Estimated Survival Time Research Articles

Disease trajectories in interstitial lung diseases – data from the EXCITING-ILD registry

BackgroundInterstitial lung diseases (ILD) comprise a heterogeneous group of mainly chronic lung diseases with different disease trajectories. Progression (PF-ILD) occurs in up to 50% of patients and is associated with increased mortality.MethodsThe EXCITING-ILD (Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases) registry was analysed for disease trajectories in different ILD. The course of disease was classified as significant (absolute forced vital capacity FVC decline > 10%) or moderate progression (FVC decline 5–10%), stable disease (FVC decline or increase < 5%) or improvement (FVC increase ≥ 5%) during time in registry. A second definition for PF-ILD included absolute decline in FVC % predicted ≥ 10% within 24 months or ≥ 1 respiratory-related hospitalisation. Risk factors for progression were determined by Cox proportional-hazard models and by logistic regression with forward selection. Kaplan-Meier curves were utilised to estimate survival time and time to progression.ResultsWithin the EXCITING-ILD registry 28.5% of the patients died (n = 171), mainly due to ILD (n = 71, 41.5%). Median survival time from date of diagnosis on was 15.5 years (range 0.1 to 34.4 years). From 601 included patients, progression was detected in 50.6% of the patients (n = 304) with shortest median time to progression in idiopathic NSIP (iNSIP; median 14.6 months) and idiopathic pulmonary fibrosis (IPF; median 18.9 months). Reasons for the determination as PF-ILD were mainly deterioration in lung function (PFT; 57.8%) and respiratory hospitalisations (40.6%). In multivariate analyses reduced baseline FVC together with age were significant predictors for progression (OR = 1.00, p < 0.001). Higher GAP indices were a significant risk factor for a shorter survival time (GAP stage III vs. I HR = 9.06, p < 0.001). A significant shorter survival time was found in IPF compared to sarcoidosis (HR = 0.04, p < 0.001), CTD-ILD (HR = 0.33, p < 0.001), and HP (HR = 0.30, p < 0.001). Patients with at least one reported ILD exacerbation as a reason for hospitalisation had a median survival time of 7.3 years (range 0.1 to 34.4 years) compared to 19.6 years (range 0.3 to 19.6 years) in patients without exacerbations (HR = 0.39, p < 0.001).ConclusionDisease progression is common in all ILD and associated with increased mortality. Most important risk factors for progression are impaired baseline forced vital capacity and higher age, as well as acute exacerbations and respiratory hospitalisations for mortality. Early detection of progression remains challenging, further clinical criteria in addition to PFT might be helpful.

Effect of complete mesocolic excision (cme) on long-term survival after right colectomy for cancer: multivariate meta-analysis and restricted mean survival time estimation.

Debate exists concerning the impact of complete mesocolic excision (CME) on long-term oncological outcomes. The aim of this review was to condense the updated literature and assess the effect of CME on long-term survival after right colectomy for cancer. PubMed, MEDLINE, Scopus, and Web of Science were searched through July 2023. The included studies evaluated the effect of CME on survival. The primary outcome was long-term overall survival. Restricted mean survival time difference (RMSTD), hazard ratio (HR), and 95% confidence intervals (CI) were used as pooled effect size measures. GRADE methodology was used to summarize the certainty of evidence. Ten studies (3665 patients) were included. Overall, 1443 (39.4%) underwent CME. The RMSTD analysis shows that at 60-month follow-up, stage I-III CME patients lived 2.5months (95% CI 1.1-4.1) more on average compared with noCME patients. Similarly, stage III patients that underwent CME lived longer compared to noCME patients at 55-month follow-up (6.1months; 95% CI 3.4-8.5). The time-dependent HRs analysis for CME vs. noCME (stage I-III disease) shows a higher mortality hazard in patients with noCME at 6months (HR 0.46, 95% CI 0.29-0.71), 12months (HR 0.57, 95% CI 0.43-0.73), and 24months (HR 0.73, 95% CI 0.57-0.92) up to 27months. This study suggests that CME is associated with unclear OS benefit in stage I-III disease. Caution is recommended to avoid overestimation of the effect of CME in stage III disease since the marginal benefit of a more extended resection may have been influenced by tumor biology/molecular profile and multimodal adjuvant treatments.

