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Nevin Manimala Statistics

Predicting the total number of retrieved oocytes following double ovarian stimulation (DuoStim)

Hum Reprod. 2023 Jul 20:dead148. doi: 10.1093/humrep/dead148. Online ahead of print.

ABSTRACT

STUDY QUESTION: Can anti-Müllerian hormone (AMH) help predict how many oocytes will be retrieved following double stimulation (DuoStim)?

SUMMARY ANSWER: A simple clinical tool can use serum AMH values to predict ovarian response following DuoStim in IVF cycles.

WHAT IS ALREADY KNOWN: The knowledge that multiple follicular waves arise during a single ovarian cycle has led to the introduction of unconventional ovarian stimulation protocols. The DuoStim protocol involves two successive ovarian stimulations performed during a single ovarian cycle and has been proposed as an approach for patients with poor ovarian response and for medical fertility preservation. As AMH has been used as a marker of ovarian reserve and stimulation response, the current study aimed to investigate the diagnostic performance of AMH in predicting the number of retrieved oocytes following DuoStim.

STUDY DESIGN, SIZE, DURATION: This is a retrospective observational study involving 116 patients who received IVF treatment from January 2021 to September 2022.

PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at a private IVF centre. Only patients who had their AMH measured prior to treatment and had complete patient records regarding their clinical and IVF/ICSI cycle characteristics were included. The primary outcome was the correlation between AMH values and the number of oocytes retrieved following DuoStim. Parametric and non-parametric tests were used to compare baseline characteristics and outcomes. Spearman’s R was used to analyse correlations between variables, while the C statistic was used to calculate the diagnostic performance of AMH.

MAIN RESULTS AND THE ROLE OF CHANCE: AMH levels were significantly correlated with the total number of oocytes retrieved after the DuoStim (R 0.61; CI 0.44-0.70; P < 0.0001). The difference in the total number of oocytes retrieved between the first (median 4 oocytes, interquartile range (IQR) 2-6) and second (median 6 oocytes, IQR 3.2-8) stimulation was statistically significant (P < 0.0001). However, there was no significant difference in the number of mature oocytes that were retrieved (median of 3 and 4 in the first and second stimulations, respectively). After the first stimulation, 68% of patients had at least one blastocyst available, while after the second stimulation, 74% did (NS). Based on linear regression, each 0.25 ng/ml increase in basal AMH corresponds to one additional oocyte recovered at the end of both stimulations (R2: 0.32, P < 0.0001).

LIMITATIONS, REASONS FOR CAUTION: The results are limited owing to the observational nature of the study and the number of participants.

WIDER IMPLICATIONS OF THE FINDINGS: Counselling infertile couples regarding the intermediate outcome of IVF (i.e. number of retrieved oocytes) is one of the most demanding tasks that clinicians face. To our knowledge, this is the first study that provides an easy-to-use clinical tool that enables the quantitative prediction of ovarian response following DuoStim, based on serum AMH values.

STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. The authors declare no conflicts of interest.

TRIAL REGISTRATION NUMBER: N/A.

PMID:37470235 | DOI:10.1093/humrep/dead148

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Nevin Manimala Statistics

Variation in mortality burden of the COVID-19 pandemic across federal states in Germany

Eur J Public Health. 2023 Jul 20:ckad110. doi: 10.1093/eurpub/ckad110. Online ahead of print.

ABSTRACT

BACKGROUND: Intra-annual excess mortality is the most reliable measure of losses of lives due to short-term risk factors. The objectives of our study are (i) to estimate excess mortality across German states in the course of the coronavirus disease 2019 (COVID-19) pandemic years 2020 and 2021 and (ii) to identify possible regional-level determinants of spatial inequality in pandemic-related excess mortality.

METHODS: We use weekly mortality data series for the calculation of weekly death rates, standardized by age for each federal state of Germany. We estimate the expected level of mortality as state-specific mortality trends and excess mortality in 2020 and 2021. We explore ecological statistical relationships between excess mortality, COVID-19 morbidity, and selected regional socioeconomic indicators using fixed-effects regression models.

