Nevin Manimala

Pediatr Neurol. 2021 Jun 26;123:43-49. doi: 10.1016/j.pediatrneurol.2021.06.009. Online ahead of print.

ABSTRACT

BACKGROUND: The neurodevelopmental impairment in tuberous sclerosis complex (TSC) has a multifactorial origin. Various factors have been proposed as predictors of neurological outcome such as tuber load, seizure onset, and TSC2 mutation. Cerebellar lesions have been associated with worse neuroradiological phenotype, but their contribution is not well understood.

METHODS: A partly retrospective and partly prospective pediatric cohort study was conducted at three hospitals in Greece between 2015 and 2020. Patients aged ≤ 18 years with a confirmed TSC daignosis were included and underwent brain imaging, a semistructured interview (authorized Greek version of the tuberous sclerosis-associated neuropsychiatric disorders, or TAND, checklist), and intellectual ability assessment.

RESULTS: The study populations consisted of 45 patients with TSC (22 females, 23 males; mean age 9.53 years). Twenty patients (44.4%) had cerebellar lesions. Cerebellar involvement was the most powerful predictor of tuber load (P = 0.03). Cerebellar lesions were associated with giant cell astrocytomas (SEGAs) (P = 0.01) and severe neurological outcome (P = 0.01). Even though in the univariate analysis early seizure onset, tuber load, and cerebellar involvement were associated with intellectual impairment and neurological severity, none of them was an independent predictor of cognitive outcome and neurological severity.

CONCLUSIONS: Cerebellar lesions are common among individuals with TSC. Cerebellar involvement correlates with supratentorial derangement and the development of SEGAs, which is suggestive of a more severe clinical and neuroradiological phenotype. Cerebellar involvement and early seizure onset were not independent predictors of either neurological severity or intellectual disability or neurobehavioral outcome; their role in TSC clinical phenotype should be further investigated.

PMID:34399109 | DOI:10.1016/j.pediatrneurol.2021.06.009

Ann Intern Med. 2021 Aug 17. doi: 10.7326/M21-1814. Online ahead of print.

ABSTRACT

BACKGROUND: Acupuncture has promising effects on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but high-quality evidence is scarce.

OBJECTIVE: To assess the long-term efficacy of acupuncture for CP/CPPS.

DESIGN: Multicenter, randomized, sham-controlled trial. (ClinicalTrials.gov: NCT03213938).

SETTING: Ten tertiary hospitals in China.

PARTICIPANTS: Men with moderate to severe CP/CPPS, regardless of prior exposure to acupuncture.

INTERVENTION: Twenty sessions of acupuncture or sham acupuncture over 8 weeks, with 24-week follow-up after treatment.

MEASUREMENTS: The primary outcome was the proportion of responders, defined as participants who achieved a clinically important reduction of at least 6 points from baseline on the National Institutes of Health Chronic Prostatitis Symptom Index at weeks 8 and 32. Ascertainment of sustained efficacy required the between-group difference to be statistically significant at both time points.

RESULTS: A total of 440 men (220 in each group) were recruited. At week 8, the proportions of responders were 60.6% (95% CI, 53.7% to 67.1%) in the acupuncture group and 36.8% (CI, 30.4% to 43.7%) in the sham acupuncture group (adjusted difference, 21.6 percentage points [CI, 12.8 to 30.4 percentage points]; adjusted odds ratio, 2.6 [CI, 1.8 to 4.0]; P < 0.001). At week 32, the proportions were 61.5% (CI, 54.5% to 68.1%) in the acupuncture group and 38.3% (CI, 31.7% to 45.4%) in the sham acupuncture group (adjusted difference, 21.1 percentage points [CI, 12.2 to 30.1 percentage points]; adjusted odds ratio, 2.6 [CI, 1.7 to 3.9]; P < 0.001). Twenty (9.1%) and 14 (6.4%) adverse events were reported in the acupuncture and sham acupuncture groups, respectively. No serious adverse events were reported.

