Publications by authors named "G K Balasubramani"

125 Publications

Comparison of local influenza vaccine effectiveness using two methods.

Vaccine 2021 Feb 21;39(8):1283-1289. Epub 2021 Jan 21.

University of Pittsburgh Department of Family Medicine, Suite 520 Schenley Place, 4420 Bayard St., Pittsburgh, PA 15260 USA. Electronic address:

Background: In some settings, research methods to determine influenza vaccine effectiveness (VE) may not be appropriate because of cost, time constraints, or other factors. Administrative database analysis of viral testing results and vaccination history may be a viable alternative. This study compared VE estimates from outpatient research and administrative databases.

Methods: Using the test-negative, case-control design, data for 2017-2018 and 2018-2019 influenza seasons were collected using: 1) consent, specimen collection, RT-PCR testing and vaccine verification using multiple methods; and 2) an administrative database of outpatients with a clinical respiratory viral panel combined with electronic immunization records. Odds ratios for likelihood of influenza infection by vaccination status were calculated using multivariable logistic regression. VE = (1 - aOR) × 100.

Results: Research participants were significantly younger (P < 0.001), more often white (69% vs. 59%; P < 0.001) than non-white and less frequently enrolled through the emergency department (35% vs. 72%; P < 0.001) than administrative database participants. VE was significant against all influenza and influenza A in each season and both seasons combined (37-49%). Point estimate differences between methods were evident, with higher VE in the research database, but insignificant due to low sample sizes. When enrollment sites were separately analyzed, there were significant differences in VE estimates for all influenza (66% research vs. 46% administrative P < 0.001) and influenza A (67% research vs. 49% administrative; P < 0.001) in the emergency department.

Conclusions: The selection of the appropriate method for determining influenza vaccine effectiveness depends on many factors, including sample size, subgroups of interest, etc., suggesting that research estimates may be more generalizable. Other advantages of research databases for VE estimates include lack of clinician-related selection bias for testing and less misclassification of vaccination status. The advantages of the administrative databases are potentially shorter time to VE results and lower cost.
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http://dx.doi.org/10.1016/j.vaccine.2021.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825890PMC
February 2021

Effectiveness of Influenza Vaccine for Preventing Laboratory-Confirmed Influenza Hospitalizations in Immunocompromised Adults.

Clin Infect Dis 2021 Jan 3. Epub 2021 Jan 3.

University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Background: Yearly influenza immunization is recommended for immunocompromised (IC) individuals, although immune responses are lower than that for the non-immunocompromised and the data on vaccine effectiveness (VE) in the IC is scarce. We evaluated VE against influenza-associated hospitalization among IC adults.

Methods: We analyzed data from adults ≥ 18 years hospitalized with acute respiratory illness (ARI) during the 2017-2018 influenza season at 10 hospitals in the United States. IC adults were identified using pre-specified case-definitions, utilizing electronic medical record data. VE was evaluated with a test-negative case-control design using multivariable logistic regression with PCR-confirmed influenza as the outcome and vaccination status as the exposure, adjusting for age, enrolling site, illness onset date, race, days from onset to specimen collection, self-reported health, and self-reported hospitalizations.

Results: Of 3,524 adults hospitalized with ARI, 1,210 (34.3%) had an immunocompromising condition. IC adults were more likely to be vaccinated than non-IC (69.5% vs 65.2%), and less likely to have influenza (22% vs 27.8%). The mean age did not differ among IC and non-IC (61.4 vs 60.8 years old). The overall VE against influenza hospitalization, including immunocompetent adults, was 33% (95% CI, 21% to 44%). VE among IC vs non-IC adults was lower at 5% (-29% to 31%) vs. 41% (27% to 52%) (p<0.05 for interaction term).

Conclusions: VE in one influenza season was very low among IC individuals. Future efforts should include evaluation of VE among the different immunocompromising conditions and whether enhanced vaccines improve the suboptimal effectiveness among the immunocompromised.
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http://dx.doi.org/10.1093/cid/ciaa1927DOI Listing
January 2021

Corneal Endothelial Cell Changes After Phacoemulsification Combined with Excisional Goniotomy with the Kahook Dual Blade or iStent: A Prospective Fellow-Eye Comparison.

Clin Ophthalmol 2020 24;14:4047-4053. Epub 2020 Nov 24.

Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.

Purpose: To characterize changes in endothelial cell density and morphology following phacoemulsification combined with either excisional goniotomy with the Kahook Dual Blade (KDB-phaco) or first-generation iStent trabecular microbypass implantation (iStent-phaco).

Setting: A single clinical practice.

Methods: Twenty-one adult subjects from one center with visually significant cataract and mild-moderate open-angle glaucoma underwent KDB-phaco or iStent-phaco in one eye and the alternate procedure in the fellow eye as part of a prospective, multicenter, randomized trial. Specular microscopy and pachymetry were performed before and 6-29 months after surgery. Parameters analyzed included change from baseline of endothelial cell density (ECD), the coefficient of variation (CV), the percent of hexagonal cells (%HEX), and central corneal thickness (CCT).

Results: Baseline ECD, CV, %HEX, and CCT were similar between groups. A mean (standard deviation) of 18.2 (5.8) months postoperatively (range 12.5-28.7 months), the change from baseline in ECD was -90 ± 226 cells/mm (-3.4%) in KDB-phaco eyes (p=0.083) and -239 ± 247 cells/mm (-9.0%) in iStent-phaco eyes (p<0.001); the change in iStent-phaco eyes was significantly greater than in KDB-phaco eyes (p=0.013). The magnitude of Endothelial Cell Loss (ECL) was not correlated with length of postoperative follow-up time in either group. No significant differences in change from baseline in CV, %HEX, or CCT were noted with the exception of a decrease in %HEX in iStent-phaco eyes (p=0.017). No eyes manifested corneal edema, decompensation, or other cornea-related complications.

Conclusion: Both KDB-phaco and iStent-phaco are associated with postoperative ECL, with iStent-phaco producing significantly greater ECL than KDB-phaco. The clinical significance of these findings is unclear, and future studies are warranted to more robustly characterize long-term effects of glaucoma surgical procedures-with and without permanent implants-on ECD and corneal health and to develop evidence-based guidelines for the pre- and post-operative evaluation of corneal health in eyes undergoing glaucoma surgery.
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http://dx.doi.org/10.2147/OPTH.S263072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700000PMC
November 2020

Treatment selection and survival outcomes in Early-Stage peripheral T-Cell lymphomas: does anaplastic lymphoma kinase mutation impact the benefit of consolidative radiotherapy?

Leuk Lymphoma 2020 Nov 30:1-11. Epub 2020 Nov 30.

Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

The role of consolidative radiotherapy (RT) is less substantiated in uncommon peripheral T-cell lymphomas (PTCLs). Anaplastic lymphoma kinase (ALK) mutation sub-categorizes PTCLs, with ALK (+) having a distinctly favorable prognosis. We aimed to use the National Cancer Database to examine the potential role of RT in PTCLs and if ALK mutation can be used to predict the benefit of consolidative RT after multi-agent chemotherapy (combined modality therapy). We identified 3670 stage I-II PTCL patients treated with multi-agent chemotherapy alone or combined modality therapy (CMT) between 1998-2012. After adjusting for immortal-time and indication bias, CMT was associated with better OS than multi-agent chemotherapy alone for ALK (-) patients (HR 0.69, 95% CI 0.52-0.92,  = .01); no significant difference was noted for ALK (+) (HR 1.03, 95% CI 0.75-1.41,  = .85). CMT is associated with improved OS for ALK (-) PTCLs; while no such benefit was seen for the ALK (+) subgroup.
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http://dx.doi.org/10.1080/10428194.2020.1842398DOI Listing
November 2020

Using Capture-Recapture Methods to Estimate Local Influenza Hospitalization Incidence Rates.

medRxiv 2020 Nov 5. Epub 2020 Nov 5.