Optimal lymph node yield in oesophagectomy for oesophageal cancer: a nationwide population-based study.

The desirable lymph node count was determined to maximize the survival time expectancy according to the lymph node count among patients who have undergone oesophagectomy for oesophageal cancer. The data of national Finnish population-based cohort including all patients who have undergone oesophagectomy due to oesophageal cancer during 2002-2016 were used. Restricted mean survival time (RMST) estimates were determined by lymph node count, and the desirable count was determined using locally estimated scatterplot smoothing regression. A total of 883 patients with the median follow-up time of 3.73 (interquartile range 1.43-7.50) years were included. The lymph node count of 27 (95% confidence interval 25-28) was associated with the highest RMST estimates. Sensitivity analyses indicated that in pN0 patients, the highest RMST estimates was observed at 26 (95% confidence interval 24-28) lymph nodes and in pN+ patients, the RMST estimates peaked at 28 (95% confidence interval 25-33) lymph nodes. According to the findings of this study, at least 24 examined lymph nodes is the recommended target for the lymph node count after oesophagectomy for oesophageal cancer. The beneficial effect of this count on survival may be achieved regardless of nodal metastases.

Differences in heroin overdose deaths in Australia by age, 2020-2022: Disease and estimated survival times

BackgroundThe age of people who use illicit opioids has increased, with a clinical picture of accelerated ageing. The study aimed to determine, stratified by age: 1. The circumstances and characteristics of heroin-related toxicity deaths in Australia, 2020–2022; 2. The toxicological profile and autopsy findings; 3. The proportion of cases in which blood 6-acetyl morphine (6AM) was detected, as a measure of survival time. MethodsRetrospective study of 610 cases of fatal heroin-related drug toxicity in Australia, 2020–2022. Cases were stratified as: <30 years, 30–39 years, 40–49 years, ≥50 years. ResultsCompared to the youngest group, those aged ≥50 years were more likely to have a history of chronic pain (12.4 v 3.3 %), to have their death attributed to combined drug toxicity/disease (20.1 v 3.3 %), and to have evidence of a sudden collapse (21.3 v 11.1 %). There were no differences in free morphine concentrations or glucuronide concentrations. Compared to the youngest group, however, the two older groups were significantly more likely to have 6AM present in blood, a proxy measure of a shorter survival time (52.0, 55.2 v 34.5 %). Compared to the youngest group, cases aged ≥50 years were more likely to be diagnosed with cardiomegaly (44.0 v 16.7 %), coronary artery disease (46.0 v 15.0 %), emphysema (35.0 v 5.1 %), hepatic steatosis (15.4 v 3.4 %), hepatic fibrosis (17.6 v 3.4 %), and cirrhosis (19.8 v 0.0 %). ConclusionsOlder cases of heroin overdose had more extensive heart, lung, and liver disease, and appeared more likely to have shorter survival times.

Long-Term Impact of D2 Lymphadenectomy during Gastrectomy for Cancer: Individual Patient Data Meta-Analysis and Restricted Mean Survival Time Estimation.

Debate exists concerning the impact of D2 vs. D1 lymphadenectomy on long-term oncological outcomes after gastrectomy for cancer. PubMed, MEDLINE, Scopus, and Web of Science were searched and randomized controlled trials (RCTs) analyzing the effect of D2 vs. D1 on survival were included. Overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were assessed. Restricted mean survival time difference (RMSTD) and 95% confidence intervals (CI) were used as effect size measures. Five RCTs (1653 patients) were included. Overall, 805 (48.7%) underwent D2 lymphadenectomy. The RMSTD OS analysis shows that at 60-month follow-up, D2 patients lived 1.8 months (95% CI -4.2, 0.7; p = 0.14) longer on average compared to D1 patients. Similarly, 60-month CSS (1.2 months, 95% CI -3.9, 5.7; p = 0.72) and DFS (0.8 months, 95% CI -1.7, 3.4; p = 0.53) tended to be improved for D2 vs. D1 lymphadenectomy. Compared to D1, D2 lymphadenectomy is associated with a clinical trend toward improved OS, CSS, and DFS at 60-month follow-up.