RESULTS: Our study shows that during the first pandemic year, there was South-to-North gradient in excess mortality in Germany, with excess mortality being higher in the South. Over the course of the second pandemic year 2021, this gradient changed to become an East-to-West gradient, with excess mortality being higher in the East. The results of the study show stronger effects of COVID-19 morbidity on excess mortality in East Germany. State-level indicators reflecting economic activity, employment, and capacity of intensive care units show significant correlations with excess mortality across the states.

CONCLUSIONS: The results show pronounced state-level differences in the magnitude of excess mortality during the COVID-19 pandemic in Germany. Economic activity, employment and capacity of intensive care units were the most important state-level characteristics associated with the observed spatial variations in excess mortality.

PMID:37470231 | DOI:10.1093/eurpub/ckad110

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Nevin Manimala Statistics

Race- and Sex-Specific Factors Associated With Age-Related Slopes in Systolic Blood Pressure: Findings From the CARDIA Study

Hypertension. 2023 Jul 20. doi: 10.1161/HYPERTENSIONAHA.123.21217. Online ahead of print.

ABSTRACT

BACKGROUND: Although blood pressure (BP) increases throughout young adulthood for most individuals, the age-related slope is not uniform. This study aimed to assess associations of demographic, clinical, behavioral, psychosocial, and neighborhood characteristics with age-related BP slope among 4 race-sex groups who participated in the Coronary Artery Risk Development in Young Adults study.

METHODS: Individuals (n=3554) aged 18 to 30 years were included in this analysis if they had normal BP at baseline and ≥2 BP measurements during the years 1985/1986 to 2015/2016. Associations of exposure variables with systolic BP slope were assessed using multivariate linear models.

RESULTS: Over a mean follow-up of ~30 years, greater decade increases in systolic BP were estimated among Black than White participants (mean difference between Black females and White females: 3.0 mm Hg/decade; between Black males and White males: 4.7 mm Hg/decade). The exposure risk factors associated with greater increases in systolic BP throughout adulthood varied by race and sex. None of these factors were associated with increases in systolic BP in all race-sex groups. Parent history of high BP was associated with a steeper positive slope among Black females (effect size per decade: 1.1 [95% CI, 0.6-1.6]; P<0.01), Black males (0.6 [95% CI, 0.02-1.2]; P<0.05), and White females (0.6 [95% CI, 0.2-1.0]; P<0.01). Other risk factors were associated with greater age-related yearly increases in systolic BP among 1 or 2 of the 4 race-sex groups or were not statistically significant.

CONCLUSIONS: Culturally tailored BP reduction approach should be considered in conjunction with primordial prevention, to moderate increases in BP throughout adulthood.

PMID:37470199 | DOI:10.1161/HYPERTENSIONAHA.123.21217

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Phenotypic evolution of SARS-CoV-2: a statistical inference approach

Evolution. 2023 Jul 20:qpad133. doi: 10.1093/evolut/qpad133. Online ahead of print.

ABSTRACT

Since its emergence in late 2019, the SARS-CoV-2 virus has spread globally, causing the ongoing COVID-19 pandemic. In the fall of 2020, the Alpha variant (lineage B.1.1.7) was detected in England and spread rapidly, outcompeting the previous lineage. Yet, very little is known about the underlying modifications of the infection process that can explain this selective advantage. Here, we try to quantify how the Alpha variant differed from its predecessor on two phenotypic traits: the transmission rate and the duration of infectiousness. To this end, we analysed the joint epidemiological and evolutionary dynamics as a function of the Stringency Index, a measure of the amount of Non-Pharmaceutical Interventions. Assuming that these control measures reduce contact rates and transmission, we developed a two-step approach based on SEIR models and the analysis of a combination of epidemiological and evolutionary information. First, we quantify the link between the Stringency Index and the reduction in viral transmission. Secondly, based on a novel theoretical derivation of the selection gradient in an SEIR model, we infer the phenotype of the Alpha variant from its frequency changes. We show that its selective advantage is more likely to result from a higher transmission than from a longer infectious period. Our work illustrates how the analysis of the joint epidemiological and evolutionary dynamics of infectious diseases can help understand the phenotypic evolution driving pathogen adaptation.

PMID:37470192 | DOI:10.1093/evolut/qpad133

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Phase behaviour of coarse-grained fluids

Soft Matter. 2023 Jul 20. doi: 10.1039/d3sm00835e. Online ahead of print.

