Nevin Manimala

Target Oncol. 2022 Apr 23. doi: 10.1007/s11523-022-00878-x. Online ahead of print.

ABSTRACT

BACKGROUND: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors are the standard first-line treatment for patients with advanced and recurrent EGFR-positive non-small cell lung cancer.

OBJECTIVE: The main objective of the present study was to compare the clinical efficacies between osimertinib and afatinib as first-line treatment in patients with EGFR-mutant non-small cell lung cancer.

METHODS: We retrospectively analyzed patients with advanced and recurrent non-small cell lung cancer who harbored an exon 19 deletion or an exon 21 L858R mutation and were being given either osimertinib or afatinib as first-line treatment from January 2018 to December 2020.

RESULTS: A total of 128 patients were selected for this study. The osimertinib group included 47 patients, while 81 patients received afatinib. The median follow-up time was 20.1 months in the osimertinib group and 22.7 months in the afatinib group. The median progression-free survival was 18.8 months and 13.1 months in the osimertinib and afatinib groups, respectively (hazard ratio 0.75 [95% confidence interval 0.48-1.18]). The median overall survival was not reached in the osimertinib group and was 41.7 months in the afatinib group (hazard ratio 0.79 [95% confidence interval 0.36-1.72]). In patients without brain metastasis, the median progression-free survival was 17.9 months and 17.2 months in the osimertinib and afatinib groups, respectively (hazard ratio 1.02 [95% confidence interval 0.56-1.85]). In patients with brain metastasis at baseline, the median progression-free survival was 22.1 months in the osimertinib group, and 10.9 months in the afatinib group (adjusted hazard ratio 0.45 [95% confidence interval 0.21-0.96]).

CONCLUSIONS: Our research demonstrates that there was no strong evidence showing that patients taking osimertinib as first-line treatment experienced longer median progression-free survival and overall survival than patients treated with afatinib. However, there was a statistical significance revealing that osimertinib provided better median progression-free survival than afatinib in patients with brain metastasis at baseline.

PMID:35460474 | DOI:10.1007/s11523-022-00878-x

Qual Life Res. 2022 Apr 23. doi: 10.1007/s11136-022-03133-y. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this systematic review with meta-analysis was to evaluate the effectiveness of RMT in internal and central nervous system disorders, on pulmonary function, exercise capacity and quality of life.

METHODS: The inclusion criteria were (1) publications designed as Randomized Controlled Trial (RCT), with (2) participants being adults with pulmonary dysfunction caused by an internal disease or central nervous system disorder, (3) an intervention defined as RMT (either IMT or EMT) and (4) with the assessment of exercise capacity, respiratory function and quality of life. For the methodological quality assessment of risk of bias, likewise statistical analysis and meta-analysis the RevMan version 5.3 software and the Cochrane Risk of Bias Tool were used. Two authors independently analysed the following databases for relevant research articles: PubMed, Scopus, Cochrane Library, Web of Science, and Embase.

RESULTS: From a total of 2200 records, the systematic review includes 29 RCT with an overall sample size of 1155 patients. Results suggest that patients with internal and central nervous system disorders who underwent RMT had better quality of life and improved significantly their performance in exercise capacity and in respiratory function assessed with FVC and MIP when compared to control conditions (i.e. no intervention, sham training, placebo or conventional treatments).

CONCLUSION: Respiratory muscle training seems to be more effective than control conditions (i.e. no intervention, sham training, placebo or conventional treatment), in patients with pulmonary dysfunction due to internal and central nervous system disorders, for quality of life, exercise capacity and respiratory function assessed with MIP and FVC, but not with FEV1.

PMID:35460472 | DOI:10.1007/s11136-022-03133-y

Indian J Pediatr. 2022 Apr 23. doi: 10.1007/s12098-021-04065-0. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the growth and neurodevelopmental outcome of term, singleton babies conceived by assisted reproduction with those of naturally conceived babies.

METHODS: A cohort study evaluating the growth delay in terms of proportion of babies with wasting (W/L < -2SD) at 6, 12 and 24 mo follow-up. Developmental delay was defined as either motor or mental developmental quotient < 70 in DASII.

RESULTS: Amongst the 128 artificially conceived babies, at 6 and 12 mo, the proportions of babies with wasting (21.1% and 17.2%), motor (7.03%, 6.3%), and mental developmental delays (5.5% and 3.9%) were significantly higher (p < 0.05) compared to the naturally conceived babies (10.94%, 8.6%, 1.6%, 0.8%, 0.8% and 0%, respectively). However, at 24 mo, the difference in outcomes were not statistically significant (p > 0.05).

