Tag: statistics

J Nucl Med. 2021 Dec 9:jnumed.121.262713. doi: 10.2967/jnumed.121.262713. Online ahead of print.

ABSTRACT

The objective of this study was to determine the safety, kinetics and dosimetry of ¹⁷⁷Lu labeled prostate specific membrane antigen (PSMA) small molecules ¹⁷⁷Lu-PSMA-I&T and ¹⁷⁷Lu-PSMA-617 in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing PSMA radioligand therapy (PRLT). Methods: A total of 138 patients (mean age, 70±9 y; age range 46-90 y) with progressive mCRPC and PSMA expression verified by ⁶⁸Ga-PSMA-11 PET/CT underwent PRLT. 51 patients received 6.1±1.0 GBq (range, 3.4-7.6 GBq) ¹⁷⁷Lu-PSMA I&T and 87 patients received 6.5±1.1 GBq (range, 3.5-9.0 GBq) ¹⁷⁷Lu-PSMA-617. Dosimetry was performed in all patients on the identical protocol. The mean absorbed doses were estimated with OLINDA software (MIRD Scheme). Treatment-related adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Results: The whole-body half-lives were shorter for ¹⁷⁷Lu PSMA I&T (35 h) as compared to ¹⁷⁷Lu PSMA-617 (42 h). The mean whole-body dose of ¹⁷⁷Lu-PSMA-617 was higher as compared to ¹⁷⁷Lu-PSMA-I&T (0.04 Gy/GBq vs. 0.03 Gy/GBq, p<0.00001). Despite the longer half-life of ¹⁷⁷Lu-PSMA-617, the renal dose of ¹⁷⁷Lu-PSMA-617 was lower than for ¹⁷⁷Lu-PSMA-I&T (0.77 Gy/GBq vs 0.92 Gy/GBq, P = 0.0015). Both PSMA small molecules demonstrated a comparable dose to parotid glands (0.5 Gy/GBq, P = 0.27). Among all normal organs, lacrimal glands exhibited the highest mean absorbed dose of 5.1 Gy/GBq and 3.7 Gy/GBq for ¹⁷⁷Lu-PSMA-617 and ¹⁷⁷Lu-PSMA I&T, respectively. All tumor metastases exhibited a higher initial uptake when using ¹⁷⁷Lu-PSMA I&T, as well as shorter tumor half-life as compared to ¹⁷⁷Lu-PSMA-617 (p<0.00001). The mean absorbed tumor doses were comparable for both ¹⁷⁷Lu-PSMA I&T and ¹⁷⁷Lu-PSMA-617 (5.8 Gy/GBq vs. 5.9 Gy/GBq, P = 0.96). All patients tolerated the therapy without any acute adverse effects. There was a small, statistically significant reduction in hemoglobin, leukocyte counts and platelet counts after ¹⁷⁷Lu-PSMA-617 and ¹⁷⁷Lu-PSMA I&T which did not need any clinical intervention. No nephrotoxicity was observed after either ¹⁷⁷Lu-PSMA I&T or ¹⁷⁷Lu-PSMA-617 PRLT. Conclusion: Both ¹⁷⁷Lu-PSMA I&T and ¹⁷⁷Lu-PSMA-617 PRLT demonstrated favorable safety in mCRPC patients. Highest absorbed dose amongst healthy organs were observed for the lacrimal and parotid glands, however, not resulting in any significant clinical sequel. ¹⁷⁷Lu-PSMA-617 demonstrated higher whole-body and lacrimal glands absorbed dose, but lower renal doses as compared to ¹⁷⁷Lu-PSMA-I&T. The mean absorbed tumor doses were comparable for both ¹⁷⁷Lu-PSMA I&T and ¹⁷⁷Lu-PSMA-617. There was a large inter-patient variability of the dosimetry parameters. Therefore, individual patient-based dosimetry seems favorable for personalized PRLT.

PMID:34887335 | DOI:10.2967/jnumed.121.262713

BMJ Open. 2021 Dec 9;11(12):e050598. doi: 10.1136/bmjopen-2021-050598.

ABSTRACT

BACKGROUND: Overweight/obesity increased dramatically among Indian women since 2000. We evaluated the independent contributions of economic and nutrition context to the changing distribution of overweight/obesity among women from 1998 to 2016 across India.