LIMITATION: Sham acupuncture might have had certain physiologic effects.

CONCLUSION: Compared with sham therapy, 20 sessions of acupuncture over 8 weeks resulted in greater improvement in symptoms of moderate to severe CP/CPPS, with durable effects 24 weeks after treatment.

PRIMARY FUNDING SOURCE: China Academy of Chinese Medical Sciences and the National Administration of Traditional Chinese Medicine.

PMID:34399062 | DOI:10.7326/M21-1814

Ann Intern Med. 2021 Aug 17. doi: 10.7326/M20-7003. Online ahead of print.

ABSTRACT

BACKGROUND: Despite expected initial universal susceptibility to a novel pandemic pathogen like SARS-CoV-2, the pandemic has been characterized by higher observed incidence in older persons and lower incidence in children and adolescents.

OBJECTIVE: To determine whether differential testing by age group explains observed variation in incidence.

DESIGN: Population-based cohort study.

SETTING: Ontario, Canada.

PARTICIPANTS: Persons diagnosed with SARS-CoV-2 and those tested for SARS-CoV-2.

MEASUREMENTS: Test volumes from the Ontario Laboratories Information System, number of laboratory-confirmed SARS-CoV-2 cases from the Integrated Public Health Information System, and population figures from Statistics Canada. Demographic and temporal patterns in incidence, testing rates, and test positivity were explored using negative binomial regression models and standardization. Sources of variation in standardized ratios were identified and test-adjusted standardized infection ratios (SIRs) were estimated by metaregression.

RESULTS: Observed disease incidence and testing rates were highest in the oldest age group and markedly lower in those younger than 20 years; no differences in incidence were seen by sex. After adjustment for testing frequency, SIRs were lowest in children and in adults aged 70 years or older and markedly higher in adolescents and in males aged 20 to 49 years compared with the overall population. Test-adjusted SIRs were highly correlated with standardized positivity ratios (Pearson correlation coefficient, 0.87 [95% CI, 0.68 to 0.95]; P < 0.001) and provided a case identification fraction similar to that estimated with serologic testing (26.7% vs. 17.2%).

LIMITATIONS: The novel methodology requires external validation. Case and testing data were not linkable at the individual level.

CONCLUSION: Adjustment for testing frequency provides a different picture of SARS-CoV-2 infection risk by age, suggesting that younger males are an underrecognized group at high risk for SARS-CoV-2 infection.

PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

PMID:34399059 | DOI:10.7326/M20-7003

J Drugs Dermatol. 2021 Aug 1;20(8):880-887. doi: 10.36849/JDD.6101.

ABSTRACT

BACKGROUND: Long-term efficacy, safety, and quality of life with ixekizumab (IXE) through 5 years in UNCOVER-1 and UNCOVER-2 patients with baseline scalp, nail, or palmoplantar psoriasis were assessed.

METHODS: Patients included in this intent-to-treat subanalysis had baseline involvement in at least one of the three anatomic areas (scalp, fingernail, or palmoplantar locations) and 1) received IXE through week 60, with a 160-mg starting dose 80 mg Q2W through week 12 and Q4W thereafter, 2) achieved a static Physician&rsquo;s Global Assessment score of 0 or 1 at week 12, and 3) completed week 60 and continued treatment with IXE Q4W or were escalated to Q2W during the long-term extension. Efficacy outcomes (e.g., percent improvement in Psoriasis Scalp Severity Index [PSSI], Nail Psoriasis Severity Index [NAPSI], Palmoplantar Psoriasis Area and Severity [PPASI], and Dermatology Life Quality Index [DLQI]) were summarized by descriptive statistics through week 264.

