Nevin Manimala

Andrologia. 2021 Jul 11:e14188. doi: 10.1111/and.14188. Online ahead of print.

ABSTRACT

In this study, we aimed to elucidate the relationship between AZF deletion type and clinical information of azoospermic patients with AZF microdeletion in the Turkish population. Azoospermic patients with normal karyotype and AZF microdeletion were analysed retrospectively by collecting clinical data including hormone profile, demographic characteristics and micro-TESE results. As a result of the AZF microdeletion tests of 42 cases with 46 XY karyotype, AZFa deletion was detected in 3 cases, AZFb deletion in 2 cases, AZFc deletion in 31 cases, AZFb + AZFc deletion in 4 cases and AZFa + AZFb + AZFc deletion in 2 cases respectively. Spermatozoon was obtained in 16 cases with AZFc microdeletion with micro-TESE. Pregnancy was achieved in 2 cases. There was no statistically significant difference between the type of deletion and age, height, weight, body mass index, hormone profile and testicular volume. When AZF is evaluated according to the type of microdeletion, it will be appropriate to plan the medical and surgical options more carefully in a multidisciplinary manner in cases with deletions including AZFa, AZFb or their combinations. Also, genotype-phenotype correlation was found to be consistent with the literature; particularly patients having AZFc deletions were found to have a chance for pregnancy.

PMID:34247421 | DOI:10.1111/and.14188

Biom J. 2021 Jul 11. doi: 10.1002/bimj.202000269. Online ahead of print.

ABSTRACT

Motivated by a clinical trial conducted by Janssen Pharmaceutica in which a flexible dosing regimen is compared to placebo, we evaluate how switchers in the treatment arm (i.e., patients who were switched to the higher dose) would have fared had they been kept on the low dose. This is done in order to understand whether flexible dosing is potentially beneficial for them. Simply comparing these patients’ responses with those of patients who stayed on the low dose does not likely entail a satisfactory evaluation because the latter patients are usually in a better health condition. Because the available information in the considered trial is too limited to enable a reliable adjustment, we will instead transport data from a fixed dosing trial that has been conducted concurrently on the same target, albeit not in an identical patient population. In particular, we propose an estimator that relies on an outcome model, a model for switching, and a propensity score model for the association between study and patient characteristics. The proposed estimator is asymptotically unbiased if either the outcome or the propensity score model is correctly specified, and efficient (under the semiparametric model where the randomization probabilities are known and independent of baseline covariates) when all models are correctly specified. The proposed method for transporting information from an external study is more broadly applicable in studies where a classical confounding adjustment is not possible due to near positivity violation (e.g., studies where switching takes place in a (near) deterministic manner). Monte Carlo simulations and application to the motivating study demonstrate adequate performance.

PMID:34247409 | DOI:10.1002/bimj.202000269

Biom J. 2021 Jul 11. doi: 10.1002/bimj.202100019. Online ahead of print.

ABSTRACT

Cluster randomized trials evaluate the effect of a treatment on persons nested within clusters, with clusters being randomly assigned to treatment. The optimal sample size at the cluster and person level depends on the study cost per cluster and per person, and the outcome variance at the cluster and the person level. The variances are unknown in the design stage and can differ between treatment arms. As a solution, this paper presents a Maximin design that maximizes the minimum relative efficiency (relative to the optimal design) over the variance parameter space, for trials with two treatment arms and a quantitative outcome. This maximin relative efficiency design (MMRED) is compared with a published Maximin design which maximizes the minimum efficiency (MMED). Both designs are also compared with the optimal designs for homogeneous costs and variances (balanced design) and heterogeneous costs and homogeneous variances (cost-conscious design), for a range of variances based upon three published trials. Whereas the MMED is balanced under high uncertainty about the treatment-to-control variance ratio, the MMRED then tends towards a balanced budget allocation between arms, leading to an unbalanced sample size allocation if costs are heterogeneous, similar to the cost-conscious design. Further, the MMRED corresponds to an optimal design for an intraclass correlation (ICC) in the lower half of the assumed ICC range (optimistic), whereas the MMED is the optimal design for the maximum ICC within the ICC range (pessimistic). Attention is given to the effect of the Welch-Satterthwaite degrees of freedom for treatment effect testing on the design efficiencies.

