Category: Nevin Manimala

J Clin Oncol. 2023 Jan 31:JCO2202186. doi: 10.1200/JCO.22.02186. Online ahead of print.

ABSTRACT

PURPOSE: The phase III ADAURA (ClinicalTrials.gov identifier: NCT02511106) primary analysis demonstrated a clinically significant disease-free survival (DFS) benefit with adjuvant osimertinib versus placebo in EGFR-mutated stage IB-IIIA non-small-cell lung cancer (NSCLC) after complete tumor resection (DFS hazard ratio [HR], 0.20 [99.12% CI, 0.14 to 0.30]; P < .001). We report an updated exploratory analysis of final DFS data.

METHODS: Overall, 682 patients with stage IB-IIIA (American Joint Committee on Cancer/Union for International Cancer Control, seventh edition) EGFR-mutated (exon 19 deletion/L858R) NSCLC were randomly assigned 1:1 (stratified by stage, mutational status, and race) to receive osimertinib 80 mg once-daily or placebo for 3 years. The primary end point was DFS by investigator assessment in stage II-IIIA disease analyzed by stratified log-rank test; following early reporting of statistical significance in DFS, no further formal statistical testing was planned. Secondary end points included DFS in stage IB-IIIA, overall survival, and safety. Patterns of recurrence and CNS DFS were prespecified exploratory end points.

RESULTS: At data cutoff (April 11, 2022), in stage II-IIIA disease, median follow-up was 44.2 months (osimertinib) and 19.6 months (placebo); the DFS HR was 0.23 (95% CI, 0.18 to 0.30); 4-year DFS rate was 70% (osimertinib) and 29% (placebo). In the overall population, DFS HR was 0.27 (95% CI, 0.21 to 0.34); 4-year DFS rate was 73% (osimertinib) and 38% (placebo). Fewer patients treated with osimertinib had local/regional and distant recurrence versus placebo. CNS DFS HR in stage II-IIIA was 0.24 (95% CI, 0.14 to 0.42). The long-term safety profile of osimertinib was consistent with the primary analysis.

CONCLUSION: These updated data demonstrate prolonged DFS benefit over placebo, reduced risk of local and distant recurrence, improved CNS DFS, and a consistent safety profile, supporting the efficacy of adjuvant osimertinib in resected EGFR-mutated NSCLC.

PMID:36720083 | DOI:10.1200/JCO.22.02186

Menopause. 2023 Jan 31. doi: 10.1097/GME.0000000000002138. Online ahead of print.

ABSTRACT

OBJECTIVE: Neurokinin (NK)-3 and NK-1 receptors have been implicated in the etiology of vasomotor symptoms (VMS) and sleep disturbances associated with menopause. This phase 2b, adaptive, dose-range finding study aimed to assess the efficacy and safety of multiple doses of elinzanetant (NT-814), a selective NK-1,3 receptor antagonist, in women experiencing VMS associated with menopause, and investigate the impact of elinzanetant on sleep and quality of life.

METHODS: Postmenopausal women aged 40 to 65 years who experienced seven or more moderate-to-severe VMS per day were randomized to receive elinzanetant 40, 80, 120, or 160 mg or placebo once daily using an adaptive design algorithm. Coprimary endpoints were reduction in mean frequency and severity of moderate-to-severe VMS at weeks 4 and 12. Secondary endpoints included patient-reported assessments of sleep and quality of life.

RESULTS: Elinzanetant 120 mg and 160 mg achieved reductions in VMS frequency versus placebo from week 1 throughout 12 weeks of treatment. Least square mean reductions were statistically significant versus placebo at both primary endpoint time points for elinzanetant 120 mg (week 4: -3.93 [SE, 1.02], P < 0.001; week 12: -2.95 [1.15], P = 0.01) and at week 4 for elinzanetant 160 mg (-2.63 [1.03]; P = 0.01). Both doses also led to clinically meaningful improvements in measures of sleep and quality of life. All doses of elinzanetant were well tolerated.

