Category: Nevin Manimala

Diagn Microbiol Infect Dis. 2021 Apr 21;101(2):115392. doi: 10.1016/j.diagmicrobio.2021.115392. Online ahead of print.

ABSTRACT

Real-time reverse transcription-polymerase chain reaction (RT-PCR) on upper respiratory tract (URT) samples is the primary method to diagnose SARS-CoV-2 infections and guide public health measures, with a supportive role for serology. We reinforce previous findings on limited sensitivity of PCR testing, and solidify this fact by statistically utilizing a firm basis of multiple tests per individual. We integrate stratifications with respect to several patient characteristics such as severity of disease and time since onset of symptoms. Bayesian statistical modelling was used to retrospectively determine the sensitivity of RT-PCR using SARS-CoV-2 serology in 644 COVID-19-suspected patients with varying degrees of disease severity and duration. The sensitivity of RT-PCR ranged between 80% – 95%; increasing with disease severity, it decreased rapidly over time in mild COVID-19 cases. Negative URT RT-PCR results should be interpreted in the context of clinical characteristics, especially with regard to containment of viral transmission based on ‘test, trace and isolate’. Keywords: SARS-CoV-2, RT-PCR, serology, sensitivity, public health.

PMID:34161880 | DOI:10.1016/j.diagmicrobio.2021.115392

J Surg Res. 2021 Jun 20;267:260-266. doi: 10.1016/j.jss.2021.04.025. Online ahead of print.

ABSTRACT

BACKGROUND: Morbidity and Mortality Conference (MMC) is a traditional quality assessment tool among surgical residencies to evaluate complications within their care and to integrate and educate best practices. Unfortunately, it is difficult to validate and measure loop closure as a result of MMC. This may result in repeating past mistakes or worse, becoming a meeting of anecdotal experiences. The goal of this study is to present results from a morbidity and mortality assessment tool (MMAT) which provides a means of measuring and tracking factors related to those surgical complications discussed within the MMC.

MATERIALS AND METHODS: Three years of MMC presentations were organized into a database and further divided and organized into variables which included case by the class year of the presenting resident, service line, month the case was presented, and potential contributing factors. Contributing factors considered for each case were categorized as: Systems-Based, Direct Patient Care, and Interpersonal Communication. Contributing factors were assigned to cases by a review committee consisting of residents and faculty members.

RESULTS: The lack of knowledge, technical error, lack of experience, lack of supervision, failure to communicate with team members were present in greater than 10% of the presented cases. There was a “July Effect” in the Trauma service, where there was a statistically significant difference between the percentage of cases presented that involved Failure to Communicate errors when compared with the remainder of the year.

CONCLUSIONS: MMAT allows longitudinal collection of data from each MMC to recognize patterns that facilitate improvements in systems of care and institutional memory.

PMID:34161841 | DOI:10.1016/j.jss.2021.04.025

Spine J. 2021 Jun 20:S1529-9430(21)00778-6. doi: 10.1016/j.spinee.2021.06.014. Online ahead of print.

ABSTRACT

BACKGROUND CONTEXT: There is growing interest among payers in profiling hospital value and quality-of-care, including both the cost and safety of common surgeries, such as lumbar fusion. Nonetheless, there is sparse evidence describing the statistical reliability of such measures when applied to lumbar fusion for spondylolisthesis.

PURPOSE: To evaluate the reliability of 90-day inpatient hospital costs, overall complications, and rates of serious complications for profiling hospital performance in lumbar fusion surgery for spondylolisthesis.

STUDY DESIGN/SETTING: Data for this analysis came from State Inpatient Databases from nine states made available through the Healthcare Cost and Utilization Project.

PATIENT SAMPLE: Patients undergoing elective lumbar spine fusion for spondylolisthesis from 2010-2017 in participating states.

OUTCOME MEASURES: Statistical reliability, defined as the ability to distinguish true performance differences across hospitals relative to statistical noise. Reliability was assessed separately for 90-day inpatient costs (standardized across years to 2019 dollars), overall complications, and serious complication rates.

