Therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Arba Minch Zuria District, Gamo Zone, Southwest Ethiopia.

BACKGROUND: Artemether-lumefantrine (AL) has been the primary anti-malarial drug used to treat uncomplicated Plasmodium falciparum malaria in Ethiopia since 2004. However, there have been recent reports of AL resistance mutations in different African countries, including Ethiopia. This is concerning and requires periodic monitoring of anti-malarial drug resistance. Therefore, the current study aimed to evaluate the therapeutic efficacy of AL in treating uncomplicated P. falciparum malaria in the Arba Minch Zuria District, Gamo Zone, Southwest Ethiopia. METHODS: A single-arm prospective study with a 28-day follow-up period was conducted from July to October 2022. Capillary blood samples were collected for RDT and microscopic examination. The study enrolled monoinfected P. falciparum patients aged ≥ 18 years at Ganta Sira Health Post. Sociodemographic and clinical data were recorded, and a dried blood spot (DBS) was prepared for each participant. Nested polymerase chain reaction (nPCR) genotyping of the msp-1 and msp-2 genes was only performed for recurrent cases to distinguish between recurrence and reinfection. Data entry and analysis were performed using the WHO Excel spreadsheet and SPSS version 26. RESULTS: A total of 89 patients were enrolled, and 67 adequately completed the 28-day follow-up period. AL showed a 100% clearance rate for fever on day 2 and asexual parasites on day 3. Gametocytes were detected in 13.5% (12/89) of the participants. The gametocyte clearance rate was 58.3% (7/12) until day 7 and 100% (12/12) until day 14. Five participants developed recurrent malaria, three of whom experienced relapse and two of whom experienced reinfection. Based on the Kaplan-Meier survival analysis, the PCR-uncorrected and PCR-corrected cumulative incidence of success were 93.7% (95% CI 85.5-97.3) and 96.2% (95% CI 85.5-98.7), respectively. CONCLUSION: AL was efficacious in treating uncomplicated P. falciparum malaria in the study area. However, the detection of recurrent patients highlights the need for continuous efficacy studies in this area.

Two-phase designs with failure time processes subject to nonsusceptibility.

Epidemiological studies based on 2-phase designs help ensure efficient use of limited resources in situations where certain covariates are prohibitively expensive to measure for a full cohort. Typically, these designs involve 2 steps: In phase I, data on an outcome and inexpensive covariates are acquired, and in phase II, a subsample is chosen in which the costly variable of interest is measured. For right-censored data, 2-phase designs have been primarily based on the Cox model. We develop efficient 2-phase design strategies for settings involving a fraction of long-term survivors due to nonsusceptibility. Using mixture models accommodating a nonsusceptible fraction, we consider 3 regression frameworks, including (a) a logistic "cure" model, (b) a proportional hazards model for those who are susceptible, and (c) regression models for susceptibility and failure time in those susceptible. Importantly, we introduce a novel class of bivariate residual-dependent designs to address the unique challenges presented in scenario (c), which involves 2 parameters of interest. Extensive simulation studies demonstrate the superiority of our approach over various phase II subsampling schemes. We illustrate the method through applications to the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Evaluation of the benefit of the addition of 1% topical luliconazole versus topical bland emollient to the systemic itraconazole therapy for the management of disseminated dermatophytosis: A randomised control trial.

