Category: Statistics

J Acquir Immune Defic Syndr. 2023 Nov 10. doi: 10.1097/QAI.0000000000003337. Online ahead of print.

ABSTRACT

BACKGROUND: Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with demonstrated efficacy as a third agent in treatment-naive and treatment-experienced people living with HIV (PLWH) in registration studies. However, limited real-world data are available.

METHODS: By searching electronic healthcare records, PLWH using doravirine-based regimens were selected with at least one year of follow-up after their first prescription. All stable PLWH who were switched to a doravirine-based regimen were included in the analysis. The primary outcome was the durability of a doravirine-based regimen one year after prescription. Reasons for stopping were also collected. Secondary outcomes for PLWH continuing a doravirine-based regimen after one year were routine laboratory assessment, BMI, and differences in medication costs compared with their prior cART.

RESULTS: A total of 689 patients (92% men) were included from September 2019 to August 2022: 97.7% switched to doravirine/tenofovir/lamivudine (DOR/TDF/3TC). After one year 94/689 (13.6%) PLWH stopped this therapy. The main reason for discontinuation was patient-reported adverse events in 70/689 (10.2%). Medical reasons for discontinuation included increased ALT levels in 6/689 (0.9%), decreased eGFR in 3/684 (0.4%), and precautions after diagnosis of osteoporosis in 2/689 (0.3%) patients. Virologic failure occurred in 4/689 cases (0.6%), and one case demonstrated resistance mutations. The secondary outcomes demonstrated a statistically significant increase in ALT levels and decrease in LDL-C levels. The switch to a doravirine-based regimen in the Netherlands reduced medication costs by 27%.

CONCLUSION: This study demonstrated that switching to a doravirine-based regimen, mostly DOR/TDF/3TC, was highly effective and generally well tolerated, with substantial cost savings.

PMID:37963350 | DOI:10.1097/QAI.0000000000003337

Menopause. 2023 Nov 14. doi: 10.1097/GME.0000000000002274. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to compare the efficacy of CO2 laser, radiofrequency, and promestriene in treating genitourinary syndrome of menopause in women with breast cancer receiving adjuvant therapy and to analyze the clinical and histological findings of the vulvar vestibule.

METHODS: Women with moderate-to-severe symptoms of vulvar atrophy were enrolled. The participants were evaluated according to pretreatment and posttreatment protocols using the visual analog scale and clinical assessments, which included a gynecological examination and vestibular biopsy. Participants were randomly assigned into the laser, radiofrequency, or promestriene groups. Participants in the energy treatment groups underwent three consecutive monthly outpatient vulvovaginal treatment sessions, whereas those in the control group were administered promestriene for 4 months. During a follow-up visit 30 days posttreatment, the participant global posttreatment impression of improvement was evaluated using a Likert scale.

RESULTS: Seventy women completed treatment. Histological vulvar atrophy was identified in four (5.7%) of the pretreatment vulvar samples. Postintervention, all histological parameters were normalized. Significant improvements in symptoms were observed, as all three groups showed a reduction in the visual analog scale score, with no statistically significant differences among them. A high level of satisfaction was reported posttreatment in all groups. No damage to the histological structure of the vulvar vestibule or relevant clinical adverse events were identified posttreatment.

CONCLUSIONS: Laser, radiofrequency, and promestriene delivered comparable, significant symptom improvements among women with breast cancer receiving adjuvant therapy. These treatments did not cause structural tissue damage or other clinical complications.

PMID:37963315 | DOI:10.1097/GME.0000000000002274

J Clin Oncol. 2023 Nov 14:JCO2202668. doi: 10.1200/JCO.22.02668. Online ahead of print.

ABSTRACT

PURPOSE: GemPred, a transcriptomic signature predictive of the efficacy of adjuvant gemcitabine (GEM), was developed from cell lines and organoids and validated retrospectively. The phase III PRODIGE-24/CCTG PA6 trial has demonstrated the superiority of modified folinic acid, fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) over GEM as adjuvant therapy in patients with resected pancreatic ductal adenocarcinoma at the expense of higher toxicity. We evaluated the potential predictive value of GemPred in this population.

PATIENTS AND METHODS: Routine formalin-fixed paraffin-embedded surgical specimens of 350 patients were retrieved for RNA sequencing and GemPred prediction (167 in the GEM arm and 183 in the mFOLFIRINOX [mFFX] arm). Survival analyses were stratified by resection margins, lymph node status, and cancer antigen 19-9 level.