METHODS: Statistical reliability was measured as the amount of variation between hospitals relative to the total amount of variation for each measure. Total variation includes both between-hospital variation (“signal”) and within-hospital variation (“statistical noise”). Thus, reliability equals signal over (signal plus noise) and ranges from 0 to 1. To adjust for differences in patient-level risk and procedural characteristics, hierarchical linear and logistic regression models were created for the cost and complication outcomes. Random hospital intercepts were used to assess between-hospital variation. We evaluated the reliability of each measure by study year and examined the number of hospitals meeting different thresholds of reliability by year.

RESULTS: We included a total of 66,571 elective lumbar fusion surgeries for spondylolisthesis performed at 244 hospitals during the study period. The mean 90-day hospital cost was $30,827 (2019 dollars). 12.0% of patients experienced a complication within 90 days of surgery, including 7.8% who had a serious complication. The median reliability of 90-day cost ranged from 0.97-0.99 across study years, and there was a narrow distribution of reliability values. By comparison, the median reliability for the overall complication metric ranged from 0.22 to 0.44, and the reliability of the serious complication measure ranged from 0.30 to 0.49 across the study years. At least 96% of hospitals had high (> 0.7) reliability for cost in any year, whereas only 0-9% and 0-11% of hospitals reached this cutoff for the overall and serious complication rate in any year, respectively. By comparison, 10-69% of hospitals per year achieved a more moderate threshold of 0.4 reliability for overall complications, compared to 21-80% of hospitals who achieved this lower reliability threshold for serious complications.

CONCLUSIONS: 90-day inpatient costs are highly reliable for assessing variation across hospitals, whereas overall and serious complications are only moderately reliable for profiling performance. These results support the viability of emerging bundled payment programs that assume true differences in costs of care exist across hospitals.

PMID:34161844 | DOI:10.1016/j.spinee.2021.06.014

Am J Med Sci. 2021 Jun 20:S0002-9629(21)00240-8. doi: 10.1016/j.amjms.2021.06.009. Online ahead of print.

ABSTRACT

BACKGROUND: The therapeutic benefits and rationale for treating fevers with external cooling methods remain unclear. We aimed to describe the clinical settings in which cooling blankets (CBs) are used.

DESIGN: We conducted a retrospective chart review of CB use in adult patients admitted to our tertiary care center over a one-year period. We measured how they are used and correlations between clinical variables and their duration of use.

RESULTS: 561 patients were included in our study. The mean highest temperature during hospitalization was 39.35°C (SD, 0.67). Shivering occurred in 176 patients (31.4%) while on a CB although 303 patients (54%) had no data regarding shivering. Discontinuation of CBs was recorded in only 177 (30.5%) cases. Among these, the median duration of use was 33.37 hours (IQR: 18.13-80.38) while the median duration of fever was 22.13 hours (IQR 6.67-51.98). Duration of CB use was highly correlated with fever duration (Spearman’s rho, 0.771, p<.001), moderately with length of stay (LOS) (rho, 0.425, p<.001), LOS after CB initiation (rho, 0.475, p<.001) and antipyretic use (rho, 0.506, p<.001). No other statistically significant correlations were observed.

CONCLUSION: Documentation of CB use including temperature set points, time of discontinuation and duration in EMRs was poor. We could not establish benefits of CB use in this study but observed that almost a third of patients developed adverse effects in the form of shivering. Thus, adverse effects of CB use may outweigh potential benefits. Their use should be reevaluated and institutional protocols developed for their use.

PMID:34161829 | DOI:10.1016/j.amjms.2021.06.009

J Oral Maxillofac Surg. 2021 May 19:S0278-2391(21)00518-8. doi: 10.1016/j.joms.2021.05.019. Online ahead of print.

ABSTRACT

PURPOSE: We aim to reveal postoperative morphological correlations between the nasolabial components in patients with unilateral cleft lip (UCL). The hypothetical correlations are first, a correlation between the vertical height of the cleft-side alar base and the length of the cleft-side red lip, and second, a correlation between the length of the cleft-side red lip and the vertical position of the cleft-side oral commissure. We explain how these morphological balances are controlled by surgery.

