Category: Statistics

Sci Rep. 2021 Apr 30;11(1):9361. doi: 10.1038/s41598-021-88679-6.

ABSTRACT

Deterioration is sometimes unexpected in SARS-CoV2 infection. The aim of our study is to establish laboratory predictors of mortality in COVID-19 disease which can help to identify high risk patients. All patients admitted to hospital due to Covid-19 disease were included. Laboratory biomarkers that contributed with significant predictive value for predicting mortality to the clinical model were included. Cut-off points were established, and finally a risk score was built. 893 patients were included. Median age was 68.2 ± 15.2 years. 87(9.7%) were admitted to Intensive Care Unit (ICU) and 72(8.1%) needed mechanical ventilation support. 171(19.1%) patients died. A Covid-19 Lab score ranging from 0 to 30 points was calculated on the basis of a multivariate logistic regression model in order to predict mortality with a weighted score that included haemoglobin, erythrocytes, leukocytes, neutrophils, lymphocytes, creatinine, C-reactive protein, interleukin-6, procalcitonin, lactate dehydrogenase (LDH), and D-dimer. Three groups were established. Low mortality risk group under 12 points, 12 to 18 were included as moderate risk, and high risk group were those with 19 or more points. Low risk group as reference, moderate and high patients showed mortality OR 4.75(CI95% 2.60-8.68) and 23.86(CI 95% 13.61-41.84), respectively. C-statistic was 0-85(0.82-0.88) and Hosmer-Lemeshow p-value 0.63. Covid-19 Lab score can very easily predict mortality in patients at any moment during admission secondary to SARS-CoV2 infection. It is a simple and dynamic score, and it can be very easily replicated. It could help physicians to identify high risk patients to foresee clinical deterioration.

PMID:33931677 | DOI:10.1038/s41598-021-88679-6

Proc Natl Acad Sci U S A. 2021 May 4;118(18):e2019909118. doi: 10.1073/pnas.2019909118.

ABSTRACT

The similarity in mechanical properties of dense active matter and sheared amorphous solids has been noted in recent years without a rigorous examination of the underlying mechanism. We develop a mean-field model that predicts that their critical behavior-as measured by their avalanche statistics-should be equivalent in infinite dimensions up to a rescaling factor that depends on the correlation length of the applied field. We test these predictions in two dimensions using a numerical protocol, termed “athermal quasistatic random displacement,” and find that these mean-field predictions are surprisingly accurate in low dimensions. We identify a general class of perturbations that smoothly interpolates between the uncorrelated localized forces that occur in the high-persistence limit of dense active matter and system-spanning correlated displacements that occur under applied shear. These results suggest a universal framework for predicting flow, deformation, and failure in active and sheared disordered materials.

PMID:33931504 | DOI:10.1073/pnas.2019909118

Neurology. 2021 Apr 30:10.1212/WNL.0000000000012112. doi: 10.1212/WNL.0000000000012112. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the safety and efficacy of intra-arterial thrombolysis (IAT) as an adjunct to endovascular thrombectomy (EVT) in ischemic stroke, we performed a systematic review and meta-analysis of the literature.

METHODS: Searches were performed using Medline, Embase, and Cochrane databases for studies that compared EVT to EVT with adjunctive IAT (EVT+IAT). Safety outcomes included symptomatic intracerebral hemorrhage (sICH) and mortality at three months. Efficacy outcomes included successful reperfusion (Thrombolysis in Cerebral Infarction score of 2b to 3), and functional independence, defined as a modified Rankin Scale score of 0 to 2 at three months.