Analysis of the survival time of patients with heart failure with reduced ejection fraction: a Bayesian approach via a competing risk parametric model

PurposeHeart failure (HF) is a widespread ailment and is a primary contributor to hospital admissions. The focus of this study was to identify factors affecting the extended-term survival of patients with HF, anticipate patient outcomes through cause-of-death analysis, and identify risk elements for preventive measures.MethodsA total of 435 HF patients were enrolled from the medical records of the Rajaie Cardiovascular Medical and Research Center, covering data collected between March and August 2018. After a five-year follow-up (July 2023), patient outcomes were assessed based on the cause of death. The survival analysis was performed with the AFT method with the Bayesian approach in the presence of competing risks.ResultsBased on the results of the best model for HF-related mortality, age [time ratio = 0.98, confidence interval 95%: 0.96–0.99] and ADHF [TR = 0.11, 95% (CI): 0.01–0.44] were associated with a lower survival time. Chest pain in HF-related mortality [TR = 0.41, 95% (CI): 0.10–0.96] and in non-HF-related mortality [TR = 0.38, 95% (CI): 0.12–0.86] was associated with a lower survival time. The next significant variable in HF-related mortality was hyperlipidemia (yes): [TR = 0.34, 95% (CI): 0.13–0.64], and in non-HF-related mortality hyperlipidemia (yes): [TR = 0.60, 95% (CI): 0.37–0.90]. CAD [TR = 0.65, 95% (CI): 0.38–0.98], CKD [TR = 0.52, 95% (CI): 0.28–0.87], and AF [TR = 0.53, 95% (CI): 0.32–0.81] were other variables that were directly related to the reduction in survival time of patients with non-HF-related mortality.ConclusionThe study identified distinct predictive factors for overall survival among patients with HF-related mortality or non-HF-related mortality. This differentiated approach based on the cause of death contributes to the estimation of patient survival time and provides valuable insights for clinical decision-making.

Oral health-related quality of life and survival analysis after preventive and restorative treatment of molar-incisor hypomineralisation

The aim of this study was to assess the impact of molar-incisor hypomineralisation (MIH) on oral health-related quality of life (OHRQoL) in children and adolescents, including information on restorative care, tooth sensitivity, as well as sociodemographic factors. Thirty-five patients aged between 7 and 17 years underwent a comprehensive oral examination. Severity of MIH was graded using the MIH Treatment Need Index (MIH-TNI), OHRQoL using the Child Oral Health Impact Profile (COHIP-19). Clinical quality of restorations was assessed according to modified FDI-criteria, tooth sensitivity using the Schiff Cold Air Sensitivity Scale (SCASS). The mean age was 11.3 ± 3.0 years, 34% were female. On average, 6.9 ± 2.8 teeth were affected, 62,9% had hypersensitive teeth (SCASS ≥ 1). Eighty-nine percent of patients had received restorative care, with a mean of 3.3 ± 2.1 teeth restored, most often with composite, followed by fissure sealing. Nine percent of restorations failed by the FDI-criteria. Mean estimated survival times for success were 4.9 years (95% CI 3.5; 6.2) and 5.6 years (95% CI 5.0; 6.3) for fissure sealants and composite restorations, respectively. The mean COHIP-19 score was 64.3 ± 8.2 (max. possible score = 76). A higher severity of MIH-TNI correlated significantly with impaired OHRQoL (rs = − 0.38, p = 0.013). However, this was not mirrored in multiple regression analysis. Despite the high rate of restorative treatment with an acceptable failure rate, OHRQoL is reduced in children with MIH. Many teeth affected by MIH remain sensitive. Further studies are needed to assess the benefits of different restorative options.

Clinical and Genetic Characteristics Associated With Survival Outcome in Late-Onset Huntington's Disease in South Korea.