METHODS: Three-dimensional bilateral measurements of the length of the red lip, vertical height of the nasal alar base, and vertical height of the oral commissure were conducted retrospectively on 31 patients with UCL and palate (complete UCL: 26; incomplete UCL: 5) who underwent primary lip plasty at Osaka Women’s and Children’s Hospital from 2017 to 2019.

RESULTS: We found a statistically significant correlation between the vertical height of the cleft-side alar base and cleft-side red lip length (P = .012, r = 0.45); thus, the longer the red lip, the lower was the nasal alar base. The correlation between the cleft-side red lip length and the vertical height of the cleft-side oral commissure also showed a statistically significant (P = .00074, r = 0.57); thus, the shorter the red lip, the higher was the oral commissure.

CONCLUSIONS: The present results provided objective evidence showing basic morphological relationships between the postoperative nasolabial features of patients with UCL. The results lead to a reasonable approach to define the proposed peak of the Cupid’s bow, an unsettled major controversy in cleft lip surgery.

PMID:34161809 | DOI:10.1016/j.joms.2021.05.019

Exp Eye Res. 2021 Jun 20:108680. doi: 10.1016/j.exer.2021.108680. Online ahead of print.

ABSTRACT

Accumulation of bisretinoids such as A2E and its isomer iso-A2E is thought to mediate blue light-induced oxidative damage associated with age-related macular degeneration (AMD) and autosomal recessive Stargardt disease (STGD1). We hypothesize that increasing dietary intake of the macular carotenoids lutein and zeaxanthin in individuals at risk of AMD and STGD1 can inhibit the formation of bisretinoids A2E and iso-A2E, which can potentially ameliorate macular degenerative diseases. To study the beneficial effect of macular carotenoids in a retinal degenerative diseases model, we used ATP-binding cassette, sub-family A member 4 (Abca4^-/-)/β,β-carotene-9′,10′-oxygenase 2 (Bco2^-/-) double knockout (KO) mice that accumulate elevated levels of A2E and iso-A2E in the retinal pigment epithelium (RPE) and macular carotenoids in the retina. Abca4^-/-/Bco2^-/- and Abca4^-/- mice were fed a lutein-supplemented chow, zeaxanthin-supplemented chow or placebo chow (∼2.6 mg of carotenoid/mouse/day) for three months. Visual function and electroretinography (ERG) were measured after one month and three months of carotenoid supplementation. The lutein and zeaxanthin supplemented Abca4^-/-/Bco2^-/- mice had significantly lower levels of RPE/choroid A2E and iso-A2E compared to control mice fed with placebo chow and improved visual performance. Carotenoid supplementation in Abca4^-/- mice minimally raised retinal carotenoid levels and did not show much difference in bisretinoid levels or visual function compared to the control diet group. There was a statistically significant inverse correlation between carotenoid levels in the retina and A2E and iso-A2E levels in the RPE/choroid. Supplementation with retinal carotenoids, especially zeaxanthin, effectively inhibits bisretinoid formation in a mouse model of STGD1 genetically enhanced to accumulate carotenoids in the retina. These results provide further impetus to pursue oral carotenoids as therapeutic interventions for STGD1 and AMD.

PMID:34161819 | DOI:10.1016/j.exer.2021.108680

Ann Epidemiol. 2021 Jun 20:S1047-2797(21)00154-X. doi: 10.1016/j.annepidem.2021.06.003. Online ahead of print.

NO ABSTRACT

PMID:34161794 | DOI:10.1016/j.annepidem.2021.06.003

Chembiochem. 2021 Jun 23. doi: 10.1002/cbic.202100193. Online ahead of print.

ABSTRACT

The oxidation of proteins generates reactive amino acid (AA) residue intermediates, leading to protein modification and cross-linking. Aerobic studies with peptides and photosensitizers allow for the controlled generation of reactive oxygen species (ROS) and reactive AA residue intermediates, providing mechanistic insights as to how natural protein modifications form. Such studies have inspired the development of abiotic methods for protein modification and crosslinking, including applications of biomedical importance. Dityrosine linkages derived from oxidation at tyrosine (Tyr) residues represent one of the more well-understood oxidation-induced modifications. Here we demonstrate an aerobic, visible light-dependent oxidation reaction of Tyr-containing substrates promoted by a water-soluble 4-amino-1,8-naphthalimide-based photosensitizer. The developed procedure converts Tyr-containing substrates into o,o’- Tyr-Tyr linked dimers. The regioselectively formed o,o’ -Tyr-Tyr linkage is consistent with dimeric standards prepared using a known enzymatic method. A crossover study with two peptides provides a statistical mixture of three distinct o,o’ -Tyr-Tyr linked dimers, supporting a mechanism that involves Tyr residue oxidation followed by intermolecular combination.