PMID:34247406 | DOI:10.1002/bimj.202100019

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Jul 10;38(7):681-685. doi: 10.3760/cma.j.cn511374-20200430-00318.

ABSTRACT

OBJECTIVE: To assess the association of polymorphisms of receptor of advanced glycation end products (RAGE) gene, monocyte to high-density lipoprotein cholesterol ratio (MHR) and variability of heart rate among patients with coronary heart disease (CHD).

METHODS: 120 patients with CHD and 120 healthy individuals were respectively selected as the observation group and the control group. Allelic and genotypic differences of -429T>C, 1704G>T, 82G>S, MHR ratio and heart rate variability between the two groups and patients with different severity were analyzed. The correlation between their genotypes and MHR ratio and heart rate variability was analyzed.

RESULTS: The 82G>S polymorphism of the RAGE gene and the allelic difference between the two groups and patients with different severity were statistically significant (P< 0.05). Compared with the control group and patients with mild to moderate phenotype, monocyte, total cholesterol, triglyceride, low density lipoprotein, MHR, low frequency in the observation group and patients with severe symptoms were significantly higher, while their high density lipoprotein, standard deviation of NN intervals (SDNN), standard deviation average of NN intervals (SDANN), root mean square successive differences, percentage of differences exceeding 50ms between adjacent normal number of intervals (PMN50), high frequency (HF) were significantly lower. The gene frequencies of G-Gly-T, T-Gly-T, G-Ser-T and G-Gly-C were correlated with SDNN, SDANN, rMSSD, PMN50, HF and MHR, but negatively correlated with low frequency.

CONCLUSION: Polymorphisms of the RAGE gene in patients with coronary heart disease are associated with the MHR ratio and heart rate variability, which can be used as markers for the diagnosis and efficacy evaluation.

PMID:34247378 | DOI:10.3760/cma.j.cn511374-20200430-00318

Ann Surg Oncol. 2021 Jul 10. doi: 10.1245/s10434-021-10441-z. Online ahead of print.

ABSTRACT

BACKGROUND: Management of axillary lymph nodes in breast cancer has undergone significant change over the past decade through landmark clinical trials. This study aimed to assess national practice patterns in axillary management in patients undergoing upfront mastectomy and examines what guides provider recommendations.

METHODS: A national case-based survey study was performed of surgeons and radiation oncologists from July to August 2020. Surgeons were identified through the American Society of Breast Surgeons (ASBrS) after review and approval by the ASBrS Research Committee, and radiation oncologists were identified through an institutional database. Both descriptive and comparative statistical analyses were performed.

RESULTS: Overall, 994 providers responded-680 surgeons and 314 radiation oncologists. Surgeons were older and in practice longer (p < 0.05) and treated a higher percentage of breast patients (81% vs. 40%, p < 0.001). Most surgeons were hospital-employed (43%), whereas most radiation oncologists were in private practice (40%; p < 0.001). Fifty-two percent of surgeons routinely send sentinel lymph nodes (SLNs) for frozen section (52%) during mastectomy, of which 78% proceed directly to axillary lymph node dissection (ALND) if positive. There was significant variability in treatment recommendations between the two groups among the hypothetical cases (p < 0.001). In the setting of low disease burden in the SLNs, > 30% of surgeons recommended ALND, while radiation oncologists recommend axillary radiotherapy over axillary clearance (p < 0.001).

CONCLUSION: There is significant heterogeneity in the management of the axilla in mastectomy patients with pathologically positive SLNs, both between and among surgeons and radiation oncologists. Efforts should be made to assist both groups in identifying de-escalation opportunities to ensure that mastectomy patients with positive SLNs are treated appropriately.