CONCLUSIONS: Elinzanetant is an effective and well-tolerated nonhormone treatment option for postmenopausal women with VMS and associated sleep disturbance. Elinzanetant also improves quality of life in women with VMS.

PMID:36720081 | DOI:10.1097/GME.0000000000002138

Menopause. 2023 Jan 31. doi: 10.1097/GME.0000000000002155. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to describe the menopause experience of people with cystic fibrosis (CF).

METHODS: We conducted a computer-based cross-sectional survey of women with CF 25 years or older at 10 US CF centers exploring a range of sexual and reproductive health concerns, including menopause. We used descriptive statistics to analyze results.

RESULTS: Of 460 participants, 5 (3%) were perimenopausal and 34 (7%) were postmenopausal. Of participants perimenopausal or menopausal (n = 39), 97% reported the following menopausal symptoms occurring at least once a week: most commonly early wake-up (83%); stiffness/soreness in joints, neck, or shoulders (65%); and night sweats (65%). Among menopausal participants, the median self-reported age at menopause was 48.5 years (interquartile range, 5.5 y). Thirty percent experienced worsened CF symptoms during menopause, and 42% experienced worsening CF symptoms after menopause. Twenty-four percent of menopausal participants were on estrogen therapy and 15% on estrogen and progesterone therapy. Three-fourths of participants using hormone therapy reported no change in their CF symptoms. One percent of the 460 survey participants reported discussing menopause with their CF provider, despite 19% wanting to discuss this topic with their CF team.

CONCLUSIONS: This is the first study to describe menopause symptoms of people with CF. People with CF experience a variety of menopausal symptoms and often report a worsening of their CF symptoms after menopause, suggesting an interplay between female sex hormones and CF. Larger studies are needed comparing the sexual and reproductive health experiences and care needs of people with CF in the menopause transition to the general population.

PMID:36720079 | DOI:10.1097/GME.0000000000002155

Int J Pharm Compd. 2023 Jan-Feb;27(1):39-46.

ABSTRACT

Whether sterile compounds are prepared in a brand new state-of-the-art cleanroom suite or in an aging space, compounders rely heavily on their primary and secondary engineering controls when sterilizing or maintaining sterility of the final preparation. With the release of the latest revision to United States Pharmacopeia Chapter <797>, organizations that prepare sterile compounds must now sample and test each classified area for the presence of microbiological contaminants at a higher frequency. Facilities that are not purpose-built, as well as those that do not operate within a state of control, are predicted to repeatedly exceed action levels as set by the United States Pharmacopeia Convention, Inc. Before the United States Pharmacopeia revision becomes active and enforceable, it is advised that sterile compounding practice sites undergo an environmental-baseline study to gather statistically significant data to demonstrate how the cleanroom(s) perform and to assess whether or not dynamic operations increase the levels of bioburden.

PMID:36720062

Dimens Crit Care Nurs. 2023 Mar-Apr 01;42(2):104-114. doi: 10.1097/DCC.0000000000000572.

ABSTRACT

PURPOSE: The present research was conducted to reveal the impact of abdominal massage on enteral nutrition-induced ventilator-associated pneumonia and the gastrointestinal system in mechanically ventilated patients.

MATERIALS AND METHODS: The present research is a prospective, randomized, controlled clinical trial. This study was completed with 63 patients (31 in the experimental group and 32 in the control group). Data collection was performed using a patient information form, a patient follow-up form, and the Bristol Stool Scale. After patients were under mechanical ventilation for 48 hours, the data collection tools were filled out twice a day for 3 days by visiting the mechanical ventilation patients. The experimental group received 15 minutes of abdominal massage twice a day before nursing care was delivered in the morning and the evening.

RESULTS: According to the intergroup evaluations, the experimental group had lower gastric residual volume and abdominal distension, types of stool closer to normal, and higher defecation frequency. Differences between the groups were statistically significant (P < .05). In accordance with the intragroup evaluations, the experimental group had lower gastric residual volume, abdominal distension, and ventilator-associated pneumonia. The difference between the groups was revealed to be statistically significant (P < .05).

