Nevin Manimala

JAMA Neurol. 2021 Dec 1;78(12):1484-1493. doi: 10.1001/jamaneurol.2021.3723.

ABSTRACT

IMPORTANCE: Compared with normothermia, hypothermia has been shown to reduce death or disability in neonatal hypoxic ischemic encephalopathy but data on seizures during rewarming and associated outcomes are scarce.

OBJECTIVE: To determine whether electrographic seizures are more likely to occur during rewarming compared with the preceding period and whether they are associated with abnormal outcomes in asphyxiated neonates receiving hypothermia therapy.

DESIGN, SETTING, AND PARTICIPANTS: This prespecified nested cohort study of infants enrolled in the Optimizing Cooling (OC) multicenter Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network trial from December 2011 to December 2013 with 2 years’ follow-up randomized infants to either 72 hours of cooling (group A) or 120 hours (group B). The main trial included 364 infants. Of these, 194 were screened, 10 declined consent, and 120 met all predefined inclusion criteria. A total of 112 (90%) had complete data for death or disability. Data were analyzed from January 2018 to January 2020.

INTERVENTIONS: Serial amplitude electroencephalography recordings were compared in the 12 hours prior and 12 hours during rewarming for evidence of electrographic seizure activity by 2 central amplitude-integrated electroencephalography readers blinded to treatment arm and rewarming epoch. Odds ratios and 95% CIs were evaluated following adjustment for center, prior seizures, depth of cooling, and encephalopathy severity.

MAIN OUTCOMES AND MEASURES: The primary outcome was the occurrence of electrographic seizures during rewarming initiated at 72 or 120 hours compared with the preceding 12-hour epoch. Secondary outcomes included death or moderate or severe disability at age 18 to 22 months. The hypothesis was that seizures during rewarming were associated with higher odds of abnormal neurodevelopmental outcomes.

RESULTS: A total of 120 newborns (70 male [58%]) were enrolled (66 in group A and 54 in group B). The mean (SD) gestational age was 39 (1) weeks. There was excellent interrater agreement (κ, 0.99) in detection of seizures. More infants had electrographic seizures during the rewarming epoch compared with the preceding epoch (group A, 27% vs 14%; P = .001; group B, 21% vs 10%; P = .03). Adjusted odd ratios (95% CIs) for seizure frequency during rewarming were 2.7 (1.0-7.5) for group A and 3.2 (0.9-11.6) for group B. The composite death or moderate to severe disability outcome at 2 years was significantly higher in infants with electrographic seizures during rewarming (relative risk [95% CI], 1.7 [1.25-2.37]) after adjusting for baseline clinical encephalopathy and seizures as well as center.

CONCLUSIONS AND RELEVANCE: Findings that higher odds of electrographic seizures during rewarming are associated with death or disability at 2 years highlight the necessity of electroencephalography monitoring during rewarming in infants at risk.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01192776.

PMID:34882200 | DOI:10.1001/jamaneurol.2021.3723

Brief Bioinform. 2021 Dec 9:bbab497. doi: 10.1093/bib/bbab497. Online ahead of print.

ABSTRACT

Multiple statistical methods for aggregate association testing have been developed for whole-genome sequencing (WGS) data. Many aggregate variants in a given genomic window and ignore existing knowledge to define test regions, resulting in many identified regions not clearly linked to genes, and thus, limiting biological understanding. Functional information from new technologies (such as Hi-C and its derivatives), which can help link enhancers to their effector genes, can be leveraged to predefine variant sets for aggregate testing in WGS data. Here, we propose the eSCAN (scan the enhancers) method for genome-wide assessment of enhancer regions in sequencing studies, combining the advantages of dynamic window selection in SCANG (SCAN the Genome), a previously developed method, with the advantages of incorporating putative regulatory regions from annotation. eSCAN, by searching in putative enhancers, increases statistical power and aids mechanistic interpretation, as demonstrated by extensive simulation studies. We also apply eSCAN for blood cell traits using NHLBI Trans-Omics for Precision Medicine WGS data. Results from real data analysis show that eSCAN is able to capture more significant signals, and these signals are of shorter length (indicating higher resolution fine-mapping capability) and drive association of larger regions detected by other methods.

PMID:34882196 | DOI:10.1093/bib/bbab497

Angle Orthod. 2021 Dec 9. doi: 10.2319/022521-156.1. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the effect of fixed orthodontic treatment on periodontal parameters in periodontally compromised adult orthodontic patients.