Background: Accurate population estimates of disease incidence and burden are needed to set appropriate public health policy. The capture-recapture (C-R) method combines data from multiple sources to better estimate prevalence than is possible using single sources. This study used the C-R method to estimate influenza cases using research and administrative databases to calculate county-wide influenza hospitalization burden.

Methods: Data were derived from a database of clinical virology test results and research data from an influenza vaccine effectiveness study from seasons 2015-2016 to 2018-2019. Missed influenza cases were estimated using C-R method. These estimates were used to calculate disease burden using the multiplier method to correct for underreporting due to curtailing data collection before the end of influenza circulation.

Results: Over all seasons, 422 influenza cases were reported in the administrative database and 382 influenza cases in the research database. Seventy-five cases (18%) reported in the administrative database were not captured in the research database, and 35 (9%) cases in the research database were not captured in the administrative database. Completeness of the influenza hospitalization was estimated to be 76%. Influenza hospitalizations were higher among unvaccinated (32%) than vaccinated (22%) in the current season and among unvaccinated (28%) than vaccinated (23%) in the previous year. The incidence rates for influenza hospitalizations varied by age and season and averaged 421 cases/100,000 population annually.

Conclusion: The capture-recapture method offers a more accurate method for estimating influenza hospitalization than relying on a single data source. Using the multiplier method with adjustments improves the detection of influenza disease burden through a matched database. The incidence rates are consistent with national estimates.
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http://dx.doi.org/10.1101/2020.11.03.20225482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654879PMC
November 2020

Proposed clinical indicators for efficient screening and testing for COVID-19 infection using Classification and Regression Trees (CART) analysis.

Hum Vaccin Immunother 2020 Oct 20:1-4. Epub 2020 Oct 20.

Department of Epidemiology, University of Pittsburgh Graduate School of Public Health , Pittsburgh, PA, USA.

The introduction and rapid transmission of SARS-CoV-2 in the United States resulted in methods to assess, mitigate, and contain the resulting COVID-19 disease derived from limited knowledge. Screening for testing has been based on symptoms typically observed in inpatients, yet outpatient symptoms may differ. Classification and regression trees recursive partitioning created a decision tree classifying participants into laboratory-confirmed cases and non-cases. Demographic and symptom data from patients ages 18-87 years enrolled from March 29-June 8, 2020 were included. Presence or absence of SARS-CoV-2 was the target variable. Of 832 tested, 77 (9.3%) tested positive. Cases significantly more often reported diarrhea (12 percentage points (PP)), fever (15 PP), nausea/vomiting (9 PP), loss of taste/smell (52 PP), and contact with a COVID-19 case (54 PP), but less frequently reported sore throat (-27 PP). The 4-terminal node optimal tree had sensitivity of 69%, specificity of 78%, positive predictive value of 20%, negative predictive value of 97%, and AUC of 76%. Among those referred for testing, negative responses to two questions could classify about half (49%) of tested persons with low risk for SARS-CoV-2 and would save limited testing resources. Outpatient symptoms of COVID-19 appear to be broader than the inpatient syndrome. Initial supplies of anticipated COVID-19 vaccines may be limited and administration of first such available vaccines may need to be prioritized for essential workers, the most vulnerable, or those likely to have a robust response to vaccine. Another priority group could be those not previously infected. Those who screen out of testing may be less likely to have been infected by SARS-CoV-2 virus thus may be prioritized for vaccination when supplies are limited.
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http://dx.doi.org/10.1080/21645515.2020.1822135DOI Listing
October 2020

Two-Year Clinical Outcomes of Combined Phacoemulsification, Goniosynechialysis, and Excisional Goniotomy For Angle-Closure Glaucoma.

Asia Pac J Ophthalmol (Phila) 2020 Oct 6. Epub 2020 Oct 6.

University of Pittsburgh, Department of Epidemiology, Pittsburgh, PA, USA.

Purpose: The aim of this study was to describe changes in intraocular pressure (IOP) and IOP medications after phacoemulsification with Kahook Dual Blade-assisted goniosynechialysis and excisional goniotomy in eyes with angle-closure glaucoma and cataract.

Design: Retrospective case series.

Methods: Data were collected retrospectively through 24 months of follow-up in 42 eyes of 24 subjects.

Results: Preoperative mean (SE) IOP was 25.5 (0.7) mm Hg using a mean of 2.3 (0.1) medications per eye. At month 24, mean IOP had decreased to 13.5 (0.4) mm Hg [a reduction of 12.0 mm Hg (47.1%); P < 0.0001]. Medication use declined to a mean of 0.6 (0.2) medications per eye [a reduction of 1.7 medications per eye (76%); P < 0.0001]. At month 24, 40 of 42 eyes (95.2%) achieved IOP ≤18 mm Hg, 42 of 42 eyes (100%) achieved IOP reduction of ≥20%, 36 of 42 eyes (85.7%) required ≥1 fewer medications for IOP control, and 29 of 42 (69.0%) were medication-free. No eyes required additional glaucoma surgery throughout 24 months of follow-up.

Conclusions: Phaco plus Kahook Dual Blade-assisted goniosynechialysis/excisional goniotomy provides statistically and clinically meaningful reductions in both IOP and medications in eyes with angle-closure glaucoma throughout 2 years of follow-up. These findings are consistent with our previously reported outcomes in this cohort at months 6 and 12 postoperatively, demonstrating a significant and sustained benefit of this procedure in eyes with angle-closure glaucoma and cataract.
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http://dx.doi.org/10.1097/APO.0000000000000321DOI Listing
October 2020

Relative effectiveness of high dose versus standard dose influenza vaccines in older adult outpatients over four seasons, 2015-16 to 2018-19.

Vaccine 2020 09 13;38(42):6562-6569. Epub 2020 Aug 13.

Centers for Disease Control and Prevention, Influenza Division, National Center for Immunization and Respiratory Diseases, Atlanta, GA, USA.

Background: New influenza vaccine formulations are designed to improve vaccine effectiveness and protect those most vulnerable to infection. High dose trivalent inactivated influenza vaccine (HD-IIV3), licensed for ages ≥65 years, produces greater antibody responses and efficacy in clinical trials, but post-licensure vaccine effectiveness (VE) compared to standard dose (SD-IIV3/4) vaccine remains an open question.

Methods: Using a test-negative, case control design and propensity analyses to adjust for confounding, US Influenza VE Network data from the 2015-2016 through 2018-2019 seasons were analyzed to determine relative VE (rVE) between HD-IIV3 and SD-IIV3/4 among outpatients ≥65 years old presenting with acute respiratory illness. Influenza vaccination status was derived from electronic medical records and immunization registries.

Results: Among 3861 enrollees, 2993 (78%) were vaccinated; 1573 (53%) received HD-IIV3 and 1420 (47%) received SD-IIV3/4. HD-IIV3 recipients differed from SD-IIV3/4 recipients by race, previous vaccination, number of outpatient visits in the previous year and timing of vaccination, and were balanced in the propensity model except the timing of vaccination. Compared with no vaccination, significant protection against any influenza A was observed from both HD-IIV3 (VE = 29%; 95%CI = 10%, 44%) and SD-IIV3/4 (VE = 24%; 95%CI = 5%, 39%); rVE = 18% (95%CI = 0%, 33%, SD as referent). When stratified by virus type, against A/H1N1, HD-IIV3 VE was 30% (95%CI = -7%, 54%), SD-IIV3/4 VE was 40% (95%CI = 10%, 61%), and rVE = -32%; (95%CI = -94%, 11%); Against A/H3N2, HD-IIV3 VE was 31% (95%CI = 9%, 47%), SD-IIV3/4 VE was 19% (95%CI = -5%, 37%), and rVE = 27%; (95% CI = 9%, 42%).

Conclusions: Among adults ≥65 years of age, recipients of standard and high dose influenza vaccines differed significantly in their characteristics. After adjusting for these differences, high dose vaccine offered more protection against A/H3N2 and borderline significant protection against all influenza A requiring outpatient care during the 2015-2018 influenza seasons.
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http://dx.doi.org/10.1016/j.vaccine.2020.08.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508973PMC
September 2020

Tight junction protein claudin-1 is downregulated by TGF-β1 via MEK signaling in benign prostatic epithelial cells.