The onset of Huntington's disease (HD) usually occurs before the age of 50 years, and the median survival time from onset is 15 years. We investigated survival in patients with late-onset HD (LoHD) (age at onset ≥60 years) and the associations of the number of mutant CAG repeats and age at onset (AAO) with survival in patients with HD. Patients with genetically confirmed HD at six referral centers in South Korea between 2000 and 2020 were analyzed retrospectively. Baseline demographic, clinical, and genetic characteristics and the survival status as at December 2020 were collected. Eighty-seven patients were included, comprising 26 with LoHD (AAO=68.77±5.91 years, mean±standard deviation; 40.54±1.53 mutant CAG repeats) and 61 with common-onset HD (CoHD) (AAO=44.12±8.61 years, 44.72±4.27 mutant CAG repeats). The ages at death were 77.78±7.46 and 53.72±10.86 years in patients with LoHD and CoHD, respectively (p<0.001). The estimated survival time was 15.21±2.49 years for all HD patients, and 10.74±1.95 and 16.15±2.82 years in patients with LoHD and CoHD, respectively. More mutant CAG repeats and higher AAO were associated with shorter survival (hazard ratio [HR]=1.05, 95% confidence interval [CI]=1.01-1.09, p=0.019; and HR=1.17, 95% CI=1.03-1.31, p=0.013; respectively) for all HD patients. The LoHD group showed no significant factors associated with survival after disease onset, whereas the number of mutant CAG repeats had a significant effect (HR=1.12, 95% CI=1.01-1.23, p=0.034) in the CoHD group. Survival after disease onset was shorter in patients with LoHD than in those with CoHD. More mutant CAG repeats and higher AAO were associated with shorter survival in patients with HD.

Oral implant rehabilitation under general anesthesia for patients with cognitive and physical disabilities: A 14-year cohort study

Statement of problemOral rehabilitation with implants is an alternative to the provision of removable dentures in all patients for whom missing teeth require replacement. However, individuals with cognitive, mental health issues, and/or physical disabilities are often excluded from implant-supported prostheses because of the high perceived risk of failure linked to poor oral health, presence of parafunction, or systemic conditions. PurposeThe purpose of this cohort study was to describe the protocols, outcomes, and survival rates of oral rehabilitation with implant-supported prostheses in patients with cognitive and physical disabilities treated under general anesthesia (GA) in a French unit of Special Care Dentistry. Material and methodsA retrospective cohort study was conducted on patient files. Data collected included demographics and information about the surgical and prosthetic phases of rehabilitation. Clinical and radiological reports were retrieved to establish the survival, success, and failure rates of implant placement according to the Health Scale for Dental Implants (HDSI) classification. ResultsA total of 298 dental implants had been placed under GA in 57 patients between January 2007 and August 2021. The prevalence of technical and biological postoperative complications was found to be 14% and 13% respectively. Thirty implants were determined to be failures. The estimated survival time in the population studied for loaded implants was 144.7 months [138.0; 151.3]. The cumulative survival rate was estimated to be 86% at 157 months. ConclusionsImplant-supported prostheses were found to be effective, and oral rehabilitation carried out under the conditions described was determined to be stable.

Influence of the postoperative restrictive methodologies and efficacy of the Baerveldt 350 implant after 12 months follow‐up