MATERIALS AND METHODS: This was a prospective, randomized, controlled clinical trial. Thirty-six periodontally compromised adult patients (mean age: 29.67 ± 4.8 years) were randomly allocated to either test (perio-ortho) or control group (perio). After periodontal stabilization in both groups, orthodontic treatment was started in the test group, whereas the control group remained on periodontal maintenance only. Evaluation and comparison of clinical parameters (plaque index [PI]; gingival index [GI]; bleeding on probing [BOP]; probing depth [PD]; clinical attachment level [CAL]) of both groups was assessed at three time intervals: T0 (base line), T1 (at start of orthodontic treatment), and T2 (1 year after start of orthodontic treatment). Radiological parameters (alveolar bone levels [ABL]) were recorded using CBCT at T1 and T2.

RESULTS: Intragroup analysis showed statistically significant improvement in all clinical and radiological periodontal parameters in both groups (P ≤ .05). Intergroup comparison revealed improvement in the periodontal parameters was not statistically significant between the groups (P ≥ .05). Subgroup analysis showed reduction in the number of moderate and severe periodontitis sites in both groups with significant more gains in ABL in the test group compared to the control group.

CONCLUSIONS: Orthodontic treatment after periodontal stabilization does not have any detrimental effect on periodontal health in adult periodontally compromised orthodontic patients and may add to the benefits achieved by periodontal treatment alone.

PMID:34882193 | DOI:10.2319/022521-156.1

JAMA Netw Open. 2021 Dec 1;4(12):e2136809. doi: 10.1001/jamanetworkopen.2021.36809.

ABSTRACT

IMPORTANCE: Patients with large annular defects following lumbar microdiscectomy for disc herniation are at increased risk for symptomatic recurrence and reoperation.

OBJECTIVE: To determine whether a bone-anchored annular closure device in addition to lumbar microdiscectomy resulted in lower reherniation and reoperation rates vs lumbar microdiscectomy alone.

DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a multicenter randomized clinical trial reports 5-year follow-up for enrolled patients between December 2010 and October 2014 at 21 clinical sites. Patients in this study had a large annular defect (6-10 mm width) following lumbar microdiscectomy for treatment of lumbar disc herniation. Statistical analysis was performed from November to December 2020.

INTERVENTIONS: Lumbar microdiscectomy with additional bone-anchored annular closure device (device group) or lumbar microdiscectomy only (control group).

MAIN OUTCOMES AND MEASURES: The incidence of symptomatic reherniation, reoperation, and adverse events as well as changes in leg pain, Oswestry Disability Index, and health-related quality of life when comparing the device and control groups over 5 years of follow-up.

RESULTS: Among 554 randomized participants (mean [SD] age: 43 [11] years; 327 [59%] were men), 550 were included in the modified intent-to-treat efficacy population (device group: n = 272; 270 [99%] were White); control group: n = 278; 273 [98%] were White) and 550 were included in the as-treated safety population (device group: n = 267; control group: n = 283). The risk of symptomatic reherniation (18.8% [SE, 2.5%] vs 31.6% [SE, 2.9%]; P < .001) and reoperation (16.0% [SE, 2.3%] vs 22.6% [SE, 2.6%]; P = .03) was lower in the device group. There were 53 reoperations in 40 patients in the device group and 82 reoperations in 58 patients in the control group. Scores for leg pain severity, Oswestry Disability Index, and health-related quality of life significantly improved over 5 years of follow-up with no clinically relevant differences between groups. The frequency of serious adverse events was comparable between the treatment groups. Serious adverse events associated with the device or procedure were less frequent in the device group (12.0% vs 20.5%; difference, -8.5%; 95% CI, -14.6% to -2.3%; P = .008).

CONCLUSIONS AND RELEVANCE: In patients who are at high risk of recurrent herniation following lumbar microdiscectomy owing to a large defect in the annulus fibrosus, this study’s findings suggest that annular closure with a bone-anchored implant lowers the risk of symptomatic recurrence and reoperation over 5 years of follow-up.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01283438.

PMID:34882183 | DOI:10.1001/jamanetworkopen.2021.36809

JAMA Netw Open. 2021 Dec 1;4(12):e2138219. doi: 10.1001/jamanetworkopen.2021.38219.

ABSTRACT

IMPORTANCE: In March 2018, Medicare issued a national coverage determination (NCD) for next-generation sequencing (NGS) to facilitate access to NGS testing among Medicare beneficiaries. It is unknown whether the NCD affected health equity issues for Medicare beneficiaries and the overall population.