BACKGROUND: The present epidemic of dermatophytosis in India is marked by an increase in chronic, recurrent and disseminated cases. A combination of oral itraconazole and topical luliconazole is being increasingly utilised by dermatologists in India. The superiority of this combination is not supported by robust clinical trial data. OBJECTIVE: We conducted this randomised, open-label, two arms, parallel assignment intervention trial between November 2022 and May 2023 to determine the superiority of topical 1% Luliconazole over bland emollient as adjuvant to systemic Itraconazole therapy in the management of dermatophytosis. METHOD: In this study, 135 patients of either sex were randomised to two study cohorts. Major exclusions being concomitant medical illness, use of concomitant medication and substance abuse. Participants were randomly assigned to receive topical bland emollient, (Cohort I, n = 67) or topical luliconazole, (Cohort II, n = 68). Both cohorts received oral itraconazole 200 mg/day (100 mg BID) and levocetirizine 5 mg twice a day as a systemic regime. Clinical and mycological cure at the end of 6 weeks and clinical relapse among cure patients during 10-week follow-up were observed. RESULTS: The cure rates for Cohorts I and II at 6 weeks were 50 (74.62%) and 56 (82.35%), (p = .46), respectively. During the 4-week follow-up period, clinical relapses were observed in 16 (32%) of the 50 patients in Cohort I and 12 (21.43%) of the 56 patients in Cohort II (p = .18). Luliconazole cohort shows a significantly higher medical cost (p < .05). CONCLUSION: Our study shows a similar cure rate and relapse rate for patients receiving topical Luliconazole versus topical bland emollient as an adjuvant to the systemic itraconazole regime.

A New Mixture Model With Cure Rate Applied to Breast Cancer Data.

We introduce a new modelling for long-term survival models, assuming that the number of competing causes follows a mixture of Poisson and the Birnbaum-Saunders distribution. In this context, we present some statistical properties of our model and demonstrate that the promotion time model emerges as a limiting case. We delve into detailed discussions of specific models within this class. Notably, we examine the expected number of competing causes, which depends on covariates. This allows for direct modeling of the cure rate as a function of covariates. We present an Expectation-Maximization (EM) algorithm for parameter estimation, to discuss the estimation via maximum likelihood (ML) and provide insights into parameter inference for this model. Additionally, we outline sufficient conditions for ensuring the consistency and asymptotic normal distribution of ML estimators. To evaluate the performance of our estimation method, we conduct a Monte Carlo simulation to provide asymptotic properties and a power study of LR test by contrasting our methodology against the promotion time model. To demonstrate the practical applicability of our model, we apply it to a real medical dataset from a population-based study of incidence of breast cancer in São Paulo, Brazil. Our results illustrate that the proposed model can outperform traditional approaches in terms of model fitting, highlighting its potential utility in real-world scenarios.

A New Approach to Modeling the Cure Rate in the Presence of Interval Censored Data.

We consider interval censored data with a cured subgroup that arises from longitudinal followup studies with a heterogeneous population where a certain proportion of subjects is not susceptible to the event of interest. We propose a two component mixture cure model, where the first component describing the probability of cure is modeled by a support vector machine-based approach and the second component describing the survival distribution of the uncured group is modeled by a proportional hazard structure. Our proposed model provides flexibility in capturing complex effects of covariates on the probability of cure unlike the traditional models that rely on modeling the cure probability using a generalized linear model with a known link function. For the estimation of model parameters, we develop an expectation maximization-based estimation algorithm. We conduct simulation studies and show that our proposed model performs better in capturing complex effects of covariates on the cure probability when compared to the traditional logit link-based two component mixture cure model. This results in more accurate (smaller bias) and precise (smaller mean square error) estimates of the cure probabilities, which in-turn improves the predictive accuracy of the latent cured status. We further show that our model's ability to capture complex covariate effects also improves the estimation results corresponding to the survival distribution of the uncured. Finally, we apply the proposed model and estimation procedure to an interval censored data on smoking cessation.

Nonparametric scanning tests of homogeneity for hierarchical models with continuous covariates.

In many applications of hierarchical models, there is often interest in evaluating the inherent heterogeneity in view of observed data. When the underlying hypothesis involves parameters resting on the boundary of their support space such as variances and mixture proportions, it is a usual practice to entertain testing procedures that rely on common heterogeneity assumptions. Such procedures, albeit omnibus for general alternatives, may entail a substantial loss of power for specific alternatives such as heterogeneity varying with covariates. We introduce a novel and flexible approach that uses covariate information to improve the power to detect heterogeneity, without imposing unnecessary restrictions. With continuous covariates, the approach does not impose a regression model relating heterogeneity parameters to covariates or rely on arbitrary discretizations. Instead, a scanning approach requiring continuous dichotomizations of the covariates is proposed. Empirical processes resulting from these dichotomizations are then used to construct the test statistics, with limiting null distributions shown to be functionals of tight random processes. We illustrate our proposals and results on a popular class of two-component mixture models, followed by simulation studies and applications to two real datasets in cancer and caries research.

