Category: Nevin Manimala

J Clin Sleep Med. 2022 Sep 23. doi: 10.5664/jcsm.10308. Online ahead of print.

ABSTRACT

STUDY OBJECTIVES: The purpose of this study was to conduct a comprehensive assessment of sleep and circadian rhythms in individuals with and without coronary artery disease (CAD).

METHODS: This was a cross-sectional study. Participants were 32 individuals; mean age = 70.9; female 46.9%; 19 with CAD; and 13 without CAD. We assessed sleep quality and 24-hour rest-activity rhythms for 14 days using wrist actigraphy and self-report measures, and circadian rhythm using dim light melatonin onset (DLMO).

RESULTS: Melatonin levels prior to habitual bedtime were significantly lower in individuals with CAD than in those without CAD (median AUC = 12.88 vs. 26.33 pg/ml × h, p = .049). The median circadian timing measured by DLMO was the same for the two groups with 20:26 [hh:mm] for individuals with CAD and 19:53 for the control group (p = .64, r = 0.14). Compared to the control group, the CAD group had significantly lower amplitude (p = .03, r = -.48), and lower overall rhythmicity (pseudo-F-statistic p = .004, r = -.65) in their 24-hour rest-activity rhythms.

CONCLUSIONS: This is one of the first study to comprehensively assess both sleep and circadian rhythm in individuals with CAD. Compared to non-CAD controls, individuals with CAD had lower levels of melatonin prior to habitual bedtime and a lower 24-hour rest-activity rhythm amplitude and overall rhythmicity. Future studies using larger sample sizes should further investigate the possibility of suppressed circadian rhythmicity in individuals with CAD.

PMID:36148612 | DOI:10.5664/jcsm.10308

Global Spine J. 2022 Sep 23:21925682221121093. doi: 10.1177/21925682221121093. Online ahead of print.

ABSTRACT

STUDY DESIGN: Case control study.

OBJECTIVE: Micro-lumbar discectomy or Interbody fusion procedure are work-horse surgical procedures in management of lumbar disc disease. Spine surgeon in their early years of practice gets confused in choosing ideal surgical plan when dealing with a complex scenario. A clinical score is needed to guide spine surgeons in choosing an optimal surgical plan.

MATERIALS AND METHODS: Study was done with research grant approval from AO Spine. A predictive score was formulated as per hypothesis following a pilot study. Two fellowship trained spine surgeons-one using the score (Group A) and other not using score (Group B-control) treated 40 patients included in their respective group. All patients were analysed preoperatively, post-surgery at 12 months follow-up with Visual analog scale score for back pain, leg pain, Oswestry disability index score, SF-36 score. Change in parameters at 12 months follow-up were analysed statistically. P ≤ .05 was considered statistically significant. Success rate of individual surgeon who managed respective group of patients and Difficulty index of surgeon who managed without using score was evaluated at 12 months follow-up.

RESULTS: Success rate of Group A-surgeon was higher than Group B-surgeon .15% of Group B patients had poor surgical outcome at follow-up. Statistically significant improvement in Group A patients were seen in all 3 evaluated parameters when compared to Group B patients at 12 months of follow-up (P ≤ .05). Difficulty index of surgeon who didn’t use the score was 15%.

CONCLUSION: The proposed predictive score comprising all risk factors, can be used by spine surgeons when they are confronted with difficult scenario in decision-making. Accuracy, reliability and validity of the score needs to be evaluated in a larger scale.

LEVEL OF EVIDENCE: Ⅲ.

PMID:36148599 | DOI:10.1177/21925682221121093

FEBS Open Bio. 2022 Sep 23. doi: 10.1002/2211-5463.13492. Online ahead of print.