PMID:34161648 | DOI:10.1002/cbic.202100193

S D Med. 2021 Feb;74(2):54-57.

ABSTRACT

INTRODUCTION: Vaccinations are one of the greatest public health achievements of the 20th century, leading to a reduction in morbidity and mortality associated with the infectious diseases they prevent. Unfortunately, vaccination rates within the U.S. have been declining, and many of these vaccine-preventable diseases are again on the rise. Due to this, methods to increase vaccination rates are being explored. Vaccine standing orders are one method being employed. This pilot study explored the effects vaccine standing orders placed in the electronic medical record (EMR) had on the number of pediatric vaccinations administered in one South Dakota clinic.

METHODS: Nursing staff reviewed the EMR and state records to determine what immunizations the pediatric patients, defined as those 18 years of age and under, were due for according to the Center for Disease Control’s (CDC) recommended vaccination schedule. They then placed vaccine standing orders in the EMR for each delinquent vaccination based on these findings. The number of vaccines administered during a five-month period before (Jan. 1 – May 31, 2019) and a five-month period after (June 1 – Oct.31, 2019) implementation of standing orders were compared. Results were analyzed using an independent samples t-test.

RESULTS: The absolute number of vaccinations administered after standing orders were instituted was greater than those administered prior to standing orders. The average number of vaccines given per month more than doubled, resulting in a statistically significant increase in vaccination rates by 117 percent.

CONCLUSIONS: This pilot study demonstrated a significant increase in the number of immunizations administered with the use of standing orders.

PMID:34161683

Am J Hematol. 2021 Jun 23. doi: 10.1002/ajh.26276. Online ahead of print.

ABSTRACT

Eliglustat, an oral substrate reduction therapy, is approved for eligible adults with Gaucher disease type 1. In the Phase 3 ENGAGE trial of previously untreated adults with Gaucher disease type 1, eliglustat-treated patients had statistically significant improvements in organ volumes and hematologic parameters compared with placebo in the 9-month primary analysis. We report final outcomes by time on eliglustat among all patients who participated in the ENGAGE trial and extension. No patient deteriorated clinically or withdrew due to adverse events; 39/40 patients entered the open-label extension period and 34/40 (85%) remained in the trial until completion or switching to commercial eliglustat after its approval (2.3 to 6 years). Clinically meaningful improvements in Gaucher disease manifestations were seen in all patients concomitant with reductions in pathological lipid substrate levels (glucosylceramide and glucosylsphingosine). Among patients with 4.5 years of eliglustat exposure, mean spleen volume decreased by 66% (from 17.1 to 5.8 multiples of normal [MN], n=13)mean liver volume decreased by 23% (from 1.5 to 1.1 MN, n=13), mean hemoglobin increased 1.4 g/dL (from 11.9 to 13.4 g/dL, n=12), mean platelet count increased by 87% (from 67.6 to 122.6 x 10⁹ /L, n=12), median chitotriosidase decreased by 82% (from 13,394 to 2312 nmol/hr/ml, n=11), median glucosylceramide decreased by 79% (from 11.5 to 2.4 μg/mL, n=11), median glucosylsphingosine decreased by 84% (from 518.5 to 72.1 ng/mL, n=10), and mean spine T-score increased from -1.07 (osteopenia) to -0.53 (normal) (n=9). Together, these outcomes regardless of time on eliglustat showed comparable improvements in Gaucher manifestations and disease biomarkers. Eliglustat was well-tolerated and led to clinically significant improvements in previously untreated patients with Gaucher disease type 1 during 4.5 years of treatment. This article is protected by copyright. All rights reserved.

PMID:34161616 | DOI:10.1002/ajh.26276