Platelet-rich plasma in the treatment of anal fistula: a systematic review and meta-analysis.

OBJECTIVE: To analyse the safety and effectiveness of platelet-rich plasma (PRP) in anal fistula patients. METHODS: Online databases including PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to December 5, 2022, for eligible studies about evaluating the efficacy of platelet-rich plasma (PRP) in treating anal fistula. Literature search, screening, data extraction, and quality assessment were carried out by two independent investigators. The overall cure rate, the complete cure rate, the recurrence rate, and the adverse event rate with their 95% confidence intervals (95% CI) were the primary calculation indexes. Subgroup analyses were conducted primarily according to whether PRP was combined with other treatments. Softwares of MedCalc 18.2 and Review Manager 5.3 were used for meta-analysis. RESULTS: A total of 14 studies with 514 patients were included in the meta-analysis. The overall cure rate of 14 studies was 72.11% (95% CI 0.64-0.79). The cure rate of PRP alone was 62.39% (95% CI 0.55-0.69). The combined cure rate of PRP with other treatments was 83.12% (95% CI 0.77-0.88). The cure rate of interventions involving PRP were superior to the cure rate of surgery methods without using PRP significantly in the 4 randomized controlled studies (RR = 1.30, 95% CI 1.10-1.54, p = 0.002). The complete cure rate of the 8 studies was 66.37% (95% CI 0.52-0.79). The recurrence rate of the 12 studies was 14.84% (95% CI 0.08-0.24). The adverse event rate of the 12 studies was 6.31% (95% CI 0.02-0.12). CONCLUSION: PRP showed favorable safety and effectiveness in the treatment of anal fistula, especially combined with other treatment procedures.

Efficacy and Safety of Vonoprazan and Amoxicillin Dual Therapy for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis.

INTRODUCTION: Vonoprazan, a novel potassium-competitive acid blocker, has a strong acid suppression effect and potent efficacy in acid-associated diseases, including Helicobacter pylori eradication. We performed a systematic review and meta-analysis to investigate the efficacy and safety of vonoprazan/amoxicillin dual therapy for H. pylori eradication. METHODS: We conducted a systematic literature search through PubMed, Web of Science, EMBASE, and the Cochrane Library up to June 2022, to identify randomized controlled trials and cohort studies comparing vonoprazan/amoxicillin dual therapy and triple therapies for H. pylori eradication. Primary outcomes were cure rates and relative efficacy. Secondary outcomes included adverse events, dropout rate, and subgroup analysis. RESULTS: Five studies with 1,852 patients were included in the analysis. The cure rates of vonoprazan/amoxicillin dual therapy were 85.6% with 95% confidence interval (CI) of 79.7-91.5% and 88.5% (95% CI: 83.2-93.8%) in the intention-to-treat and per-protocol analyses. The efficacy of vonoprazan/amoxicillin dual therapy was not inferior to that of triple therapy with pooled risk ratio (RR) of 1.03 (95% CI: 0.97-1.10) and 1.02 (95% CI: 0.98-1.08) in intention-to-treat and per-protocol analyses; while it was significantly superior to the omeprazole or lansoprazole-based triple therapy (RR = 1.15, 95% CI: 1.05-1.25, p = 0.001). For clarithromycin-resistant strains, vonoprazan/amoxicillin dual therapy showed superiority to vonoprazan-based triple therapy (86.7% vs. 71.4%, RR = 1.20, 95% CI: 1.03-1.39, p = 0.02); however, vonoprazan/amoxicillin dual therapy was significant inferior to vonoprazan-based triple therapy for clarithromycin-sensitive strains (83.0% vs. 92.8%, RR = 0.90, 95% CI: 0.85-0.95, p = 0.0002). The adverse effects of vonoprazan/amoxicillin dual therapy were lower than those of triple therapy (21.2% vs. 26.5%, RR = 0.86, 95% CI: 0.73-1.01, p = 0.06), especially the incidence of diarrhea (p = 0.01). CONCLUSIONS: The efficacy of vonoprazan/amoxicillin dual therapy is noninferior to vonoprazan-based triple therapy but superior to the omeprazole or lansoprazole-based triple therapy and has less side effects. Patients with clarithromycin-resistant strains are particularly expected to benefit from vonoprazan/amoxicillin dual therapy.