CONCLUSION: The growth and neurodevelopment of artificially conceived babies may be delayed in early infancy but they normalize to catch up with their naturally conceived peers by 24 mo.

PMID:35460463 | DOI:10.1007/s12098-021-04065-0

Eat Weight Disord. 2022 Apr 23. doi: 10.1007/s40519-022-01397-4. Online ahead of print.

ABSTRACT

PURPOSE: Anorexia nervosa (AN) is a life-threatening condition in which temperament, anxiety, depression, and core AN body-related psychopathology (drive for thinness, DT, and body dissatisfaction, BD) are intertwined. This relationship has not been to date disentangled; therefore, we performed a multiple mediation analysis aiming to quantify the effect of each component.

METHODS: An innovative multiple mediation statistical method has been applied to data from 184 inpatients with AN completing: Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire, Eating Disorders Inventory-2, State-Trait Anxiety Inventory, and Beck Depression Inventory.

RESULTS: All affective temperaments but the hyperthymic one were involved in the relationship with DT and BD. Only the anxious temperament had a significant unmediated direct effect on DT after the strictest correction for multiple comparisons, while the depressive temperament had a significant direct effect on DT at a less strict significance level. State anxiety was the strongest mediator of the link between affective temperament and core AN body-related psychopathology. Depression showed intermediate results while trait anxiety was not a significant mediator at all.

CONCLUSION: Affective temperaments had a relevant impact on body-related core components of AN; however, a clear direct effect could be identified only for the anxious and depressive temperaments. Also, state anxiety was the strongest mediator thus entailing interesting implications in clinical practice.

LEVEL OF EVIDENCE: V, cross-sectional study.

PMID:35460450 | DOI:10.1007/s40519-022-01397-4

Clin Oral Investig. 2022 Apr 23. doi: 10.1007/s00784-022-04492-z. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess whether implant macrodesign parameters interacting with implant time in function (Tf) could influence the peri-implantitis occurrence.

MATERIALS AND METHODS: One hundred and two patients (55.17 ± 11.2 years old) with diagnosed early/moderate peri-implantitis around endosseous implants with implant-supported prosthetics reconstruction (n = 139) were recruited. Implant macrodesign (implant shape, thread number, implant collar), clinical parameters (peri-implant probing depth (PPD), clinical attachment level (CAL), keratinised tissue width (KTW), plaque index, bleeding on probe), implant placement localisation and region, and Tf were assessed and compared.

RESULTS: Peri-implantitis occurred approximately 6.1 ± 3.38 years after implant loading. There was a significant positive correlation between the implant macrodesign and Tf. Peri-implantitis rates were statistically significantly higher in implants with a cylindric shape and triple-thread in the posterior part of the mandible (p = 0.037 and 0.012, respectively). The thread number and implant shape interacting with Tf showed statistically significant influences on CAL and PPD increase (p < 0.05). Results indicated a statistically positive interaction between Tf and KTW decrease around the implants with microthreaded collar (p < 0.001).

CONCLUSION: Peri-implantitis might be presented as a time-dependent disease. Implant-based factors, such as Tf and implant macrodesign, could influence peri-implantitis occurrence, exacerbate clinical parameters, and promote progressive bone loss.

CLINICAL RELEVANCE: Peri-implantitis can be affected by implant macrodesign and Tf. The implant body shape, thread number, and design of the implant collar may be considered peri-implantitis-related risk indicators that should be taken into account in proper implant planning and therapy.

PMID:35460428 | DOI:10.1007/s00784-022-04492-z

Support Care Cancer. 2022 Apr 23. doi: 10.1007/s00520-022-07035-0. Online ahead of print.

ABSTRACT

PURPOSE: During the COVID-19 pandemic, childhood cancer survivors (CCS) may have felt more at risk of having severe consequences of COVID-19 and therefore may have been more likely to defer their health care use. We aimed to assess the risk perceptions of CCS related to COVID-19 (perceived infection risk, perceived risk of experiencing a severe illness in the event of infection), and their forgoing of health care during the year 2020.

METHODS: In December 2020, we interviewed through an online self-report questionnaire 580 5-year CCS participating in the French Childhood Cancer Survivor Study (FCCSS) cohort. Combining clinical and patient-reported outcomes, we studied predictors of perceived risks related to COVID-19 and forgoing health care.