Aims/Purpose: To assess the clinical outcomes subsequent to the implantation of a Baerveldt 350 drainage device, utilizing different restrictive methodologies to prevent sudden postoperative hypotony (HT) (IOP &lt;6 mmHg), and their subsequent impact on the incidence of a Hypertensive phase (HP).Methods: A retrospective observational analysis of 71 consecutive eyes that had a Baerveldt 350 implanted. 50 eyes had 6 or 7/0 polyglactin tube ligation (ligature group = LG) and 21 eyes had a 3/0 polypropylene intraluminal tear cord 3/0 added to the ligation (ripcord‐ligature group = RLG), which was manually removed at the surgeon's discretion after spontaneous opening of the polyglactin. Intraocular pressure (IOP) and ocular hypotensive medication (OHM) lowering, failure rate, complete and partial success (CS and PS) and presence of HP were analysed.Results: The mean preoperative IOP was 26.14 (11.34) mmHg with 2.98 OHM for the LG and 28 (8.76) mmHg with 3.35 OHM for the RLG (p = 0.545 and p = 0.397). At the end of the follow‐up, the mean postoperative IOP was 13.35 (3.87) mmHg for the LG and 10.81(2.66) mmHg for the RLG (p = 0.01). The mean reduction of OHM was 2.25 (1.38) for the LG and 2.81 (1.6) for the RLG (p = 0.168). HP was noted in 26 patients (37.14%), 25 of them took place in the LG (50%); however, only 1 took place in the RLG (5%) (p = 0.00023). 35% of the patients who exhibited HP achieved CS, compared to 67.7% of the patients that did not show HP (p = 0.022). The survival analysis for a 12 months follow‐up period, showed that the estimate survival time for the LG was 10.97 (±0.521), and 11.64 (±0.342) for the RLG (p = 0.216). Two predictors were identified for risk of failure and CS: age of the patient before surgery (OR 0.157; 95% CI 0.029–0.865; p = 0.033) and the presence of HP (OR 3.90; 95% CI 1.189–12.794; p = 0.025). Lastly, HT was noted in 55 patients (80.9%), 45 of them took place in the LG (81.8%); however, only 10 took place in the RLG (18.2%) (Pearson Chi‐S p = 0.000225).Conclusions: Baerveldt 350 drainage device implantation has proven to be an effective procedure for glaucoma control. The use of the ripcord added to the absorbable ligature was associated with less risk of HP, and with better IOP results at the 12‐months follow‐up. Nevertheless, further research with larger population and larger follow‐up is needed to obtain robust results.

Evaluation of critical congenital heart disease from 2018 to 2020 in Turkey: a retrospective cohort study

BackgroundThe aim of this study is to examine the features of critical congenital heart disease (CCHD).MethodsThe study was planned as a retrospective cohort study. Data for the study were obtained through national data collection systems and 2018–2020 CCHD cohort was established. In this study, we divided the patients into two groups: Group 1 included seven primary target diseases of the newborn CCHD screening program and Group 2 included secondary target diseases.ResultsThere were 9884 CCHD cases, with a prevalence of 27.8 per 10,000 live births. Of the cases 44.4% were in Group 1 (12.3 per 10,000) and 54.8% were in Group 2 (15.2 per 10,000). Of all cases 55.5% were male and the female/male ratio was 1/1.2. While 21.8% of the cases were premature, 23.0% were babies with low birth weight (LBW), 4.8% were born from multiple pregnancies. The highest prevalence of CCHD was found in LBW (84.8 per 10,000), premature infants (57.8 per 10,000) (p < 0.001). The fatality rate in the cohort was 16.6% in the neonatal period, 31.6% in the first year of life respectively. The mean estimated survival time in the birth cohort was 40.0 months (95% CI: 39.5–40.6). The mean survival time for Group 1 diseases was 33.4 months (95% CI: 32.5–34.2), while it was 45.4 months (95% CI: 44.7–46.0) for Group 2 diseases (p < 0.001). Preterm birth, LBW, maternal age and region were evaluated as factors associated with mortality risk.ConclusionThis study showed that CCHDs are common in Turkey and mortality rates are high. There are regional differences in CCHD both prevalence and survival. Improving prenatal diagnosis rates and expanding neonatal CCHD screening are of key importance.

Predictors of mortality among under-five children in rural Ethiopia: a cross sectional study

BackgroundUnder-five child mortality (UFCM) is one of the major significant and sensitive indicators of the health status of the public. Although the world has seen a remarkable and substantial decrease in UFCM since 1990, its progression rate still remains alarmingly high in Sub-Saharan African (SSA) countries, particularly in Ethiopia. Therefore, this study aimed to assess associations between mortality and under-five children in rural Ethiopia.MethodsThis study used a secondary data analysis of the 2019 Ethiopia Mini Demographic and Health Survey (EMDHS) report. A total of 4,425 under-five children were included in the final analysis. The Kaplan-Meier (K-M) and Cox proportional hazard (PH) model analyses were utilized to estimate survival time and investigate the major predictors of mortality in under-five children, respectively. An adjusted hazard ratio (AHR) along with a 95% confidence interval (CI) was employed to measure the association size and direction of the association (STATA 12).ResultsThe study showed that 6.2% (95% CI: 5.43, 6.86) of children died beforehand celebrating their fifth birthday in rural Ethiopia. The multivariable Cox PH regression model analysis revealed associations of large spacing preceding birth interval (16–26 months) (AHR = 0.61; 95% CI: (0.402–0.920)), 27–38 months (AHR = 0.72; 95% CI: (0.496–1.03)), and ≥ 39 months, multiple births (AHR = 3.9; 95% CI: (2.77–5.62)), being breastfeeding (AHR = 0.13; 95% CI: (0.099–0.162)), and unvaccinated child (AHR = 11.6; 95% CI: (1.62–83.1)) were significant associations of under-five children mortality.ConclusionsIn this study, the UFCM rate was present, with 6.2% in the rural areas of Ethiopia. The birth type, preceding birth interval, vaccination of the child, and breastfeeding are identified as significant associations with under-five child mortality in rural Ethiopia. Therefore, public health interventions should be given attention to multiple births, unvaccinated, and non-breastfeeding children, as well as mothers’ better encouragement to have a large spacing preceding the birth interval. Moreover, investigators should conduct continuous research on UFCM, which is imperative to provide current information and inform interventions in a timely manner.