Long-term control of acromegaly after pituitary surgery in South-Eastern Norway.

PURPOSE: Sustained cure of acromegaly can only be achieved by surgery. Most growth hormone (GH) secreting pituitary adenomas are macroadenomas (≥ 10 mm) at diagnosis, with reported surgical cure rates of approximately 50%. Long-term data on disease control rates after surgery are limited. Our aim was to estimate short- and long-term rates of biochemical control after pituitary surgery in acromegaly and identify predictive factors. METHODS: Patients operated for GH-secreting pituitary adenomas between 2005-2020 were included from the local pituitary registry (n = 178). Disease activity and treatment data were recorded at one-year (short-term) and five-year (long-term) postoperative follow-up. Biochemical control was defined as insulin-like growth factor 1 (IGF-1) ≤ 1.2 × upper limit of normal value. Multivariate regression models were used to identify factors potentially predicting biochemical control. RESULTS: A total of 178 patients with acromegaly (median age at diagnosis 49 (IQR: 38-59) years, 46% women) were operated for a pituitary adenoma. Biochemical control was achieved by surgery in 53% at short-term and 41% at long-term follow-up, without additional treatment for acromegaly. Biochemical control rates by surgery were of same magnitude in paired samples (45% vs. 41%, p = 0.213) for short- and long-term follow-up, respectively. At short-term, 62% of patients with microadenomas and 51% with macroadenomas, achieved biochemical control. At long-term, the biochemical control rate was 58% for microadenomas and 37% for macroadenomas (p = 0.058). With adjunctive treatment, 82% achieved biochemical control at long-term. Baseline IGF-1 levels significantly predicted biochemical control by surgery at short-term (OR: 0.98 (95% CI: 0.96-0.99), p = 0.011), but not at long-term (OR: 0.76 (95% CI: 0.57-1.00), p = 0.053). CONCLUSION: In unselected patients with acromegaly, the long-term biochemical control rate remains modest. Our findings indicate a need to identify patients at an earlier stage and improve therapeutic methods and surgical outcomes.

Cure rate of infections is not an argument for spacer in two-stage revision arthroplasty of the hip.

INTRODUCTION:  A devastating complication after total hip arthroplasty (THA) is chronic periprosthetic joint infection (PJI). Most frequently spacers (Sp) with or without antibiotics are implanted in a two-stage procedure even though not always indicated due to unknown pathogen, femoral and acetabular defects or muscular insufficiency. MATERIALS AND METHODS:  A retrospective analysis of a prospectively collected database was conducted, analyzing the treatment of 44 consecutive cases with chronic PJI undergoing two-stage revision using a Girdlestone situation (GS) in the interim period between 01/2015 and 12/2018. Diagnostics included intraoperative microbiological cultures, histological analysis, sonication of the initial implant, analysis of hip aspiration, as well as laboratory diagnostics and blood cultures. We analyzed the general and age-group-specific success rate of treatment using GS. Furthermore, we compared our data with the current literature on spacer implantation regarding common complications. RESULTS: In total, 21 female and 23 male patients at a mean age of 59.3 ± 9.6 years were included. Age groups were divided into young, mid-age, and elderly. In most patients, microbiology revealed Staphylococcus epidermidis in 39.1% of cases, following Staphylococcus lugdunensis and Staphylococcus aureus in 10.9% after THA explantation. For histology, Krenn and Morawietz type 2 (infectious type) was diagnosed in 40.9%, type 3 (infectious and abrade-induced type) in 25.0%. With GS, the total cure rate was 84.1% compared to 90.1% (range 61-100%) using Sp as described in the literature. Among age-groups, cure rate varied between 77.8 and 100%. Other complications, which only occurred in the mid-age and elderly group, included the necessity of transfusion in 31.1%, and in total, one periprosthetic fracture was identified (2.3%). CONCLUSION: GS shows an acceptable cure rate at a minimum of 2 years when compared to the cure rate reported in the literature for Sp without major complications. For patients with increased risks for treatment failure using spacer, GS seems to be an alternative for chronic PJI when looking at the success rate of treatment. LEVEL OF EVIDENCE: III, Retrospective trial.