RESULTS: Eighty-nine patients’ tumors (25.5%) were GemPred+ and were thus predicted to be gemcitabine-sensitive. In the GEM arm, GemPred+ patients (n = 50, 30%) had a significantly longer disease-free survival (DFS) than GemPred- patients (n = 117, 70%; median 27.3 v 10.2 months, hazard ratio [HR], 0.43 [95% CI, 0.29 to 0.65]; P < .001) and cancer-specific survival (CSS; median 68.4 v 28.6 months, HR, 0.42 [95% CI, 0.27 to 0.66]; P < .001). GemPred had no prognostic value in the mFFX arm. DFS and CSS were similar in GemPred+ patients who received adjuvant GEM and mFFX (median 27.3 v 24.0 months, and 68.4 v 51.4 months, respectively). The statistical interaction between GEM and GemPred+ status was significant for DFS (P = .008) and CSS (P = .004). GemPred+ patients had significantly more adverse events of grade ≥3 in the mFFX arm (76%) compared with those in the GEM arm (40%; P = .001).

CONCLUSION: This ancillary study of a phase III randomized trial demonstrates that among the quarter of patients with a GemPred-positive transcriptomic signature, survival was comparable with that of mFOLFIRINOX, whereas those receiving adjuvant gemcitabine had fewer adverse events.

PMID:37963313 | DOI:10.1200/JCO.22.02668

Menopause. 2023 Nov 14. doi: 10.1097/GME.0000000000002280. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to advance understanding of vasomotor symptom (VMS) outcomes measurement using pooled data from three Menopause Strategies Finding Lasting Answers to Symptoms and Health (MsFLASH) trials.

METHODS: Participants self-reported VMS frequency, severity, and bother using daily diaries; completed standardized measures of VMS interference, insomnia severity, and sleep quality/disturbance; and completed four treatment satisfaction items. Analyses included descriptive statistics, Pearson correlations (baseline pooled sample, posttreatment pooled sample, posttreatment placebo only), t tests, and analysis of variance.

RESULTS: Participants were mostly postmenopausal (82.9%) and a mean of 54.5 years old. VMS frequency was fairly correlated with severity, bother, and interference for pooled baseline and placebo posttreatment samples (r values = 0.21-0.39, P values < 0.001) and moderately correlated with severity, bother, and interference for pooled posttreatment (r values = 0.40-0.44, P values < 0.001). VMS severity, bother, and interference were moderately correlated (r values = 0.37-0.48, P values < 0.001), with one exception. VMS severity and bother were strongly correlated (r values = 0.90-0.92, P values < 0.001). VMS interference was moderately correlated with insomnia (r values = 0.45-0.54, P values < 0.001) and fairly to moderately correlated with sleep quality/disturbance (r values = 0.31-0.44, P values < 0.001). Other VMS outcomes were weakly to fairly correlated with insomnia (r values = 0.07-0.33, P values < 0.001 to < 0.05) and sleep quality/disturbance (r values = 0.06-0.26, P values < 0.001 to > 0.05). Greater improvement in VMS and sleep over time was associated with higher treatment satisfaction (P values < 0.001).

CONCLUSIONS: This pooled analysis advances understanding of VMS outcomes measurement and has implications for selecting measures and creating future research.

PMID:37963308 | DOI:10.1097/GME.0000000000002280

Bol Med Hosp Infant Mex. 2023;80(5):302-311. doi: 10.24875/BMHIM.22000159.

ABSTRACT

BACKGROUND: Neonatal surgery is one of the most specialized and demanding areas of pediatric surgery due to the specific anatomical and physiological characteristics of this vulnerable group of patients. This study aimed to present the experience of 10 years of neonatal surgical management in a secondary care perinatal hospital in Mexico.

METHODS: We conducted a descriptive, observational, cross-sectional, and retrospective study in a perinatal hospital in Toluca, Mexico, from August 01, 2012, to July 31, 2022. We included patients who underwent surgery within the hospital facilities by the Service of Pediatric Surgery. We studied demographic, clinical, and surgical variables and performed descriptive and inferential statistics.