CONCLUSION: Abdominal massage reduces ventilator-associated pneumonia development to a statistically significant degree. Furthermore, it decreases gastric residual volume and abdominal distension, causes stools to be closer to the normal/ideal stool, increases defecation frequency, and regulates bowel movements and excretion (P < .05).

PMID:36720035 | DOI:10.1097/DCC.0000000000000572

Clin J Am Soc Nephrol. 2023 Jan 1;18(1):28-35. doi: 10.2215/CJN.0000000000000035.

ABSTRACT

BACKGROUND: Prediction tools that incorporate self-reported health information could increase CKD awareness, identify modifiable lifestyle risk factors, and prevent disease. We developed and validated a survey-based prediction equation to identify individuals at risk for incident CKD (eGFR <60 ml/min per 1.73 m2), with and without a baseline eGFR.

METHODS: A cohort of adults with an eGFR ≥70 ml/min per 1.73 m2 from Ontario, Canada, who completed a comprehensive general population health survey between 2000 and 2015 were included (n=22,200). Prediction equations included demographics (age, sex), comorbidities, lifestyle factors, diet, and mood. Models with and without baseline eGFR were derived and externally validated in the UK Biobank (n=15,522). New-onset CKD (eGFR <60 ml/min per 1.73 m2) with ≤8 years of follow-up was the primary outcome.

RESULTS: Among Ontario individuals (mean age, 55 years; 58% women; baseline eGFR, 95 (SD 15) ml/min per 1.73 m2), new-onset CKD occurred in 1981 (9%) during a median follow-up time of 4.2 years. The final models included lifestyle factors (smoking, alcohol, physical activity) and comorbid illnesses (diabetes, hypertension, cancer). The model was discriminating in individuals with and without a baseline eGFR measure (5-year c-statistic with baseline eGFR: 83.5, 95% confidence interval [CI], 82.2 to 84.9; without: 81.0, 95% CI, 79.8 to 82.4) and well calibrated. In external validation, the 5-year c-statistic was 78.1 (95% CI, 74.2 to 82.0) and 66.0 (95% CI, 61.6 to 70.4), with and without baseline eGFR, respectively, and maintained calibration.

CONCLUSIONS: Self-reported lifestyle and health behavior information from health surveys may aid in predicting incident CKD.

PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast.aspx?p=CJASN&e=2023_01_10_CJN05650522.mp3.

PMID:36720027 | DOI:10.2215/CJN.0000000000000035

Coron Artery Dis. 2023 Mar 1;34(2):119-126. doi: 10.1097/MCA.0000000000001211. Epub 2022 Dec 23.

ABSTRACT

BACKGROUND: Patientswho present with acute ST elevation myocardial infarction (STEMI) need emergent revascularization. Our study aims to investigate the outcomes in patients with STEMI admitted during weekends versus weekdays.

METHODS: We conducted a retrospective analysis of the nationwide inpatient sample database. Patients with an admitting diagnosis of STEMI identified by the International Classification of Disease code for the year 2016 were analyzed. A weighted descriptive analysis was performed to generate national estimates. Patients admitted over the weekend were compared to those admitted over the weekday. Patients were stratified by demographic and clinical factors including the Elixhauser comorbidity index. The primary outcome was in-hospital mortality and secondary outcomes were percutaneous coronary intervention (PCI) utilization rate, rate of transfer-out, length of stay (LOS), and total hospital charges. Statistical analysis including linear and logistic regression was performed using STATA.

RESULTS: A total of 163 715 adult patients were admitted with STEMI, of which 27.9% (45 635) were admitted over the weekend. There were 76.2% Caucasians, 9.3% African Americans, and 8.0% Hispanics. Mean age of the patients was 63.2 years (95% CI, 62.9-63.5) for the weekend group and 63.7 years (95% CI, 63.5-63.9) for weekday admissions. The majority of the patients in both groups had Medicare (43.7% and 45.8% on weekends and weekdays, respectively; P = 0.0047). After adjusting for age, sex, race, income, Elixhauser comorbidity index, PCI use, hospital location, teaching status, and bed size, mortality was not significantly different in weekend versus weekday admissions (odds ratios 1.04; P = 0.498; 95% CI, 0.93-1.16). There was no significant difference in mean total charge per admission during the weekend versus weekday admissions ($107 093 versus $106 869; P = 0.99.) Mean LOS was 4.1 days for both groups (P = 0.81).