ABSTRACT

Homologous proteins can display high structural variation due to evolutionary divergence at low sequence identity. This classical inverse relationship between sequence identity and structural similarity, established many years ago, has remained true between homologous proteins of known structure over time. However, a large number of heteromeric proteins also exist in the structural data bank, where the interacting subunits belong to the same fold and maintain low sequence identity between themselves. It is not clear if there is any selection pressure to deviate from the inverse sequence-structure relationship for such interacting distant homologues, in comparison to pairs of homologues which are not known to interact. We examined 12,824 fold pairs of interacting homologues of known structure, which includes both heteromers and multi-domain proteins. These were compared with monomeric proteins, resulting in 26,082 fold pairs as a dataset of non-interacting homologous systems. Interacting homologues were found to retain higher structural similarity than non-interacting homologues at diminishing sequence identity in a statistically significant manner. Interacting homologues are more similar in their 3D structures than non-interacting homologues and have a preference towards symmetric association. There appears to be a structural constraint between remote homologues due to this commitment.

PMID:36148593 | DOI:10.1002/2211-5463.13492

Am J Health Syst Pharm. 2022 Sep 23:zxac243. doi: 10.1093/ajhp/zxac243. Online ahead of print.

ABSTRACT

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: To track and analyze the growth of 12 Board of Pharmacy Specialties (BPS) specialties from 2008 to 2020 and, subject to criteria, to project specialty numbers through 2025. The analysis considered residency data and Bureau of Labor Statistics projections.

METHODS: BPS data were used to determine numeric growth, growth rates, and trends for 12 BPS specialties from 2008 to 2020. Specialties begun after 2008 were analyzed from their start date. For specialties with more than 2 data points and coefficients of determination greater than 0.80, we calculated projections through 2025. We also estimated the percentage of BPS-certified pharmacists with postgraduate year 1 training.

RESULTS: BPS-certified pharmacists grew in number from 3,004 (2008) to 41,802 (2020), an over 13-fold increase. Currently, 4 of the 5 largest specialties (pharmacotherapy, ambulatory care, oncology, and critical care) continue to grow at a fast rate. Pharmacotherapy experienced the largest numeric growth (20,624) despite the ongoing introduction of new specialties. Critical care and infectious diseases had the highest growth rates (both 32%). We were able to make projections for 10 of 12 specialties, with greater than 62,000 certifications projected by 2025. Growth to these projected levels will require more residencies and more certification preparation opportunities. Residency-trained BPS specialists currently constitute slightly less than 50% of the BPS-certified population.

CONCLUSION: Specialization in the pharmacy profession is growing at a rapid pace. As more clinical privileges are approved, the demand for more specialized pharmacists will likely continue to increase. Data from this study document the growth of the pharmacy specialty workforce. The data and analysis can be used to estimate potential pharmacist contributions across the healthcare spectrum in clinical areas where BPS-certified pharmacists practice.

PMID:36148562 | DOI:10.1093/ajhp/zxac243

Stat Med. 2022 Sep 23. doi: 10.1002/sim.9584. Online ahead of print.

ABSTRACT

Blinded sample size re-estimation (BSSR) is an adaptive design to prevent the power reduction caused by misspecifications of the nuisance parameters in the sample size calculation of comparative clinical trials. However, conventional BSSR methods used for overdispersed count data may not recover the power as expected under the misspecification of the working variance function introduced by the specified analysis model. In this article, we propose a BSSR method that is robust to the misspecification of the working variance function. A weighted estimator of the dispersion parameter for the BSSR is derived, where the weights are introduced to incorporate the difference in the distribution of follow-up length between the interim analysis with BSSR and the final analysis. Simulation studies demonstrated the power of the proposed BSSR method was relatively stable under misspecifications of the working variance function. An application to a hypothetical randomized clinical trial of a treatment to reduce exacerbation rate in patients with chronic obstructive pulmonary disease is provided.

PMID:36148560 | DOI:10.1002/sim.9584

Mol Genet Genomic Med. 2022 Sep 23:e2063. doi: 10.1002/mgg3.2063. Online ahead of print.

ABSTRACT

BACKGROUND: ACE1 I/D rs1799752 and ACE2 rs2285666 genetic polymorphisms could play a critical role in altering the clinical outcomes of SARS-CoV-2. The findings of previous studies remained inconclusive. This meta-analysis was performed to evaluate the association and provide a more reliable outcome.