RESULTS: Overall, 60% of respondents stated that COVID-19 could have severe consequences for their health if infected. Survivors with a cardiovascular disease and those who felt more at risk of being infected were more likely to think that COVID-19 could have severe health consequences for them. Moreover, 30% of respondents seeking care declared they had forgone at least one medical appointment in 2020. Forgoing medical appointments was more common among CCS who reported a deterioration in their financial situation in 2020 and those who felt more at risk of being infected.

CONCLUSIONS: This study shows that a considerable proportion of survivors had forgone medical appointments because of the pandemic; forgoing care was more frequent among the most socioeconomically disadvantaged survivors.

IMPLICATIONS FOR CANCER SURVIVORS: This study presents data hitherto absent in the literature and suggests the need to develop telehealth to ensure appropriate long-term follow-up of CCS.

PMID:35460426 | DOI:10.1007/s00520-022-07035-0

Mol Biol Evol. 2022 Apr 11;39(4):msac076. doi: 10.1093/molbev/msac076.

ABSTRACT

Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.

PMID:35460423 | DOI:10.1093/molbev/msac076

Int J Epidemiol. 2022 Apr 23:dyac073. doi: 10.1093/ije/dyac073. Online ahead of print.

ABSTRACT

BACKGROUND: Estimates of effect heterogeneity (i.e. the extent to which the causal effect of one exposure varies across strata of a second exposure) can be biased if the exposure-outcome relationship is subject to uncontrolled confounding whose severity differs across strata of the second exposure.

METHODS: We propose methods, analogous to the E-value for total effects, that help to assess the sensitivity of effect heterogeneity estimates to possible uncontrolled confounding. These E-value analogues characterize the severity of uncontrolled confounding strengths that would be required, hypothetically, to ‘explain away’ an estimate of multiplicative or additive effect heterogeneity in the sense that appropriately controlling for those confounder(s) would have shifted the effect heterogeneity estimate to the null, or alternatively would have shifted its confidence interval to include the null. One can also consider shifting the estimate or confidence interval to an arbitrary non-null value. All of these E-values can be obtained using the R package EValue.

RESULTS: We illustrate applying the proposed E-value analogues to studies on: (i) effect heterogeneity by sex of the effect of educational attainment on dementia incidence and (ii) effect heterogeneity by age on the effect of obesity on all-cause mortality.

CONCLUSION: Reporting these proposed E-values could help characterize the robustness of effect heterogeneity estimates to potential uncontrolled confounding.

PMID:35460421 | DOI:10.1093/ije/dyac073

Hum Reprod. 2022 Apr 23:deac076. doi: 10.1093/humrep/deac076. Online ahead of print.

ABSTRACT

STUDY QUESTION: Are patients’ characteristics, such as anti-Müllerian hormone (AMH) and BMI, reliable factors to predict ovarian response in couples with unexplained subfertility undergoing IUI with ovarian hyperstimulation (IUI-OH)?

SUMMARY ANSWER: We observed no solid relationship between serum AMH and ovarian response.

WHAT IS KNOWN ALREADY: Ovarian stimulation during IUI treatment could lead to a higher chance of pregnancy, but also a higher incidence of multiple pregnancies, unless strict cancellation criteria are being used. Several factors could influence the result of the stimulation, such as age, BMI and hormonal status of the female. In IVF treatment, AMH has shown to be a useful predictor of ovarian stimulation to optimize the outcome; however, in a milder stimulation protocol, such as IUI, this has not been investigated.

STUDY DESIGN, SIZE, DURATION: We performed a prospective cohort study and evaluated the first IUI stimulation cycle of 492 patients. The study was conducted between 2012 and 2017. Follow-up ended if patients were not pregnant after the first cycle. If pregnancy did occur, follow-up lasted until delivery.

PARTICIPANTS/MATERIALS, SETTING, METHODS: PRORAILS is a large multicentre nationwide cohort study executed in the Netherlands. Eligible women aged 18-43 years who were diagnosed with unexplained subfertility or mild male subfertility according to the Dutch guideline, with a regular indication for IUI-OH, were asked to participate. Ovarian response was assessed using a transvaginal ultrasound 5-7 days after initiation of the stimulation and was repeated according to the size of the leading follicles. Ovarian response was defined as optimal or suboptimal based on the total number of dominant follicles >15 mm. A successful stimulation was defined as the presence of two to three follicles >15 mm on the day of hCG administration. Serum AMH (µg/l) was measured by ELISA, and samples were taken on day 2, 3 or 4 of the menstrual cycle. Poisson regression was used to estimate the risk of a suboptimal ovarian response.

