusions based on the results of the primary analysis. There was, however, no clear increase in the risk of dementia associated with adult ADHD among those who received psychostimulant medication, and evidence of reverse causation was mild.

CONCLUSIONS AND RELEVANCE: In this cohort study of individuals born between 1933 and 1952 and followed up in old age, adult ADHD was associated with an increased risk of dementia. Policy makers, caregivers, patients, and clinicians may wish to monitor reliably for ADHD in old age.

PMID:37847497 | DOI:10.1001/jamanetworkopen.2023.38088

J Med Syst. 2023 Oct 17;47(1):105. doi: 10.1007/s10916-023-01997-2.

ABSTRACT

In health care, auditory alarms are an important aspect of an informatics system that monitors patients and alerts clinicians attending to multiple concurrent tasks. However, the volume, design, and pervasiveness of existing Intensive Care Unit (ICU) alarms can make it difficult to quickly distinguish their meaning and importance. In this study, we evaluated the effectiveness of two design approaches not yet explored in a smartwatch-based alarm system designed for ICU use: (1) using audiovisual spatial colocalization and (2) adding haptic (i.e., touch) information. We compared the performance of 30 study participants using ICU smartwatch alarms containing auditory icons in two implementations of the audio modality: colocalized with the visual cue on the smartwatch’s low-quality speaker versus delivered from a higher quality speaker located two feet away from participants (like a stationary alarm bay situated near patients in the ICU). Additionally, we compared participant performance using alarms with two sensory modalities (visual and audio) against alarms with three sensory modalities (adding haptic cues). Participants were 10.1% (0.24s) faster at responding to alarms when auditory information was delivered from the smartwatch instead of the higher quality external speaker. Meanwhile, adding haptic information to alarms improved response times to alarms by 12.2% (0.23s) and response times on their primary task by 10.3% (0.08s). Participants rated learnability and ease of use higher for alarms with haptic information. These small but statistically significant improvements demonstrate that audiovisual colocalization and multisensory alarm design can improve user response times.

PMID:37847469 | DOI:10.1007/s10916-023-01997-2

Breast Cancer Res Treat. 2023 Oct 17. doi: 10.1007/s10549-023-07118-4. Online ahead of print.

ABSTRACT

PURPOSE: The International Ki67 Working Group (IKWG) has developed training for immunohistochemistry (IHC) scoring reproducibility and recommends cut points of ≤ 5% and ≥ 30% for prognosis in ER+, HER2-, stage I/II breast cancer. We examined scoring reproducibility following IKWG training and evaluated these cut points for selecting patients for further testing with the 21-gene Recurrence Score (RS) assay.

METHODS: We included 307 women aged 50+ years with node-negative, ER+PR+HER2- breast cancer and with available RS results. Slides from the diagnostic biopsy were stained for Ki67 and scored using digital image analysis (IA). Two IHC pathologists underwent IKWG training and visually scored slides, blinded to each other and IA readings. Interobserver reproducibility was examined using intraclass correlation (ICC) and Kappa statistics.

RESULTS: Depending on reader, 8.8-16.0% of our cohort had Ki67 ≤ 5% and 11.4-22.5% had scores ≥ 30%. The ICC for Ki67 scores by the two pathologists was 0.82 (95% CI 0.78-0.85); it was 0.79 (95% CI 0.74-0.83) for pathologist 1 and IA and 0.76 (95% CI 0.71-0.80) for pathologist 2 and IA. For Ki67 scores ≤ 5%, the percentages with RS < 26 were 92.6%, 91.8%, and 90.9% for pathologist 1, pathologist 2, and IA, respectively. For Ki67 scores ≥ 30%, the percentages with RS ≥ 26 were 41.5%, 51.4%, and 27.5%, respectively.

CONCLUSION: The IKWG’s Ki67 training resulted in moderate to strong reproducibility across readers but cut points had only moderate overlap with RS cut points, especially for Ki67 ≥ 30% and RS ≥ 26; thus, their clinical utility for a 21-gene assay testing pathway remains unclear.

