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Nevin Manimala Statistics

Investigation into the effect of mixtures comprising related people on non-donor likelihood ratios, and potential practises to mitigate providing misleading opinions

Forensic Sci Int Genet. 2022 Mar 21;59:102691. doi: 10.1016/j.fsigen.2022.102691. Online ahead of print.

ABSTRACT

The interpretation of mixtures containing related individuals can be difficult due to allele sharing between the contributors. Challenges include the assignment of the number of contributors (NoC) to the mixture with the under assignment of NoC resulting in false exclusions of true donors. Non-donating relatives of the true contributors to mixtures of close relatives can result in likelihood ratios supporting their adventitious inclusion within the mixture. We examine the effect of non-donor likelihood ratios on mixtures of first order relatives. Mixtures of full siblings and parent-child were created by mixing the DNA from known family members in vitro, or by in silico simulation. Mixtures were interpreted using the probabilistic genotyping software STRmix™ and likelihood ratios were assigned for the true donors and non-donors who were either further relatives of the true donors or unrelated to the true donors. The two donor balanced mixtures deconvoluted straightforwardly when analysed as NoC = 2 giving approximately the experimental design 1:1 ratio. When analysed as NoC = 3 a very large number of non-donor genotypes produced LRs close to 1 including many instances of adventitious support. The in vitro three donor balanced mixtures proved difficult to assign as NoC = 3 by a blind examination of the profile. It is likely that many of these would be misassigned as NoC = 2. The analysis of the in vitro and in silico mixtures assuming NoC = 3 with no use of a conditioning profile or with the use of a conditioning profile but without informed priors on the mixture proportions (Mx priors) was ineffective. If the profile can be assigned as NoC = 3 then assignment of the Mx priors is straightforward. This analysis gave no false exclusions. Adventitious support did happen for relatives with high allele sharing. Adventitious support was not observed for any unrelated non-donors. The analysis of the three-person mixtures as NoC = 2 produced many false exclusions and fewer instances of adventitious support. The three donor unbalanced mixtures could all be assigned as NoC= 3. Analysis without Mx priors produced an alternate genotype explanation.

PMID:35390645 | DOI:10.1016/j.fsigen.2022.102691

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Nevin Manimala Statistics

Rapid ultrasensitive detection of hexavalent chromium in soil and groundwater by a microProbing imaging platform

J Hazard Mater. 2022 Mar 29;433:128809. doi: 10.1016/j.jhazmat.2022.128809. Online ahead of print.

ABSTRACT

Rapid detection methods are needed to investigate the environmental quality risk of soil and groundwater in contaminated lands. Currently there is lack of rapid detection methods to sensitively and accurately analyze contaminations of hexavalent chromium in soil due to the challenge of complex sample pretreatment or expensive instrumentation. Here we report a rapid accurate detection platform for quantifying hexavalent chromium in soil and groundwater with ultrasensitivity. The platform consists of a novel sensor of microProbing beads and a portable microscope. Each microProbing bead was a nanoliter reactor to selectively sequestrate Cr (VI) with the enrichment factor up to 150 ×. The microProbing beads presented the signal uniformity of ~97% for the statistical colorimetric imaging analysis. Combined with a miniaturized microscope, the microProbing beads allowed for detecting aqueous Cr (VI) and soluble Cr (VI) in soil within 45 min. The platform achieved high sensitivity with the detection limits of 0.003 ppb for aqueous Cr (VI) and 0.07 ppm for soil Cr (VI). It accurately detected soil and groundwater samples from a chromium contaminated land in Yangtze River Basin of China. The consistency to the laboratory standard methods was achieved with the low cost of ~0.20 US dollar per test. The microProbing imaging platform with the operational simplicity and device portability is highly promising for the field analysis of Cr (VI) in contaminated lands.