MAIN RESULTS AND THE ROLE OF CHANCE: Of the 492 participants, the mean age was 33 years and the mean subfertility duration was 2.5 years. The median serum AMH was 2.1 (µg/l). The majority of patients had a suboptimal response: 326 women (66%), of whom 224 (45%) had a hypo response (defined as <two follicles sized > 15 mm) and 102 (21%) had a hyper response (defined as more than three follicles sized >15 mm). The lowest AMH category showed a trend towards a smaller risk of a suboptimal response (relative risk ratio 0.76 (95% CI 0.54, 1.06)), but this effect did not reach statistical significance. In the prediction models, BMI and serum basal FSH were significant predictors of a hypo response, while for hyper response the factors age, BMI and serum FSH were significant. A higher BMI showed a higher risk for hypo response, as did a higher FSH whereas a lower BMI and lower FSH showed a higher risk for hyper response. The addition of AMH to the models did not improve the predictive abilities.

LIMITATIONS, REASONS FOR CAUTION: Although the study was prospective, the main analyses were cross-sectional with characteristics measured at one time-point. The study was not powered to provide insight into predictors of pregnancy and live births and, therefore, the result for pregnancy should be interpreted with caution.

WIDER IMPLICATIONS OF THE FINDINGS: This was the first large multicentre study that investigated the characteristics of ovarian response categories using standardized methods and centrally analysed laboratory measures. PRORAILS is a nationwide study with 15 hospitals and, therefore, these results are generalizable to other hospitals in the Netherlands. This study provides high-quality outcomes advancing the subfertility research field. Future studies would benefit from a randomized design investigating the effectiveness of an individualized approach versus a fixed dose. Also, the relation between a good ovarian stimulation and pregnancy rate could be further investigated.

STUDY FUNDING/COMPETING INTEREST(S): The PRORAILS study is sponsored by Merck B.V., Schiphol-Rijk, the Netherlands, an affiliation of Merck KGaA, Darmstadt, Germany (EMR700623_612). Merck KGaA, Darmstadt, Germany, reviewed the manuscript prior to submission. The opinions remain those of the authors. Merck KGaA, Darmstadt, Germany, had no influence on the use of medication in this study. The recombinant FSH was mostly provided by Merck B.V. or MSD. F.B. is a member of the external advisory board for Merck B.V., Schiphol-Rijk, the Netherlands, and has received a research grant from Merck B.V., Schiphol-Rijk. H.v.B. is an employee from IQVIA, which is a commercial data-analysing company, and received payment for her part in the article.

TRIAL REGISTRATION NUMBER: NCT01662180.

PMID:35460412 | DOI:10.1093/humrep/deac076

Age Ageing. 2022 Apr 1;51(4):afac092. doi: 10.1093/ageing/afac092.

ABSTRACT

OBJECTIVE: To assess the effectiveness of a pharmacist-led intervention using validated tools to reduce medicine-induced deterioration and adverse reactions.

DESIGN AND SETTING: Multicenter, open-label parallel randomised controlled trial involving 39 Australian aged-care facilities.

PARTICIPANTS: Residents on ≥4 medicines or ≥1 anticholinergic or sedative medicine.

INTERVENTION: Pharmacist-led intervention using validated tools to detect signs and symptoms of medicine-induced deterioration which occurred every 8 weeks over 12 months.

COMPARATOR: Usual care (Residential Medication Management Review) provided by accredited pharmacists.

OUTCOMES: Primary outcome was change in Frailty Index at 12 months. Secondary outcomes included changes in cognition, 24-hour movement behaviour by accelerometry, grip strength, weight, adverse events and quality of life.

RESULTS: 248 persons (median age 87 years) completed the study; 120 in the interventionand, 128 in control arms. In total 575 pharmacist, sessions were undertaken in the intervention arm. There was no statistically significant difference for change in frailty between groups (mean difference: 0.009, 95% CI: -0.028, 0.009, P = 0.320). A significant difference for cognition was observed, with a mean difference of 1.36 point change at 12 months (95% CI: 0.01, 2.72, P = 0.048). Changes in 24-hour movement behaviour, grip strength, adverse events and quality of life were not significantly different between groups. Point estimates favoured the intervention arm at 12 months for frailty, 24-hour movement behaviour and grip strength.

CONCLUSIONS: The use of validated tools by pharmacists to detect signs of medicine-induced deterioration is a model of practice that requires further research, with promising results from this trial, particularly with regards to improved cognition.

PMID:35460410 | DOI:10.1093/ageing/afac092