Tag: statistics

J Wildl Dis. 2023 Jun 1. doi: 10.7589/JWD-D-22-00052. Online ahead of print.

ABSTRACT

Increasing reports of canine distemper virus (CDV) in a variety of hosts, and changing CDV dynamics, have led to renewed interest in the ecology of CDV infections in wildlife. Longitudinal serologic studies provide insights into intrapopulation and intraindividual pathogen dynamics, but few studies in wildlife have been conducted. We used data from 235 raccoons (Procyon lotor) captured on more than one occasion between May 2011 and November 2013 to investigate CDV dynamics in Ontario, Canada. Using mixed multivariable logistic regression, we found that juvenile raccoons were more likely to be seronegative from August to November than from May to July. Using paired titers from CDV-exposed individual raccoons, we determined that the winter breeding season, when there is high intraspecific contact and an increase in susceptible juveniles, may be a period of high risk for CDV exposure. Interestingly, CDV seropositive adult raccoons had nondetectable titers ranging from 1 mo to 1 yr later. Based on our preliminary investigation using two different statistical approaches, CDV exposure was associated with a decrease in parvovirus titer. This result raises important questions about whether virus-induced immune amnesia occurs after CDV exposure, which has been described for measles virus, a closely related pathogen. Overall, our results provide significant insights into CDV dynamics. Further research is needed to investigate whether CDV-induced immune amnesia occurs in raccoons and to determine the potential impacts of a reduced population immunity that may occur secondary to CDV exposure, particularly as it relates to rabies control efforts.

PMID:37270706 | DOI:10.7589/JWD-D-22-00052

JAMA Oncol. 2023 Jun 4. doi: 10.1001/jamaoncol.2023.1891. Online ahead of print.

ABSTRACT

IMPORTANCE: For patients with advanced non-small cell lung cancer (NSCLC) treated with frontline immunotherapy-based treatment, the optimal duration of immune checkpoint inhibitor (ICI) treatment is unknown.

OBJECTIVE: To assess practice patterns surrounding ICI treatment discontinuation at 2 years and to evaluate the association of duration of therapy with overall survival in patients who received fixed-duration ICI therapy for 2 years vs those who continued therapy beyond 2 years.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based cohort study included adult patients in a clinical database diagnosed with advanced NSCLC from 2016 to 2020, who received frontline immunotherapy-based treatment. The data cutoff was August 31, 2022; data analysis was conducted from October 2022 to January 2023.

EXPOSURES: Treatment discontinuation at 2 years (between 700 and 760 days, fixed duration) vs continued treatment beyond 2 years (greater than 760 days, indefinite duration).

MAIN OUTCOMES AND MEASURES: Overall survival from 760 days was analyzed using Kaplan-Meier methods. Multivariable Cox regression that adjusted for patient-specific and cancer-specific factors was used to compare survival beyond 760 days between the fixed-duration group and the indefinite-duration group.

RESULTS: Of 1091 patients in the analytic cohort who were still on ICI treatment at 2 years after exclusion criteria for death and progression were applied, 113 patients (median [IQR] age, 69 [62-75] years; 62 [54.9%] female; 86 [76.1%] White) were in the fixed-duration group, and 593 patients (median [IQR] age, 69 [62-76] years; 282 [47.6%] female; 414 [69.8%] White) were in the indefinite-duration group. Patients in the fixed-duration group were more likely to have a history of smoking (99% vs 93%; P = .01) and be treated at an academic center (22% vs 11%; P = .001). Two-year overall survival from 760 days was 79% (95% CI, 66%-87%) in the fixed-duration group and 81% (95% CI, 77%-85%) in the indefinite-duration group. There was no statistically significant difference in overall survival between patients in the fixed-duration and indefinite-duration groups, either on univariate (hazard ratio [HR] 1.26; 95% CI, 0.77-2.08; P = .36) or multivariable (HR 1.33; 95% CI, 0.78-2.25; P = .29) Cox regression. Approximately 1 in 5 patients discontinued immunotherapy at 2 years in the absence of progression.