OBJECTIVE: To examine the association between the Medicare NCD and NGS use by insurance types and race and ethnicity.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort analysis was conducted using electronic health record data derived from a real-world database. Data originated from approximately 280 cancer clinics (approximately 800 sites of care) in the US. Patients with advanced non-small cell lung cancer (aNSCLC), metastatic colorectal cancer (mCRC), metastatic breast cancer (mBC), or advanced melanoma diagnosed from January 1, 2011, through March 31, 2020, were included.

EXPOSURE: Pre- vs post-NCD period.

MAIN OUTCOMES AND MEASURES: Patients were classified by insurance type and race and ethnicity to examine patterns in NGS testing less than or equal to 60 days after diagnosis. Difference-in-differences models examined changes in average NGS testing in the pre- and post-NCD periods by race and ethnicity, and interrupted time-series analysis examined whether trends over time varied by insurance type and race and ethnicity.

RESULTS: Among 92 687 patients with aNSCLC, mCRC, mBC, or advanced melanoma, mean (SD) age was 66.6 (11.2) years, 51 582 (55.7%) were women, and 63 864 (68.9%) were Medicare beneficiaries. The largest racial and ethnic categories according to the database used and further classification were Black or African American (8605 [9.3%]) and non-Hispanic White (59 806 [64.5%]). Compared with Medicare beneficiaries, changes in pre- to post-NCD NGS testing trends were similar in commercially insured patients (odds ratio [OR], 1.03; 95% CI, 0.98-1.08; P = .25). Pre- to post-NCD NGS testing trends increased at a slower rate among patients in assistance programs (OR, 0.93; 95% CI, 0.87-0.99; P = .03) compared with Medicare beneficiaries. The rate of increase for patients receiving Medicaid was not statistically significantly different compared with those receiving Medicare (OR, 0.92; 95% CI, 0.84-1.01; P = .07). The NCD was not associated with statistically significant changes in NGS use trends by racial and ethnic groups within Medicare beneficiaries alone or across all insurance types. Compared with non-Hispanic White individuals, increases in average NGS use from the pre-NCD to post-NCD period were 14% lower (OR, 0.86; 95% CI, 0.74-0.99; P = .04) among African American and 23% lower (OR, 0.77; 95% CI, 0.62-0.96; P = .02) among Hispanic/Latino individuals; increases among Asian individuals and those with other races and ethnicities were similar.

CONCLUSIONS AND RELEVANCE: The findings of this study suggest that expansion of Medicare-covered benefits may not occur equally across insurance types, thereby further widening or maintaining disparities in NGS testing. Additional efforts beyond coverage policies are needed to ensure equitable access to the benefits of precision medicine.

PMID:34882180 | DOI:10.1001/jamanetworkopen.2021.38219

JAMA Oncol. 2021 Dec 9. doi: 10.1001/jamaoncol.2021.5948. Online ahead of print.

ABSTRACT

IMPORTANCE: Nearly 96% of patients with high-grade glioma (HGG) report moderate-to-severe fatigue. Armodafinil is a psychostimulant that might help cancer-related fatigue in patients with HGG.

OBJECTIVE: To determine whether armodafinil reduces fatigue in patients with HGG and moderate-to-severe fatigue.

DESIGN, SETTING, AND PARTICIPANTS: In this randomized multicenter, phase 3, double-blinded, placebo-controlled clinical trial, adults with HGG and moderate-to-severe fatigue who were clinically stable at least 4 weeks after completing radiation therapy were randomized to receive armodafinil daily (150 mg or 250 mg) or placebo over 8 weeks. A score of at least 6 out of 10 on severity scale for the brief fatigue inventory scale, with 10 being the worst, was required to suggest moderate-to-severe fatigue. Patients were allowed stable doses of corticosteroids but were excluded if they required increasing amounts of corticosteroids, were receiving some other treatment for fatigue, or had an uncontrolled seizure disorder. The study was conducted from June 2013 to December 15, 2019.

INTERVENTIONS: Patients were randomized to 150 mg of armodafinil, 250 mg of armodafinil, or placebo for a total of 8 weeks with assessments at weeks 4 and 8.