PMID:35390613 | DOI:10.1016/j.jhazmat.2022.128809

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Nevin Manimala Statistics

Prescription trends of disease-modifying treatments for multiple sclerosis in Iran over the past 30 years

Mult Scler Relat Disord. 2022 Mar 27;61:103777. doi: 10.1016/j.msard.2022.103777. Online ahead of print.

ABSTRACT

BACKGROUND: Iran, as a middle income country, is one of the places with high and rising prevalence of multiple sclerosis (MS). Regarding the substantial economic burden, reviewing the trend in prescribed disease modifying treatments (DMTs) could be of help. Here we studied the DMT information of nearly 14000 MS cases and its trends change for 30 years to improve health services to patients.

METHODS: The population base of this descriptive-analytical (cross-sectional) study consisted of all MS patients in the nationwide MS registry of Iran (NMSRI), up to August 1, 2021. Registrars from 15 provinces, 24 cities, 13 hospitals,8 MS associations, 16 private offices, and 7 clinics had entered the data.

RESULTS: Overall, 14316 cases were enrolled. The majority (76.1%) were female. The youngest and eldest patients were 5 and 78 years old, respectively. Diagnosis delay was under one year in most cases (median: 0, IQR: 0 – 1). Most (61.4%) had RRMS. Generally, platform injectables (IFN beta, glatiramer acetate) were the most used DMTs until 2010. It seems that introduction of newer agents (antiCD20s and oral DMTs) resulted in a decrease in the use of former drugs since around 2015. Some unusual practices are prominent such as using not approved DMTs for PPMS over the years, or administering high efficacy drugs like natalizumab for CIS. The results indicate the remaining popularity of first line injectable DMTs in female and pediatric patients.

DISCUSSION: Mean age (SD) at onset in our study (29 ± 8.8) is near the statistics in Asia and Oceania (28 ± 0.7). Concerns about COVID-19 had a noticeable impact on administering high efficacy drugs like rituximab and fingolimod. However, in male patients this approach has not been the case. It may be related to more aggressive disease course in this group. The other possible explanation could be planning for pregnancy in female cases. The popularity of platform injectable drugs in pediatric MS may be related to its favorable safety profile over the years. Another point in this group, is the superiority of rituximab over other highly efficient medications.

PMID:35390594 | DOI:10.1016/j.msard.2022.103777

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Nevin Manimala Statistics

Incidence patterns of childhood non-Wilms renal tumors: Comparing data of the Nationwide Registry of Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST), Greece, and the Surveillance, Epidemiology, and End Results Program (SEER), USA

Cancer Epidemiol. 2022 Apr 4;78:102153. doi: 10.1016/j.canep.2022.102153. Online ahead of print.

ABSTRACT

BACKGROUND: We used, for the first time, data registered in the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST)-Greece to estimate incidence/time trends of the rare childhood (0-14 years) non-Wilms tumors (non-WT), and compared the results of malignant non-WT to those from the Surveillance, Epidemiology, and End Results Program (SEER)-USA.

METHODS: Fifty-five cases (n = 33 malignant-only) were extracted from NARECHEM-ST (2001-2020) and 332 malignant cases from SEER (1990-2017). To allow between-country comparisons, age-standardized incidence rates (AIR) of malignant-only non-WT were calculated, and temporal trends were evaluated using Poisson and joinpoint regressions.

RESULTS: In NARECHEM-ST, malignant and non-malignant non-WT accounted for 22.6% of all renal tumors. Among malignant tumors, the AIR was 1.0/106 children in Greece, similar to that calculated for SEER, USA (AIR=0.9/106). The proportion of infant malignant and non-malignant non-WT was 27% (20% before 6 months) in NARECHEM-ST. Most common non-WT in Greece were congenital mesoblastic nephromas (CMN) diagnosed mainly in infancy (CIR=7.2/106). The proportion of infant malignant non-WT was 20% in SEER (AIRinfancy=2.5/106), mainly attributed to rhabdoid tumors (CIR=1.6/106). The male-to-female (M:F) ratio of malignant non-WT was 0.9 in NARECHEM-ST vs. 1.2 in SEER, whereas boys outnumbered girls with clear cell sarcoma in NARECHEM-ST (M:F=4.0). Lastly, significantly increasing trends in incidence rates were noted in NARECHEM-ST [+ 6.8%, 95% confidence intervals (CI): 0.5, 13.3] and in SEER (+7.3%, 95%CI: 5.6, 9.0).