METHODS: Individual-level data from 473 912 ever married Indian women aged 18-49 in the National Family Health Surveys (1998-1999, 2005-2006, 2015-2016) were merged with year-matched state-level economic and nutrition context indicators. Cross-classified generalised linear mixed models were estimated to quantify associations of contextual characteristics with overweight/obesity (body mass index ≥25 kg/m²) across survey rounds.

RESULTS: Between 1998 and 2016, age-standardised prevalence of overweight/obesity increased from 13.9% to 27.5% nationally at an annual growth rate of 0.8%. After accounting for a woman’s age, parity and social class, the adjusted OR (aOR) for overweight/obesity was 2.02 times higher for every unit of state log per capita gross domestic product (GDP) (95% credible interval (CrI) 2.00 to 2.03). Yet, the association of state GDP with overweight/obesity generally decreased over survey round. Women in states with higher per capita daily oil (aOR 1.02 per gram; 95% CrI 1.01 to 1.03) and sugar (aOR 1.05 per gram; 95% CrI 1.04 to 1.05) consumption were more likely to be overweight/obese, while women in states with higher cereal consumption were less likely to be overweight/obese (aOR 0.93 per 10 gram; 95% CrI 0.93 to 0.93).

CONCLUSIONS: Indicators of state economic development and nutrition transition were independently associated with a woman’s likelihood of being overweight/obese. The impact of state wealth waned over survey round, suggesting that risks for overweight/obesity may be increasingly shaped by individual factors as economic development expands in India.

PMID:34887275 | DOI:10.1136/bmjopen-2021-050598

BMJ Open. 2021 Dec 9;11(12):e052901. doi: 10.1136/bmjopen-2021-052901.

ABSTRACT

INTRODUCTION: Therapeutic management of neonatal pain is essential to reduce changes in initial and subsequent development. Although glucose has been shown to be effective in relieving pain, concentrations and dosages remain to be standardised. The objective of this systematic review and meta-analysis is to identify the efficacy of glucose as an analgesic in preterm infants.

METHODS AND ANALYSIS: The Web of Science, Science Direct, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, PubMed, Medline, Latin American and Caribbean Health Sciences Literature and Embase databases will be researched for randomised studies published until December 2021. This systematic review and meta-analysis will include studies investigating the use of glucose for pain control in premature neonates. The primary outcome will be pain relief. Three independent reviewers will select the studies and extract the data from original publications. The risk of bias was assessed using the Cochrane risk of bias tool. Data synthesis will be performed using the Review Manager software (RevMan V.5.2.3). We will evaluate heterogeneity based on I² statistics. In addition, quantitative synthesis will be performed if the included studies are sufficiently homogeneous.

ETHICS AND DISSEMINATION: Ethical approval for the research will not be required for this systematic review. The results of this study will be published in an international journal.

TRIAL REGISTRATION NUMBER: This protocol was submitted to the International Prospective Register of Systematic Reviews (PROSPERO, number CRD42021236217).

PMID:34887278 | DOI:10.1136/bmjopen-2021-052901

Explore (NY). 2021 Nov 24:S1550-8307(21)00242-1. doi: 10.1016/j.explore.2021.11.007. Online ahead of print.

ABSTRACT

OBJECTIVE: This study explored if human primary mesenchymal stem cells (MSCs), derived from two donors and cultivated in a medium made with intentionally treated water, would exhibit more growth and pluripotency than MSCs from the same source but grown in untreated (control) water.

DESIGN: To create the treated water, three Buddhist monks directed their attention toward commercially bottled water while holding the intention that the water would enhance the growth of MSCs. Under double-blind conditions, cell culture growth mediums were prepared with the treated and untreated water, which was in turn used to grow the primary MSCs. Primary cells obtained from two donors were designated as Cells #1 and Cells #2. The prediction was that treated water would result in increased cell proliferation, that more cells would enter the cell cycle growth phase, and that there would be increased expression of genes (NANOG, OCT4 and SOX2) associated with improved cell growth and decreased expression of genes (p16, p21, and p53) associated with a decline in cell growth. The improved growth hypothesis was directional, thus one-tailed p-values were used to evaluate the results.