MAIN OUTCOMES AND MEASURES: The primary outcome was efficacy in treating cancer-related fatigue. Secondary outcomes included safety, neurocognitive function, and quality of life. Patients were evaluated at baseline and at weeks 4 and 8. Efficacy between the placebo and the 2 doses of study drug was determined by an improvement by 2 points on the 0 to 10 brief fatigue inventory scale. Kruskal-Wallis and χ2 tests were used and followed by confirmatory analyses.

RESULTS: A total of 328 patients were enrolled, of whom 297 had evaluable end point data. Of these, 103 received 150 mg of armodafinil (mean [SD] age, 58.5 [11.9] years; 42 women [40.8%]), 97 250 mg of armodafinil (mean [SD] age, 56.6 [12.5] years; 37 women [38.1%]), and 97 placebo (mean [SD] age, 57.1 [12.5] years; 39 women [40.2%]). There was no difference in the proportion of patients who achieved clinically meaningful fatigue reduction between arms (28% [95% CI 20%-30%] for 150 mg of armodafinil, 28% [95% CI 19%-38%] for 250 mg of armodafinil, and 30% [95% CI 21%-40%] for placebo). There was a statistically significant reduction in global fatigue for corticosteroid users compared with nonusers (-0.7 [95% CI, -1.5 to -0.3] vs -1.7 [95% CI, -2.1 to -1.3]; P < .001). More patients (2 vs 7) reported insomnia with treatment with 250 mg of armodafinil.

CONCLUSIONS AND RELEVANCE: The results of this randomized clinical trial found no meaningful benefit of using treatment with armodafinil to reduce cancer-related fatigue in patients with HGG.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01781468.

PMID:34882169 | DOI:10.1001/jamaoncol.2021.5948

Ann Ig. 2021 Dec 9. doi: 10.7416/ai.2021.2484. Online ahead of print.

ABSTRACT

INTRODUCTION: The significance of herbal medicine (HM) during the COVID-19 pandemic has been confirmed. Nevertheless, limited studies have included the people perspectives on COVID-19 prevention/treatment using herbal medicine in Vietnam. Thus, this study tackled the aforementioned issue.

METHODS: Online-based cross-sectional study was conducted in Vietnamese adults between February- April 2021. Descriptive analysis, regression and Chi-squared tests were implemented for the statistical purposes.

RESULTS: A total of 787 respondents attended the study, 368 (46.8%) confirmed that they use herbal medicine/ nutritional supplements for COVID-19 prevention/treatment. Over 50% of the respondents possessed positive perspective on vitamin C ingestion. Using herbal medicine for external use as a disinfectant was mostly preferred. Respondents who had a ‘very good’ health self-perception or who lived in rural areas, were more likely to have a positive opinion in the COVID-19 prevention/treatment using herbal medicine. The main barrier for herbal medicine utilization was the deficiency of personal experience or expert advice.

CONCLUSION: The Vietnamese people commonly utilize herbal medicine for the COVID-19 prevention/ treatment. These data might help policy-makers in managing the public knowledge and practice on herbal medicine use in Vietnam.

PMID:34882168 | DOI:10.7416/ai.2021.2484

Med Pr. 2021 Dec 9:143538. doi: 10.13075/mp.5893.01189. Online ahead of print.

ABSTRACT

BACKGROUND: Following the declaration of the COVID-19 pandemic by the WHO, many people in the public sector have switched to remote work, including teachers. This could have contributed to the occurrence of back pain in this group. The aim of the study was to assess back pain in a group of teachers before and after the introduction of distance learning due to the COVID-19 pandemic.

MATERIAL AND METHODS: The study was based upon an online diagnostic survey and included 361 teachers and university lecturers from 16 provinces of Poland. In order to assess the intensity of pain, a Numerical Rating Scale (NRS) was used. Statistical analysis was performed using IBM SPSS Statistics 26 and Microsoft Excel 2021. The level of statistical significance was adopted on the level p < 0.05.

RESULTS: Among the surveyed teachers, the mean degree of declared cervical and lumbar spine pain increased significantly after the COVID-19 pandemic (p < 0.001). The mean value of the declared degree of cervical pain increased from 2.49±2.81 before the pandemic to 5.44±1.83 during the pandemic. Before the pandemic, the mean low back pain intensity was 2.81±2.73 on the NRS, while after the introduction of remote working, it was 5.53±2.20.

CONCLUSIONS: There is a relationship between the occurrence of back pain and the change in the nature of work in the group of teachers in connection with the declaration of the COVID-19 pandemic. There has been a statistically significant increase in teachers’ back pain intensity since the introduction of distance learning. Depending on the number of hours spent at the computer, the average degree of the declared back pain in the study group increased statistically significantly. There is a need to set the goals of physioprophylaxis and introduce education in the field of ergonomics of computer work in a group of teachers. Med Pr. 2021;72(6).