Neonatal mortality and its predictors among neonates in Jabitehnan district, Northwest Ethiopia: A single-arm retrospective cohort study.

Neonatal period is the most vulnerable time in which children face the greatest risk of death. Worldwide, each year, millions of newborns died in the first month of life. Sub-Saharan Africa, Ethiopia, in particular, is largely affected. However, there is a dearth of information regarding the survival status of neonates and determinants of their mortality in the study area. Therefore, this study was aimed at investigating neonatal mortality and its predictors in Jabitehnan district, Northwest Ethiopia. A single-arm community-based retrospective cohort study was conducted in March 2021 among 952 neonates born between August 2020 and February 2021. Data were collected by a semi-structured questionnaire, and a multistage stratified sampling technique was employed to select one urban and 10 rural kebeles from the district. Then, the total sample size was proportionally allocated to these selected kebeles. Neonatal death was ascertained by community diagnosis. Kaplan-Meier curve was used to estimate survival time. Cox regression was used to identify factors, the hazard ratio was estimated, and a p-value < 0.05 was considered statistically significant. The neonatal mortality rate was 44 (95% confidence interval [CI]: 33-60) per 1000 live births; and the incidence rate was 1.64 (95% CI: 1.21-2.23) per 1000 neonate days. Three-quarters of deaths occurred in the first week of life. Medium household wealth index (adjusted hazard ratio [AHR] = 3.54; 95 CI: 1.21-10.35), increased number of pregnancies (AHR = 1.22; 95%CI: 1.01-1.47), being male (AHR = 2.45, 95% CI: 1.12-5.35) and not starting breastfeeding in the first hour of life (AHR = 4.00; 95% CI: 1.52-11.10) were found to be predictors of neonatal mortality. Neonatal mortality was high compared to the national target. Wealth, number of pregnancies, sex of the neonate, and breastfeeding initiation were factors associated with neonatal death. Hence, strengthening interventions such as providing sexual education in the population, considering households with a medium wealth index in the exemption service, and counseling mothers about early breastfeeding initiation would improve neonatal survival.

A retrospective review of cats with suspected false positive results in point-of-care feline leukemia virus tests and concurrent immune-mediated anemia.

To describe clinical findings, diagnosis, treatment, and survival in 18 cats with anemia of suspected immune-mediated origin (ASIMO) and conflicting results using FeLV diagnosis tests, and to suggest an accurate way to assess their FeLV diagnosis. 18 cats. Medical records from 5 veterinary institutions were retrospectively reviewed to identify cats with ASIMO, positive results on p27 SNAP ELISA, and negative results on pro-virus PCR testing in peripheral blood, in the absence of other identified triggers. Follow-up was recorded from diagnosis to the time of writing, and survival analysis was performed to assess similarities with previous published data. 18 cats were enrolled from referral centers in Spain, Italy, and the United Kingdom. Both peripheral immune-mediated hemolytic anemia (IMHA; 12/18) and precursor targeted immune-mediated anemia (PIMA; 6/18) were described. When the SNAP ELISA test was rechecked in patients with disease control, SNAP ELISA positive results had become negative. Two cats had a relapse of the ASIMO, and the FeLV SNAP ELISA tested positive again. Other signs of FeLV disease did not appear in any of these patients despite immunosuppression. 14 cats (14/18 [78%]) were alive at the time of writing, and the mean estimated survival time was 769 days. This study describes incongruent FeLV results in cats with ASIMO. It supports the necessity to confirm FeLV SNAP ELISA positive results using additional tools, such as pro-virus PCR testing, as different p27 point-of-care and external serological tests may be inconsistent.