Bayesian Design of Clinical Trials Using Joint Cure Rate Models for Longitudinal and Time-to-Event Data.

For clinical trial design and analysis, there has been extensive work related to using joint models for longitudinal and time-to-event data without a cure fraction (i.e., when all patients are at risk for the event of interest), but comparatively little treatment has been given to design and analysis of clinical trials using joint models that incorporate a cure fraction. In this paper, we develop a Bayesian clinical trial design methodology focused on evaluating the treatment's effect on a time-to-event endpoint using a promotion time cure rate model, where the longitudinal process is incorporated into the hazard model for the promotion times. A piecewise linear hazard model for the period after assessment of the longitudinal measure ends is proposed as an alternative to extrapolating the longitudinal trajectory. This may be advantageous in scenarios where the period of time from the end of longitudinal measurements until the end of observation is substantial. Inference for the time-to-event endpoint is based on a novel estimand which combines the treatment's effect on the probability of cure and its effect on the promotion time distribution, mediated by the longitudinal outcome. We propose an approach for sample size determination such that the design has a high power and a well-controlled type I error rate with both operating characteristics defined from a Bayesian perspective. We demonstrate the methodology by designing a breast cancer clinical trial with a primary time-to-event endpoint where longitudinal outcomes are measured periodically during follow up.

A general class of promotion time cure rate models with a new biological interpretation.

Over the last decades, the challenges in survival models have been changing considerably and full probabilistic modeling is crucial in many medical applications. Motivated from a new biological interpretation of cancer metastasis, we introduce a general method for obtaining more flexible cure rate models. The proposal model extended the promotion time cure rate model. Furthermore, it includes several well-known models as special cases and defines many new special models. We derive several properties of the hazard function for the proposed model and establish mathematical relationships with the promotion time cure rate model. We consider a frequentist approach to perform inferences, and the maximum likelihood method is employed to estimate the model parameters. Simulation studies are conducted to evaluate its performance with a discussion of the obtained results. A real dataset from population-based study of incident cases of melanoma diagnosed in the state of São Paulo, Brazil, is discussed in detail.

Efficacy and safety of Ginkgo biloba extract as an adjuvant in the treatment of Chinese patients with sudden hearing loss: a meta-analysis.

CONTEXT: Ginkgo biloba Linn (Ginkgoaceae) [leaves extract (GBE)] is authorized for the treatment of sudden hearing loss (SHL); however, its clinical feasibility in SHL has not been thoroughly investigated. OBJECTIVE: To evaluate the efficacy and safety of adjuvant GBE in the treatment of SHL. MATERIALS AND METHODS: We used PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, Chinese Scientific Journal Database, China Biomedical Database for literature research, starting from inception to 30 June 2022. The key terms: Ginkgo biloba extract, Sudden Sensorineural Deafness. This meta-analysis contained randomized controlled trials that compared the safety and efficacy of the combination of GBE and general treatments (GT) with GT alone for SHL. The extracted data were analyzed using Revman5.4 software with risk ratio (RR), 95% confidence intervals (CI) and mean difference (MD). RESULTS: Our meta-analysis included 27 articles with a total of 2623 patients. The results revealed that the effects of GBE adjuvant therapy was superior than GT (total effective rate: RR = 1.22, 95% CI: 1.18-1.26, p < 0.00001), the pure tone hearing threshold (MD = 12.29, 95% CI: 11.74-12.85, p < 0.00001) and hemorheology indexes (whole blood high shear viscosity: MD = 1.46, 95% CI: 0.47-2.44, p = 0.004) after treatment were significantly improved compared to non-treatment, while there was no significant difference as for hematocrit (red blood cells) (MD = 4.15, 95% CI: -7.15-15.45, p = 0.47). CONCLUSION: The efficacy of GBE + GT for the treatment of SHL may be more promising than GT alone.