ABSTRACT

Soft condensed matter structures often challenge us with complex many-body phenomena governed by collective modes spanning wide spatial and temporal domains. In order to successfully tackle such problems, mesoscopic coarse-grained (CG) statistical models are being developed, providing a dramatic reduction in computational complexity. CG models provide an intermediate step in the complex statistical framework of linking the thermodynamics of condensed phases with the properties of their constituent atoms and molecules. These allow us to offload part of the problem to the CG model itself and reformulate the remainder in terms of reduced CG phase space. However, such exchange of pawns to chess pieces, or ‘Hamiltonian renormalization’, is a radical step and the thermodynamics of the primary atomic and CG models could be quite distinct. Here, we present a comprehensive study of the phase diagram including binodal and interfacial properties of a dissipative particle dynamics (DPD) model, extended to include finite-range attraction to support the liquid-gas equilibrium. Despite the similarities with the atomic model potentials, its phase envelope is markedly different featuring several anomalies such as an unusually broad liquid range, change in concavity of the liquid coexistence branch with variation of the model parameters, volume contraction on fusion, temperature of maximum density in the liquid phase and negative thermal expansion in the solid phase. These results provide new insight into the connection between simple potential models and complex emergent condensed matter phenomena.

PMID:37470164 | DOI:10.1039/d3sm00835e

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Nevin Manimala Statistics

Open vs robotic radical cystectomy: pentafecta and trifecta achievement comparison from a rct

BJU Int. 2023 Jul 20. doi: 10.1111/bju.16134. Online ahead of print.

ABSTRACT

OBJECTIVES: to compare USC pentafecta and trifecta achievement comparing open radical cystectomy (ORC) vs robot-assisted RC (RARC) with totally intracorporeal UD (i-UD) from a randomised controlled trial (RCT) MATERIALS AND METHODS: Patients were eligible for randomization if they had a diagnostic TURBt with cT2-4, cN0, cM0, or recurrent HG NMIBC and no anesthesiologic contraindications to robotic surgery. Patients were enrolled with a covariate adaptive randomization process based on the following variables: BMI, ASA score, preoperative haemoglobin, planned UD, neoadjuvant chemotherapy and cT-stage. USC pentafecta was defined as the combination, 1-yr after surgery, of negative soft tissue surgical margins, ≥ 16 lymph node (LN) yield, absence of major (Clavien≥3) complications at 90 days, absence of UD-related long-term sequalae and absence of clinical recurrence. Trifecta was defined as the coexistence of daytime urinary continence, absence of major complications and recurrence-free status, all assessed at 1 year. Continuous and categorical variables were compared using Student t and Chi-Square tests, respectively. Univariable logistic regression analysis was performed to assess the role of USC pentafecta and trifecta achievement on HRQoL.

RESULTS: No statistically significant difference was observed in USC pentafecta and trifecta achievement between groups. Among secondary outcomes, univariable logistic regression analysis was performed and both 1yr USC Pentafecta and trifecta achievement were predictors of 2yrs unmodified global QoL.

CONCLUSIONS: This study supports equivalence of RARC-iUD and ORC with regard to surgical quality as described by USC pentafecta and trifecta. We described a significant impact of USC pentafecta and trifecta achievement on global health status/QoL, providing a strict correlation between objective evaluation of surgical outcomes and self-reported HRQoL.

PMID:37470132 | DOI:10.1111/bju.16134

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A comparison of alveolar ridge mucosa thickness in completely edentulous patients

J Prosthodont. 2023 Jul 20. doi: 10.1111/jopr.13738. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this cross-sectional clinical study was to determine and compare alveolar ridge mucosa thickness at crestal, buccal, and lingual locations of the maxillary and mandibular arches in completely edentulous patients using a dedicated, ultrasonic gingival scanner.

MATERIALS AND METHODS: Thirty-eight completely edentulous subjects were included in the study. In each subject, soft tissue thickness was measured at 28 sites of the edentulous ridge by a single calibrated examiner. Intra-observer reliability was calculated with Intraclass Correlation Coefficients by measuring 10 subjects twice, after 1 week. Measurements (mm) were taken at the buccal, lingual, and crestal aspects of the ridge with a dedicated ultrasonic scanner. Repeated measures ANOVA and paired t-tests were used to compare the mean buccal, lingual, and crestal soft tissue thicknesses at each site. The Generalized Estimating Equations model was used to study the effects of age, gender, and race. Confidence level was set to 95%.