A Prospective Phase II Dose Escalation Study Using IMRT for High Risk N0M0 Prostate Cancer.

Published data supports the use of very high dose intensity modulated radiotherapy (IMRT) in achieving high efficacy and low toxicity for high-risk prostate cancer (HRPCa). This phase II multi-institutional non-randomized prospective dose escalation study using intensity modulated radiotherapy (IMRT) for high risk N0M0 prostate cancer was designed to investigate dose escalation using 1.8 Gy increments from baseline 75.6 Gy up to maximum 81 Gy, once dose volume constraints were adhered to. Inclusion criteria were patients undergoing a radical course of RT for high and very high-risk disease, defined as one or more of the criteria ≥ T3*, ≥ Gleason 8, Prostate specific antigen (PSA) > 20ng/ml. All patients received Androgen Deprivation Therapy (ADT) and none had radiological evidence of distant metastatic disease. The primary objective was to determine if dose escalated IMRT for high risk localized prostate cancer could provide freedom from biochemical relapse (BR; PSA rising > nadir +2ng/mL or initiation of salvage hormone therapy) similar to that reported in the literature. The Kaplan-Meier method was used to estimate survival times. Secondary objectives included OS, Disease Free Survival (DFS), and the incidence and severity of Genito-urinary (GU), Gastro-intestinal (GI) and erectile dysfunction (ED) toxicities (CTCAE v.3). Toxicities and performance status were collected and graded weekly during RT, 2 months after completing RT, 8 months' post RT, and 6 monthly thereafter to year five and annually thereafter to year nine. A total of 230 evaluable patients were enrolled between April 2009 and June 2016. The median follow-up was 7.3 years. The cumulative proportion of patients surviving without BR at 5 years was 91% (95% Confidence Interval (CI): 86% to 94%). Overall survival at 5 and 7 years was 92% (88% to 95%) and 89% (83% to 92%) respectively, while the cumulative proportion of patients free from disease was 89% (84% to 93%) at 5 years and 81% (75% to 86%) at 7 years. The incidence of acute G2 and G3 toxicities were; GU; 57.8% G2, 12.6% G3, GI; 15.2% G2, 0.4% G3, ED; 30.0% G2 and 61.7% G3. The incidence of late G2, G3 and G4 toxicities were; GU; 40.9% G2, 8.7% G3, GI; 36.5% G2, 2.2% G3, 0.4% G4, ED; 11.7% G2 and 86.1% G3. The percentage of patients receiving each dose level was; 3.5% received 75.6Gy in 42 fractions, 2.2% received 77.4Gy in 43 fractions, 93% received 81Gy in 45 fractions. The findings indicate that high-dose IMRT is well tolerated and is associated with excellent long-term tumor-control outcomes in patients with localized high and very high-risk prostate cancer, with 91% of patients surviving at 5 years without biochemical relapse. The rates of long term G3 GU and GI toxicity were low at 8.7% and 0.4% respectively.

Semiparametric estimation of restricted mean survival time as a function of restriction time.

The restricted mean survival time (RMST) is an appealing measurement in clinical or epidemiological studies with censored survival outcome and receives a lot of attention in the past decades. It provides a useful alternative to the Cox model for evaluating the covariate effect on survival time. The covariate effect on RMST usually varies with the restriction time. However, existing methods cannot address this problem properly. In this article, we propose a semiparametric framework that directly models RMST as a function of the restriction time. Our proposed model adopts a widely-used proportional form, enabling the estimation of RMST predictions across an interval using a unified model. Furthermore, the covariate effect for multiple restriction time points can be derived simultaneously. We develop estimators based on estimating equations theories and establish the asymptotic properties of the proposed estimators. The finite sample properties of the estimators are evaluated through extensive simulation studies. We further illustrate the application of our proposed method through the analysis of two real data examples. Supplementary Material are available online.