Predicting ultrasound-guided thermal ablation benefit in primary hyperparathyroidism.

OBJECTIVES: Ultrasound (US)-guided thermal ablation for primary hyperparathyroidism (PHPT) is a relatively novel minimally invasive treatment. The recurrence rate after ablation is between 10 and 15%. The characteristics of patients who can benefit from thermal ablation therapy are not clear yet. The aim of this research was to investigate the validity of a parathyroid hormone (PTH)-based classifier for stratifying patients with PHPT. METHODS: A total of 171 patients were screened, 148 (86.5%) of whom were eligible and were divided into development (n = 104) and external validation (n = 44) cohorts. The potential relationship between the PTH-based classifier and the cure rate of patients was initially assessed in the primary cohort and then validated in the external validation cohort. The nomogram was computed from the logistic regression model. RESULTS: A cut-off of PTH < 269.1 pg/mL or ≥ 269.1 pg/mL as the optimal prognostic threshold in the training cohort was generated to stratify the patients into low-risk and high-risk groups. Patients with PTH levels < 269.1 pg/mL in the training cohort had a higher cure rate than patients with PTH levels ≥ 269.1 pg/mL (p < 0.001). The PTH level remained the strongest predictor of the cure rate in all cohorts. Furthermore, a nomogram based on the PTH level was developed to predict the cure rate in the training cohort and it performed well in the external validation cohort (AUC: 0.816, 95%CI 0.703 to 0.930; AUC: 0.816, 95%CI 0.677 to 0.956). CONCLUSIONS: The PTH-based classifier may help with individualised treatment planning for selecting patients who may benefit from thermal ablation. KEY POINTS: • This is the first analysis of predictors affecting the outcome of US-guided thermal ablation of primary hyperparathyroidism and the findings can be used to identify the potential beneficiary population of thermal ablation of primary hyperparathyroidism. • Parathyroid hormone (PTH) was confirmed as an independent prognostic factor, as it not only showed good accuracy in stratifying patients into high- and low-risk groups in the training and validation cohorts but also outperformed the clinical model. • This study developed and validated a model to predict the treatment success of thermal ablation of primary hyperparathyroidism.

Ultrasound-guided microwave and radiofrequency ablation for primary hyperparathyroidism: a prospective, multicenter study.

OBJECTIVES: To prospectively investigate the efficacy and safety of ultrasound (US)-guided microwave ablation (MWA) and radiofrequency ablation (RFA) for primary hyperparathyroidism (PHPT). METHODS: We performed a prospective multicenter study of MWA and RFA for PHPT between August 2017 and October 2020 at five centers. Laboratory testing was performed pre- and post-ablation and followed for at least 6 months. The primary outcome was the cure rate. Secondary outcomes were complications and dynamic changes in serum levels of PTH, calcium, phosphorus, and ALP after ablation. RESULTS: A total of 132 participants (mean age, 57.33 ± 13.90 years), with 141 parathyroid nodules (median maximal diameter, 1.55 cm) undergoing either MWA or RFA, were enrolled in the study. The technique success rate was 99.29% (140/141). The follow-up period was 6-36 months (median, 12 months). The cure rate was 80.30% (106/132). Pre-ablation PTH level was the independent factor associated with cure rate (Odds ratio (OR), 0.22; 95% CI, 0.07-0.69; p = 0.0090). There was no difference in cure rate between the MWA group and the RFA group (80.22% vs. 80.49%, p = 0.971). The only main complication was hoarseness (5.30%). CONCLUSIONS: US-guided MWA and RFA for PHPT is an effective and safe procedure in the treatment of PHPT. Pre-ablation PTH level is the key factor affecting the cure rate after MWA and RFA. KEY POINTS: • To our knowledge, this is the first prospective multicenter clinical trial with ultrasound-guided MWA and RFA for primary hyperparathyroidism. • There was no difference in cure rate between the MWA and RFA groups for primary hyperparathyroidism. The overall cure rate was 80.30%. • Pre-ablation PTH level was the independent factor associated with cure rate (odds ratio (OR), 0.22; 95% CI, 0.07-0.69; p = 0.0090).