PMID:37847456 | DOI:10.1007/s10549-023-07118-4

Antonie Van Leeuwenhoek. 2023 Oct 17. doi: 10.1007/s10482-023-01869-2. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa is one of the top-listed pathogens in nosocomial infection. It is notorious for its complicated virulence system and rapid adaptability to drugs or antimicrobials. In this study, we aimed to evaluate the prevalence of sixteen virulence genes in four groups including type III secretion system, biofilm formation, extracellular toxin biosynthesis and enzymes amongst 209 clinical Pseudomonas aeruginosa strains. We investigated the different distribution patterns of virulence genotypes based on carbapenem-resistant phenotype or the carriage of carbapenemase genes. The detection rate of each virulence gene varied greatly. phzM and plcN were detected in all collected strains, while pilB and exoU were only carried by a small portion of isolates (6.7% and 16.3%). Additionally, the number of genotypes observed in each group of examined virulence genes ranged from 4 to 8. Only the distribution of genotypes of type III secretion system showed statistical difference between carbapenem-mediated or carbapenem-resistant and carbapenem-sensitive strains. The virulence genotype of Pseudomonas aeruginosa was possibly interrelated to its resistance mechanism. Further research suggested that one particular TTSS genotype exhibited higher ratio in carbapenemase-producing strains and exoS was less frequently detected in CRPA strains carrying carbapenemase gene. Generally, the significant genetic diversity of virulence genes amongst Pseudomonas aeruginosa strains was highlighted in this study. Specific TTSS genotypes were associated with carbapenem-resistance. In particular, certain incompatibility might exist between exoS and carbapenemase genes, which provided valuable information for further understanding the relationship between carbapenem resistance and virulence.

PMID:37847452 | DOI:10.1007/s10482-023-01869-2

Support Care Cancer. 2023 Oct 17;31(12):638. doi: 10.1007/s00520-023-08104-8.

ABSTRACT

Nasopharyngeal carcinoma (NPC) patients usually presented malnutrition under chemoradiotherapy (CRT)/radiotherapy (RT). Few studies stratified by age to investigate the association of nutritional status with overall survival (OS) in NPC patients. This study aimed to explore the nutritional parameters related prognosis of NPC patients in different age. The total 1365 NPC patients were classified into young (18~45), middle-aged (46~60), and old groups (> 60). PG-SGA scores, NRS-2002 scores, Karnofsky performance status scores, anthropometric, and blood indicators (albumin, prealbumin, transferrin, C-reactive protein, hemoglobin, and total lymphocyte) were assessed. Cox regression analysis was performed to evaluate the association between risk factors of nutritional status and the overall survival in different age group of NPC patients. Kaplan-Meier (KM) survival analysis was used to estimate the effect of nutritional indexes on prognosis. The abnormal rate of albumin, prealbumin, hemoglobin, hand grip strength, and calf circumference increased with age. The malnutrition occurred in all age group and low calf circumference (HR, 4.427, 1.167-16.791) was an independent death risk in young adults. Distant metastasis (HR, 4.754, 2.737-8.260), low albumin (HR, 3.530, 1.708-7.296), hand grip strength (HR, 1.901, 1.160-3.115), and the nutritional intervention requirement (NRS-2002 ≥ 3) (HR, 2.802, 1.211-6.483) was significantly correlated with poor OS in NPC patients with middled age adults. Distant metastasis (HR, 2.546, 1.497-4.330), low albumin (HR, 1.824, 0.949-3.507), low hemoglobin (HR, 1.757, 1.015-3.044), low hand grip strength (HR, 1.771, 1.112-2.818), and low calf circumference (HR, 1.951, 1.074-3.545) were associated with increased risk of death in the elderly. KM analysis indicated that over 60 years, distant metastasis, low albumin, low hand grip strength, low calf circumference, and malnutritional risk (NRS-2002 ≥ 3) were correlated to prognosis of NPC patients. Low calf circumference could be a prognosis not only in elderly but also in young adults of NPC patients, whereas low albumin and distant metastasis were the prognostic factors in middle-aged and elderly patients. Patients aged over 60 years exhibited poorer OS compared with young and middle-aged adults.

PMID:37847417 | DOI:10.1007/s00520-023-08104-8