Nevin Manimala

JAMA Netw Open. 2021 Jun 1;4(6):e216105. doi: 10.1001/jamanetworkopen.2021.6105.

ABSTRACT

IMPORTANCE: Although early fluid administration has been shown to lower sepsis mortality, positive fluid balance has been associated with adverse outcomes. Little is known about associations in non-intensive care unit settings, with growing concern about readmission from excess fluid accumulation in patients with sepsis.

OBJECTIVE: To evaluate whether positive fluid balance among non-critically ill patients with sepsis was associated with increased readmission risk, including readmission for heart failure.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective cohort study was conducted between January 1, 2012, and December 31, 2017, among 57 032 non-critically ill adults hospitalized for sepsis at 21 hospitals across Northern California. Kaiser Permanente Northern California is an integrated health care system with a community-based population of more than 4.4 million members. Statistical analysis was performed from January 1 to December 31, 2019.

EXPOSURES: Intake and output net fluid balance (I/O) measured daily and cumulatively at discharge (positive vs negative).

MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day readmission. The secondary outcomes were readmission stratified by category and mortality after living discharge.

RESULTS: The cohort included 57 032 patients who were hospitalized for sepsis (28 779 women [50.5%]; mean [SD] age, 73.7 [15.5] years). Compared with patients with positive I/O (40 940 [71.8%]), those with negative I/O (16 092 [28.2%]) were older, with increased comorbidity, acute illness severity, preexisting heart failure or chronic kidney disease, diuretic use, and decreased fluid administration volume. During 30-day follow-up, 8719 patients (15.3%) were readmitted and 3639 patients (6.4%) died. There was no difference in readmission between patients with positive vs negative I/O (HR, 1.00; 95% CI, 0.95-1.05). No association was detected between readmission and I/O using continuous, splined, and quadratic function transformations. Positive I/O was associated with decreased heart failure-related readmission (HR, 0.80 [95% CI, 0.71-0.91]) and increased 30-day mortality (HR, 1.23 [95% CI, 1.15-1.31]).

CONCLUSIONS AND RELEVANCE: In this large observational study of non-critically ill patients hospitalized with sepsis, there was no association between positive fluid balance at the time of discharge and readmission. However, these findings may have been limited by variable recording and documentation of fluid intake and output; additional studies are needed to examine the association of fluid status with outcomes in patients with sepsis to reduce readmission risk.

PMID:34086036 | DOI:10.1001/jamanetworkopen.2021.6105

JAMA Netw Open. 2021 Jun 1;4(6):e2112551. doi: 10.1001/jamanetworkopen.2021.12551.

ABSTRACT

IMPORTANCE: Elevated systolic blood pressure (SBP) after acute ischemic stroke and transient ischemic attack (TIA) is associated with future stroke risk.

OBJECTIVE: To explore the association of dual antiplatelet therapy (DAPT) with stroke recurrence among patients with acute ischemic stroke and TIA with or without elevated baseline SBP.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study performed a post hoc subgroup analysis of the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which was a multicenter trial conducted from 2010 to 2018 at 269 sites in 10 countries in North America, Europe, Australia, and New Zealand. Patients enrolled in POINT with available blood pressure and outcome data were included in this cohort. Statistical analysis was performed from November 2020 to January 2021.

EXPOSURES: Baseline SBP less than 140 mm Hg vs greater than or equal to 140 mm Hg and the interaction term of SBP (<140 mm Hg vs ≥140 mm Hg) × treatment group (aspirin vs DAPT).

MAIN OUTCOMES AND MEASURES: The primary outcome was ischemic stroke during 90 days of follow-up. The statistical analysis fit Cox proportional hazards models adjusted for patient age, race, premorbid hypertension, diabetes, and final diagnosis of the qualifying event (stroke vs TIA).

