Category: Nevin Manimala

Cornea. 2022 May 13. doi: 10.1097/ICO.0000000000003058. Online ahead of print.

ABSTRACT

PURPOSE: The objective of this study was to compare the effectiveness and safety of short versus standard riboflavin induction times in cross-linking (CXL) for keratoconus.

METHODS: A retrospective comparative study was conducted with data from the Save Sight Keratoconus Registry. Inclusion criteria were epithelium-off technique, standard UVA CXL protocol (3 mW/cm2 for 30 minutes), riboflavin induction for 15 minutes (short) or 30 minutes (standard), and 1 year of follow-up data after CXL. Outcome measures included changes in best-corrected visual acuity (BCVA), keratometry in the steepest meridian (K2), maximum keratometry (Kmax), thinnest pachymetry (TCT), and adverse events. Analysis was conducted using mixed-effects regression models adjusted for age, sex, visual acuity, keratometry, pachymetry, practice, and eye laterality.

RESULTS: Two hundred eighty eyes (237 patients; mean, 27.3 ± 10.5 years old; 30% female) were included. The riboflavin induction time was short in 102 eyes (82 patients) and standard in 178 eyes (155 patients). The baseline characteristics (sex, mean age, BCVA, keratometry, and pachymetry [TCT]) were similar between the groups. At the 1-year follow-up visit, no statistically significant differences were observed in flattening in K2 and improvement in BCVA. Greater Kmax flattening [-1.5 diopters (D) vs. -0.5D, P = 0.031] and a greater proportion of >2% increase in TCT (23.5 vs. 11.3, P = 0.034) and haze (29 vs. 15, P = 0.005) were observed with short riboflavin induction.

CONCLUSIONS: Short and standard riboflavin induction times achieved similar degrees of flattening in K2 and improvement in vision. Greater improvements in Kmax and TCT were seen with short riboflavin times; however, this group had higher rates of haze.

PMID:35588392 | DOI:10.1097/ICO.0000000000003058

J Comput Biol. 2022 May 19. doi: 10.1089/cmb.2021.0600. Online ahead of print.

ABSTRACT

Nitrogen uptake in legumes is facilitated by bacteria such as Rhizobium leguminosarum. For this bacterium, gene expression data are available, but functional gene annotation is less well developed than for other model organisms. More annotations could lead to a better understanding of the pathways for growth, plant colonization, and nitrogen fixation in R. leguminosarum. In this study, we present a pipeline that combines novel scores from gene coexpression network analysis in a principled way to identify the genes that are associated with certain growth conditions or highly coexpressed with a predefined set of genes of interest. This association may lead to putative functional annotation or to a prioritized list of genes for further study.

PMID:35588362 | DOI:10.1089/cmb.2021.0600

Jpn J Radiol. 2022 May 19. doi: 10.1007/s11604-022-01290-1. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of the study was to evaluate whether ultra-low-dose computed tomography (ULD-CT) could replace conventional-dose CT (CD-CT) for diagnosis of acute wrist, ankle, knee, and shoulder fractures in emergency departments (ED).

METHODS: We developed CD-CT and ULD-CT scanning schemes for the various joints of the four limbs and scanned emergency patients prospectively. When performing CD-CT, a conventional bone reconstruction algorithm was used, while ULD-CT used both soft tissue and bone algorithms. A five-point scale was used to evaluate whether ULD-CT image quality affected surgical planning. The image quality and diagnostic performance of different types of scanned and reconstructed images for diagnosing fractures were evaluated and compared. Effective radiation dose of each group was calculated.

RESULTS: Our study included 56 normal cases and 185 fracture cases. The combination of bone and soft tissue algorithms on ULD-CT can improve diagnostic performance, such that on ULD-CT, the sensitivity improved from 96.7% to 98.9%, specificity from 98.2% to 100%, positive predictive value from 99.4% to 100%, negative predictive value from 90.2% to 96.6% and diagnostic accuracy ranged from 97.5% to 99.1%. There were no statistically significant differences between ULD-CT and CD-CT on diagnostic performance (p values, 0.40-1.00). The radiation doses for ULD-CT protocols were only 3.0-7.7% of those for CD-CT protocols (all p < 0.01).

CONCLUSIONS: In the emergency department, the 320-row detector ULD-CT could replace CD-CT in the diagnosis of limb joint fractures. The combination of bone algorithm with soft tissue algorithm reconstruction can further improve the image quality and diagnostic performance.