Prostate 2020 10 21;80(14):1203-1215. Epub 2020 Jul 21.

Department of Urology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.

Background: Benign prostatic hyperplasia (BPH) is arguably the most common disease in aging men. Although the etiology is not well understood, chronic prostatic inflammation is thought to play an important role in BPH initiation and progression. Our recent studies suggest that the prostatic epithelial barrier is compromised in glandular BPH tissues. The proinflammatory cytokine transforming growth factor beta 1 (TGF-β1) impacts tight junction formation, enhances epithelial barrier permeability, and suppresses claudin-1 messenger RNA expression in prostatic epithelial cells. However, the role of claudin-1 in the prostatic epithelial barrier and its regulation by TGF-β1 in prostatic epithelial cells are not clear.

Methods: The expression of claudin-1 was analyzed in 22 clinical BPH specimens by immunohistochemistry. Human benign prostate epithelial cell lines BPH-1 and BHPrE1 were treated with TGF-β1 and transfected with small interfering RNAs specific to claudin-1. Epithelial monolayer permeability changes in the treated cells were measured using trans-epithelial electrical resistance (TEER). The expression of claudin-1, E-cadherin, N-cadherin, snail, slug, and activation of mitogen-activated proteins kinases (MAPKs) and AKT was assessed following TGF-β1 treatment using Western blot analysis.

Results: Claudin-1 expression was decreased in glandular BPH tissue compared with adjacent normal prostatic tissue in patient specimens. TGF-β1 treatment or claudin-1 knockdown in prostatic epithelial cell lines increased monolayer permeability. TGF-β1 decreased levels of claudin-1 and increased levels of snail and slug as well as increased phosphorylation of the MAPK extracellular signal-regulated kinase-1/2 (ERK-1/2) in both BPH-1 and BHPrE1 cells. Overexpression of snail or slug had no effect on claudin-1 expression. In contrast, PD98059 and U0126, inhibitors of the upstream activator of ERK-1/2 (ie, MEK-1/2) restored claudin-1 expression level as well as the epithelial barrier.

Conclusion: Our findings suggest that downregulation of claudin-1 by TGF-β1 acting through the noncanonical MEK-1/2/ERK-1/2 pathway triggers increased prostatic epithelial monolayer permeability in vitro. These findings also suggest that elevated TGF-β1 may contribute to claudin-1 downregulation and compromised epithelial barrier in clinical BPH specimens.
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http://dx.doi.org/10.1002/pros.24046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710618PMC
October 2020

Proposed Clinical Indicators for Efficient Screening and Testing for COVID-19 Infection from Classification and Regression Trees (CART) Analysis.

medRxiv 2020 May 14. Epub 2020 May 14.

Background: The introduction and rapid transmission of SARS CoV2 in the United States resulted in implementation of methods to assess, mitigate and contain the resulting COVID-19 disease based on limited knowledge. Screening for testing has been based on symptoms typically observed in inpatients, yet outpatient symptom complexes may differ.

Methods: Classification and regression trees (CART) recursive partitioning created a decision tree classifying enrollees into laboratory-confirmed cases and non-cases. Demographic and symptom data from patients ages 18-87 years who were enrolled from March 29-April 26, 2020 were included. Presence or absence of SARSCoV2 was the target variable.

Results: Of 736 tested, 55 were positive for SARS-CoV2. Cases significantly more often reported chills, loss of taste/smell, diarrhea, fever, nausea/vomiting and contact with a COVID-19 case, but less frequently reported shortness of breath and sore throat. A 7-terminal node tree with a sensitivity of 96% and specificity of 53%, and an AUC of 78% was developed. The positive predictive value for this tree was 14% while the negative predictive value was 99%. Almost half (44%) of the participants could be ruled out as likely non-cases without testing.

Discussion: Among those referred for testing, negative responses to three questions could classify about half of tested persons with low risk for SARS-CoV2 and would save limited testing resources. These questions are: was the patient in contact with a COVID-19 case? Has the patient experienced 1) a loss of taste or smell; or 2) nausea or vomiting? The outpatient symptoms of COVID-19 appear to be broader than the well-known inpatient syndrome.
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http://dx.doi.org/10.1101/2020.05.11.20097980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274237PMC
May 2020

Improving Cost-effectiveness and Access to Cognitive Behavior Therapy for Depression: Providing Remote-Ready, Computer-Assisted Psychotherapy in Times of Crisis and Beyond.

Psychother Psychosom 2020 12;89(5):307-313. Epub 2020 May 12.

Unversity of Louisville, Louisville, Kentucky, USA.

Introduction: There is growing evidence that computer-delivered or computer-assisted forms of cognitive behavior therapy (CCBT) are helpful, but cost-effectiveness versus standard therapies is not well established.

Objective: To evaluate the cost-effectiveness of a therapist-supported method for CCBT in comparison to standard cognitive behavior therapy (CBT).

Methods: A total of 154 drug-free major depressive disorder outpatients were randomly assigned to either 16 weeks of standard CBT (up to twenty 50-min sessions) or CCBT using the Good Days Ahead program (including up to 5.5 h of therapist contact). Outcomes were assessed at baseline, weeks 8 and 16, and at 3 and 6 months post-treatment. Economic analyses took into account the costs of services received and work/social role impairment.

Results: In the context of almost identical efficacy, a form of CCBT that used only about one third the amount of therapist contact as conventional CBT was highly cost-effective compared to conventional therapy and reduced the adjusted cost of treatment by USD 945 per patient.

Conclusions: A method of CCBT that blended internet-delivered modules and abbreviated therapeutic contact reduced the cost of treatment substantially without adversely affecting outcomes. Results suggest that use of this approach can more than double the access to CBT. Because clinician support in CCBT can be provided by telephone, videoconference, and/or email, this highly efficient form of treatment could be a major advance in remote treatment delivery.
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http://dx.doi.org/10.1159/000508143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483890PMC
May 2020

Excisional goniotomy vs trabecular microbypass stent implantation: a prospective randomized clinical trial in eyes with mild to moderate open-angle glaucoma.

J Cataract Refract Surg 2020 Aug;46(8):1165-1171

From the Gundersen Health System (Falkenberry), La Crosse, Wisconsin, The Eye Centers of Racine & Kenosha (Singh), Racine, Wisconsin, Northern New Jersey Eye Institute (Crane), South Orange, New Jersey, University of Louisville (Haider), Louisville, Kentucky, Ochsner Clinic Baton Rouge (Morgan, Grenier), Baton Rouge, Louisiana, Sacramento Eye Consultants (Brubaker), Sacramento, California, University of Pittsburgh (Balasubramani), Pittsburgh, Pennsylvania, Mayo Clinic (Dorairaj), Jacksonville, Florida, USA.

Purpose: To compare reduction in intraocular pressure (IOP) and IOP-lowering medication in eyes undergoing excisional goniotomy with Kahook Dual Blade (KDB) vs iStent microbypass implantation, both combined with phacoemulsification, in eyes with mild to moderate open-angle glaucoma (OAG).

Setting: Nine practices in the United States.

Design: Prospective, randomized, active-controlled, parallel-group clinical trial.

Methods: Eyes were randomized to KDB-Phaco or iStent-Phaco group. Demographics, corrected distance visual acuity, IOP, IOP-lowering medications, and adverse events were collected at baseline and at day 1, week 1, and months 1, 3, 6, and 12 postoperatively. The primary outcome measure was the proportion of eyes at 12 months with IOP reduction of 20% or greater or IOP medication reduction of 1 or more compared with baseline.

Results: For this study, 164 eyes of 164 patients were analyzed (82 in each group). Mean IOP was reduced at 12 months compared with baseline from 18.5 (standard of error 0.4) to 15.4 (0.4) mm Hg in the KDB-Phaco group and from 18.5 (0.3) to 16.1 (0.4) mm Hg in the iStent-Phaco group (P = .24). Mean IOP-lowering medications were reduced from 1.3 (0.1) to 0.3 (0.1) in the KDB-Phaco group and from 1.4 (0.1) to 0.4 (0.1) in the iStent-Phaco group (P = .17). Among study completers, the primary outcome was attained in 74 (93.7%) of 79 patients of KDB-Phaco eyes and 65 (83.3%) of 78 patients of iStent-Phaco eyes (P = .04). Both procedures had similar safety profiles.