PMID:34247336 | DOI:10.1245/s10434-021-10441-z

Curr HIV/AIDS Rep. 2021 Jul 11. doi: 10.1007/s11904-021-00567-w. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: To provide the current state of the development and application of cardiovascular disease (CVD) prediction tools in people living with HIV (PLWH).

RECENT FINDINGS: Several risk prediction models developed on the general population are available to predict CVD risk, the most notable being the US-based pooled cohort equations (PCE), the Framingham risk functions, and the Europe-based SCORE (Systematic COronary Risk Evaluation). In validation studies in cohorts of PLWH, these models generally underestimate CVD risk, especially in individuals who are younger, women, Black race, or predicted to be at low/intermediate risk. An HIV-specific CVD prediction model, the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) model, is available, but its performance is modest, especially in US-based cohorts. Enhancing CVD prediction with novel biomarkers of inflammation or coronary artery calcification is of interest but has not yet been evaluated in PLWH. Finally, studies on CVD risk prediction are lacking in diverse PLWH globally. While available risk models for CVD prediction in PLWH remain suboptimal, clinicians should remain vigilant of higher CVD risk in this population and should use any of these risk scores for risk stratification to guide preventive interventions. Focus on established traditional risk factors such as smoking remains critical in PLWH. Risk prediction functions tailored to PLWH in diverse settings will enhance clinicians’ ability to deliver optimal preventive care.

PMID:34247329 | DOI:10.1007/s11904-021-00567-w

Infection. 2021 Jul 10. doi: 10.1007/s15010-021-01659-w. Online ahead of print.

ABSTRACT

BACKGROUND: Laboratory parameters and the associated clinical outcomes have been an area of focus in COVID-19 research globally.

PURPOSE: We performed a scoping review to synthesize laboratory values described in the literature and their associations with mortality and disease severity.

METHODS: We identified all primary studies involving laboratory values with clinical outcomes as a primary endpoint by performing data searches in various systematic review databases until 10th August, 2020. Two reviewers independently reviewed all abstracts (13,568 articles) and full text (1126 articles) data. A total of 529 studies involving 165,020 patients from 28 different countries were included. Investigation of the number of studies and patients from a geographical perspective showed that the majority of published literature from January-March 2020 to April-June 2020 was from Asia, though there was a temporal shift in published studies to Europe and the Americas. For each laboratory value, the proportion of studies that noted a statistically significant (p < 0.05) correlation with adverse clinical outcomes (e.g., mortality, disease severity) was tabulated.

RESULTS AND CONCLUSION: Among frequently reported laboratory values, blood urea nitrogen was the most often reported predictor of mortality (91%); neutrophil-to-lymphocyte ratio was the most frequent statistically significant laboratory parameter in predicting disease severity (96%). This review highlights the temporal progression of laboratory value frequencies, as well as potentially distinct utilities of different markers for clinical outcomes of COVID-19. Future research pathways include using this collected data for focused quantitative meta-analyses of particular laboratory values correlated with clinical outcomes of mortality and disease severity.

PMID:34247320 | DOI:10.1007/s15010-021-01659-w

Support Care Cancer. 2021 Jul 11. doi: 10.1007/s00520-021-06406-3. Online ahead of print.

ABSTRACT

PURPOSE: Cancer patients have been shown to frequently suffer from financial burden before, during, and after treatment. However, the financial toxicity of patients with sarcoma has seldom been assessed. Therefore, the aim of this study was to evaluate whether financial toxicity is a problem for sarcoma patients in Germany and identify associated risk factors.

METHODS: Patients for this analysis were obtained from a multicenter prospective cohort study conducted in Germany. Using the financial difficulties scale of the EORTC QLQ-C30, financial toxicity was considered to be present if the score exceeded a pre-defined threshold for clinical importance. Comparisons to an age- and sex-matched norm population were performed. A multivariate logistic regression using stepwise backward selection was used to identify factors associated with financial toxicity.