CONCLUSIONS AND RELEVANCE: In a retrospective clinical cohort of patients with advanced NSCLC who were treated with immunotherapy and were progression-free at 2 years, approximately only 1 in 5 discontinued treatment. The lack of statistically significant overall survival advantage for the indefinite-duration cohort on adjusted analysis provides reassurance to patients and clinicians who wish to discontinue immunotherapy at 2 years.

PMID:37270700 | DOI:10.1001/jamaoncol.2023.1891

J Clin Oncol. 2023 Jun 4:JCO2300903. doi: 10.1200/JCO.23.00903. Online ahead of print.

ABSTRACT

PURPOSE: The standard of care for locally advanced rectal cancer in North America is neoadjuvant pelvic chemoradiation with fluorouracil (5FUCRT). Neoadjuvant chemotherapy with fluorouracil and oxaliplatin (FOLFOX) is an alternative that may spare patients the morbidity of radiation. Understanding the relative patient experiences with these options is necessary to inform treatment decisions.

METHODS: PROSPECT was a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX versus 5FUCRT, which enrolled adults with rectal cancer clinically staged as T2N+, cT3N-, or cT3N+ who were candidates for sphincter-sparing surgery. Neoadjuvant FOLFOX was given in six cycles over 12 weeks, followed by surgery. Neoadjuvant 5FUCRT was delivered in 28 fractions over 5.5 weeks, followed by surgery. Adjuvant chemotherapy was suggested but not mandated in both groups. Enrolled patients were asked to provide patient-reported outcomes (PROs) at baseline, during neoadjuvant treatment, and at 12 months after surgery. PROs included 14 symptoms from the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Additional PRO instruments measured bowel, bladder, sexual function, and health-related quality of life (HRQL).

RESULTS: From June 2012 to December 2018, 1,194 patients were randomly assigned, 1,128 initiated treatment, and 940 contributed PRO-CTCAE data (493 FOLFOX; 447 5FUCRT). During neoadjuvant treatment, patients reported significantly lower rates of diarrhea and better overall bowel function with FOLFOX while anxiety, appetite loss, constipation, depression, dysphagia, dyspnea, edema, fatigue, mucositis, nausea, neuropathy, and vomiting were lower with 5FUCRT (all multiplicity adjusted P < .05). At 12 months after surgery, patients randomly assigned to FOLFOX reported significantly lower rates of fatigue and neuropathy and better sexual function versus 5FUCRT (all multiplicity adjusted P < .05). Neither bladder function nor HRQL differed between groups at any time point.

CONCLUSION: For patients with locally advanced rectal cancer choosing between neoadjuvant FOLFOX and 5FUCRT, the distinctive PRO profiles inform treatment selection and shared decision making.

PMID:37270691 | DOI:10.1200/JCO.23.00903

Ann Saudi Med. 2023 May-Jun;43(3):172-178. doi: 10.5144/0256-4947.2023.172. Epub 2023 Jun 1.

ABSTRACT

BACKGROUND: Cancer patients are highly prone to develop bacterial bloodstream infections (BSI) and are also at risk of neutropenia. Knowledge of the prevalence of these infections and whether neutropenia is associated with a change in mortality is important to more effective management and reducing mortality and morbidity.

OBJECTIVES: Estimate the prevalence of bacterial BSI among oncology inpatients and assess the associations of 30-day mortality with Gram stain results and neutropenia.

DESIGN: Retrospective cross-sectional SETTING: University hospital in Saudi Arabia.

PATIENTS AND METHODS: We retrieved records of oncology inpatients at King Khalid University Hospital, excluding patients without malignancy and with non-bacterial BSI. The number of records included in the analysis was reduced based on a sample size calculation and systematic random sampling used to select patients to include in the study.

MAIN OUTCOME MEASURES: Prevalence of bacterial BSI and association between neutropenia and 30-day mortality.

SAMPLE SIZE: 423.