METHODS: This study was completed following the updated recommendations of PRISMA using RevMan 5.4.1 statistical software.

RESULTS: A total of 11 studies with 950 severe cases and 1573 non-severe cases with COVID-19 infection were included. Pooled analysis showed that ACE1 I/D polymorphism was correlated with the severity of SARS-CoV-2 in the DD genotype and D allele for the fixed-effects model (OR:1.27 and OR:1.17). Besides, codominant 3, recessive, and allele models were associated with the severity of the fixed-effects model (OR:1.35, OR:1.37, and OR:1.20) in Caucasian ethnicity. ACE2 rs2285666 was linked with the severity in codominant 3 (OR:2.63, for both random- and fixed effects-models), overdominant (OR:1.97, for random-effects model and OR:1.97, for fixed effects-model), and recessive model (OR:0.41 for fixed- and random-effects model). Allele model of rs2285666 showed a significant association in the fixed-effects model (OR:1.61).

CONCLUSION: Our present meta-analysis suggests that ACE1 I/D rs1799752 and ACE2 rs2285666 variants may enhance the severity in SARS-CoV-2 infected patients. Future studies are warranted to verify our findings.

PMID:36148537 | DOI:10.1002/mgg3.2063

Orthop Surg. 2022 Sep 23. doi: 10.1111/os.13493. Online ahead of print.

ABSTRACT

OBJECTIVE: Both-column acetabular fracture is a type that accumulates both the pelvis and acetabulum with complex fracture line alignment and has variant fracture fragments. The selection of different reduction landmarks and sequences produces different qualities of reduction. This study aims to compare the operation-related items, quality of reduction, and hip functional outcome by using different reduction landmarks and sequences for management of both-column acetabular fractures (BCAF).

METHODS: A consecutive cohort of 42 patients from January 2013 to January 2019 with BCAF were treated operatively with different reduction landmarks and sequences: pelvic ring fractures reduction first (PRFRF group) and acetabular fractures reduction first (AFRF group). Preoperative computer visual surgical procedures were applied. There were 22 patients in PRFRF group and 20 patients in AFRF group. The surgical details, complications, radiographic and clinical results were recorded. The quality of reduction was assessed by the Matta scoring system. The functional outcome was evaluated by the modified Merle d’Aubigné and Postel scoring system. The measurement data were analyzed using the t-test of independent samples and rank-sum test of ranked data.

RESULTS: The real reduction sequence in both groups was almost identical to the preoperative surgical procedures. The excellent/good quality of reduction in PRFRF group (21/22) was better than AFRF group (17/20). Operative time (152.3 ± 16.3 mins) and intra-operative blood loss (639.5 ± 109.9ml) were significantly reduced in PRFRF group (p < 0.05). The incidence of deep vein thrombosis in PRFRF group (2/22) was less than AFRF group (4/20), but without statistical signification.

CONCLUSION: Selection of an appropriate reduction landmark and sequence could result in better quality of reduction, operative time, and decreased blood loss during treatment of BCAF.

PMID:36148520 | DOI:10.1111/os.13493

J Gerontol A Biol Sci Med Sci. 2022 Sep 23:glac201. doi: 10.1093/gerona/glac201. Online ahead of print.