RESULTS: Among 4781 patients in the cohort, the mean (SD) age was 64.6 (13.1) years; 2142 (44.8%) were male individuals, 3487 (72.9%) were White individuals, and 266 (5.6%) had a primary outcome of ischemic stroke during follow-up. There were 946 patients (19.8%) with baseline SBP less than 140 mm Hg and 3835 (80.2%) with SBP greater than or equal to 140 mm Hg. The interaction term (SBP × treatment) was significant (P for interaction = .03). In the subgroup of patients with SBP less than 140 mm Hg, the hazard ratio (HR) of DAPT vs aspirin alone for ischemic stroke was 0.36 (95% CI, 0.18-0.72; P = .004), whereas the HR in the subgroup with SBP greater than or equal to 140 mm Hg was 0.79 (95% CI, 0.60-1.02; P = .08). When evaluating the outcome of ischemic stroke within 7 days of randomization, the interaction term was significant (P for interaction = .02), and the HR for patients with DAPT with SBP less than 140 mm Hg was 0.19 (95% CI, 0.07-0.55; P = .002).

CONCLUSIONS AND RELEVANCE: In the POINT trial, patients with SBP less than 140 mm Hg at presentation received a greater benefit from 90 days of DAPT than those with higher baseline SBP, particularly for reduction of early ischemic stroke recurrence. Additional research is needed to replicate these findings and potentially test whether mild SBP reduction and DAPT within 12 hours of stroke onset lowers early risk of stroke recurrence.

PMID:34086033 | DOI:10.1001/jamanetworkopen.2021.12551

Invest Radiol. 2021 Jul 1;56(7):450-457. doi: 10.1097/RLI.0000000000000760.

ABSTRACT

OBJECTIVES: In the United States, prostate cancer (PCa) is the most common cancer in men. Multi-parametric magnetic resonance imaging (MRI) is increasingly being relied upon for the diagnosis and characterization of PCa, but differentiating malignancy from benign prostatic hyperplasia (BPH) in the transition zone using MRI can be challenging. The characteristically high levels of zinc in human prostate tissue and a close relationship between malignant proliferation and zinc homeostatic dysregulation create opportunities to visualize PCa with novel contrast media. In mouse models, glucose-stimulated zinc secretion (GSZS) can be preferentially observed in healthy prostate tissue compared with malignant tissue; in vivo, these differences can be captured with MRI by using Gdl1, a gadolinium-based zinc-responsive contrast agent. In this study, we examined whether this technology can be applied in a large animal model by imaging older dogs with clinically diagnosed BPH.

MATERIALS AND METHODS: Four intact male dogs 6 years or older with enlarged prostates were imaged (T1-weighted turbo spin-echo, TE/TR, 12/400 milliseconds and T2-weighted, TE/TR, 112/5000 milliseconds) using a 3 T scanner before and at multiple time points after intravenous injection of 0.05 mmol/kg GdL1 plus either (a) 2 mL/kg of 50% dextrose in 1 session or (b) 2 mL/kg normal saline in another session. The two sessions were one week apart, and their order was randomly determined for each dog. During postprocessing, regions of interest were generated in prostate tissue and in paraspinal muscles to evaluate the contrast-to-noise ratio (CNR). The ratio of CNR at any postinjection time point compared with baseline CNR was defined as r-CNR. After the second imaging session, the dogs were euthanized, and their prostates were harvested for histopathological examination. Baseline and postintervention plasma and urine samples were analyzed for total zinc by inductively coupled plasma mass spectrometry.

RESULTS: The mean ± SD r-CNR values at 13 minutes postinjection in the dextrose versus saline imaging sessions were 134% ± 10% and 127% ± 7%, respectively (P < 0.01). The histopathologic evaluation of prostate tissues confirmed BPH in all dogs. Interestingly, prostatic intraepithelial neoplasia was detected in 1 animal, and a suspicious mass was found in the same region on T2-weighted scans. The r-CNR of the mass was calculated as 113% ± 4% and 111% ± 6% in the dextrose and saline groups, respectively, with no significant differences between the 2 interventions (P = 0.54), whereas there was a statistically significant difference between the r-CNR of the whole prostate in the dextrose (130% ±11%) and saline (125% ± 9%) interventions (P = 0.03). Inductively coupled plasma mass spectrometry analyses showed a significantly higher urinary zinc in the dextrose versus saline groups, but no differences were found in plasma zinc levels.