Surgical selection and prognostic analysis in patients with unilateral sporadic medullary thyroid carcinoma.

PURPOSE: The extent of thyroid surgery and cervical lymph node dissection of unilateral sporadic medullary thyroid carcinoma (sMTC) is still controversial, and the aim of this study was to investigate whether hemithyroidectomy was adequate as a locally curative surgery for patients with unilateral sMTC. METHODS: This study is a retrospective case series of patients with sMTC who underwent curative total thyroidectomy or hemithyroidectomy in our institution from January 2011 to December 2019. RESULTS: In total, 129 patients who met the inclusion criteria were enrolled including 49 (38.0%) patients who underwent total thyroidectomy and 80 (62.0%) patients who underwent hemithyroidectomy. About 80 (62.0%) patients achieved a biochemical cure (BC), whereas there was no significant difference between two groups in biochemical cure rate (61.2% versus 62.5%, P = 0.885). A logistic regression analysis showed a strong negative correlation between the factors of preoperative calcitonin level and pTNM stage and biochemical cure. In the log-rank test, no significant difference in OS (P = 0.314) and DFS (P = 0.409) was found between the two surgical groups. Lateral cervical lymph node metastasis and pTNM stage were significant prognostic factors affecting DFS in univariate analysis; moreover, absence of biochemical cure, tumor size ≥ 4 cm and lateral cervical lymph node metastasis were independent risk factors of unilateral sMTC patients in our analysis. CONCLUSION: For patients with unilateral sMTC, hemithyroidectomy was adequate as a locally curative surgery, because the patients underwent total thyroidectomy did not benefit more from it in the aspects of BC/OS/RFS, while the postoperative increasing incidence rate of postoperative hypocalcemia could not improve patients' quality of life.

Probiotics are a good choice for the treatment of bacterial vaginosis: a meta-analysis of randomized controlled trial.

BACKGROUND: Bacterial vaginosis (BV) is one of the most common vaginal infectious diseases in female reproductive period. Although the existing view is that probiotic treatment may be one of the feasible methods for the treatment of BV, different intervention methods lead to different treatment results. Therefore, up-to-date and comprehensive evidence in this regard is essential for the development of intervention strategies. OBJECTIVE: This meta-analysis aims to systematically evaluate the role of probiotics in the treatment of BV in adult women. METHODS: We searched the databases of Embase, Cochrane Library, PubMed, Web of Science and ClinicalTrials.gov for Randomized Controlled Trials published until November 7, 2021. Meta-analysis was performed by Revman5.3 software to systematically evaluate the clinical efficacy of probiotics adjunctive therapy in the treatment of BV. The literatures were screened and evaluated according to the inclusion and exclusion criteria. Chi-square test was used to test the heterogeneity between trials. Random or Fixed effect models were used to analyze the cure rate of BV. RESULTS: Fourteen randomized controlled trials compared the efficacy of probiotics with antibiotic therapy (probiotics + antibiotics group) versus antibiotics alone or plus placebo (antibiotics (+ placebo) group) for BV [Risk Ratios (RR) = 1.23, 95% CI (1.05, 1.43), P = 0.009]. Three compared the efficacy of probiotics regimen (probiotics group) and antibiotics (antibiotics group) in the treatment of BV [RR = 1.12, 95% CI (0.60, 2.07), P = 0.72]. Another Three compared the efficacy of probiotics regimen (probiotics group) with placebo (placebo group) [RR = 15.20, 95% CI (3.87, 59.64), P < 0.0001]. CONCLUSION: Our meta-analysis suggests probiotics may play a positive role in the treatment of BV, but more strong evidence is needed.