PMID:35588348 | DOI:10.1007/s11604-022-01290-1

Pharmaceut Med. 2022 May 19. doi: 10.1007/s40290-022-00427-x. Online ahead of print.

ABSTRACT

BACKGROUND: In 2007, the priority review voucher (PRV) was implemented in the US to incentivize research and development (R&D) for tropical diseases. The PRV is issued by the US FDA and grants a quicker review to manufacturers upon successful development of a product for a disease eligible for the program.

OBJECTIVE: The objective of this analysis was to assess whether the PRV has incentivized R&D (measured as clinical trial activity) for the intended tropical diseases.

METHOD: We used a difference-in-difference-in-differences (DDD) strategy by exploiting variation in its implementation across diseases and registries around the world. Clinical trials were retrieved from the World Health Organization International Clinical Trials Registry Platform for the years 2005-2019.

RESULTS: We found a positive, but not statistically significant, effect of the PRV on stimulating R&D activity. Delayed effects of the policy could not be found.

CONCLUSION: Our findings, which were robust across a series of robustness tests, suggest that the PRV program is not associated with a trigger in innovation for neglected diseases and therefore should not be considered as a stand-alone solution. It should be supplemented with other government measures to incentivize R&D activity. To increase the value of the program, we recommend that the PRV only be awarded to novel products and not to products that have already been licensed outside the US. Doing so would restrict the number of vouchers awarded and slow down their ongoing market depreciation. Finally, we propose that product sponsors be required to submit an access plan for PRV-awarded products.

PMID:35588350 | DOI:10.1007/s40290-022-00427-x

Tech Coloproctol. 2022 May 19. doi: 10.1007/s10151-022-02633-w. Online ahead of print.

ABSTRACT

BACKGROUND: The effectiveness of laparoscopic ventral mesh rectopexy (LVMR) in patients with defecatory disorders secondary to internal rectal prolapse is poorly evidenced. A UK-based multicenter randomized controlled trial was designed to determine the clinical efficacy of LVMR compared to controls at medium-term follow-up.

METHODS: The randomized controlled trial was conducted from March 1, 2015 TO January 31, 2019. A stepped-wedge RCT design permitted observer-masked data comparisons between patients awaiting LVMR (controls) with those who had undergone surgery. Adult participants with radiologically confirmed IRP refractory to conservative treatment were randomized to three arms with different delays before surgery. Efficacy outcome data were collected at equally stepped time points (12, 24, 36, 48, 60, and 72 weeks). Clinical efficacy of LVMR compared to controls was defined as ≥ 1.0-point reduction in Patient Assessment of Constipation-Quality of Life and/or Symptoms (PAC-QOL and/or PAC-SYM) scores at 24 weeks. Secondary outcome measures included 14-day diary data, the Generalized Anxiety Disorder scale (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), St Marks incontinence score, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), the chronic constipation Behavioral Response to Illness Questionnaire (CC-BRQ), and the Brief Illness Perception Questionnaire (BIPQ).

RESULTS: Of a calculated sample size of 114, only 28 patients (100% female) were randomized from 6 institutions (due mainly to national pause on mesh-related surgery). Nine were assigned to the T0 arm, 10 to T12, and 9 to T24. There were no substantial differences in baseline characteristics between the three arms. Compared to baseline, significant reduction (improvement) in PAC-QOL and PAC-SYM scores were observed at 24 weeks post-surgery (- 1.09 [95% CI – 1.76, – 0.41], p = 0.0019, and – 0.92 [- 1.52, – 0.32], p = 0.0029, respectively) in the 19 patients available for analysis (9 were excluded for dropout [n = 2] or missing primary outcome [n = 7]). There was a clinically significant long-term reduction in PAC-QOL scores (- 1.38 [- 2.94, 0.19], p = 0.0840 at 72 weeks). Statistically significant improvements in PAC-SYM scores persisted to 72 weeks (- 1.51 [- 2.87, – 0.16], p = 0.0289). Compared to baseline, no differences were found in secondary outcomes, except for significant improvements at 24 and 48 weeks on CC-BRQ avoidance behavior (- 14.3 [95% CI – 23.3, – 5.4], and – 0.92 [- 1.52, – 0.32], respectively), CC-BRQ safety behavior (- 13.7 [95% CI – 20.5, – 7.0], and – 13.0 [- 19.8, – 6.1], respectively), and BIPQ negative perceptions (- 16.3 [95% CI – 23.5, – 9.0], and – 10.5 [- 17.9, – 3.2], respectively).