RESULTS: Mean tissue thickness ranged from 0.96 mm to 1.98 mm with a mean of 1.63 ± 0.25 mm. Intraclass Correlation Coefficients were >0.97. No significant differences between buccal, crestal, and lingual sites were noted for the mandibular arch as well as at 4 sites on the maxillary arch (maxillary right second molar, maxillary right canine, maxillary left first premolar, maxillary left second molar). However, significant differences in soft tissue thickness were noted for all remaining maxillary sites. Race was found to be positively correlated with tissue thickness, with black individuals showing a significantly greater thickness than whites at four sites (maxillary right first molar, maxillary left canine, mandibular right second premolar, mandibular right first molar). Age was found to be positively correlated with tissue thickness at 4 sites (maxillary left central incisor, maxillary left first molar, maxillary left second molar, mandibular left second premolar) and negatively correlated at 2 sites (mandibul0ar right canine, mandibular right second molar). Female gender was positively (maxillary left second premolar, maxillary left second molar) and negatively (mandibular right canine) correlated, respectively, with tissue thickness at 3 sites. When data for anterior and posterior sites was respectively pooled, tissue thickness was significantly less at anterior sextant lingual and crestal sites, while no difference was seen for buccal sites.

CONCLUSION: Statistically significant differences for alveolar ridge mucosa thickness were found at several sites in the maxilla and between anterior and posterior sextants for lingual and crestal sites in the maxillary and mandibular arches. Tissue thickness differences were also noted for race with black individuals showing greater tissue thickness at some sites. Age and gender did not show a clear effect on tissue thickness. Recorded differences in tissue thickness were however small and appear of uncertain clinical significance. This article is protected by copyright. All rights reserved.

PMID:37470112 | DOI:10.1111/jopr.13738

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Rationale and design of ENDEAVOR: a sequential phase 2b-3 randomized clinical trial to evaluate the effect of myeloperoxidase inhibition on symptoms and exercise capacity in heart failure with preserved or mildly reduced ejection fraction

Eur J Heart Fail. 2023 Jul 20. doi: 10.1002/ejhf.2977. Online ahead of print.

ABSTRACT

AIMS: Mitiperstat (formerly AZD4831) is a novel selective myeloperoxidase inhibitor. Currently, no effective therapies target comorbidity-induced systemic inflammation, which may be a key mechanism underlying heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). Circulating neutrophils secrete myeloperoxidase, causing oxidative stress, microvascular endothelial dysfunction, interstitial fibrosis, cardiomyocyte remodelling and diastolic dysfunction. Mitiperstat may therefore improve function of the heart and other organs, and ameliorate heart failure symptoms and exercise intolerance. ENDEAVOR is a combined, seamless phase 2b-3 study of the efficacy and safety of mitiperstat in patients with HFpEF/HFmrEF.

METHODS: In phase 2b, approximately 660 patients with heart failure and ejection fraction >40% are being randomized 1:1:1 to mitiperstat 2.5 mg, 5 mg or placebo for 48 weeks. Eligible patients have baseline 6-min walk distance (6MWD) of 30-400 m with a < 50 m difference between screening and randomization and Kansas City Cardiomyopathy Questionnaire – total symptom score (KCCQ-TSS) ≤90 points at screening and randomization. The dual primary endpoints are change from baseline to week 16 in 6MWD and KCCQ-TSS. The sample size provides 85% power to detect placebo-adjusted improvements of 21 m in 6MWD and 6.0 points in KCCQ-TSS at overall two-sided alpha of 0.05. Safety is monitored throughout treatment, with a focus on maculopapular rash. In phase 3 of ENDEAVOR, approximately 820 patients will be randomized 1:1 to mitiperstat or placebo.

CONCLUSION: ENDEAVOR is the first phase 2b-3 study to evaluate whether myeloperoxidase inhibition can improve symptoms and exercise capacity in patients with HFpEF/HFmrEF. Clincaltrials.gov: NCT04986202 This article is protected by copyright. All rights reserved.