RESULTS: The prevalence of bacterial bloodstream infections was 18.9% (n=80). Gram-negative bacteria were more prevalent (n=48, 60.0%) than gram-positive bacteria, with the most common being Escherichia coli (n=20, 25.0%). The 23 patients (28.8%) who died included 16 (69.6%) with gram-negative infections and 7 (30.4%) with gram-positive infections. There was no statistically significant association of bacterial BSI-related 30-day mortality with Gram stain (P=.32). Of 18 patients (22.5%) who were neutropenic, only one (5.6%) died. Sixty-two (77.5%) patients were non-neutropenic, of whom 22 (35.50%) died. We found a statistically significant association between the presence of neutropenia and bacterial BSI-related 30-day mortality (P=.016), with mortality being lower among neutropenic patients.

CONCLUSIONS: Gram-negative bacteria are more prevalent in bacterial BSI than gram-positive bacteria. No statistically significant association of Gram stain result with mortality was found. However, the 30-day mortality rate was lower among neutropenic patients than among non-neutropenic patients. We recommend further investigation with a larger sample size in multiple regions to further unravel the association of neutropenia with bacterial bloodstream infection-related 30-day mortality.

LIMITATIONS: Lack of regional data and sample size.

CONFLICT OF INTEREST: None.

PMID:37270682 | DOI:10.5144/0256-4947.2023.172

Ann Saudi Med. 2023 May-Jun;43(3):143-153. doi: 10.5144/0256-4947.2023.143. Epub 2023 Jun 1.

ABSTRACT

BACKGROUND: Non-pharmaceutical interventions (NPIs) applied to limit the SARS-CoV-2 pandemic also affect the circulation and seasonal characteristics of other respiratory viruses.

OBJECTIVES: Assess the impact of NPIs on the spread and seasonal characteristics of non-SARS-CoV-2 respiratory viruses and examine viral respiratory co-infections.

DESIGN: Retrospective cohort SETTING: Single center in Turkey.

PATIENTS AND METHODS: Syndromic multiplex viral polymerase chain reaction (mPCR) panel results of patients admitted to the Ankara Bilkent City Hospital with symptoms of acute respiratory tract infection between April 1, 2020 and October 30, 2022 were evaluated. Two study periods before and after 1 July 2021, when the restrictions were discontinued, were statistically analyzed and compared to determine the effect of NPIs on circulating respiratory viruses.

MAIN OUTCOME MEASURES: Prevalence of respiratory viruses as determined by syndromic mPCR panel.

SAMPLE SIZE: 11300 patient samples were evaluated.

RESULTS: At least one respiratory tract virus was detected in 6250 (55.3%) patients. Of these, at least one respiratory virus was detected in 5% in the first period (between April 1, 2020 and June 30, 2021, when NPIs were applied), and in 95% in the second period (between July 1, 2021 and October 30, 2022, when NPIs were relaxed). After the removal of NPIs, there was a statistically significant increase in hRV/EV, RSV-A/B, Flu A/H3, hBoV, hMPV, PIV-1, PIV-4, hCoV-OC43, PIV-2 and hCoV-NL63 (P<.05). In the 2020-2021 season, when strict NPIs were applied, all respiratory viruses evaluated did not have the usual seasonal peak and there were no seasonal influenza epidemics during this period.

CONCLUSIONS: NPIs resulted in a dramatic decrease in the prevalence of respiratory viruses and notable disruption of seasonal characteristics.

LIMITATIONS: Single-center study and retrospective.

CONFLICT OF INTEREST: None.

PMID:37270680 | DOI:10.5144/0256-4947.2023.143

Ann Saudi Med. 2023 May-Jun;43(3):154-160. doi: 10.5144/0256-4947.2023.154. Epub 2023 Jun 1.

ABSTRACT

BACKGROUND: During the induction of general anesthesia, hemodynamic instability is a common occurrence in elderly hypertensive patients with increased arterial stiffness, which can cause undesirable complications. Pulse wave velocity (PWV) is an important indicator of arterial stiffness.

OBJECTIVES: Investigate if preoperatively measured PWV is related to hemodynamic changes during induction of general anesthesia.

DESIGN: Prospective, case control.

SETTING: University hospital.