Conclusions: Both procedures lowered both IOP and the need for IOP-lowering medications effectively and safely in eyes with mild to moderate OAG and cataract. Significantly, more KDB-Phaco eyes than iStent-Phaco eyes met the primary outcome of 20% or greater IOP reduction or 1 or more medication reduction at 12 months.
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http://dx.doi.org/10.1097/j.jcrs.0000000000000229DOI Listing
August 2020

Influenza vaccine effectiveness among outpatients in the US Influenza Vaccine Effectiveness Network by study site 2011-2016.

Influenza Other Respir Viruses 2020 07 16;14(4):380-390. Epub 2020 Apr 16.

Department of Family Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Background: Influenza vaccination is recommended for all US residents aged ≥6 months. Vaccine effectiveness (VE) varies by age, circulating influenza strains, and the presence of high-risk medical conditions. We examined site-specific VE in the US Influenza VE Network, which evaluates annual influenza VE at ambulatory clinics in geographically diverse sites.

Methods: Analyses were conducted on 27 180 outpatients ≥6 months old presenting with an acute respiratory infection (ARI) with cough of ≤7-day duration during the 2011-2016 influenza seasons. A test-negative design was used with vaccination status defined as receipt of ≥1 dose of any influenza vaccine according to medical records, registries, and/or self-report. Influenza infection was determined by reverse-transcription polymerase chain reaction. VE estimates were calculated using odds ratios from multivariable logistic regression models adjusted for age, sex, race/ethnicity, time from illness onset to enrollment, high-risk conditions, calendar time, and vaccination status-site interaction.

Results: For all sites combined, VE was statistically significant every season against all influenza and against the predominant circulating strains (VE = 19%-50%) Few differences among four sites in the US Flu VE Network were evident in five seasons. However, in 2015-16, overall VE in one site was 24% (95% CI = -4%-44%), while VE in two other sites was significantly higher (61%, 95% CI = 49%-71%; P = .002, and 53%, 95% CI = 33,67; P = .034).

Conclusion: With few exceptions, site-specific VE estimates aligned with each other and overall VE estimates. Observed VE may reflect inherent differences in community characteristics of the sites and highlights the importance of diverse settings for studying influenza vaccine effectiveness.
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http://dx.doi.org/10.1111/irv.12741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298285PMC
July 2020

Transforming growth factor beta 1 impairs benign prostatic luminal epithelial cell monolayer barrier function.

Am J Clin Exp Urol 2020 25;8(1):9-17. Epub 2020 Feb 25.

UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine Pittsburgh, PA, USA.

Our recent studies identifying the presence of luminal secretory protein PSA in the stroma, decreased E-cadherin expression, and reduced number of tight junction kiss points in benign prostatic hyperplasia (BPH) tissues suggest that epithelial barrier permeability is increased in BPH. However, the cause of increased epithelial permeability in BPH is unclear. Transforming growth factor beta 1 (TGF-β1) has been reported to be up-regulated in clinical BPH specimens and TGF-β1 overexpression induced fibrosis and inflammation in a murine model. TGF-β1 was reported to repress the expression of E-cadherin in benign prostatic cells. However, whether and how TGF-β1 up-regulation affects epithelial barrier permeability is unknown. Here, benign prostatic epithelial cell lines BHPrE1 and BPH-1 were utilized to determine the impact of TGF-β1 treatment on epithelial barrier, tight junctions, and expression of E-cadherin and claudin 1 by transepithelial electrical resistance (TEER) measurement, FITC-dextran trans-well diffusion assays, qPCR, as well as transmission electron microscopy (TEM) observation. Laser capture micro-dissection (LCM) combined with reverse transcription-polymerase chain reaction (qPCR) were utilized to determine the expression of E-cadherin and claudin 1 in BPH patient specimens. TGF-β1 treatment decreased TEER, increased FITC-dextran diffusion, and reduced the mRNA expression of junction protein claudin 1 in cultured cell monolayers. Claudin 1 mRNA but not E-cadherin mRNA was down-regulated in the luminal epithelial cells in BPH nodules compared to normal prostate tissues. Our studies suggest that TGF-β1 could increase the permeability through decreasing the expression of claudin 1 and inhibiting the formation of tight junctions in BHPrE1 and BPH-1 monolayers. These results suggest that TGF-β1 might play an important role in BPH pathogenesis through increasing the permeability of luminal epithelial barrier in the prostate.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076294PMC
February 2020

Declining brachytherapy utilization for cervical cancer patients - Have we reversed the trend?

Gynecol Oncol 2020 03 8;156(3):583-590. Epub 2020 Jan 8.

Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America. Electronic address:

Objective: Studies examining temporal trends in cervical brachytherapy use are conflicting and examined different health insurance populations. This study examined brachytherapy utilization over time by health insurance type and whether reported declines in brachytherapy have reversed.

Methods: The National Cancer Database (NCDB) was queried for patients with FIGO IIB-IVA cervical cancer treated with definitive chemoradiotherapy between 2004 and 2014, identifying 17,442 patients. Brachytherapy utilization over time and by insurance type and other sociodemographic factors were compared using binary logistic regression. A sensitivity analysis was done in a sub-cohort of patients using the boost modality variable in the NCDB.

Results: Brachytherapy utilization declined during 2008-10 (52.6%) compared to 2004-2007 (54.4%; odds ratio [OR] 0.93, 95% confidence interval [CI] 0.86-1.01) and declines were disproportionately larger for patients with government insurance (49.4% vs 52.3%, respectively) than privately-insured patients (57.6% vs 58.9%, respectively). However, rates of brachytherapy use subsequently recovered during 2011-14 in all insurance groups (58.0%, OR 1.24, 95% CI 1.16-1.34) and was especially improved for Medicaid (OR 1.44, 95% CI 1.26-1.65) and uninsured patients (OR 1.28, 95% CI 1.03-1.57). Sensitivity analysis using the boost modality variable confirmed these trends.

Conclusions: In patients with FIGO IIB-IVA cervical cancer treated with definitive chemoradiotherapy from 2004 to 2014, brachytherapy utilization declined during the late 2000s and disproportionately affected patients with government insurance, but subsequently recovered in the early 2010s. Since government insurance covers vulnerable patient populations at-risk for future declines in brachytherapy use, proposed alternative payment models should incentivize cervical brachytherapy to solidify gains in brachytherapy utilization.
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http://dx.doi.org/10.1016/j.ygyno.2019.12.032DOI Listing
March 2020

SIRPB1 promotes prostate cancer cell proliferation via Akt activation.

Prostate 2020 03 6;80(4):352-364. Epub 2020 Jan 6.

Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

Background: Signal regulatory protein β1 (SIRPB1) is a signal regulatory protein member of the immunoglobulin superfamily and is capable of modulating receptor tyrosine kinase-coupled signaling. Copy number variations at the SIRPB1 locus were previously reported to associate with prostate cancer aggressiveness in patients, however, the role of SIRPB1 in prostate carcinogenesis is unknown.

Methods: Fluorescence in situ hybridization and laser-capture microdissection coupled with quantitative polymerase chain reaction was utilized to determine SIRPB1 gene amplification and messenger RNA expression in prostate cancer specimens. The effect of knockdown of SIRPB1 by RNA interference in PC3 prostate cancer cells on cell growth in colony formation assays and cell mobility in wound-healing, transwell assays, and cell cycle analysis was determined. Overexpression of SIPRB1 in C4-2 prostate cancer cells on cell migration, invasion, colony formation and cell cycle progression and tumor take rate in xenografts was also determined. Western blot assay of potential downstream SIRPB1 pathways was also performed.