RESULTS: Patients rapidly achieved and sustained improvements in scalp, nail, and palmoplantar psoriasis for up to 5 years with IXE. Patients achieved complete clearance at year 5: observed (scalp, 82%; nail, 73%; palmoplantar, 96%) and mNRI (scalp, 77%; nail, 67%; palmoplantar, 85%). Up to 80% of patients reported DLQI 0,1 responses at week 12, which were sustained through week 264. No increases in the number of annual treatment-emergent adverse events were observed from years 1&ndash;5.

CONCLUSION: Patients receiving IXE for 5 years sustained high rates of improvement in scalp, nail, and palmoplantar psoriasis, with a long-term quality of life benefit with no unexpected safety signals. J Drugs Dermatol. 2021;20(8):880-887. doi:10.36849/JDD.6101.

PMID:34397207 | DOI:10.36849/JDD.6101

J Drugs Dermatol. 2021 Aug 1;20(8):865-867. doi: 10.36849/JDD.6037.

ABSTRACT

BACKGROUND: New development of cell-targeted therapies to enable site-specific skin tissue drug delivery may reduce off-target effects, decrease unwanted toxicities, and enhance drug efficacy. These efforts have led to several targeting strategies that modulate active product delivery to include small molecule-, nucleic acid-, peptide-, antibody-, and cell-based strategies. Tissue specific cell-targeting strategies such as these may be useful in cosmetic dermatologic applications.

OBJECTIVE: The aim of this 16-week clinical trial of a skin brightening composition containing melanocyte cell-targeted biodelivery was to assess its effectiveness in restoring the skin complexion evenness by modulating melanocyte activity in a cohort of 50 Fitzpatrick type I&ndash;VI subjects with moderate to severe dyspigmentation.

RESULTS: Data from expert grading, skin surface colorimetry, and subject self-assessments reflected significant improvement in facial skin tone as early as 2 weeks after treatment initiation, with continual improvement through week 16. The most dramatic pigmentation improvement, based on investigator assessments, was a statistically significant improvement in skin brightness at week 2 that progressed to week 8 with significant improvement in skin evenness and brightness. By weeks 12 and 16, progressive levels of significant improvement in skin evenness and brightening became apparent. Colorimetry demonstrated progressive improvement in skin dyspigmentation starting at 2 weeks and continuing to week 16. Subject self-assessment data supported similar improvements in skin dyspigmentation.

CONCLUSION: These results demonstrate the ability of a cell-targeted topical therapy to achieve improvements in skin pigmentation through site-specific suppression of melanocyte activity. J Drugs Dermatol. 2021;20(8):865-867. oi:10.36849/JDD.6037 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL fTEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

PMID:34397200 | DOI:10.36849/JDD.6037

Arthritis Care Res (Hoboken). 2021 Aug 16. doi: 10.1002/acr.24769. Online ahead of print.

ABSTRACT

OBJECTIVE: To quantify vehicle control as a metric of automobile driving performance in patients with rheumatoid arthritis (RA).

METHODS: Naturalistic driving assessments were completed in patients with active RA and controls without disease. Data were collected using in-car, sensor-based instrumentation installed in the participants’ own vehicles to observe typical driving habits. RA disease status, disease activity, and functional status were associated with vehicle control (lateral [steering] and longitudinal [braking/accelerating] acceleration variability [AV]) using mixed-effect linear regression models stratified by road type (defined by roadway speed limit).

RESULTS: Across 1,292 driving hours, RA drivers (n=33) demonstrated differences in vehicle control compared to controls (n=23) with evidence of significant statistical interaction between disease status and road type (p<0.001). On residential roads, participants with RA demonstrated overall lower braking/accelerating variability than controls (p≤0.004) and, when disease activity was low, lower steering variability (p=0.03). On interstates/highways, RA was associated with increased steering variability among those with moderate/high CDAI scores (p=0.04). In models limited to RA, increases in disease activity and physical disability over 12-weeks of observation were associated with a significant increase in braking/accelerating variability on interstate/highways (both p<0.05).