PATIENTS AND METHODS: The study was carried out between December 2018 and December 2019 in patients 50 years or older scheduled for elective otolaryngology with endotracheal intubation and who had an American Society of Anesthesiologists (ASA) score of I or II. Patients diagnosed with hypertension (HT) or receiving treatment for hypertension for systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg were compared with non-hypertensive patients (non-HT) of matching age and gender.

MAIN OUTCOME MEASURES: PWV values between HT and non-HT patients and hypotension rates at the 30th second of induction, the 30th second of intubation, and the 90th second of intubation between the HT and non-HT groups.

SAMPLE SIZE: 139 (95 with HT and 44 non-HT) RESULTS: PWV was higher in the HT group than in the non-HT group (P<.001). Hypotension at the 30th second of intubation in the HT group was significantly more frequent than in the non-HT group (P=.025). PWV was higher in hypotensive (n=62) than in non-hypotensive patients but the difference was statistically significant only for PWV measured at 30th second of intubation (n=77) (P=.018).

CONCLUSIONS: The easily and non-invasively measured preoperative PWV may be an effective means of predicting hypotension during the induction of general anesthesia at the 30th second of intubation in HT patients.

LIMITATIONS: Numbers of patients in the groups were not the same, and the study was not sufficiently powered to investigate the effect of hypertensive medications on PWV and arterial stiffness.

CONFLICT OF INTEREST: None.

PMID:37270679 | DOI:10.5144/0256-4947.2023.154

Ann Saudi Med. 2023 May-Jun;43(3):179-195. doi: 10.5144/0256-4947.2023.179. Epub 2023 Jun 1.

ABSTRACT

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are surgical methods used for rectal neuroendocrine tumors (NETs) with diameters of ≤ 10 mm. However, which method has a higher performance remains uncertain.

OBJECTIVES: Evaluate which of the two methods shows a higher performance.

DESIGN: Systematic review and meta-analysis METHODS: Data from PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to 12 April 2022. Outcomes, including complete resection, en bloc resection, recurrence, perforation, bleeding, and procedure time, were pooled by 95% confidence intervals (95% CI) using a fixed- or random-effects model.

MAIN OUTCOME MEASURES: Complete resection, en bloc resection, and recurrence.

SAMPLE SIZE: 18 studies, including 1168 patients were included in the study.

RESULTS: Eighteen retrospective cohort studies were included in this meta-analysis. There were no statistical differences in the rates of complete resection, en bloc resection, recurrence, perforation, and bleeding rates between EMR and ESD. However, a statistical difference was detected in the procedure time; EMR had a significantly shorter time (MD=-17.47, 95% CI=-22.31 – -12.62, P<.00001).

CONCLUSIONS: EMR and ESD had similar efficacies and safety profiles in resectioning rectal NETs ≤ 10 mm. Even so, the advantages of EMR included a shorter operation time and expenditure. Thus, with respect to health economics, EMR outperformed ESD.

LIMITATION: Most of these studies are retrospective cohort studies instead of RCTs.

CONFLICT OF INTEREST: None.

PMID:37270677 | DOI:10.5144/0256-4947.2023.179

Sci Rep. 2023 Jun 3;13(1):9016. doi: 10.1038/s41598-023-36125-0.

ABSTRACT

Current evidence indicate that cancer-associated fibroblasts (CAFs) play an important role in prostate cancer (PCa) development and progression. In this study, we identified CAF-related molecular subtypes and prognostic index for PCa patients undergoing radical prostatectomy through integrating single-cell and bulk RNA sequencing data. We completed analyses using software R 3.6.3 and its suitable packages. Through single-cell and bulk RNA sequencing analysis, NDRG2, TSPAN1, PTN, APOE, OR51E2, P4HB, STEAP1 and ABCC4 were used to construct molecular subtypes and CAF-related gene prognostic index (CRGPI). These genes could clearly divide the PCa patients into two subtypes in TCGA database and the BCR risk of subtype 1 was 13.27 times higher than that of subtype 2 with statistical significance. Similar results were observed in MSKCC2010 and GSE46602 cohorts. In addtion, the molucular subtypes were the independent risk factor of PCa patients. We orchestrated CRGPI based on the above genes and divided 430 PCa patients in TCGA database into high- and low- risk groups according to the median value of this score. We found that high-risk group had significant higher risk of BCR than low-risk group (HR: 5.45). For functional analysis, protein secretion was highly enriched in subtype 2 while snare interactions in vesicular transport was highly enriched in subtype 1. In terms of tumor heterogeneity and stemness, subtype 1 showd higher levels of TMB than subtype 2. In addition, subtype 1 had significant higher activated dendritic cell score than subtype 2. Based on eight CAF-related genes, we developed two prognostic subtypes and constructed a gene prognostic index, which could predict the prognosis of PCa patients very well.