CONCLUSIONS: T1-weighted MRI of the enlarged canine prostate showed higher r-CNR after injection of GdL1 plus dextrose compared with GdL1 plus saline, consistent with GSZS from BPH tissues. One small region of neoplastic tissue was identified in a single dog on the basis of less GSZS from that region by MRI. These findings suggest a new method for the detection of PCa by MRI that could facilitate the differentiation of BPH from PCa in the transition zone.

PMID:34086013 | DOI:10.1097/RLI.0000000000000760

Genet Epidemiol. 2021 Jun 3. doi: 10.1002/gepi.22393. Online ahead of print.

ABSTRACT

Interest in analyzing X chromosome single nucleotide polymorphisms (SNPs) is growing and several approaches have been proposed. Prior studies have compared power of different approaches, but bias and interpretation of coefficients have received less attention. We performed simulations to demonstrate the impact of X chromosome model assumptions on effect estimates. We investigated the coefficient biases of SNP and sex effects with commonly used models for X chromosome SNPs, including models with and without assumptions of X chromosome inactivation (XCI), and with and without SNP-sex interaction terms. Sex and SNP coefficient biases were observed when assumptions made about XCI and sex differences in SNP effect in the analysis model were inconsistent with the data-generating model. However, including a SNP-sex interaction term often eliminated these biases. To illustrate these findings, estimates under different genetic model assumptions are compared and interpreted in a real data example. Models to analyze X chromosome SNPs make assumptions beyond those made in autosomal variant analysis. Assumptions made about X chromosome SNP effects should be stated clearly when reporting and interpreting X chromosome associations. Fitting models with SNP × Sex interaction terms can avoid reliance on assumptions, eliminating coefficient bias even in the absence of sex differences in SNP effect.

PMID:34082482 | DOI:10.1002/gepi.22393

Genet Epidemiol. 2021 Jun 3. doi: 10.1002/gepi.22391. Online ahead of print.

ABSTRACT

Multitrait tests can improve power to detect associations between individual single-nucleotide polymorphisms (SNPs) and several related traits. Here, we develop methods for multi-SNP transcriptome-wide association (TWAS) tests to test the association between predicted gene expression levels and multiple phenotypes. We show that the correlation in TWAS test statistics for multiple phenotypes has the same form as multitrait statistics for the single-SNP setting. Thus, established methods for combining single-SNP test statistics across multiple traits can be extended directly to the TWAS setting. We performed an extensive evaluation across eight multitrait methods in simulations that varied gene-phenotype effect sizes in addition to the underlying covariance structure among the phenotypes. We found that all multitrait TWAS tests have well-calibrated Type I error (except ASSET, which can have a slightly elevated or depressed Type I error rate). Our results show that multitrait TWAS can improve statistical power compared with multiple single-trait TWAS followed by Bonferroni correction. To illustrate our approach to real data, we conducted a multitrait TWAS of four circulating lipid traits from the Global Lipids Genetics Consortium. We found that our multitrait Wald TWAS approach identified 506 genes associated with lipid levels compared with 87 identified through Bonferroni-corrected single-trait TWAS. Overall, we find that our proposed multitrait TWAS framework outperforms single-trait approaches to identify new genetic associations, especially for functionally correlated phenotypes and phenotypes with overlapping genome-wide association studies samples, leading to insights into the genetic architecture of multiple phenotypes.

PMID:34082479 | DOI:10.1002/gepi.22391

Neurourol Urodyn. 2021 Jun 3. doi: 10.1002/nau.24726. Online ahead of print.

ABSTRACT

AIM: Examine the effects of treating underlying neuromuscular dysfunction in chronic pelvic pain (CPP) patients.

METHODS: A retrospective longitudinal study of 200 female and male patients with CPP was performed upon an Institutional Review Board (IRB) approval (IRB# 17-0761). The outpatient protocol consisted of ultrasound-guided trigger point injections to the pelvic floor musculature with peripheral nerve blocks once a week for 6 weeks in an outpatient setting. Pelvic pain and functionality were measured before and after treatment using the Visual Analogue Scale and the Functional Pelvic Pain Scale. Functionality categories assessed were intercourse, bladder, bowel, working, walking, running, lifting, and sleeping.