RESULTS: Five studies were identified that compared combined EVT+IAT (IA alteplase or urokinase) to EVT-only, and were included in the random effects meta-analysis. There were 1693 EVT patients, including 269 patients treated with combined EVT+IAT and 1424 patients receiving EVT-only. Pooled analysis did not demonstrate any differences between EVT+IAT and EVT-only in rates of sICH (OR: 0.61, 95% CI: 0.20-1.85; P=0.78), mortality (OR: 0.77, 95% CI: 0.54-1.10; P=0.15), or successful reperfusion (OR: 1.05, 95% CI: 0.52-2.15; P=0.89). There was a higher rate of functional independence in patients treated with EVT+IAT, although this was not statistically significant (OR: 1.34, 95% CI: 1.00-1.80; P=0.053).

CONCLUSIONS: Adjunctive IAT appears to be safe. In specific situations, neurointerventionists may be justified in administering small doses of intraarterial alteplase or urokinase as rescue therapy during EVT.

PMID:33931539 | DOI:10.1212/WNL.0000000000012112

J Neurosci. 2021 Apr 30:JN-RM-3074-19. doi: 10.1523/JNEUROSCI.3074-19.2021. Online ahead of print.

ABSTRACT

We developed a method for single-cell resolution longitudinal bioluminescence imaging of PERIOD (PER) protein and TIMELESS (TIM) oscillations in cultured male adult Drosophila brains that captures circadian circuit-wide cycling under simulated day/night cycles. Light input analysis confirms that CRYPTOCHROME (CRY) is the primary circadian photoreceptor and mediates clock disruption by constant light, and that eye light input is redundant to CRY. 3hr light phase delays (Friday) followed by 3hr light phase advances (Monday morning) simulate the common practice of staying up later at night on weekends, sleeping in later on weekend days then returning to standard schedule Monday morning (weekend light shift, WLS). PER and TIM oscillations are highly synchronous across all major circadian neuronal subgroups in unshifted light schedules for 11 days. In contrast, WLS significantly dampens PER oscillator synchrony and rhythmicity in most circadian neurons during and after exposure. Lateral ventral neuron (LNv) oscillations are the first to desynchronize in WLS and the last to resynchronize in WLS. Surprisingly, the dorsal neuron group-3 (DN3s), increase their within-group synchrony in response to WLS. In vivo, WLS induces transient defects in sleep stability, learning, and memory that temporally coincide with circuit desynchrony. Our findings suggest that WLS schedules disrupt circuit-wide circadian neuronal oscillator synchrony for much of the week, thus leading to observed behavioral defects in sleep, learning, and memory.SIGNIFICANCE STATEMENTThe circadian clock controls numerous aspects of daily animal physiology, metabolism and behavior. Much of our understanding of circadian circuit-level oscillations stem from ex vivo imaging of mammalian suprachiasmatic nucleus (SCN) brain slices. Humans regularly subject themselves to weekday/weekend light shifts but the effects of phase-shifting light signals cannot be measured in SCN. We measured circuit-level circadian responses to a weekday/weekend light shift (WLS) protocol in light-sensitive ex vivo Drosophila whole-brain preparation that shows temporal coincidence to circadian behavioral events. Robust sub-circuit-specific oscillator desynchrony/resynchrony responses to light coincide with functional defects in learning and memory, and sleep pattern disruption in vivo Our results reflect that WLS causes circadian-circuit desynchronization and correlates with disrupted cognitive and sleep performance.

PMID:33931552 | DOI:10.1523/JNEUROSCI.3074-19.2021

BMJ Open Respir Res. 2021 Apr;8(1):e000773. doi: 10.1136/bmjresp-2020-000773.

ABSTRACT

BACKGROUND: Although asthma has emerged as an important public health problem over recent decades in Latin America, there are limited published data on national hospital admission and mortality rates for asthma from countries in the region.

OBJECTIVE: To analyse trends in asthma hospitalisation and mortality rates in Ecuador over a 19-year period from 2000 to 2018.

METHODS: Hospital discharge and death certificates listing asthma, as defined in the International Classification of Diseases 10th Revision codes (J45 and J46), were used to analyse time trends in rates of hospital admissions and mortality for asthma. The data were obtained from the Ecuadorian National Institute of Statistics and Census. Crude and age-standardised rates were estimated for the entire population. Additionally, specific rates by sex, age and region were estimated. We used joinpoint analysis to identify national trends.