PMID:37270661 | DOI:10.1038/s41598-023-36125-0

Sci Rep. 2023 Jun 3;13(1):9037. doi: 10.1038/s41598-023-36259-1.

ABSTRACT

Nicotine delivery and subjective effects are determinants of the ability of potentially less harmful tobacco products such as heated tobacco products (HTPs) to support adult smokers in switching away from cigarettes, and therefore to support tobacco harm reduction. This open-label, randomised, crossover, clinical study in 24 healthy adult smokers study assessed nicotine pharmacokinetics and subjective effects of the Pulze Heated Tobacco System (HTS; Pulze HTP device and three iD stick variants-Intense American Blend, Regular American Blend and Regular Menthol) compared with subjects’ usual brand cigarettes (UBC). C_max and AUC_t were highest for UBC and significantly lower for each Pulze HTS variant. C_max and AUC_t were significantly higher for Intense American Blend compared with Regular American Blend, while AUC_t was significantly higher for Intense American Blend compared with Regular Menthol. Median T_max was lowest (i.e., nicotine delivery was fastest) for subjects’ usual brand cigarettes and similar across the iD stick variants, although no between-product differences were statistically significant. All study products reduced urges to smoke; this effect was greatest for cigarettes although this was not statistically significant. Product evaluation scores for each Pulze HTS variant in the domains of ‘satisfaction’, ‘psychological reward’ and ‘relief’ were similar, and lower than those for UBC. These data demonstrate that the Pulze HTS effectively delivers nicotine and generates positive subjective effects, including satisfaction and reduced urge to smoke. This supports the conclusion that the Pulze HTS may be an acceptable alternative to cigarettes for adult smokers while having a lower abuse liability than cigarettes.

PMID:37270650 | DOI:10.1038/s41598-023-36259-1

Sci Rep. 2023 Jun 3;13(1):9022. doi: 10.1038/s41598-023-34720-9.

ABSTRACT

Multicenter studies in pediatric cardiovascular magnetic resonance (CMR) improve statistical power and generalizability. However, a structured process for identifying important research topics has not been developed. We aimed to (1) develop a list of high priority knowledge gaps, and (2) pilot the use of a wiki survey to collect a large group of responses. Knowledge gaps were defined as areas that have been either unexplored or under-explored in the research literature. High priority goals were: (1) feasible and answerable from a multicenter research study, and (2) had potential for high impact on the field of pediatric CMR. Seed ideas were contributed by a working group and imported into a pairwise wiki survey format which allows for new ideas to be uploaded and voted upon ( https://allourideas.org ). Knowledge gaps were classified into 2 categories: ‘Clinical CMR Practice’ (16 ideas) and ‘Disease Specific Research’ (22 ideas). Over a 2-month period, 3,658 votes were cast by 96 users, and 2 new ideas were introduced. The 3 highest scoring sub-topics were myocardial disorders (9 ideas), translating new technology & techniques into clinical practice (7 ideas), and normal reference values (5 ideas). The highest priority gaps reflected strengths of CMR (e.g., myocardial tissue characterization; implementation of technologic advances into clinical practice), and deficiencies in pediatrics (e.g., data on normal reference values). The wiki survey format was effective and easy to implement, and could be used for future surveys.

PMID:37270629 | DOI:10.1038/s41598-023-34720-9