CONCLUSIONS: Observed incidence, time trends and sociodemographic variations of non-WT may reflect differential registration practices and healthcare delivery patterns including differences regarding surveillance, coding and treatment practices.

PMID:35390585 | DOI:10.1016/j.canep.2022.102153

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Nevin Manimala Statistics

Surgical Rib Fixation of Multiple Rib Fractures and Flail Chest: A Systematic Review and Meta-Analysis

J Surg Res. 2022 Apr 4;276:221-234. doi: 10.1016/j.jss.2022.02.055. Online ahead of print.

ABSTRACT

BACKGROUND: Multiple rib fractures and flail chest are common in trauma patients and may result in significant morbidity and mortality. While rib fractures have historically been treated conservatively, there is increasing interest in the benefits of surgical fixation. However, strong evidence that supports surgical rib fixation and identifies the most appropriate patients for its application is currently sparse.

METHODS: A systematic review and meta-analysis following PRISMA guidelines was performed to identify all peer-reviewed papers that examined surgical compared to conservative management of rib fractures. We undertook a subgroup analysis to determine the specific effects of rib fracture type, age, the timing of fixation and study design on outcomes. The primary outcomes were the length of hospital and ICU stay, and secondary outcomes included mechanical ventilation time, rates of pneumonia, and mortality.

RESULTS: Our search identified 45 papers in the systematic review, and 40 were included in the meta-analysis. There was a statistical benefit of surgical fixation compared to conservative management of rib fractures for length of ICU stay, mechanical ventilation, mortality, pneumonia, and tracheostomy. The subgroup analysis identified surgical fixation was most favorable for patients with flail chest and those who underwent surgical fixation within 72 h. Patients over 60 y had a statistical benefit of conservative management on length of hospital stay and mechanical ventilation.

CONCLUSIONS: Surgical fixation of flail and multiple rib fractures is associated with a reduction in morbidity and mortality outcomes compared to conservative management. However, careful selection of patients is required for the appropriate application of surgical rib fixation.

PMID:35390577 | DOI:10.1016/j.jss.2022.02.055

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Nevin Manimala Statistics

Pre-diagnosis lifestyle, health history and psychosocial factors associated with stage at breast cancer diagnosis – Potential targets to shift stage earlier

Cancer Epidemiol. 2022 Apr 4;78:102152. doi: 10.1016/j.canep.2022.102152. Online ahead of print.

ABSTRACT

BACKGROUND: Early detection of breast cancer improves survival, so identifying factors associated with stage at diagnosis may help formulate cancer prevention messages tailored for higher risk women. The goal of this study was to evaluate associations between multiple potential risk factors, including novel ones, measured before a breast cancer diagnosis and stage at diagnosis in women from Alberta, Canada.

METHODS: Women enrolled in Alberta’s Tomorrow Project completed health and lifestyle questionnaires on average 7 years before their breast cancer diagnosis. The association of previously identified and novel predictors with stage (I, II and III + IV) at diagnosis were simultaneously evaluated in partial proportional odds ordinal (PPO) regression models.

RESULTS: The 492 women in this study were predominantly diagnosed in Stage 1 (51.4%), had college or university education (75.4%), were married or had a partner (74.6%), had been pregnant (90.2%), had taken birth control pills for any reason (86.8%), and had an average body mass index of 26.6. Most had at least one mammogram (83%) with five mammograms the average number. Nearly all reported previously having a breast health examination from a medical practitioner (92.5%). Statistically significant factors identified in the PPO model included protective ones (older age at diagnosis, high household income, parity, smoking, spending time in the sun during high ultraviolet times, having a mammogram and high daily protein intake) and ones that increased risk of later stage at diagnosis (a comorbidity, current stressful situations and high daily caloric intake).