RESULTS: Proliferation averaged across Cells #1 and #2 showed overall increased growth in treated as compared to control water (p = 0.0008). Cells #1 and #2 considered separately had differences in the same direction but only Cells #2 showed a significant difference on day 6 (p = 0.01). For cell cycle, there was a significantly greater percentage of Cells #2 in the S interphase with treated vs. control water (p = 0.04). For the gene expression analysis, when considering the average across the two donor cells, only the NANOG gene expression was in the predicted direction (p = 0.01); by contrast, the p16 gene expression was significantly opposite to the predicted direction (p = 0.005, one-tailed, post-hoc). For Cells #1 considered separately, no differences were significant except for p16, which resulted in an effect opposite to the predicted outcome (p = 0.05). For Cells #2, three genes were significantly in the predicted directions: NANOG (p = 0.0008), OCT4 (p = 0.005), and P53 (p = 0.05); p16 was significantly opposite to the prediction (p = 0.001).

CONCLUSION: Intentionally treated water appeared to have some biological effects on the growth, pluripotency and senescence of human MSCs. This was especially the case in one of the two donor cells tested, but the effects were not consistently in the predicted direction. As an exploratory study, caution is warranted in interpreting these outcomes, and adjustment for multiple testing would likely reduce some of the weaker effects to nonsignificant. But given the double-blind protocol, as well as several more significant outcomes in the predicted directions, further research is warranted.

PMID:34887234 | DOI:10.1016/j.explore.2021.11.007

Epileptic Disord. 2021 Dec 9. doi: 10.1684/epd.2021.1384. Online ahead of print.

ABSTRACT

OBJECTIVE: Structural MRI is a critical component in the pre-surgical investigation of epilepsy, as identifying an epileptogenic lesion increases the chance of post-surgical seizure freedom. In general practice, 1.5T and 3T MRI scans are still the mainstream in most epilepsy centres, particularly in resource-poor countries. When 1.5T MRI is non-lesional, a repeat scan is often performed as a higher-field structural scan, usually 3T. However, it is not known whether scanning at 3T increases diagnostic yield in patients with focal epilepsy. We sought to compare lesion detection and other features of 1.5T and 3T MRI acquired in the same patients with epilepsy.

METHODS: MRI scans (1.5T and 3T) from 100 patients were presented in a blinded, randomized order to two neuroradiologists. The presence, location, and number of potentially epileptogenic lesions were compared. In addition, tissue contrast and the presence of motion/technical artifacts were compared using a 4-point subjective scale.

RESULTS: Both the qualitative tissue contrast and motion/technical artifacts were improved at 3T. However, this did not result in statistically significant improvement in lesion detection. Qualitatively, five patients had subtle lesions seen only at 3T. However, minor differences in image acquisition parameters between 1.5T and 3T scans in these cases may have resulted in greater lesion visibility at 3T in four patients. Based on a general linear model analysis, the presence of a focal abnormality on EEG was predictive of the presence of a lesion at 1.5T and 3T.

SIGNIFICANCE: Repeat MRI scanning of patients with focal epilepsy at 3T using similar scan protocols does not significantly increase diagnostic yield over scanning at 1.5T; the increased signal-to-noise ratio can potentially be better allocated for novel scan sequences in order to provide more clinical value.

PMID:34887241 | DOI:10.1684/epd.2021.1384

J Plast Reconstr Aesthet Surg. 2021 Nov 14:S1748-6815(21)00551-9. doi: 10.1016/j.bjps.2021.11.007. Online ahead of print.

ABSTRACT

BACKGROUND: In breast reduction, traditionally the inferior pedicle (IFP) technique is considered the most performed by plastic surgeons. A growing interest for the superomedial pedicle (SMP) mammoplasty technique has been documented in literature and clinical practice. Sensory recovery of the nipple-areolar complex (NAC), final areolar shape and scarring may also have a significant impact on patient satisfaction.

OBJECTIVE: This study represents a retrospective multimodal analysis comparing NAC sensation and appearance outcomes in IFP and SMP wise pattern breast reductions with 2-year follow-up.

METHODS: From 2013 to 2017, all performed reduction mammoplasty were included and divided in two groups (IFP or SMP technique). Testing included pressure perception (Semmes-Weinstein monofilaments), NAC measurement (diameters ratio and circumference) and circumareolar scar hypertrophy assessment. Measurements were repeated at 2 weeks, 6 and 24 months postoperatively.