CONCLUSIONS: With the caveat of under-powering due to poor recruitment, the study presents the first randomized trial evidence of short-term benefit of LVMR for internal rectal prolapse.

TRIAL REGISTRATION: ISRCTN Registry (ISRCTN11747152).

PMID:35588336 | DOI:10.1007/s10151-022-02633-w

Graefes Arch Clin Exp Ophthalmol. 2022 May 19. doi: 10.1007/s00417-022-05692-9. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to investigate the clinical characteristics of patients with recurrent intraocular lens (IOL) dislocation after scleral-fixated sutured IOL implantation and evaluate the long-term outcomes of scleral re-fixation of IOL.

METHODS: The medical records of patients who underwent surgery for IOL dislocation between January 2011 and January 2021 were reviewed. The study included 164 patients (male: 131, female: 33) (176 eyes). Patient demographics, preoperative, intraoperative and postoperative data, and the ocular and systemic conditions associated with IOL re-dislocation were analyzed.

RESULTS: The study included 176 consecutive cases of scleral-fixated sutured IOL. Twenty-six eyes (14.8%) showed re-dislocation of IOL after the initial IOL scleral fixation and underwent reoperation (mean 75.5 ± 62.5 months after the first surgery); three (11.5%) of them required a third surgery. Younger adults (aged less than 40 years), and patients who underwent IOL scleral fixation in complicated cataract surgery or aphakic state had a higher risk of re-dislocation. Diabetes mellitus (DM) was the only statistically significantly higher risk factor in the re-dislocated group (p = 0.041). The complication rate with scleral re-fixation was higher than that in the non-re-dislocated group. No statistically significant differences were observed, except for vitreous hemorrhage (p = 0.024).

CONCLUSIONS: Caution should be exercised when performing sutured scleral fixation of IOL in younger patients, cases of complicated cataract surgery and aphakia, and patients with DM to prevent IOL re-dislocation. Scleral-fixated sutured IOL in eyes with recurrent IOL dislocation seems to be a safe and effective procedure with a relatively low complication rate.

PMID:35588329 | DOI:10.1007/s00417-022-05692-9

Int Urogynecol J. 2022 May 19. doi: 10.1007/s00192-022-05228-z. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: Overactive bladder (OAB) and urinary incontinence (UI) are prevalent in older women. We investigated relations of toileting behaviors and urinary urge cues to OAB and UI in women ≥ 65 years. We tested mediation hypotheses that toileting behaviors lead to higher sensitivity to urinary urge cues (the mediator), which leads to both OAB and UI.

METHODS: An e-panel was recruited to respond to an electronic survey that included demographic information, Urinary Cues Scale version 2, Toileting Behaviors-Women’s Elimination Behaviors (TB-WEB) scale, and the International Consultation on Incontinence Questionnaire Short Forms for Urinary Incontinence (ICIQ-SF-UI) and Overactive Bladder (ICIQ-SF-OAB). Descriptive statistics were conducted; correlation matrices were created to explore relationships among major variables. Regression analyses were conducted to test our mediation hypotheses.

RESULTS: There were 338 respondents with average age 70.9 (SD + 5.55) years. Most were white, overweight or obese, and had UI. Urinary urge cues fully mediated the relationship of TB-WEB with OAB. Urinary urge cues partially mediated the relationship of TB-WEB with UI; the direct effect of toileting behaviors on UI remained significant. Age and body mass index had significant partial correlations with UI but not with OAB.

DISCUSSION: Toileting behaviors appear to contribute to sensitivity to urinary cues, which are related to both OAB and UI. Toileting behaviors have indirect effects on OAB and both indirect and direct effects on UI. Interventions to change toileting behaviors and extinguish urinary cues are needed.

CONCLUSIONS: Behavioral and conditioning factors contribute to UI in older women.

PMID:35588320 | DOI:10.1007/s00192-022-05228-z

Transfusion. 2022 May 19. doi: 10.1111/trf.16934. Online ahead of print.

ABSTRACT

BACKGROUND: The therapeutic benefit of convalescent plasma (CP) therapy to treat COVID-19 may derive from neutralising antibodies (nAbs) to SARS-CoV-2. To investigate effects of antigenic variation on neutralisation potency of CP, we compared nAb titres against prototype and recently emerging strains of SARS-CoV-2, including Delta and Omicron, in CP donors previously infected with SARS-CoV-2 before and after immunisation.