PMID:37470101 | DOI:10.1002/ejhf.2977

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A More Conservative Approach in the Surgical Management of Pediatric Physeal Ankle Fractures Should be Preferred: Mid to Long-term Functional Outcomes of Three Different Surgical Techniques for Salter-Harris Type II and Triplane Distal Tibial Fractures

J Pediatr Orthop. 2023 Jul 20. doi: 10.1097/BPO.0000000000002471. Online ahead of print.

ABSTRACT

BACKGROUND: Pediatric physeal ankle fractures carry a high risk of complications. This study aimed to (1) investigate the effect of anatomic reduction of the physis on mid to long-term functional outcomes in Salter-Harris type II and triplane distal tibial physeal fractures (DTPFs) and (2) compare the outcomes of 3 different surgical techniques applied in these fractures.

METHODS: The database of a single level-I trauma center was retrospectively reviewed for DTPFs between 2012 and 2022. A total of 39 eligible patients with operative Salter-Harris type II and triplane fractures between 2012 and 2022 were included. Surgical treatment methods were closed reduction-percutaneous fixation (CR-PF), open reduction-screw fixation, or open reduction-plate fixation. Patients were further divided into subgroups for fractures reduced anatomically (<1 mm) or nonanatomically (1 to 3 mm). The primary outcome measures were the American Orthopaedic Foot and Ankle Society Score, ankle range of motion, presence of premature physeal closure and angular deformities, and Takakura ankle osteoarthritis grade.

RESULTS: A total of 39 patients were included, with an average age of 12.9 ± 2.2 years. The mean follow-up time was 68.9±38.0 months. The CR-PF group had higher postoperative fracture displacement (P = 0.011). American Orthopaedic Foot and Ankle Society scores were excellent in all groups, statistically similar between surgical techniques, and similar between anatomic and nonanatomic reduction groups. The CR-PF group (P =0.030) and nonanatomic reduction (P = 0.030) provided a significantly lower ankle osteoarthritis rate. All 4 patients with premature physeal closure were observed in patients treated with open techniques.

CONCLUSIONS: CR-PF for the treatment of DTPFs should be preferred in suitable cases as it is less invasive and provides satisfactory mid to long-term functional outcomes without increasing complications compared with anatomic reduction and open techniques.

LEVEL OF EVIDENCE: Level III.

PMID:37470086 | DOI:10.1097/BPO.0000000000002471

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Neonatal mortality among preterm infants admitted to neonatal intensive care units in India and Pakistan: A prospective study

BJOG. 2023 Jul 20. doi: 10.1111/1471-0528.17581. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore potential reasons for differences in preterm neonatal mortality in neonatal intensive care units (NICUs) in India and Pakistan.

DESIGN: A prospective observational study, the Project to Understand and Research Stillbirth and Preterms in Southeast Asia (PURPOSe) was conducted July 2018 to February 2020.

SETTING: Three hospitals in Davangere, India, and a large public hospital in Karachi, Pakistan.

POPULATION: Of a total of 3,202 preterm infants enrolled, 1,512 were admitted to a study NICU.

METHODS: We collected data for neonates, including length of stay, diagnoses, and diagnostic tests.

MAIN OUTCOME MEASURES: Neonatal mortality, tests performed, diagnoses ascertained.

RESULTS: For infants of equivalent weights and gestational ages, neonatal mortality in Pakistan was twice that in the Indian NICU. The mean newborn length of stay in Pakistan was 2 days compared with 10 days for India. Fewer diagnostics and other investigations were used to determine neonatal condition or guide treatment in the Pakistani NICU. Because of limited information from testing in Pakistan concerning clinical respiratory distress, respiratory distress syndrome appeared to be over-diagnosed, whereas other conditions including pneumonia, sepsis, necrotising entercolitis and intraventricular haemorrhage were rarely diagnosed.

CONCLUSION: In the Pakistani site, the limited resources available to the NICU appeared related to a shorter length of stay and decreased diagnostic testing, likely explaining the higher mortality. With improved care, reduction in mortality among preterm neonates should be achievable.

PMID:37470084 | DOI:10.1111/1471-0528.17581