CONCLUSION: Shifting breast cancer stage at diagnosis downwards may potentially be achieved through cancer prevention programs that target higher risk groups such as women with co-morbidities, non-smokers and younger women who may be eligible for breast cancer screening.

PMID:35390584 | DOI:10.1016/j.canep.2022.102152

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Nevin Manimala Statistics

Characterization of sedation and anesthesia complications in patients with alternating hemiplegia of childhood

Eur J Paediatr Neurol. 2022 Mar 29;38:47-52. doi: 10.1016/j.ejpn.2022.03.007. Online ahead of print.

ABSTRACT

BACKGROUND: Alternating hemiplegia of childhood (AHC) pathophysiology suggests predisposition to sedation and anesthesia complications.

GOALS: Hypotheses: 1) AHC patients experience high rates of sedation-anesthesia complications. 2) ATP1A3 mutation genotype positivity, age, and AHC severity correlate with more severe complications. 3) Prior short QTc correlates with cardiac rhythm complications.

METHODS: Analysis of 34 consecutive AHC patients who underwent sedation or anesthesia. Classification of complications: mild (not requiring intervention), moderate (intervention), severe (intervention, risk for permanent injury or potential life-threatening emergency).

STATISTICS: Fisher Exact test, Spearman correlations.

RESULTS: These patients underwent 129 procedures (3.79 ± 2.75 procedures/patient). Twelve (35%) experienced complications during at least one procedure. Fourteen/129 procedures (11%) manifested one or more complications (2.3% mild, 7% moderate, 1.6% severe). Of the total 20 observed complications, six (33.3%) were severe: apneas (2), seizures (2), bradycardia (1), ventricular fibrillation that responded to resuscitation (1). Moderate complications: non-life-threatening bradycardias, apneas, AHC spells or seizures. Complications occurred during sedation or anesthesia and during procedures or recovery periods. Patients with disease-associated ATP1A3 variants were more likely to have moderate or severe complications. There was no correlation between complications and age or AHC severity. Presence of prior short QTc correlated with cardiac rhythm complications. After this series was analyzed, another patient had severe recurrent laryngeal dystonia requiring tracheostomy following anesthesia with intubation.

CONCLUSIONS: During sedation or anesthesia, AHC patients, particularly those with ATP1A3 variants and prior short QTc, are at risk for complications consistent with AHC pathophysiology. Increased awareness is warranted during planning, performance, and recovery from such procedures.

PMID:35390560 | DOI:10.1016/j.ejpn.2022.03.007

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Nevin Manimala Statistics

Determining reference data for overnight oximetry in neonates: A pilot study

Early Hum Dev. 2022 Apr 1;168:105571. doi: 10.1016/j.earlhumdev.2022.105571. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the variability of overnight oximetry parameters in a group of normal, healthy term infants; to enable the calculation of the number of subjects required to produce reliable reference ranges for neonatal overnight oximetry.

METHODS: A convenience sample of normal, healthy term neonates was recruited. Each had overnight oximetry using the Masimo SET Radical oximeter (data downloaded using Profox software). The report included the number of oxygen desaturation events (an absolute decrease in SpO2 of 4 or more), and the duration of oxygen saturations <90%.

RESULTS: 21 babies were recruited with data available from 19. 32% were female; 68% born by vaginal delivery; 37% fully breast feeding, 53% bottle and 11% by a combination of both. The mean (SD) GA was 39.2 (0.79) weeks, the mean (SD) BW was 3477 (240) grams. The median (IQR) post-natal age at the time the oximetry recording started was 31 (28-41) hours; four babies were <24 h old. All babies had some desaturation events ranging from 4 to 36 times per hour. On average babies spent 3.0% (SD 2.3) of the time with an SpO2 < 90% (range 0.12-7.94).