CONCLUSIONS: Using novel naturalistic assessments, we linked RA and worsening RA disease severity with aberrant vehicle control. These findings support the need for further research to map these observed patterns in vehicle control to metrics of driver risk, and, in turn, to link patterns of real-world driving behavior to diagnosis and disease activity.

PMID:34397172 | DOI:10.1002/acr.24769

Arthritis Care Res (Hoboken). 2021 Aug 16. doi: 10.1002/acr.24768. Online ahead of print.

ABSTRACT

OBJECTIVES: Changes of routine disease management associated with COVID-19 lockdown might have potentially affected the clinical course of juvenile idiopathic arthritis (JIA). Aim of our study was to assess the rate of disease flare before and during COVID-19 lockdown to investigate its impact on disease course in JIA children.

METHODS: A single-center retrospective study was conducted, including patients presenting inactive JIA between September 1^st , 2018 and March 9^th , 2019 (group A) and between September 1^st , 2019 and March 9^th , 2020 (group B). For each patient, demographic and clinical data were collected. The rate of JIA flare from March 10^th , 2019 to June 30^th , 2019 for group A and from March 10^th , 2020 to June 30^th , 2020 for group B was compared.

RESULTS: Group A included 126 patients and group B 124 patients. Statistical analysis did not show significant differences among the two cohorts with respect to age, sex, age of JIA onset, JIA subtype, co-occurrence of uveitis, ANA positivity and past or ongoing medications. The rate of disease flare during lockdown at time of first COVID-19 pandemic wave, was significantly higher in comparison to the previous year (16.9% vs 6.3%, p=0.009).

CONCLUSION: Our study showed that COVID-19 lockdown was associated with a higher rate of joint inflammation in JIA children. This finding has a considerable clinical implication, since restrictive measures may be necessary in order to contain pandemics. Our data highlight the need for rearrangement in the home and healthcare management of JIA children during lockdowns.

PMID:34397168 | DOI:10.1002/acr.24768

Can Rev Sociol. 2021 Aug;58(3):372-398. doi: 10.1111/cars.12348.

ABSTRACT

Young adults born at the end of the 20th century attend colleges and universities at much higher rates than did previous generations, which might give the impression of greater upward educational mobility and in turn, greater class mobility. This impression occurs, however, only because of structural expansion of the Canadian education system. In contrast to structural change, exchange mobility highlights the linkage between one’s social origins and destinations. This speaks more directly to questions of equality of educational opportunity and social fairness. Greater fairness or social progress occurs when, over time, destinations become less contingent on origins. We examine intergenerational exchange mobility in Canada by investigating how, if at all, the linkage between parents’ and their children’s education has changed over the past century. We construct a longitudinal dataset covering the 20th century by merging fifteen cross-sectional surveys from Statistics Canada’s General Social Survey (GSS) between 1986 and 2014. Comparing across synthetic birth cohorts we focus on transition probabilities, odds ratios, and logistic regression estimates to measure change. We contribute to a growing gap in the Canadian literature since social mobility has been largely neglected by sociologists as of late. We compare our results to recent findings of economists who examine intergenerational income mobility, another indicator of class mobility. Consistent with earlier sociological and economic research, our results show that despite the tremendous expansion of Canada’s education systems, intergenerational exchange mobility for both women and men has been stagnant in Canada over the past century.

PMID:34397157 | DOI:10.1111/cars.12348

J Neuroendocrinol. 2021 Jul 15:e13015. doi: 10.1111/jne.13015. Online ahead of print.