RESULTS: Pretreatment, mean VAS score was 6.44 (standard deviation [SD] = 2.50; p < 0.05, 95% confidence interval [CI] = 6.09-6.79). Posttreatment mean VAS score was 4.25 (SD = 2.63; p < 0.05, 95% CI = 3.88-4.61). The mean FPPS score before treatment was 10.77 (SD = 6.39; p < 0.05, 95% CI = 9.88-11.65). Posttreatment mean FPPS score was 7.42 (SD = 5.87; p < 0.05, 95% CI = 6.61-8.23). Analysis of subcategories within FPPS indicated statistically significant improvement in the categories of intercourse, working, and sleeping.

CONCLUSION: Findings show the treatment was efficient at decreasing pain in CPP patients. Results show promise for improving overall pelvic functionality, particularly within the categories of intercourse, sleeping, and working.

PMID:34082473 | DOI:10.1002/nau.24726

Aorta (Stamford). 2021 Jun 3. doi: 10.1055/s-0040-1719113. Online ahead of print.

ABSTRACT

BACKGROUND: Connective tissue disorders could contribute to the pathogenesis of both abdominal aortic aneurysms (AAA) and hernias. We tested the hypothesis that hernias in AAA patients contribute to increased severity of the aneurysmal disease.

METHODS: A questionnaire was used to collect information from 195 AAA patients divided into four groups: (1) survivors (n = 22) of ruptured AAA, (2) patients (n = 90) after elective open repair, (3) patients (n = 43) after elective endovascular repair (EVAR), and (4) patients (n = 40) under surveillance of AAA. The control group consisted of 100 patients without AAA whose abdominal computed tomography (CT) scans were examined for the presence of hernias. Mann-Whitney U-test, Chi-squared (χ ²) test, or Fisher’s exact test (as appropriate) were used for statistical analyses. Multivariate logistic regression was used to control for potential confounding variables such as sex and age.

RESULTS: The prevalence of inguinal hernias was significantly higher in the AAA than the control group (25 vs. 9%, p = 0.001) and did not differ between the AAA subgroups (9, 24, 35, and 23% in subgroups 1 through 4, respectively, p = 0.15) based on univariate analysis. The prevalence of inguinal hernias did not differ (p = 0.15) between the two open surgery groups (groups 1 and 2), or when comparing all three operative procedures as a combined group to group 4 (p = 0.73). The prevalences of incisional hernias were 18 and 24% for groups 1 and 2, respectively, with no significant difference (p = 0.39). Inguinal hernia demonstrated a significant association with AAA on multivariate analysis (p = 0.006; odds ratio [OR] = 4.00; 95% confidence interval [CI] = 1.49-10.66).

CONCLUSIONS: Our study confirms previous observations that patients with AAA have a high prevalence of hernias. Our results suggest that hernias do not contribute to increased severity of the aneurysmal disease.

PMID:34082466 | DOI:10.1055/s-0040-1719113

J Am Acad Audiol. 2021 Jun 3. doi: 10.1055/s-0041-1722988. Online ahead of print.

ABSTRACT

BACKGROUND: Research suggests Deaf individuals have longstanding negative perceptions of their interactions with health care providers, primarily due to communication barriers. One way to improve relations would be for audiologists to learn clinically relevant sign language.

PURPOSE: The aim of the study is to gain a better understanding of audiologists’ knowledge of Deaf culture and American Sign Language (ASL) and evaluate motivation for instruction in signing abilities.

RESEARCH DESIGN: A 21-question survey was emailed and advertised in a social media group for audiologists. The survey was divided into four sections: (1) demographics, (2) education of ASL and Deaf culture, (3) experience with ASL and Deaf culture, and (4) motivation to learn clinical signs.

DATA ANALYSIS: Descriptive statistics were analyzed for quantitative analysis of survey responses.