RESULTS: A total of 551 patients underwent surgery during this period with a prevalence of 0.5%. The number of patients operated in the neonatal period was 497 (90.1%). Forty-eight pathologies were recorded, with a predominance of congenital malformations in 64.6% and prenatal diagnosis in 40.5% of cases. The survival rate was 89.7%. In the bivariate analysis of mortality, we found an inverse relationship between weight and gestational age (p < 0.05).

CONCLUSION: Although not a local or national reference center, the hospital where the study was conducted treats various congenital and acquired diseases, with a mortality rate that tends to decrease, close to the international average, and lower than national reports.

PMID:37963301 | DOI:10.24875/BMHIM.22000159

Bol Med Hosp Infant Mex. 2023;80(5):279-287. doi: 10.24875/BMHIM.23000039.

ABSTRACT

BACKGROUND: Pediatric cancer patients in the final phase of life receive antibiotics empirically. The decision to start, maintain, or stop the antibiotic administration as part of care at this stage is a dilemma.

METHODS: We conducted a retrospective, descriptive, cross-sectional study including cancer patients in the final phase of life, hospitalized during the last 5 to 7 days of life. We included demographic variables, diagnoses, days of hospitalization, cultures, antibiotics used, prevalent symptoms in the last week of life, and principal diagnosis at the time of death, and performed descriptive statistics and a chord diagram.

RESULTS: Twenty-two patients were included; 18 (81.81%) received antibiotic treatment. The mean age was 8.75 years. The predominant pathologies were central nervous system tumors in seven patients (31.81%). Of the total, 18 (81.81%) had an infectious diagnosis reported as bloodstream infection, followed by pneumonia in three (13.63%). The main cause of death was respiratory failure (40.9%). Of the 18 patients with an infectious diagnosis, 16 (88.88%) received empiric therapy. Predominant factors for antibiotic use were more than 7 days of hospitalization (75%), ICU admission (100%), invasive devices (88.8%), and aminergic support (100%). The predominant symptoms were dyspnea (68.18%), pain (50%), and fever (40.9%), which persisted in nine (60%), two (18.18%), and five (55.5%) patients, respectively.

CONCLUSIONS: The lack of guidelines for antibiotic administration leads to excessive and potentially unnecessary use, which can lead to discomfort, prolonged hospitalization, bacterial resistance, excessive cost, and suffering without symptom control.

PMID:37963295 | DOI:10.24875/BMHIM.23000039

Genet Mol Biol. 2023 Nov 13;46(3 Suppl 1):e20230130. doi: 10.1590/1678-4685-GMB-2023-0130. eCollection 2023.

ABSTRACT

The relationship between chromosomal and morphological variation in mammals is poorly understood. We analyzed the cranial size and shape variation in Ctenomys lami concerning to the geographic variation in their chromosome numbers. This subterranean rodent occurs in a narrow range of sand-dunes in the Coastal Plain of southern Brazil. This species presents a high karyotypic variation with diploid numbers varying from 2n = 54 to 2n = 58, involving the fission and fusion of chromosome pairs 1 and 2. Due to different chromosome rearrangement frequencies along their geographic distribution, four karyotypic blocks were proposed. This study, explored cranium shape and size variation in geographical, chromosomal polymorphism, and chromosome rearrangements contexts to test whether the four karyotypic blocks reflect morphologically distinct units. For this, we measured 89 craniums using geometric morphometrics and used uni and multivariate statistics to discriminate the predicted groups and test for an association among chromosomal and morphological variation. Our results show the size and shape of sexual dimorphism, with males larger than females, and support the existence of four karyotypic blocks for Ctenomys lami based on morphological variation. However, our results do not support a direct relationship between chromosomal and cranial morphological variation in C. lami.

PMID:37963285 | DOI:10.1590/1678-4685-GMB-2023-0130

Proc Natl Acad Sci U S A. 2023 Nov 21;120(47):e2307935120. doi: 10.1073/pnas.2307935120. Epub 2023 Nov 14.

ABSTRACT

Stochastic processes on graphs can describe a great variety of phenomena ranging from neural activity to epidemic spreading. While many existing methods can accurately describe typical realizations of such processes, computing properties of extremely rare events is a hard task, particularly so in the case of recurrent models, in which variables may return to a previously visited state. Here, we build on the matrix product cavity method, extending it fundamentally in two directions: First, we show how it can be applied to Markov processes biased by arbitrary reweighting factors that concentrate most of the probability mass on rare events. Second, we introduce an efficient scheme to reduce the computational cost of a single node update from exponential to polynomial in the node degree. Two applications are considered: inference of infection probabilities from sparse observations within the SIRS epidemic model and the computation of both typical observables and large deviations of several kinetic Ising models.