CONCLUSIONS: In a cohort of healthy term neonates, as assessed by overnight oximetry, the mean SpO2 was 97% (SD 1, range 95-99). All neonates had a number of oxygen desaturation events ranging from 4 to 36 per hour. The mean proportion of time spent with oxygen saturations below 90% was around 3%.

PMID:35390559 | DOI:10.1016/j.earlhumdev.2022.105571

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Nevin Manimala Statistics

Surgical management of giant calcified thoracic disc herniation and the role of neuromonitoring. The outcome of large mono centric series

J Clin Neurosci. 2022 Apr 4;100:37-45. doi: 10.1016/j.jocn.2022.03.046. Online ahead of print.

ABSTRACT

PURPOSE: Giant thoracic disc herniations (GTDH) are considered a subgroup of TDHs with worse functional outcomes, a high calcification rate, and a considerable risk of complications. We aimed to determine whether there is a relationship between the extent of calcification of GTDH and outcomes concerning the risk of complications, the surgical technique, and changes in neuromonitoring signals.

METHODS: We present a retrospective analysis of 76 patients undergoing surgery for calcific GTDH. We introduced and defined a radiological definition of the calcified disc into”fully calcified” and “partially calcified.” We performed a statistical analysis between clinical and radiological variables, type of surgical procedure, the extent of excision, neuro-monitoring signals, and outcome, comparing a group of 58 “fully-calcified TDH” patients and 18 “partially-calcified TDH” patients.

RESULTS: Fully calcified TDHs, compared with partially calcified TDHs, do not have significant differences in outcome (worse outcome 4/58-6.9% versus 0/18, p = 0.25) and complications (10/58-17.24% versus 4/18-22.2%, p = 0.63); Fully calcified TDH is associated with a higher risk of alterations in neurophysiological potentials (14/58-24.1% versus 0/18, p = 0.02) and subtotal excision (18/58-31% versus 2/18-11%, p = 0.15), without significant differences between the approaches used.

CONCLUSION: Fully calcified TDH group has a similar outcome and complication rate as the partially calcified TDH group, but they are associated with higher intraoperative neuromonitoring signal changes. We introduced a new classificationsystem that guides the approach and helps tocounsel the patients.

PMID:35390556 | DOI:10.1016/j.jocn.2022.03.046

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Nevin Manimala Statistics

Small bowel capsule endoscopy in obscure gastrointestinal bleeding: A matched cohort comparison of patients with normal vs surgically altered gastric anatomy

Clin Res Hepatol Gastroenterol. 2022 Apr 4:101921. doi: 10.1016/j.clinre.2022.101921. Online ahead of print.

ABSTRACT

BACKGROUND: Little is known about small bowel capsule endoscopy (SBCE) outcomes in patients with surgically altered anatomy.

AIMS: To assess the feasibility and diagnostic yield of orally ingested SBCE to investigate obscure gastrointestinal bleeding (OGIB) in patients with surgically altered gastric anatomy, compared to native gastric anatomy.

METHODS: 207 patients with OGIB were selected from an open, multicenter, retrospective cohort (SAGA study) and match-paired according to age, gender and bleeding type (overt/occult) to 207 control patients from a randomized controlled trial (PREPINTEST). Primary outcomes were the diagnostic yield (P1 or P2 findings), completion rate (CR), adverse events rate AER, and small bowel transit time (SBTT).

RESULTS: The diagnostic yield was not statistically different between groups (44.9% in SAGA vs 42.5% in control patients). Inflammatory/ulcerated lesions were significantly more frequent in patients with SAGA (43.0% vs 29.3%). The median SBTT was significantly longer in the SAGA group than in control patients (283 vs 206 minutes), with a significantly lower CR (82.6% vs 89.9%); Adverse events were scarce (0.5% vs 0.0%).

CONCLUSION: Patients with surgically altered gastric anatomy should benefit from SBCE investigation for OGIB as much as non-operated patients.

PMID:35390539 | DOI:10.1016/j.clinre.2022.101921