CONCLUSIONS: There were no significant differences in mortality, LOS, or total hospital charge in STEMI patients being admitted during the weekend versus weekdays.

PMID:36720020 | DOI:10.1097/MCA.0000000000001211

Facial Plast Surg Aesthet Med. 2023 Jan 31. doi: 10.1089/fpsam.2022.0330. Online ahead of print.

ABSTRACT

Background: This study aims to evaluate three-dimensional stereophotogrammetry measured volume changes in the tear trough area after lower blepharoplasty with midface lift with or without orbital fat manipulation. Objective: Among patients undergoing midface lift surgery, volume change by three-dimensional photography in the tear trough region was compared between those having no orbital fat manipulation, fat transposition, or fat resection. Methods: This is a prospective study of 260 eyelids of 130 patients who underwent cosmetic midface surgery. All patients had an external skin muscle flap midface lift. During the procedure, medial inferior orbital fat was resected, repositioned to a preperiosteal dissection pocket, or not manipulated. Forty-six patients (35.4%) had no fat manipulation, 42 patients (32.3%) had fat preservation with repositioning to the preperiosteal pockets on the medial inferior orbital rim, and 42 patients (32.3%) had fat resection without repositioning. Results: All patients had volume gain in tear trough volume. The amount was not statistically significantly different between fat treatment groups. Mean follow-up time was 12 months (range 6-20 months). Conclusions: Midface lifting improved tear trough volume irrespective of how fat was manipulated.

PMID:36719989 | DOI:10.1089/fpsam.2022.0330

Annu Rev Phys Chem. 2022 Jan 31. doi: 10.1146/annurev-physchem-101422-030127. Online ahead of print.

ABSTRACT

Phillip L. Geissler made important contributions to the statistical mechanics of biological polymers, heterogeneous materials, and chemical dynamics in aqueous environments. He devised analytical and computational methods that revealed the underlying organization of complex systems at the frontiers of biology, chemistry, and materials science. In this retrospective we celebrate his work at these frontiers. Expected final online publication date for the Annual Review of Physical Chemistry, Volume 74 is April 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID:36719975 | DOI:10.1146/annurev-physchem-101422-030127

Epidemiology. 2023 Jan 31. doi: 10.1097/EDE.0000000000001597. Online ahead of print.

ABSTRACT

BACKGROUND: Research and reporting of mortality indicators typically focus on a single underlying cause of death selected from multiple causes recorded on a death certificate. The need to incorporate the multiple causes in mortality statistics – reflecting increasing multimorbidity and complex causation patterns – is recognized internationally. This review aims to identify and appraise relevant analytical methods and practices related to multiple causes.

METHODS: We searched Medline, PubMed, Scopus and Web of Science from their inception to December 2020 without language restrictions, supplemented by consultation with international experts. Eligible articles analyzed multiple causes of death from death certificates. The process identified 4,080 items of which we reviewed 434 full-text articles.

RESULTS: Most articles we reviewed (76%, n=332) were published since 2001. The majority examined mortality by “any mention” of cause of death (87%, n=377) and assessed pairwise combinations of causes (57%, n=245). Since 2001, applications of methods emerged to group deaths based on common cause patterns using, for example, cluster analysis (2%, n=9), and application of multiple-cause weights to re-evaluate mortality burden (1%, n=5). We describe multiple-cause methods applied to specific research objectives for approaches emerging recently.

CONCLUSION: This review confirms rapidly increasing international interest in the analysis of multiple causes of death and provides the most comprehensive overview, to our knowledge, of methods and practices to date. Available multiple-cause methods are diverse but suit a range of research objectives. With greater availability of data and technology, these could be further developed and applied across a range of settings.

PMID:36719759 | DOI:10.1097/EDE.0000000000001597