PMID:34882125 | DOI:10.13075/mp.5893.01189

Kardiologiia. 2021 Nov 30;61(11):33-41. doi: 10.18087/cardio.2021.11.n1854.

ABSTRACT

Aim Analysis of the cardioprotective effectivity of chronopharmacotherapy in patients with arterial hypertension (AH) after transient ischemic attack (TIA).Material and methods 174 patients with AH and TIA were evaluated. All patients were randomized to three groups based on the dosing schedule of chronopharmacotherapy: group 1 (n=59), patients receiving indapamide retard 1.5 mg and valsartan 160 mg, both in the morning; group 2 (n=58), indapamide retard 1.5 mg in the morning and valsartan 160 mg in the evening; group 3 (n=57), indapamide retard 1.5 mg in the morning and valsartan 80 mg in the morning and evening. Echocardiography (EchoCG) (ALOKA SSD 2500, Japan) was performed for all patients at baseline and at 12 months of the treatment. Statistical analysis of results was performed with the Statistica 12.0 (StatSoftInc, USA) software.Results Before the treatment, EchoCG parameters did not significantly differ between the patient groups. After 12 months of the treatment, positive changes in the end-systolic dimension (ESD), interventricular septal thickness (IVST), thickness of the left ventricular posterior wall (TLVPW), LV myocardial mass (LVMM), LVMM index (LVMMI), ejection fraction (EF), ratio of transmitral early peak flow velocity and late filling flow velocity (E/A), and isovolumetric velocity relaxation time (IVRT) were more pronounced in the group of sartan evening dosing (group 2) than in the group of sartan single morning dosing (group 1) (p&lt;0.05). In group 3, the changes in ESD, IVST, TLVPW, LVMM, LVMMI, EF, E/A ratio, deceleration time (DT) of LV, and IVRT were significantly greater than those in group 1, whereas the dynamics of ESD, IVST, TLVPW, LVMM, LVMMI, E/A ratio, and DT were better in group 3 than in group 2 (p&lt;0.05). In addition, a significantly greater number of patients with normalized LV geometry was registered in group 3 compared to groups 1 and 2 (p&lt;0.05). The number of patients with normal LV diastolic function after the treatment was also significantly greater in group 3 than in group 1 (p&lt;0.05) and comparable with group 2.Conclusion The morning dosing of indapamide retard and the b.i.d. dosing of valsartan provided more pronounced beneficial changes in major EcoCG indexes and improvement of LV geometry and diastolic function than the sartan single dosing only in the morning or evening in combination with the diuretic.

PMID:34882076 | DOI:10.18087/cardio.2021.11.n1854

J Matern Fetal Neonatal Med. 2021 Dec 9:1-7. doi: 10.1080/14767058.2021.2014810. Online ahead of print.

ABSTRACT

BACKGROUND: While research has examined the mental health of general population samples of postpartum women during the COVID-19 pandemic, the pandemic’s impact on women seeking treatment for postpartum depression (PPD) is not well known. This study compared levels of depression and anxiety, the quality of social relationships, and the temperament of infants of treatment-seeking mothers in Ontario, Canada prior to and during the pandemic.

METHODS: Mothers with Edinburgh Postnatal Depression Scale scores ≥10 and seeking treatment for PPD prior to COVID-19 (n = 100) were compared to those who sought treatment during the pandemic (n = 120). Mothers self-reported symptoms of depression, worry/anxiety, partner relationship quality, social support, as well as aspects of the mother-infant relationship and infant temperament.

RESULTS: There were no statistically significant differences in symptoms of depression, anxiety, or the quality of social relationships between women seeking treatment for PPD before or during the pandemic. However, mothers reported poorer relationships with their infants, and there was evidence of more negative emotionality in their infants during COVID-19.

CONCLUSIONS: The pandemic may not have worsened depression, anxiety, relationships with partners, or social support in mothers seeking treatment for PPD, but appears to have contributed to poorer mother-infant interactions and maternal reports of more negative emotionality in their infants. These findings highlight the importance of identifying women with possible PPD, supporting mother-infant interactions, and monitoring their infants during COVID-19 and beyond.

PMID:34882058 | DOI:10.1080/14767058.2021.2014810