Results: SIRPB1 gene amplification was detected in up to 37.5% of prostate cancer specimens based on in silico analysis of several publicly available datasets. SIRPB1 gene amplification and overexpression were detected in prostate cancer specimens. The knockdown of SIRPB1 significantly suppressed cell growth in colony formation assays and cell mobility. SIRPB1 knockdown also induced cell cycle arrest during the G /G phase and enhancement of apoptosis. Conversely, overexpression of SIPRB1 in C4-2 prostate cancer cells significantly enhanced cell migration, invasion, colony formation, and cell cycle progression and increased C4-2 xenograft tumor take rate in nude mice. Finally, this study presented evidence for SIRPB1 regulation of Akt phosphorylation and showed that Akt inhibition could abolish SIRPB1 stimulation of prostate cancer cell proliferation.

Conclusions: These results suggest that SIRPB1 is a potential oncogene capable of activating Akt signaling to stimulate prostate cancer proliferation and could be a biomarker for patients at risk of developing aggressive prostate cancer.
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http://dx.doi.org/10.1002/pros.23950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7421598PMC
March 2020

Pulmonary alveolar microlithiasis: A rare disease treated with lung transplantation, first case from India.

Lung India 2019 Nov-Dec;36(6):546-549

Department of Pulmonary, Critical Care and Sleep Medicine, Institute of Heart and Lung Transplant, Gleneagles Global Health City, Chennai, Tamil Nadu, India.

Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive condition characterized by widespread alveolar deposition of calcium microliths. A mutation in the SLC34A2 gene in the alveolar Type II pneumocytes is responsible for decreased phosphate clearance and accumulation of calcium as spherules in the alveoli. The presence of this gene in other organs is responsible for the systemic phenotype of the disease. PAM is characterized by the lack of defining symptoms such as cough and progressive dyspnea until it reaches the stage of cor pulmonale and presents with features of respiratory and right ventricular (RV) failure. Radiologically, it is characterized by intense calcification in the lung parenchyma producing specific signs such as the "sandstorm appearance" in the early stages to the "white out lung" with "black pleura sign" in the later stages of the disease. While conventional therapy has not been successful at treatment, bilateral lung transplantation offers to be the only effective remedy. In this report, we present the case of a 54-year-old female who presented in the stage of respiratory and RV failure, with oxygen and noninvasive ventilation (NIV) dependence. She was treated with bilateral lung transplantation. Postoperatively, she was monitored closely for immunosuppression, prophylactic anti-infective measures, and bronchoscopies to evaluate for airway complications. The patient gradually improved and was discharged from the hospital without any need for oxygen or NIV.
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http://dx.doi.org/10.4103/lungindia.lungindia_50_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852219PMC
November 2019

Twelve-month outcomes of excisional goniotomy using the Kahook Dual Blade in eyes with angle-closure glaucoma.

Clin Ophthalmol 2019 10;13:1779-1785. Epub 2019 Sep 10.

University of Pittsburgh, Department of Epidemiology, Pittsburgh, PA, USA.

Purpose: To characterize clinical outcomes following Kahook Dual Blade (KDB)-assisted goniosynechialysis and excisional goniotomy combined with phacoemulsification in eyes with angle-closure glaucoma and cataract.

Setting: Two clinical practices.

Methods: In this retrospective analysis of existing health records, data were collected from 42 eyes of 24 subjects from preoperative, operative, and postoperative encounters through 12 months of follow-up. Outcomes included changes in mean IOP, IOP-lowering medications, and logMAR best-corrected visual acuity (BCVA), as well as the proportions of patients achieving IOP reductions ≥20%, IOP ≤18 mmHg, and a reduction of ≥1 medication.

Results: Preoperative, mean (standard error) IOP was 25.5 (0.7) mmHg and at Month 12 was reduced by 12.3 (0.73) mmHg (-47.2%; <0.0001). The mean number of IOP-lowering medications used was 2.3 (0.1) preoperatively and was reduced at Month 12 by 2.2 (0.12) (-91.7%; <0.0001). At Month 12, 92.9% of eyes achieved IOP ≤18 mmHg, 100% achieved IOP reduction of ≥20%, 95.2% required ≥1 fewer medications for IOP control, and 85.7% (36/42) were medication-free. Mean LogMAR BCVA improved from 0.547 (0.06) at baseline to 0.159 (0.07) at Month 12.

Conclusion: KDB-assisted goniosynechialysis and excisional goniotomy at the time of phacoemulsification safely provide significant reductions in both IOP and IOP-lowering medication burden in eyes with angle-closure glaucoma, while simultaneously improving visual acuity.
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http://dx.doi.org/10.2147/OPTH.S221299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750200PMC
September 2019

Crystalline lens changes after selective laser trabeculoplasty in Afro-Caribbean patients with open-angle glaucoma; report 4 of the West Indies Glaucoma Laser Study (WIGLS).

J Cataract Refract Surg 2019 10;45(10):1458-1462

Harlsbro Medical Center, Roseau, Dominica.

Purpose: To characterize changes in nuclear, cortical, and posterior subcapsular lens opacities after selective laser trabeculoplasty (SLT) in Afro-Caribbean eyes with primary open-angle glaucoma (POAG).

Setting: Three clinical practices, Saint Lucia and Dominica.

Design: Prospective case series.

Methods: Patients with POAG in the West Indies Glaucoma Laser Study (WIGLS) had 360-degree SLT after medication washout. No antiinflammatory therapy was used after SLT. Nuclear, cortical, and posterior subcapsular lens opacities were graded through dilated pupils using the Lens Opacification Classification System III (LOCS III) at baseline and 12, 24, and 36 months after SLT, with the grader masked to all previous values after baseline assessment. Changes in opacity scores from baseline were evaluated using paired t tests.

Results: Seventy-two patients (142 phakic eyes) were evaluated. The mean (±SD) baseline LOCS III opacity scores in right eyes and left eyes, respectively, were 2.44 ± 1.23 and 2.40 ± 1.16 (nuclear), 0.39 ± 1.08 and 0.30 ± 0.85 (cortical), and 0.22 ± 0.59 and 0.15 ± 0.36 (posterior subcapsular). Other than a small improvement in bilateral nuclear opacity scores at 12 months, no statistically or clinically significant changes in any opacity score occurred in either eye up to 36 months postoperatively. Three eyes (2.1%) with preexisting lens opacities had cataract surgery for progressive lens changes at 3 months, 21 months, and 26 months, respectively, after SLT.

Conclusions: Selective laser trabeculoplasty was not associated with clinically significant changes in nuclear, cortical, or posterior subcapsular lens opacities in glaucomatous Afro-Caribbean eyes. The rate of cataract surgery is consistent with reported rates from longitudinal natural history studies in Caribbean and non-Caribbean populations.
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http://dx.doi.org/10.1016/j.jcrs.2019.05.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913200PMC
October 2019

Bioactive Oxylipins in Infants and Children With Congenital Heart Disease Undergoing Pediatric Cardiopulmonary Bypass.

Pediatr Crit Care Med 2020 01;21(1):33-41

Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA.

Objectives: To determine the production of 9-hydroxyoctadecadienoic acid and 13-hydroxyoctadecadienoic acid during cardiopulmonary bypass in infants and children undergoing cardiac surgery, evaluate their relationship with increase in cell-free plasma hemoglobin, provide evidence of bioactivity through markers of inflammation and vasoactivity (WBC count, milrinone use, vasoactive-inotropic score), and examine their association with overall clinical burden (ICU/hospital length of stay and mechanical ventilation duration).

Design: Prospective observational study.

Setting: Twelve-bed cardiac ICU in a university-affiliated children's hospital.

Patients: Children were prospectively enrolled during their preoperative clinic appointments with the following criteria: greater than 1 month to less than 18 years old, procedures requiring cardiopulmonary bypass INTERVENTIONS:: None.