RESULTS: A total of 489 responses were obtained and analyzed. Majority of respondents (82.6%) completed a manual ASL course, though only a third reported exposure to clinically relevant signs (37.4%). The majority of respondents rated their signing abilities at the word level, and knowing somewhere between 5 and 20 signs, expressively (50.5%) and receptively (53.9%). Results illustrate the majority of audiologists (54.5%) feel their clinical signing abilities need to be improved and were either highly (30.9%) or somewhat motivated (42.1%) to do so.

CONCLUSION: Study results suggest that although participants are enrolling in and completing ASL courses, clinical signs are not routinely included. This omission leads to reduced signing ability, potentially harming the provider-patient relationship. The majority of survey respondents reported that they are strongly motivated to improve their signing abilities. Results of the present study suggest there is need for a comprehensive clinical signs resource for audiologists to provide quality patient care to their Deaf patients. At present, there is no known, available tool to help accomplish this need.

PMID:34082464 | DOI:10.1055/s-0041-1722988

J Am Acad Audiol. 2021 Jun 3. doi: 10.1055/s-0041-1728754. Online ahead of print.

ABSTRACT

BACKGROUND: Since the hearing and vestibular organs are close to each other, the correlation between hearing and balance is one of the principal issues, especially in people with hearing loss.

PURPOSE: In this study, the effect of the auditory system on human balance performance was investigated by comparing the balance status of hearing-impaired children in the aided and unaided situations.

RESEARCH DESIGN: In this cross-sectional study a group of children were assigned the task to compare the balance sways in two aided and unaided situations.

STUDY SAMPLING: A total of 90 children aged 7 to 10 years with severe to profound congenital hearing loss and the healthy vestibular system of both genders served as the research population.

DATA COLLECTION AND ANALYSIS: After a complete evaluation of the hearing and vestibular system and validation of the hearing aid performance, body sway was recorded using the pediatric clinical test of sensory interaction for balance in aided and unaided situations in the presence of background noise from the speaker.

RESULTS: According to this study, there was no difference in body sway in aided and unaided situations for conditions 1, 2, and 3. In comparison, in conditions 4, 5, and 6 of the test, there was a statistically significant difference in body sway between aided and unaided situations. However, there was no difference in the sway of the body in aided and unaided situations between girls and boys.

CONCLUSION: According to this study, hearing aids can improve balance in challenging listening environments.

PMID:34082460 | DOI:10.1055/s-0041-1728754

AIDS Rev. 2021 Jun 3. doi: 10.24875/AIDSRev.200001071. Online ahead of print.

ABSTRACT

The safety of using different antiretroviral therapies (ART) in pediatric HIV/AIDS patients is not well-established. Therefore, this study aimed to assess the safety of ART in children. A systematic review of randomized clinical trials (RCTs) was conducted to assess the safety of ART used by pediatric patients living with HIV/AIDS. The electronic search was conducted in PubMed and Scopus, in addition to a manual search. Studies were included if they assessed the safety of ART compared to placebo or another ART. Direct and indirect meta-analyses were conducted regarding safety outcomes. The systematic review included 21 RCTs. The studies included more than 5500 participants, and age ranged from 3 months to 18 years. The drugs evaluated were nucleoside reverse transcriptase inhibitors (NRTI); non-NRTI; and protease inhibitors. The predominant route of infection was vertical. Direct meta-analyses were performed for the outcomes sleep disorders, hepatobiliary disorders, respiratory disorders, hypertransaminasemia, neutropenia, hospitalization, and death. For these outcomes, no statistically significant differences were found. Indirect meta-analyses were performed for the outcomes anemia, gastrointestinal disorders, liver disorders, severe adverse events (AE), AE that led to changes in treatment, fever, and skin manifestations. However, no statistically significant differences were found for these outcomes. In this study, non-significant differences were detected in the safety of different ART used in pediatric individuals. The choice of appropriate therapy should be based on its efficacy and the individual characteristics of each patient.

PMID:34082441 | DOI:10.24875/AIDSRev.200001071