RESULTS: amongst the 73 patients, 42 (58%) had SMP technique and 31 (42%) had IFP technique. Values at 6-months showed better sensory return in the SMP (p < 0.01**). NAC enlargement, showed no difference between groups. However, there was a statistically significant increase in both the SMP (p < 0.001***) and the IFP (p < 0.01**) groups when comparing the 2-week and 24-month follow-up visits measured ratios confirming a more oval appearance over time with both techniques. Scar hypertrophy showed statistically significant reduction in both the SMP (p < 0.001***) and the IFP (p < 0.01**) groups over time.

CONCLUSION: This 2-year follow-up study showed little difference in outcomes between the two techniques, but some advantages in NAC sensory recovery with the SMP.

PMID:34887222 | DOI:10.1016/j.bjps.2021.11.007

Wilderness Environ Med. 2021 Dec 6:S1080-6032(21)00196-4. doi: 10.1016/j.wem.2021.10.002. Online ahead of print.

ABSTRACT

INTRODUCTION: Those who work and recreate outdoors experience woodsmoke exposure during fire season. Exercise during woodsmoke exposure harms the cardiovascular system, but the acute physiologic and biochemical responses are understudied. The purpose of this pilot laboratory-based study was to examine the effect of exercise during woodsmoke exposure on acute indicators of cardiovascular function, including heart rate variability (HRV), pulse wave velocity (PWV), blood pressure (BP), augmentation index (AIx), and blood oxidative stress.

METHODS: Ten participants performed 2 moderate-intensity exercise (70% V˙O_2max) trials (clean air 0 μg·m^-3, woodsmoke 250 μg·m^-3) in a crossover design. HRV, PWV, BP, AIx, and blood oxidative stress were measured before, after, and 90 min after exercise for each trial. Blood oxidative stress was quantified through lipid damage (LOOH, 8-ISO), protein damage (3-NT, PC), and antioxidant capacity (TEAC).

RESULTS: A 45-min woodsmoke exposure combined with moderate-intensity exercise did not result in a statistically significant difference in HRV, PWV, BP, AIx, or oxidative stress (P>0.05).

CONCLUSIONS: Despite the known deleterious effects of smoke inhalation, moderate-intensity aerobic exercise while exposed to woodsmoke particulate matter (250 μg·m^-3) did not result in a statistically significant difference in HRV, PWV, or blood oxidative stress in this methodologic context. Although findings do not negate the negative impact of woodsmoke inhalation, additional research approaches are needed to better understand the acute effects of smoke exposure on the cardiovascular system.

PMID:34887190 | DOI:10.1016/j.wem.2021.10.002

Clin Lung Cancer. 2021 Nov 11:S1525-7304(21)00278-3. doi: 10.1016/j.cllc.2021.11.001. Online ahead of print.

ABSTRACT

INTRODUCTION: Patients with EGFR-mutant lung cancer who have had disease progression on osimertinib commonly receive platinum doublet chemotherapy, but whether adding immunotherapy or bevacizumab provides additional benefit is unknown.

MATERIALS AND METHODS: This was a retrospective analysis at 2 university-affiliated institutions. Patients with EGFR-mutant lung cancer who had progression on osimertinib and received next-line therapy with platinum doublet chemotherapy (chemo), platinum doublet chemotherapy plus immunotherapy (chemo-IO), or platinum doublet chemotherapy plus bevacizumab (chemo-bev), were identified; patients who continued osimertinib with these regimens were included. Efficacy outcomes including duration on treatment (DOT) and overall survival (OS) from the start of chemotherapy were assessed. Associations of treatment regimen with outcomes were evaluated using adjusted Cox regression models, using pairwise comparisons between groups.

RESULTS: 104 patients were included: 57 received chemo, 12 received chemo-IO, and 35 received chemo-bev. In adjusted models, patients who received chemo-IO had worse OS than did those who received chemo (hazard ratio (HR) 2.66, 95% CI 1.25-5.65; P= .011) or those who received chemo-bev (HR 2.37, 95% CI 1.09-5.65; P= .030). A statistically significant difference in OS could not be detected in patients who received chemo-bev versus those who received chemo (HR 1.50, 95% CI 0.84-2.69; P= .17).