Measurements And Main Results: Plasma was collected at the start and end of cardiopulmonary bypass in 34 patients. 9-hydroxyoctadecadienoic acid, 13-hydroxyoctadecadienoic acid, plasma hemoglobin, and WBC increased. 9:13-hydroxyoctadecadienoic acid at the start of cardiopulmonary bypass was associated with vasoactive-inotropic score at 2-24 hours postcardiopulmonary bypass (R = 0.25; p < 0.01), milrinone use (R = 0.17; p < 0.05), and WBC (R = 0.12; p < 0.05). 9:13-hydroxyoctadecadienoic acid at the end of cardiopulmonary bypass was associated with vasoactive-inotropic score at 2-24 hours (R = 0.17; p < 0.05), 24-48 hours postcardiopulmonary bypass (R = 0.12; p < 0.05), and milrinone use (R = 0.19; p < 0.05). 9:13-hydroxyoctadecadienoic acid at the start and end of cardiopulmonary bypass were associated with the changes in plasma hemoglobin (R = 0.21 and R = 0.23; p < 0.01). The changes in plasma hemoglobin was associated with milrinone use (R = 0.36; p < 0.001) and vasoactive-inotropic score less than 2 hours (R = 0.22; p < 0.01), 2-24 hours (R = 0.24; p < 0.01), and 24-48 hours (R = 0.48; p < 0.001) postcardiopulmonary bypass. Cardiopulmonary bypass duration, 9:13-hydroxyoctadecadienoic acid at start of cardiopulmonary bypass, and plasma hemoglobin may be risk factors for high vasoactive-inotropic score. Cardiopulmonary bypass duration, changes in plasma hemoglobin, 9:13-hydroxyoctadecadienoic acid, and vasoactive-inotropic score correlate with ICU and hospital length of stay and/mechanical ventilation days.

Conclusions: In low-risk pediatric patients undergoing cardiopulmonary bypass, 9:13-hydroxyoctadecadienoic acid was associated with changes in plasma hemoglobin, vasoactive-inotropic score, and WBC count, and may be a risk factor for high vasoactive-inotropic score, indicating possible inflammatory and vasoactive effects. Further studies are warranted to delineate the role of hydroxyoctadecadienoic acids and plasma hemoglobin in cardiopulmonary bypass-related dysfunction and to explore hydroxyoctadecadienoic acid production as a potential therapeutic target.
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http://dx.doi.org/10.1097/PCC.0000000000002036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388063PMC
January 2020

E-cadherin is downregulated in benign prostatic hyperplasia and required for tight junction formation and permeability barrier in the prostatic epithelial cell monolayer.

Prostate 2019 08 18;79(11):1226-1237. Epub 2019 Jun 18.

Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

Background: We previously reported the presence of prostate-specific antigen (PSA) in the stromal compartment of benign prostatic hyperplasia (BPH). Since PSA is expressed exclusively by prostatic luminal epithelial cells, PSA in the BPH stroma suggests increased tissue permeability and the compromise of epithelial barrier integrity. E-cadherin, an important adherens junction component and tight junction regulator, is known to exhibit downregulation in BPH. These observations suggest that the prostate epithelial barrier is disrupted in BPH and E-cadherin downregulation may increase epithelial barrier permeability.

Methods: The ultra-structure of cellular junctions in BPH specimens was observed using transmission electron microscopy (TEM) and E-cadherin immunostaining analysis was performed on BPH and normal adjacent specimens from BPH patients. In vitro cell line studies using benign prostatic epithelial cell lines were performed to determine the impact of small interfering RNA knockdown of E-cadherin on transepithelial electrical resistance and diffusion of fluorescein isothiocyanate (FITC)-dextran in transwell assays.

Results: The number of kiss points in tight junctions was reduced in BPH epithelial cells as compared with the normal adjacent prostate. Immunostaining confirmed E-cadherin downregulation and revealed a discontinuous E-cadherin staining pattern in BPH specimens. E-cadherin knockdown increased monolayer permeability and disrupted tight junction formation without affecting cell density.

Conclusions: Our results indicate that tight junctions are compromised in BPH and loss of E-cadherin is potentially an important underlying mechanism, suggesting targeting E-cadherin loss could be a potential approach to prevent or treat BPH.
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http://dx.doi.org/10.1002/pros.23806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599563PMC
August 2019

Determination of Eligibility for Influenza Research: A Clinical Informatics Approach.

Open Forum Infect Dis 2019 Jun 10;6(6):ofz231. Epub 2019 Jun 10.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania.

Background: A clinical informatics algorithm (CIA) was developed to systematically identify potential enrollees for a test-negative, case-control study to determine influenza vaccine effectiveness, to improve enrollment over manual records review. Further testing may enhance the CIA for increased efficiency.

Methods: The CIA generated a daily screening list by querying all medical record databases for patients admitted in the last 3 days, using specified terms and diagnosis codes located in admission notes, emergency department notes, chief complaint upon registration, or presence of a respiratory viral panel charge or laboratory result (RVP). Classification and regression tree analysis (CART) and multivariable logistic regression were used to refine the algorithm.

Results: Using manual records review, 204 patients (<4/day) were approached and 144 were eligible in the 2014-2015 season compared with 3531 (12/day) patients who were approached and 1136 who were eligible in the 2016-2017 season using a CIA. CART analysis identified RVP as the most important indicator from the CIA list for determining eligibility, identifying 65%-69% of the samples and predicting 1587 eligible patients. RVP was confirmed as the most significant predictor in regression analysis, with an odds ratio (OR) of 4.9 (95% confidence interval [CI], 4.0-6.0). Other significant factors were indicators in admission notes (OR, 2.3 [95% CI, 1.9-2.8]) and emergency department notes (OR, 1.8 [95% CI, 1.4-2.3]).

Conclusions: This study supports the benefits of a CIA to facilitate recruitment of eligible participants in clinical research over manual records review. Logistic regression and CART identified potential eligibility screening criteria reductions to improve the CIA's efficiency.
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http://dx.doi.org/10.1093/ofid/ofz231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557306PMC
June 2019

Larvicidal, Histopathological, Antibacterial Activity of Indigenous Fungus sp. Against L and (Say) (Diptera: Culicidae) and Its Acetylcholinesterase Inhibition and Toxicity Assessment of Zebrafish ().

Front Microbiol 2019 18;10:427. Epub 2019 Mar 18.

Natural Drug Research Laboratory, Department of Biotechnology, School of Biosciences, Periyar University, Salem, India.

Fungal metabolites are considered to be most efficient tools to overcome the issues related to insecticide resistance and environmental pollution. The present study focus on the evaluation of the mosquito larvicidal efficacy of metabolites of seven indigenous fungal isolates ( sp. , , , sp. sp. and sp.) on the larvae of and under the laboratory condition. The preliminary screening of the isolate, sp. showed better larvicidal effect when compared to other fungi. The fungus was grown on Potato Dextrose Broth (PDB) in the laboratory (at 25°C) and maintained in the relative humidity (at 76 ± 4% for 15 days). Larvicidal potency of mycelial ethyl acetate extract (MEAE) of sp. was performed against 1st to 4th instars larvae of and using four different concentrations (100, 200, 300, and 500 μg/ml) that showed better larval mortality values (μg/ml) of LC = 6.554, 5.487, 6.874, 6.892, and the LC = 11.486, 10.366, 12.879, 13.865 for and LC = 7.000, 13.943, 18.129, 25.212 and the LC = 12.541, 23.761, 30.923, 41.696 for . Exposure of metabolite to larvae resulted in behavior changes i.e., excitation, up and down with aggressive movement, anal papillae biting behavior. Further, the larvae treated with sp. metabolite exhibited significant reduction in the levels of acetylcholinesterase. The 4th instar mosquito larvae treated with the 500 μg/ml mycelia extract showed severe histological damages. During the antibacterial analysis of sp.- mycelium the maximum growth inhibition zone was recorded in (31.2 mm) and (31.1 mm) followed by others. In addition, to check the toxicity of sp. MEAE against embryos of Zebrafish, a model system, using different concentrations of metabolites (1.0, 0.5, 0.125 mg/ml, 30, 3.0, and 0.5 μg/ml) and life-stage parameters were observed at 124 hpf. Furthermore, the Fourier Transformed Infrared and GCMS spectrum analysis of mycelium reflected several chemical compounds. The outcome of the study clearly shows that sp. metabolites could serve as an ideal eco-friendly, single-step and inexpensive source for the control of and larvae.
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http://dx.doi.org/10.3389/fmicb.2019.00427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431641PMC
March 2019

West Indies Glaucoma Laser Study (WIGLS) 3. Anterior Chamber Inflammation Following Selective Laser Trabeculoplasty in Afro-Caribbeans with Open-angle Glaucoma.