METHODS AND MATERIALS: Samples were assayed from previously SARS-CoV-2 infected donors before (n=17) and after one (n=43) or two (n=71) doses of Astra-Zeneca or Pfizer vaccinations. Ab titres against Wuhan/wild type (WT), Alpha, Beta and Delta SARS-CoV-2 strains were determined by live virus microneutralization assay while titres to Omicron used a focus reduction neutralisation test. Anti-spike antibody was assayed by Elecsys anti-SARS-CoV-2 quantitative spike assay (Roche).

RESULTS: Unvaccinated donors showed a geometric mean titre (GMT) of 148 against WT, 80 against Alpha but mostly failed to neutralise Beta, Delta and Omicron strains. Contrastingly, high GMTs were observed in vaccinated donors against all SARS-CoV-2 strains after one vaccine dose (WT:703; Alpha:692; Beta:187; Delta:215; Omicron:434). By ROC analysis, reactivity in the Roche quantitative Elecsys spike assay of 20,000 U/ml was highly predictive of donations with nAb titres of ≥1:640 against Delta (90% sensitivity; 97% specificity) and ≥1:320 against Omicron (89% sensitivity; 81% specifciity) DISCUSSION: Vaccination of previously infected CP donors induced high levels of broadly neutralising antibodies against circulating antigenic variants of SARS-CoV-2. High titre donations could be reliably identified by automated quantitative anti-spike antibody assay, enabling large-scale pre- selection of high-titre convalescent plasma.

PMID:35588314 | DOI:10.1111/trf.16934

Biomark Med. 2022 May 19. doi: 10.2217/bmm-2021-1014. Online ahead of print.

ABSTRACT

Aims: To evaluate BRAK and APRIL in serum samples from healthy patients and an ovarian tumor group and analyze their effective value as biomarkers. Materials & methods: BRAK and APRIL were measured in 197 serum samples including 34 healthy controls, 48 patients with benign ovarian cysts and 115 patients with ovarian cancer, and the best statistical cutoff values were calculated. Then, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value for selected cutoff points were assessed. Results: The healthy control group had statistically significant higher BRAK and lower APRIL than the ovarian tumor group. BRAK was excellent for differentiating healthy patients from patients with ovarian tumors, showing area under the receiver operating characteristic curve 0.983, 98.16% sensitivity and 100% specificity. When BRAK was combined with APRIL and CA-125, it also played a role in distinguishing benign cysts from malignancies with area under the curve 0.864, 81.74% sensitivity and 79.17% specificity. Conclusions: BRAK and APRIL are good candidates for ovarian tumor biomarkers.

PMID:35588310 | DOI:10.2217/bmm-2021-1014

J Med Virol. 2022 May 19. doi: 10.1002/jmv.27871. Online ahead of print.

ABSTRACT

OBJECTIVE: To provide a comparative meta-analysis and systematic review of the risk and clinical outcomes of COVID-19 infection between fully vaccinated and unvaccinated groups.

METHODS: Eighteen studies of COVID-19 infections in fully vaccinated (“breakthrough infections”) and unvaccinated individuals were reviewed from Medline/PubMed, Scopus, Embase, and Web of Science databases. The meta-analysis examined the summary effects and between-study heterogeneity regarding differences in the risk of infection, hospitalization, treatments, and mortality between vaccinated and unvaccinated individuals.

RESULTS: The overall risk of infection was lower for the fully vaccinated compared to that of the unvaccinated (relative risk[RR] 0.20, 95% CI 0.19-0.21), especially for variants other than Delta (Delta: RR 0.29, 95% CI 0.13-0.65; other variants: RR 0.06, 95% CI 0.04-0.08). The risk of asymptomatic infection was not statistically significantly different between fully vaccinated and unvaccinated (RR 0.56, 95% CI 0.27-1.19). There were neither statistically significant differences in risk of hospitalization (RR 1.06, 95% CI 0.38-2.93), invasive mechanical ventilation (RR 1.65 ,95% CI 0.90-3.06), or mortality (RR 1.19, 95% CI 0.79-1.78). Conversely, the risk of supplemental oxygen during hospitalization was significantly higher for the unvaccinated (RR 1.40, 95% CI 1.08-1.82).

CONCLUSIONS: Unvaccinated people were more vulnerable to COVID-19 infection than fully vaccinated for all variants. Once infected, there were no statistically significant differences in the risk of hospitalization, invasive mechanical ventilation, or mortality. Still, unvaccinated showed an increased need for oxygen supplementation. Further prospective analysis, including patients’ risk factors, COVID-19 variants, and the utilized treatment strategies, would be warranted. This article is protected by copyright. All rights reserved.

PMID:35588301 | DOI:10.1002/jmv.27871