PMID:37963253 | DOI:10.1073/pnas.2307935120

Anal Chem. 2023 Nov 14. doi: 10.1021/acs.analchem.3c03887. Online ahead of print.

ABSTRACT

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging is used across many fields for the atomic and molecular characterization of surfaces, with both high sensitivity and high spatial resolution. When large analysis areas are required, standard ToF-SIMS instruments allow for the acquisition of adjoining tiles, which are acquired by rastering the primary ion beam. For such large area scans, tiling artifacts are a ubiquitous challenge, manifesting as intensity gradients across each tile and/or sudden changes in intensity between tiles. Such artifacts are thought to be related to a combination of sample charging, local detector sensitivity issues, and misalignment of the primary ion gun, among other instrumental factors. In this work, we investigated six different computational tiling artifact removal methods: tensor decomposition, multiplicative linear correction, linear discriminant analysis, seamless stitching, simple averaging, and simple interpolating. To ensure robustness in the study, we applied these methods to three hyperspectral ToF-SIMS data sets and one OrbiTrapSIMS data set. Our study includes a carefully designed statistical analysis and a quantitative survey that subjectively assessed the quality of the various methods employed. Our results demonstrate that while certain methods are useful and preferred more often, no one particular approach can be considered universally acceptable and that the effectiveness of the artifact removal method is strongly dependent on the particulars of the data set analyzed. As examples, the multiplicative linear correction and seamless stitching methods tended to score more highly on the subjective survey; however, for some data sets, this led to the introduction of new artifacts. In contrast, simple averaging and interpolation methods scored subjectively poorly on the biological data set, but more highly on the microarray data sets. We discuss and explore these findings in depth and present general recommendations given our findings to conclude the work.

PMID:37963228 | DOI:10.1021/acs.analchem.3c03887

PLoS One. 2023 Nov 14;18(11):e0289622. doi: 10.1371/journal.pone.0289622. eCollection 2023.

ABSTRACT

BACKGROUND: Infective endocarditis (IE) has increased in rural states such as West Virginia (WV) with high injection drug use. IE is medically managed with antimicrobial treatment alone or combined with surgical treatment. This study aimed to characterize the predictors associated with surgical treatment and rates of inpatient mortality and readmission among IE patients in WV’s rural centers.

METHODS: This retrospective review of electronic health records includes all adults hospitalized for IE at major rural tertiary cardiovascular centers in WV during 2014-2018. Descriptive statistics were presented on demographics, history of injection drug use, clinical characteristics, and hospital utilization by surgery status, and multivariable logistic regression examined the association of surgery with key predictor variables, generating odds ratios (OR).

RESULTS: Of the 780 patients with IE, 38% had surgery, with a 26-fold increase in patients undergoing surgery between 2014-2018. Comparing surgery and non-surgery patients revealed significant differences. Surgery patients were significantly younger (median age 35.6 vs. 40.5 years; p<0.001); had higher rates of drug use history (80% vs. 65%; p<0.001), psychiatric disorders (57% vs. 31%; p<0.001), and readmissions (18% vs.12%; p = 0.015). Surgery patients had lower rates of discharge against medical advice (11% vs.17%; p = 0.028) and in-hospital mortality (5% vs.12%; p<0.001). In the multivariable logistic regression, surgery was associated with injection drug use (OR: 1.9; 95% CI:1.09-3. 3), indications for surgery (OR: 1.68; 95% CI:1.48-1.91), left-sided IE (OR: 2.14; 95%CI:1.43-3.19) and later years (OR:3.75; 95%CI:2.5-5.72).

CONCLUSION: This study characterizes the predictors associated with surgical treatment and rates of inpatient mortality and readmission among IE patients across rural WV. The decision to perform cardiac surgery on IE patients is complex. Results with increased injection drug use-associated IE emphasize the importance of comprehensive care by a multidisciplinary team for optimal management of patients with IE.

PMID:37963173 | DOI:10.1371/journal.pone.0289622