J Glaucoma 2019 07;28(7):622-625

Department of Epidemiology, Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh, PA.

Precis: In the absence of prophylactic anti-inflammatory therapy, anterior chamber inflammation (characterized by cells and less commonly flare) is minimal and transient after selective laser trabeculoplasty in Afro-Caribbean glaucoma patients.

Purpose: The purpose of this study was to characterize the prevalence, severity, and duration of anterior chamber inflammation (cells and flare) following selective laser trabeculoplasty (SLT) in Afro-Caribbean eyes with primary open-angle glaucoma (POAG).

Methods: In total 144 eyes of 72 POAG patients underwent first-time 360-degree SLT treatment following washout of all topical medications in the prospective West Indies Glaucoma Laser Study. No anti-inflammatory therapy was used post-SLT. Anterior chamber cells and flare were characterized pre-SLT after medication washout, and 1 week, 6 weeks, and 3, 6, 9 and 12 months post-SLT using the standardized methodology described by the Society for Uveitis Nomenclature (SUN) in which cells and flare are each graded on a scale of 0-4+ using specific slit-lamp settings.

Results: Mean cell scores in both right and left eyes rose significantly (P<0.0001) from baseline to week 1 after SLT before returning to baseline values at all subsequent time points. Mean flare scores in right eyes (P=0.0185) but not left eyes (P=0.1816) rose from baseline to week 1 after SLT before returning to baseline values at all subsequent time points. Cells appeared in 40.3% of eyes and flare appeared in 9.7% of eyes after SLT. One subject developed bilateral symptomatic anterior iritis one day postoperatively and reported a previously undisclosed history of recurrent iritis; the iritis resolved with topical steroid therapy.

Conclusions: SLT in Afro-Caribbean people with POAG is associated with mild, short-lived and self-limited anterior chamber inflammation. Routine anti-inflammatory therapy to suppress posttreatment inflammation after SLT is unnecessary in this population.
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http://dx.doi.org/10.1097/IJG.0000000000001250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610644PMC
July 2019

Does influenza vaccination status change physician ordering patterns for respiratory viral panels? Inspection for selection bias.

Hum Vaccin Immunother 2019 19;15(1):91-96. Epub 2018 Sep 19.

b Department of Family Medicine , University of Pittsburgh , Pittsburgh , PA , USA.

Purpose: Hospitalized patients with an acute respiratory illness (ARI) were compared to determine if demographic characteristics, timing or influenza vaccination biased who received clinical respiratory viral panel (RVP) testing.

Methods: 171 enrollees in an influenza vaccine effectiveness study and a sample of non-enrollees (N = 1029) admitted to a community hospital with ARI during December 2015 through April 2016 comprised the study sample. Those who received clinical RVP testing (n = 292) were compared to those who did not by age, sex, influenza vaccination status, and period (pre-peak influenza season vs. peak/post peak influenza season), using Chi square- and t-tests, and logistic regression.

Results: Mean age of participants was 70 years, 58% was female and 45% had been vaccinated against influenza in the 2015-2016 season. Those with clinical RVP testing were significantly younger (67 years) than those without RVP (71 years; P < 0.001), but did not differ with respect to sex or vaccination status. The odds of clinical RVP testing were significantly (P = 0.004) related to younger age (< 65 years) (Odds ratio (OR) = 1.51; 95% CI = 1.14-2.00) and to later period (peak/post peak influenza season; OR = 2.64; 95% CI = 1.84-3.79) but were unrelated to influenza vaccination status or the interaction of time and vaccination status.

Conclusion: RVP testing was significantly higher among younger hospitalized patients with an ARI and during the peak and post peak influenza periods than earlier in the season, but influenza vaccination status was not a significant factor. Studies that enroll based on clinical RVP testing should account for potential differences by age.
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http://dx.doi.org/10.1080/21645515.2018.1514226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586174PMC
February 2020

Presenting Characteristics Associated With Outcome in Children With Severe Traumatic Brain Injury: A Secondary Analysis From a Randomized, Controlled Trial of Therapeutic Hypothermia.

Pediatr Crit Care Med 2018 10;19(10):957-964

Department of Neurological Surgery, Barrow Neurological Institute of Phoenix Children's Hospital, Phoenix, AZ.

Objectives: To identify injury patterns and characteristics associated with severe traumatic brain injury course and outcome, within a well-characterized cohort, which may help guide new research and treatment initiatives.

Design: A secondary analysis of a phase 3, randomized, controlled trial that compared therapeutic hypothermia versus normothermia following severe traumatic brain injury in children.

Setting: Fifteen sites in the United States, Australia, and New Zealand.

Patients: Children (< 18 yr old) with severe traumatic brain injury.

Measurements And Main Results: Baseline, clinical, and CT characteristics of patients (n = 77) were examined for association with mortality and outcome, as measured by the Glasgow Outcome Scale-Extended Pediatric Revision 3 months after traumatic brain injury. Data are presented as odds ratios with 95% CIs. No demographic, clinical, or CT characteristic was associated with mortality in bivariate analysis. Characteristics associated with worse Glasgow Outcome Scale-Extended Pediatric Revision in bivariate analysis were two fixed pupils (14.17 [3.38-59.37]), abdominal Abbreviated Injury Severity score (2.03 [1.19-3.49]), and subarachnoid hemorrhage (3.36 [1.30-8.70]). Forward stepwise regression demonstrated that Abbreviated Injury Severity spine (3.48 [1.14-10.58]) and midline shift on CT (8.35 [1.05-66.59]) were significantly associated with mortality. Number of fixed pupils (one fixed pupil 3.47 [0.79-15.30]; two fixed pupils 13.61 [2.89-64.07]), hypoxia (5.22 [1.02-26.67]), and subarachnoid hemorrhage (3.01 [1.01-9.01]) were independently associated with worse Glasgow Outcome Scale-Extended Pediatric Revision following forward stepwise regression.

Conclusions: Severe traumatic brain injury is a clinically heterogeneous disease that can be accompanied by a range of neurologic impairment and a variety of injury patterns at presentation. This secondary analysis of prospectively collected data identifies several characteristics associated with outcome among children with severe traumatic brain injury. Future, larger trials are needed to better characterize phenotypes within this population.
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http://dx.doi.org/10.1097/PCC.0000000000001676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170689PMC
October 2018

Influenza Vaccine Intention After a Medically Attended Acute Respiratory Infection.

Health Promot Pract 2019 07 13;20(4):539-552. Epub 2018 Jul 13.

1 University of Pittsburgh, Pittsburgh, PA, USA.

. Little is known about vaccine intention behavior among patients recovering from a medically attended acute respiratory infection. . Adults ≥ 18 years old with an acute respiratory infection in the 2014-2015, 2015-2016, and 2016-2017 influenza seasons were tested for influenza and completed surveys. Across seasons, unvaccinated participants were grouped into those who intended to receive the influenza vaccine in the following season (vaccine intention) and those who did not (no vaccine intention). In 2016-2017, participants were asked the reasons for their vaccination behavior. . Of the 837 unvaccinated participants, 308 (37%) intended to be vaccinated the next season. The groups did not differ in demographic or overall health factors. In logistic regression, non-Whites, those reporting wheezing or nasal congestion, and those receiving an antiviral prescription were more likely to be in the vaccine intention group. That group was significantly more likely to cite perceived behavioral control reasons for not being vaccinated (forgot), while the no vaccine intention group was significantly ( < .001) more likely to report knowledge/attitudinal reasons (side effects). . Because influenza vaccine is given annually, adults must make a conscious decision to receive the vaccine each year. Understanding the factors related to vaccination behavior and intent can help shape interventions to improve influenza vaccination rates. A medical visit at the time of an acute respiratory illness, especially one in which the provider suspects influenza, as evidenced by an antiviral prescription, is an ideal opportunity to recommend influenza vaccine in the next season, to prevent a similar experience.
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http://dx.doi.org/10.1177/1524839918782137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389426PMC
July 2019

West Indies Glaucoma Laser Study (WIGLS)-2: Predictors of Selective Laser Trabeculoplasty Efficacy in Afro-Caribbeans With Glaucoma.