RESULT: During 2000-2018, a total of 58 250 hospitalisations and 1328 deaths due to asthma were identified. The average annual rates for hospitalisation and mortality attributed to asthma were estimated to be 21 (95% CI 19.3 to 22.8) and 5.2 (95% CI 4.4 to 6.0) per 100 000 population, respectively, over this period. Asthma hospital admissions decreased from 28 to 13.7 per 100 000 population between 2000 and 2018, and asthma mortality decreased from 0.8 to 0.3 per 100 000 population over the same period. Based on jointpoint analysis, two temporal trends were identified for hospital admissions. Between 2000 and 2011, hospital admissions decreased 0.8% per year and between 2011 and 2018 decreased 6.6% per year (p<0.05). On average, hospitalisation rates decreased 3.1% per year (p<0.05) over the entire study period. Mortality rate decreased 5.6% per year (p<0.05) over the 19-year period. Hospitalisation rates were higher among females, those aged 5 to 19 years and those living in the Coast region.

CONCLUSIONS: Our analysis shows a temporal trend of reduction in rates of hospitalisations and deaths attributed to asthma between 2000 and 2018 in Ecuador, consistent with similar trends elsewhere in the Latin American region. Health registration systems in Latin America need to be improved to provide reliable data for future between and within country comparisons of trends in asthma hospitalisations and deaths.

PMID:33931385 | DOI:10.1136/bmjresp-2020-000773

Br J Ophthalmol. 2021 Apr 30:bjophthalmol-2020-318769. doi: 10.1136/bjophthalmol-2020-318769. Online ahead of print.

ABSTRACT

AIMS: The optimal immunosuppressive therapy (IST) in patients with myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) remains uncertain. This study aimed to observe the disease course of MOG-ON and evaluate the therapeutic efficacy and tolerability of conventional immunosuppressants through Chinese cohort analysis.

METHODS: This bidirectional cohort study included 121 patients with MOG-ON between January 2015 and December 2018. The clinical features and annualised relapse rate (ARR) of patients with and without IST were analysed.

RESULTS: The median age at onset was 17.5 years, and the sex ratio (F:M) was 1.24. Of 121 patients, 77 patients relapsed and 61 patients were younger than 18 years at disease onset. The overall median ARR of 63 patients in the non-IST group was 0.5, with 46.0% patients showing relapse at a median follow-up of 33.5 months. In the IST group, the ARR decreased from 1.75 pre-IST to 0.00 post-IST in 53 patients who received IST exceeding 6 months, with 20.8% patients showing relapse at a median follow-up of 23.8 months. The relapse rates of patients treated with rituximab (RTX) and mycophenolate mofetil (MMF) were not statistically different, but the rate of discontinuation was significantly lower in the RTX-treated group (18.2% vs 57.7%, p=0.0017).

CONCLUSION: This study provides Class III evidence that both MMF and RTX may lower disease activity in patients with MOG-ON, and RTX showed better tolerability than MMF. However, observation after a single attack remains a good option because less than half of patients not on treatment suffered a relapse.

PMID:33931394 | DOI:10.1136/bjophthalmol-2020-318769

Eur Urol Focus. 2021 Apr 27:S2405-4569(21)00115-2. doi: 10.1016/j.euf.2021.04.009. Online ahead of print.

ABSTRACT

BACKGROUND: Superselective clamping of tumor-targeted arteries aims to eliminate ischemia of the remnant kidney while keeping tumor bed bloodless during excision.

OBJECTIVE: To evaluate the impact of superselective clamping on long-term renal function, compared with renal artery early unclamping.

DESIGN, SETTING, AND PARTICIPANTS: A randomized monocentric single-blind trial (1:1) was conducted from February 2018 to August 2019. Patients with a single renal tumor were candidates for a robot-assisted partial nephrectomy (RAPN) in a referral center. EMERALD (NCT03679572) was powered to include 50 patients with an interim analysis after 30 cases.