Our meta-analysis found that probiotics may play an active role in adjuvant treatment of bacterial vaginosis by conventional antibiotic therapy. It was emphasized that oral administration of L. rhamnose was more effective than vaginal application of L. rhamnose in the treatment of bacterial vaginosis. The therapeutic effect of probiotics varies with the administration route and dosage of probiotics.

On testing for homogeneity with zero-inflated models through the lens of model misspecification.

In many applications of two-component mixture models such as the popular zero-inflated model for discrete-valued data, it is customary for the data analyst to evaluate the inherent heterogeneity in view of observed data. To this end, the score test, acclaimed for its simplicity, is routinely performed. It has long been recognized that this test may behave erratically under model misspecification, but the implications of this behavior remain poorly understood for popular two-component mixture models. For the special case of zero-inflated count models, we use data simulations and theoretical arguments to evaluate this behavior and discuss its implications in settings where the working model is restrictive with regard to the true data generating mechanism. We enrich this discussion with an analysis of count data in HIV research, where a one-component model is shown to fit the data reasonably well despite apparent extra zeros. These results suggest that a rejection of homogeneity does not imply that the underlying mixture model is appropriate. Rather, such a rejection simply implies that the mixture model should be carefully interpreted in the light of potential model misspecifications, and further evaluated against other competing models.

Modified score function for monotone likelihood in the semiparametric mixture cure model.

The cure fraction models are intended to analyze lifetime data from populations where some individuals are immune to the event under study, and allow a joint estimation of the distribution related to the cured and susceptible subjects, as opposed to the usual approach ignoring the cure rate. In situations involving small sample sizes with many censored times, the detection of nonfinite coefficients may arise via maximum likelihood. This phenomenon is commonly known as monotone likelihood (ML), occurring in the Cox and logistic regression models when many categorical and unbalanced covariates are present. An existing solution to prevent the issue is based on the Firth correction, originally developed to reduce the estimation bias. The method ensures finite estimates by penalizing the likelihood function. In the context of mixture cure models, the ML issue is rarely discussed in the literature; therefore, this topic can be seen as the first contribution of our paper. The second major contribution, not well addressed elsewhere, is the study of the ML issue in cure mixture modeling under the flexibility of a semiparametric framework to handle the baseline hazard. We derive the modified score function based on the Firth approach and explore finite sample size properties of the estimators via a Monte Carlo scheme. The simulation results indicate that the performance of coefficients related to the binary covariates are strongly affected to the imbalance degree. A real illustration, in the melanoma dataset, is discussed using a relatively novel data set collected in a Brazilian university hospital.

A Bayesian Mixture Cure Rate Model for Estimating Short-Term and Long-Term Recidivism.

Mixture cure rate models have been developed to analyze failure time data where a proportion never fails. For such data, standard survival models are usually not appropriate because they do not account for the possibility of non-failure. In this context, mixture cure rate models assume that the studied population is a mixture of susceptible subjects who may experience the event of interest and non-susceptible subjects that will never experience it. More specifically, mixture cure rate models are a class of survival time models in which the probability of an eventual failure is less than one and both the probability of eventual failure and the timing of failure depend (separately) on certain individual characteristics. In this paper, we propose a Bayesian approach to estimate parametric mixture cure rate models with covariates. The probability of eventual failure is estimated using a binary regression model, and the timing of failure is determined using a Weibull distribution. Inference for these models is attained using Markov Chain Monte Carlo methods under the proposed Bayesian framework. Finally, we illustrate the method using data on the return-to-prison time for a sample of prison releases of men convicted of sexual crimes against women in England and Wales and we use mixture cure rate models to investigate the risk factors for long-term and short-term survival of recidivism.