RESULTS: We included 1103 sarcoma patients treated in 39 centers and clinics; 498 (44.7%) patients reported financial toxicity. Sarcoma patients had 2.5 times the odds of reporting financial difficulties compared to an age- and sex-matched norm population. Patient age < 40 and > 52.5 years, higher education status, higher income, and disease progression (compared to patients with complete remission) were associated with lower odds of reporting financial toxicity. Receiving a disability pension, being currently on sick leave, and having a disability pass were statistically significantly associated with higher odds of reporting financial toxicity.

CONCLUSION: Financial toxicity is present in about half of German sarcoma patients, making it a relevant quality of life topic for patients and decision-makers.

PMID:34247310 | DOI:10.1007/s00520-021-06406-3

Neurol Sci. 2021 Jul 11. doi: 10.1007/s10072-021-05431-8. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to find out whether including robotic therapy in addition to a conventional rehabilitation program affects the quality of life, motor function, cognition, and emotional status of hemiplegic patients.

DESIGN: Thirty-seven stroke patients recruited between April 2016 and April 2019 were included in the study. The patients were randomized into 2 groups (Robotic rehabilitation group-RR n:17, Control group n:20), RR was arranged to be 30-45 min, 5 days per week for 4 weeks. All patients were assessed at the beginning of therapy and the end of 4th week with Brunnstrom stages of motor recovery, Fugl-Meyer Assessment (FMA), handgrip strength, Purdue peg test, Minnesota manual dexterity test, Modified Ashworth Scale (MAS), Functional Independence Measure (FIM), Stroke Specific Quality of Life Scale (SS-QOL), Nottingham Extended Activities of Daily Living (NEADL) Scale, Montreal Cognitive Assessment (MoCA) and Center for Epidemiological Studies Depression Scale (CES- D).

RESULTS: Improvements in motor function scores, spasticity, general functioning, activities of daily living, cognitive assessment were better in the robotic group when compared to the control group but this difference was not statistically significant (p > 0.05). Improvement in the CES-D in the RR-group was better in comparison to the control group (p = 0.018).

CONCLUSION: Improvements in motor functions were observed after the treatment in both groups. Although RR group improved better in numbers, none of the outcomes except the CES-D scale were significant. Robotic rehabilitation provides a favorable alternative bringing slight benefits, and also is advantageous in terms of work power and psychological recovery, making its addition to conventional neurological rehabilitation effective and useful in patient management after stroke.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04393480.

PMID:34247295 | DOI:10.1007/s10072-021-05431-8

Skeletal Radiol. 2021 Jul 10. doi: 10.1007/s00256-021-03788-7. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the safety and efficacy of the combination of radiofrequency ablation (RFA) and vertebroplasty versus single vertebroplasty in treating spinal metastases.

MATERIALS AND METHODS: The data of 35 patients with vertebral neoplastic lesions who received RFA combined with vertebroplasty (group A, 15 patients with 17 lesions) or single vertebroplasty (group B, 20 patients with 24 lesions) from March 2016 to June 2019 were retrospectively compared. The data of patients’ Visual Analogue Scale (VAS) scores prior to the treatments, 1 week, 1 month, 3 months, and 6 months after the treatments, injected cement volume, ratios of cement leakage were compared between the two groups.

RESULTS: All procedures were successfully done without severe complications. The VAS scores in group A were decreased more rapidly 1 week after the treatments and remained more stable at 6 months than that in group B (P < 0.05). The cement injected in group A (5.95 ± 1.45 mL, range 4-9.5 mL) was significantly more than that in group B (4.09 ± 0.55 mL, range 3.1-5.5 mL) (P < 0.05). The ratio of vascular cement leakage in group A was significantly lower than that in group B (P < 0.05), while no statistical difference was found in the non-vascular cement leakage (P > 0.05).

CONCLUSIONS: Our study shows that the combination of RFA and vertebroplasty has a better analgesic effect with more injected cement and lower rates of venous cement leakage than single vertebroplasty.

PMID:34247255 | DOI:10.1007/s00256-021-03788-7