INTERVENTION: Superselective RAPN (SS-RAPN) with near-infrared fluorescence (NIRF) or conventional RAPN with renal artery early unclamping.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the percent change of estimated glomerular filtration rate (eGFR) in the operated kidney after 6 mo (combination of eGFR and relative function on ^99mTc-DMSA scintigraphy). Secondary endpoints assessed feasibility and safety of the technique.

RESULTS AND LIMITATIONS: Relative eGFR reduction in the operated kidney at 6 mo did not differ significantly (-21.4% vs -23.4%, p=0.66). This absence of difference remained after adjusting on percentage of kidney volume preserved, which was an independent predictor of functional preservation. There were no significant differences in terms of blood loss, change in hemoglobin, postoperative complications, transfusion, and conversion to radical nephrectomy (two vs zero) or to open surgery (one vs zero). Despite a good accrual, the steering committee interrupted the trial after the interim analysis for futility given the absence of trend in favor of SS-RAPN.

CONCLUSIONS: SS-RAPN using NIRF does not provide better renal function preservation than renal artery clamping, questioning the interest of this technique at a higher risk of bleeding.

PATIENT SUMMARY: In this randomized controlled trial, superselective clamping of tumor feeding arteries did not show any advantage in terms of long-term renal function compared with conventional artery clamping.

PMID:33931361 | DOI:10.1016/j.euf.2021.04.009

Reprod Biomed Online. 2021 Mar 23:S1472-6483(21)00145-0. doi: 10.1016/j.rbmo.2021.03.017. Online ahead of print.

ABSTRACT

RESEARCH QUESTION: The economic and reproductive medicine response to the coronavirus disease 2019 (COVID-19) pandemic in the USA has reduced the affordability and accessibility of fertility care. What is the impact of the 2008 financial recession and the COVID-19 recession on fertility treatments and cumulative live births?

DESIGN: The study examined annual US natality, Centers for Disease Control and Prevention IVF cycle activity and live birth data from 1999 to 2018 encompassing 3,286,349 treatment cycles, to estimate the age-stratified reduction in IVF cycles undertaken after the 2008 financial recession, with forward quantitative modelling of IVF cycle activity and cumulative live births for 2020 to 2023.

RESULTS: The financial recession of 2008 caused a 4-year plateau in fertility treatments with a predicted 53,026 (95% confidence interval [CI] 49,581 to 56,471) fewer IVF cycles and 16,872 (95% CI 16,713 to 17,031) fewer live births. A similar scale of economic recession would cause 67,386 (95% CI 61,686 to 73,086) fewer IVF cycles between 2020 and 2023, with women younger than 35 years overall undertaking 22,504 (95% CI 14,320 to 30,690) fewer cycles, compared with 4445 (95% CI 3144 to 5749) fewer cycles in women over the age of 40 years. This equates to overall 25,143 (95% CI 22,408 to 27,877) fewer predicted live births from IVF, of which only 490 (95% CI 381 to 601) are anticipated to occur in women over the age of 40 years.

CONCLUSIONS: The COVID-19 recession could have a profound impact on US IVF live birth rates in young women, further aggravating pre-existing declines in total fertility rates.

PMID:33931369 | DOI:10.1016/j.rbmo.2021.03.017

Reprod Biomed Online. 2021 Jan 30:S1472-6483(21)00049-3. doi: 10.1016/j.rbmo.2021.01.018. Online ahead of print.

ABSTRACT

RESEARCH QUESTION: Do women of racial minorities aged 40 years or older have similar reproductive and obstetric outcomes as white women undergoing IVF?

DESIGN: A retrospective cohort study conducted at a single academic university-affiliated centre. The study population included women aged 40 years or older undergoing their first IVF cycle with fresh cleavage-stage embryo transfer stratified by racial minority status: minority (black or Asian) versus white. Clinical intrauterine pregnancy and live birth rate were the primary outcomes. Preterm delivery (<37 weeks) and small for gestational age were the secondary outcomes. Odds ratios with 95% confidence intervals were estimated. P < 0.05 was considered to be statistically significant.