ABSTRACT

The quality and reporting of neuroendocrine tumour (NET) clinical trials has previously been found to be heterogeneous impairing trial interpretability. We aimed to perform an updated review of the quality of phase II/III clinical trials in NET to assess if trial design and reporting have improved since 2011. We performed a PubMed search for phase II/III trials evaluating systemic anticancer therapies or liver-directed therapies published between 2011 and 2018. Data collected comprised administrative data, study population characteristics, endpoints, reporting and statistical design parameters, and results. Sixty studies were included (5218 patients): 50 phase II and 10 phase III trials. Study populations were heterogeneous: 52% of trials allowed tumours from various primary sites, 28% allowed both well- and poorly-differentiated tumour morphology or did not specify, and 57% did not report proliferative indices and/or tumour grade in ≥80% of the study population. Only 36% of trials mandated radiological disease progression on participant enrolment using a validated measure. Statistical design and primary endpoint were clearly defined in 67% and 88% of trials, respectively. Toxicity (88%), radiological response rate (85%) and progression-free survival/time to progression (82%) were well reported in a majority of trials, but health-related quality of life was included in the minority. Of the randomised trials (n = 11), study populations were more homogeneous and study design was more often clearly defined; however, only 45% mandated radiological progression at baseline as measured per Response Evaluation Criteria In Solid Tumours, and reporting of health-related quality of life (55%) remained suboptimal. The design and reporting of NET clinical trials, predominantly of single-arm phase II trials, remains suboptimal and has not considerably improved over time despite the growth in our knowledge of the biology and unique characteristics of NETs. Higher quality is seen in randomised trials, although certain design and reporting elements remain inadequate in some studies. We must prioritise the design and conduct of NET clinical trials to effectively inform future research and guide practice change.

PMID:34397130 | DOI:10.1111/jne.13015

J Magn Reson Imaging. 2021 Aug 16. doi: 10.1002/jmri.27888. Online ahead of print.

ABSTRACT

BACKGROUND: Renal blood flow (RBF) can be measured with dynamic contrast enhanced-MRI (DCE-MRI) and arterial spin labeling (ASL). Unfortunately, individual estimates from both methods vary and reference-standard methods are not available. A potential solution is to include a third, arbitrating MRI method in the comparison.

PURPOSE: To compare RBF estimates between ASL, DCE, and phase contrast (PC)-MRI.

STUDY TYPE: Prospective.

POPULATION: Twenty-five patients with type-2 diabetes (36% female) and five healthy volunteers (HV, 80% female).

FIELD STRENGTH/SEQUENCES: A 3 T; gradient-echo 2D-DCE, pseudo-continuous ASL (pCASL) and cine 2D-PC.

ASSESSMENT: ASL, DCE, and PC were acquired once in all patients. ASL and PC were acquired four times in each HV. RBF was estimated and split-RBF was derived as (right kidney RBF)/total RBF. Repeatability error (RE) was calculated for each HV, RE = 1.96 × SD, where SD is the standard deviation of repeat scans.

STATISTICAL TESTS: Paired t-tests and one-way analysis of variance (ANOVA) were used for statistical analysis. The 95% confidence interval (CI) for difference between ASL/PC and DCE/PC was assessed using two-sample F-test for variances. Statistical significance level was P < 0.05. Influential outliers were assessed with Cook’s distance (D_i > 1) and results with outliers removed were presented.

RESULTS: In patients, the mean RBF (mL/min/1.73m² ) was 618 ± 62 (PC), 526 ± 91 (ASL), and 569 ± 110 (DCE). Differences between measurements were not significant (P = 0.28). Intrasubject agreement was poor for RBF with limits-of-agreement (mL/min/1.73m² ) [-687, 772] DCE-ASL, [-482, 580] PC-DCE, and [-277, 460] PC-ASL. The difference PC-ASL was significantly smaller than PC-DCE, but this was driven by a single-DCE outlier (P = 0.31, after removing outlier). The difference in split-RBF was comparatively small. In HVs, mean RE (±95% CI; mL/min/1.73 m² ) was significantly smaller for PC (79 ± 41) than for ASL (241 ± 85).

CONCLUSIONS: ASL, DCE, and PC RBF show poor agreement in individual subjects but agree well on average. Triangulation with PC suggests that the accuracy of ASL and DCE is comparable.

EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

PMID:34397124 | DOI:10.1002/jmri.27888