J Glaucoma 2018 10;27(10):845-848

Department of Epidemiology, Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh, PA.

Purpose: To identify factors associated with intraocular pressure (IOP) reduction following selective laser trabeculoplasty (SLT) in Afro-Caribbean people with primary open-angle glaucoma (POAG).

Design: This was a prospective stepped-wedge study.

Methods: Data were drawn from 72 Afro-Caribbean subjects with POAG participating in the ongoing West Indies Glaucoma Laser Study. Multivariable mixed-model analysis was utilized to develop a predictive model for percent IOP reduction 12 months following SLT. Putative factors (age, sex, site, baseline IOP, prior use of prostaglandin therapy, number of prewashout IOP-lowering medications, central corneal thickness, severity of glaucoma, duration of follow-up, and signs of acute postoperative inflammation) were evaluated in bivariate analysis. Factors significant at P≤0.2 were included in the final model. Right and left eye data were modeled separately.

Results: At month 12 following SLT, mean IOP reductions in the West Indies Glaucoma Laser Study were 6.2 to 6.5 mm Hg (29.7% to 31.0%) in right and left eyes. The only factor significant in both eyes (P=0.0005 in right eyes and P<0.0001 in left eyes) was time, with IOP reductions being greatest at month 3 and declining slightly over time through month 12. Vertical cup-disc ratio (P=0.006) and prior prostaglandin therapy (P=0.004) were significant only in right eyes, and central corneal thickness (P=0.014) was significant only in left eyes. Factors significant only unilaterally did not approach significance in fellow eyes, suggesting the possibility that these represent type 1 errors. Site (St. Lucia vs. Dominica) was not a significant factor, establishing generalizability of these treatment outcomes to a broader population of African-derived people.

Conclusions: This analysis did not identify any subject-specific factors consistently predictive of therapeutic response to SLT. Of note, no factors predicted a suboptimal response. These findings favorably position SLT for broad application as primary therapy in African-derived people with POAG.
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http://dx.doi.org/10.1097/IJG.0000000000001018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170666PMC
October 2018

Target and non-target toxicity of fern extracts against mosquito vectors and beneficial aquatic organisms.

Ecotoxicol Environ Saf 2018 10 6;161:221-230. Epub 2018 Jun 6.

Department of Biotechnology, School of Biosciences, Periyar University, Salem 636011, India. Electronic address:

Dengue and malaria are significant mosquito-borne diseases that are rapidly spread worldwide, mainly in temperate countries. Pteridophytes were identified to be a significant source of novel mosquitocidal agents. The present research was to explore the eco-friendly larvicides from methanol extracts of ferns, viz., Actiniopteris radiata, Adiantum caudatum, Cheilanthes swartzii, Hemionitis arifolia and Lycopodium clavatum. The larvicidal potential of the extracts screened using larvae of dengue vector Aedes aegypti (III and IV instar) and malarial vector Anopheles stephensi (III and IV instar), showed 10-100% mortality rates. Biosafety assessment was made on embryos of Danio rerio and Artemia nauplii. The phyto-constituents of the methanol extract of A. radiata leaves were identified through gas chromatography-mass spectrometry (GC-MS). Methanolic leaf extracts of A. radiata, A. caudatum and C. swartzii exhibited larvicidal activity against III and IV instar larvae of Ae. aegypti (LC: 37.47, 74.51 and 152.38 and 67.58, 95.89 and 271.46 ppm) and An. stephensi (LC: 70.35, 112.12 and 301.05 and 113.83, 175.30 and 315.19 ppm), respectively. The GC-MS of the methanol extract of A. radiata leaves revealed the presence of 7 phyto-components among which, Carbamic acid, phenyl-, (2-Nitrophenyl) methyl ester (1), Benzoic acid, 3- methylbenzoate (2) and 4-(benzylimino)- 1,4-dihydro-1-(p-toluoylmethyl) pyridine (3) were dominant. Biosafety assessment of methanol extract of A. radiata leaves on embryos of Danio rerio (Zebra fish) and Artemia nauplii (micro crustacean) revealed that there were no destructive or teratogenic effects. To conclude, the larvicidal activity and insignificant toxicity to non-target aquatic organisms of A. radiata leaves makes it a potential and environment safe biocontrol agent against dengue and malarial vectors.
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http://dx.doi.org/10.1016/j.ecoenv.2018.05.062DOI Listing
October 2018

Initiating Nutritional Support Before 72 Hours Is Associated With Favorable Outcome After Severe Traumatic Brain Injury in Children: A Secondary Analysis of a Randomized, Controlled Trial of Therapeutic Hypothermia.

Pediatr Crit Care Med 2018 04;19(4):345-352

Department of Neurological Surgery, Barrow Neurological Institute and Phoenix Children's, Phoenix, AZ.

Objectives: To understand the relationship between the timing of initiation of nutritional support in children with severe traumatic brain injury and outcomes.

Design: Secondary analysis of a randomized, controlled trial of therapeutic hypothermia (Pediatric Traumatic Brain Injury Consortium: Hypothermia, also known as "the Cool Kids Trial" (NCT 00222742).

Settings: Fifteen clinical sites in the United States, Australia, and New Zealand.

Subjects: Inclusion criteria included 1) age less than 18 years, 2) postresuscitation Glasgow Coma Scale less than or equal to 8, 3) Glasgow Coma Scale motor score less than 6, and 4) available to be randomized within 6 hours after injury. Exclusion criteria included normal head CT, Glasgow Coma Scale equals to 3, hypotension for greater than 10 minutes (< fifth percentile for age), uncorrectable coagulopathy, hypoxia (arterial oxygen saturation < 90% for > 30 min), pregnancy, penetrating injury, and unavailability of a parent or guardian to consent at centers without emergency waiver of consent.

Interventions: Therapeutic hypothermia (32-33°C for 48 hr) followed by slow rewarming for the primary study. For this analysis, the only intervention was the extraction of data regarding nutritional support from the existing database.

Measurements And Main Results: Timing of initiation of nutritional support was determined and patients stratified into four groups (group 1-no nutritional support over first 7 d; group 2-nutritional support initiated < 48 hr after injury; group 3-nutritional support initiated 48 to < 72 hr after injury; group 4-nutritional support initiated 72-168 hr after injury). Outcomes were also stratified (mortality and Glasgow Outcomes Scale-Extended for Pediatrics; 1-4, 5-7, 8) at 6 and 12 months. Mixed-effects models were performed to define the relationship between nutrition and outcome. Children (n = 90, 77 randomized, 13 run-in) were enrolled (mean Glasgow Coma Scale = 5.8); the mortality rate was 13.3%. 57.8% of subjects received hypothermia Initiation of nutrition before 72 hours was associated with survival (p = 0.01), favorable 6 months Glasgow Outcomes Scale-Extended for Pediatrics (p = 0.03), and favorable 12 months Glasgow Outcomes Scale-Extended for Pediatrics (p = 0.04). Specifically, groups 2 and 3 had favorable outcomes versus group 1.

Conclusions: Initiation of nutritional support before 72 hours after traumatic brain injury was associated with decreased mortality and favorable outcome in this secondary analysis. Although this provides a rationale to initiate nutritional support early after traumatic brain injury, definitive studies that control for important covariates (severity of injury, clinical site, calories delivered, parenteral/enteral routes, and other factors) are needed to provide definitive evidence on the optimization of the timing of nutritional support after severe traumatic brain injury in children.
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http://dx.doi.org/10.1097/PCC.0000000000001471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886794PMC
April 2018