RESULTS: A total of 2050 cycles in women over the age of 40 years were analysed, 561 (27.4%) of which were undertaken by minority women and 1489 (72.6%) by white women. Minority women were 30% less likely to achieve a pregnancy compared with their white (non-Hispanic) counterparts (adjusted OR 0.68, CI 0.54 to 0.87). Once pregnant, however, the odds of live birth were similar (adjusted OR 1.23, CI 0.91 to 1.67). Minority women were significantly more likely to have lower gestational ages at time of delivery (38.5 versus 39.2 weeks, P = 0.009) and were more likely to have extreme preterm birth delivery 24-28 weeks (5.5 versus 1.0%, P = 0.021).

CONCLUSION: Minority women of advanced reproductive age are less likely to achieve a pregnancy compared with white (non-Hispanic) women. Once pregnancy is achieved, however, live birth rates are similar albeit with minority women experiencing higher rates of preterm delivery.

PMID:33931372 | DOI:10.1016/j.rbmo.2021.01.018

Reumatol Clin. 2021 Apr 27:S1699-258X(21)00060-7. doi: 10.1016/j.reuma.2021.02.006. Online ahead of print.

ABSTRACT

INTRODUCTION: Available data for biocomparable drugs are not enough to make clear decisions with respect to the potential consequences of a change for non-medical reasons in efficacy, security and inmunogenicity in patients. In the near future, options on biological treatments, biocomparable drugs, non biocomparable drugs and new chemical synthesis options will grow. Therefore, it is important to know how patients behave in persistence of treatment after a change for non-medical reasons, which already happens on a regular basis in social security institutions in Mexico. This information will help us to better understand the standard of treatment for patients with chronic immunomediated conditions.

OBJECTIVE: The primary objective was to measure the impact of change for non-medical reasons in patients with rheumatoid arthritis (RA) treated with an innovative biological on persistence of treatment after changing to a biocomparable drug or a non-biocomparable drug, compared with those patients staying with the innovative biological.

STUDY DESIGN: This is an observational study (non-interventionist) of paired cohorts, where an historic cohort obtained by review of clinical records of stable patients in which no modifications to treatment were made for at least six months is compared with two cohorts of patients whose treatments were switched to another treatment with the same therapeutic mechanism for-non-medical reasons (cycling).

RESULTS: We included 264 RA patients (ACR/EULAR, 2010); 132 were switched for non-medical reasons, and 132 were not switched. Two-hundred and thirty (87.1%) were female. Average age was 53.9years, ranging from 16 to 84years. Two-hundred and sixty-three patients were Latino (99.6%); one was Caucasian. Persistence of treatment 12months after the change was 84.8% (85.8% in Enbrel/Infinitam, 78.9% for Remicade/Remsima). No statistical difference was found with respect to RA clinical activity measured by DAS28 12months after the switch (P>.05). In the 134 switched patients, 20 discontinued the new treatment due to lack of efficacy of the new drug and were changed to a different drug with a different biologic target. Although no differences were found in the cohorts of switched patients with respect to DAS28 after 12months of use, we did find differences in the frequency of adverse events. Forty-two patients had an adverse event in the drug switch cohorts: 33 in the Enbrel-Infinitam group and 9 in the Remicade-Remsima group.

CONCLUSIONS: The persistence of treatment after switching from an innovative drug to a biocomparable or a non-biocomparable in RA patients did not show statistically significative differences in our cohorts, but we did find a higher number of adverse events when comparing those who were changed with those who continued on an innovative drug. Twenty patients in the switch groups had to receive a new drug with a different biological target due to lack of efficacy of the switched drug.

PMID:33931335 | DOI:10.1016/j.reuma.2021.02.006