ABSTRACT

Mitochondrial dysfunction is a factor potentially contributing to the aging process. However, evidence surrounding changes in mitochondrial function and aging is still limited, therefore this study aimed to investigate further the association between them. Possible confounding factors were included in the statistical analysis to explore the possibility of any independent associations. One thousand seven hundred and sixty-nine participants (619 middle-aged adults (age<65) and 1,150 older adults (age≥65)) from the Electricity Generating Authority of Thailand were enrolled onto the study. The clinical characteristics and medical history were collected. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood and used for analysis of mitochondrial function. Several parameters pertinent to mitochondrial respiration including non-mitochondrial respiration, basal respiration, maximal respiration, proton leak, and spare respiratory capacity were found to be two to three times lower in the mitochondria isolated from the cells of older adults. Interestingly, the mitochondrial ATP production was only slightly reduced, and the percentage of coupling efficiency of PBMC mitochondria was significantly higher in the older adult group. The mitochondrial mass and oxidative stress were significantly reduced in older adult participants, however, the ratio of oxidative stress to mass was significantly increased. The association of these parameters with age were still shown to be the same from the outcome of the multivariate analyses. The mitochondrial functions and mitochondrial mass in PBMCs were shown to decline in association with age. However, the upregulation of mitochondrial oxidative stress production and mitochondrial coupling efficiency might indicate a compensatory response in mitochondria during aging.

PMID:36148512 | DOI:10.1093/gerona/glac201

Arch Esp Urol. 2022 Aug;75(6):539-543. doi: 10.56434/j.arch.esp.urol.20227506.79.

ABSTRACT

OBJECTIVE: To compare the perioperative results of adult and elderly patients undergoing laparoscopic renal surgery.

METHODOLOGY: Retrospective, analytical study. 448 who underwent kidney surgery for benign or malignant pathologies between 2011-2019 were included in the General Hospital of Mexico “Dr. Eduardo Liceaga”. They were categorized into two groups: Group 1 <60 years and Group 2 >60 years. Descriptive statistics and bivariate analysis were performed, the calculations were performed with 95% reliability and a value of p (<0.05).

RESULTS: In the group over 60 years of age, the following was found: Age: 67.1 years (60-83). IMC 28.3 kg/m² (19-48.7). Intra and postsurgical outcomes: intraoperative bleeding = 184.4cc (5-1700). Surgical Time = 112.6min (30-240). Days of hospital stay = 2 (1-7). Complications in 2.6% (Clavien-Dindo: I = 2; II = 1), no conversion was required in any patient. There were no statistically significant differences with group 1, an exception for intraoperative bleeding.

CONCLUSIONS: Our study is a pioneer in Latin America in the evaluation of the geriatric population and outcomes with laparoscopic surgery and we recommend that renal procedures with a laparoscopic approach should be considered as the best strategy in the management of benign or malignant renal pathology in geriatric patients.

PMID:36138503 | DOI:10.56434/j.arch.esp.urol.20227506.79

J Transl Med. 2022 Sep 23;20(1):424. doi: 10.1186/s12967-022-03637-8.

ABSTRACT

BACKGROUND: Detecting trans-ethnic common associated genetic loci can offer important insights into shared genetic components underlying complex diseases/traits across diverse continental populations. However, effective statistical methods for such a goal are currently lacking.

METHODS: By leveraging summary statistics available from global-scale genome-wide association studies, we herein proposed a novel genetic overlap detection method called CONTO (COmposite Null hypothesis test for Trans-ethnic genetic Overlap) from the perspective of high-dimensional composite null hypothesis testing. Unlike previous studies which generally analyzed individual genetic variants, CONTO is a gene-centric method which focuses on a set of genetic variants located within a gene simultaneously and assesses their joint significance with the trait of interest. By borrowing the similar principle of joint significance test (JST), CONTO takes the maximum P value of multiple associations as the significance measurement.

RESULTS: Compared to JST which is often overly conservative, CONTO is improved in two aspects, including the construction of three-component mixture null distribution and the adjustment of trans-ethnic genetic correlation. Consequently, CONTO corrects the conservativeness of JST with well-calibrated P values and is much more powerful validated by extensive simulation studies. We applied CONTO to discover common associated genes for 31 complex diseases/traits between the East Asian and European populations, and identified many shared trait-associated genes that had otherwise been missed by JST. We further revealed that population-common genes were generally more evolutionarily conserved than population-specific or null ones.

CONCLUSION: Overall, CONTO represents a powerful method for detecting common associated genes across diverse ancestral groups; our results provide important implications on the transferability of GWAS discoveries in one population to others.

PMID:36138484 | DOI:10.1186/s12967-022-03637-8