CONCLUSION: In this retrospective study, giving immunotherapy with platinum doublet chemotherapy after progression on osimertinib was associated with a worse OS compared with platinum doublet chemotherapy alone. Platinum doublet chemotherapy without immunotherapy (with consideration of continuation of osimertinib, in selected cases) is a reasonable choice in this setting, while we await results of clinical trials examining optimal next-line chemotherapy-based regimens in EGFR-mutant lung cancer.

PMID:34887193 | DOI:10.1016/j.cllc.2021.11.001

J Am Pharm Assoc (2003). 2021 Nov 18:S1544-3191(21)00477-5. doi: 10.1016/j.japh.2021.11.016. Online ahead of print.

ABSTRACT

BACKGROUND: The provision of enhanced services within community-based pharmacy is increasing. However, an opportunity remains to improve efficient documentation of services, and barriers to implementation exist. Electronic care (eCare) planning is the act of using health information technology to submit a pharmacist eCare plan for a patient encounter, similar to a Subjective, Objective, Assessment, Plan note.

OBJECTIVE: The primary objective was to identify barriers and best practices related to documentation of eCare plans within community-based pharmacies participating in 4 Community Pharmacy Enhanced Services Networks (CPESN).

METHODS: One of two 24-question electronic surveys was distributed to pharmacies in CPESN Florida, Georgia, Mississippi, and Ohio. Pharmacies submitting fewer than 10 eCare plans in the previous quarter received a survey to assess barriers to implementation; pharmacies submitting 10 or more eCare plans received a survey to assess best practices for implementation. Surveys remained open for 14 days, with a reminder sent on days 7 and 12. Data were analyzed using descriptive statistics. An independent-samples t test assessed for between-group differences in the overall knowledge.

RESULTS: A total of 63 responses were received (Barriers = 19; Best Practices = 44). Best Practices pharmacies earned a higher overall knowledge score than Barriers pharmacies (9.26 vs. 7.26 out of 13 points, P = 0.001). Frequently reported barriers were staffing resources (n = 11, 57.9%), perceived time commitment (n = 8, 42.1%), and lack of payment (n = 8, 42.1%). Most Best Practices pharmacies agreed or strongly agreed that they involve pharmacists (n = 36, 81.8%) and student pharmacists (n = 33, 75.5%) in eCare planning processes. Common foci of eCare plans by Best Practice pharmacies were medication synchronization (n = 35, 79.5%), drug therapy problems (n = 29, 65.9%), adherence assessment (n = 28, 63.6%).

CONCLUSIONS: A difference in knowledge and perceptions exists between pharmacies who regularly eCare plan and those who do not. Observed trends in knowledge, perceptions, barriers, and best practices should be used to create a training to increase eCare planning quality and consistency.

PMID:34887187 | DOI:10.1016/j.japh.2021.11.016

J Am Pharm Assoc (2003). 2021 Nov 17:S1544-3191(21)00475-1. doi: 10.1016/j.japh.2021.11.014. Online ahead of print.

ABSTRACT

BACKGROUND: Pharmacists with competency in writing, publishing, and peer review are essential to continue advancing the pharmacy profession, but structured training of these skills may vary.

OBJECTIVE: The authors set out to implement and assess the impact of a structured learning experience into a postgraduate year 1 pharmacy residency training program that provides tangible experience in the processes of scientific writing, publishing, and peer reviewing.

METHODS: A quarterly pharmacy newsletter process was augmented to include an editorial board that consisted of residency trained pharmacists with varying levels of experience in scientific writing, publishing, and peer reviewing. The process was designed to provide a structured writing learning experience, to reinforce important concepts and terminology, and to simulate the process of submitting a manuscript to a peer-reviewed publication. Impact of the learning experience on quality of article submissions was assessed by comparing first quarter and last quarter writing submission scores for residents between 2017 and 2020.

RESULTS: A statistically significant difference was observed in both raw scores (27 vs. 42.5 points out of 50 points possible, P < 0.05) and the proportion of pass or fail when comparing writing submission scores from the first quarter of the learning experience to submission scores from the last quarter (25% passing rate vs. 83% passing rate, P = 0.007).

CONCLUSION: This novel learning experience was successfully integrated into a quarterly pharmacy newsletter and resulted in improved writing scores. This structured writing learning experience can be readily integrated into pharmacy residency training programs, and it provides hands-on training in scientific writing, publishing, and peer review for both residents and preceptors.

PMID:34887188 | DOI:10.1016/j.japh.2021.11.014