Prognostic microRNA signature for estimating survival in patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading cancer types with increasing annual incidence and high mortality in the USA. MicroRNAs (miRNAs) have emerged as valuable prognostic indicators in cancer patients. To identify a miRNA signature predictive of survival in patients with HCC, we developed a machine learning-based HCC survival estimation method, HCCse, using the miRNA expression profiles of 122 patients with HCC. The HCCse method was designed using an optimal feature selection algorithm incorporated with support vector regression. HCCse identified a robust miRNA signature consisting of 32 miRNAs and obtained a mean correlation coefficient (R) and mean absolute error (MAE) of 0.87 ± 0.02 and 0.73 years between the actual and estimated survival times of patients with HCC; and the jackknife test achieved an R and MAE of 0.73 and 0.97 years between actual and estimated survival times, respectively. The identified signature has seven prognostic miRNAs (hsa-miR-146a-3p, hsa-miR-200a-3p, hsa-miR-652-3p, hsa-miR-34a-3p, hsa-miR-132-5p, hsa-miR-1301-3p and hsa-miR-374b-3p) and four diagnostic miRNAs (hsa-miR-1301-3p, hsa-miR-17-5p, hsa-miR-34a-3p and hsa-miR-200a-3p). Notably, three of these miRNAs, hsa-miR-200a-3p, hsa-miR-1301-3p and hsa-miR-17-5p, also displayed association with tumor stage, further emphasizing their clinical relevance. Furthermore, we performed pathway enrichment analysis and found that the target genes of the identified miRNA signature were significantly enriched in the hepatitis B pathway, suggesting its potential involvement in HCC pathogenesis. Our study developed HCCse, a machine learning-based method, to predict survival in HCC patients using miRNA expression profiles. We identified a robust miRNA signature of 32 miRNAs with prognostic and diagnostic value, highlighting their clinical relevance in HCC management and potential involvement in HCC pathogenesis.

Machine learning methods based on mammogram images to estimate survival times for breast cancer patients

Machine learning methods based on mammogram images to estimate survival times for breast cancer patients

Incidence and predictors of mortality among neonates with respiratory distress syndrome admitted at West Oromia Referral Hospitals, Ethiopia, 2022. Multi-centred institution based retrospective follow-up study.

Respiratory distress syndrome is the major cause of neonatal death. However, data on the mortality and predictors related to respiratory distress syndrome were scarce. Hence, this study aimed to assess the incidence and predictors of death among neonates admitted with respiratory distress syndrome in West Oromia Referral Hospitals, Ethiopia, 2022. A retrospective follow-up study was conducted among 406 neonates admitted with respiratory distress syndrome at five referral hospitals from, 1 January 2019 to, 31 December 2021 in West Oromia, Ethiopia. The data were collected using a structured checklist and participants were selected using simple random sampling technique. The data were entered into Epi data version 4.6.0.2 and exported to STATA version 14 for cleaning, coding and analysis. The Kaplan-Meier curve was used to estimate survival time. The Weibull regression model was fitted to identify the predictors of mortality and variables with a P-value < 0.05 was taken as significant predictors of mortality. Four hundred six neonates with respiratory distress syndrome were included in the analysis. The overall incidence of neonatal mortality was 59.87/1000 neonates-days observations (95%CI: 51.1-70.2) with a proportion of 152 (37.44%) (95% CI: 32.7-42.2). The median time of follow-up was 11 days (95% CI: 10-23). Very low birthweight (AHR = 4.5, 95%CI: 2.0-10.9) and low birth weight (AHR = 3.1, 95%CI: 1.4-6.6), perinatal asphyxia (AHR = 2.7, 95%CI: 1.8-4), Chorioamnionitis (AHR = 2.2, 95%CI: 1.4-3.5) and multiple pregnancies (AHR = 2.2, 95%CI: 1.4-3.4) increased the hazard of death, whereas, antenatal corticosteroid administration (AHR = 0.33, 95%CI: 0.2-0.7) was negatively associated with neonatal mortality. High mortality rate of neonates with respiratory distress syndrome was observed. Chorioamnionitis, perinatal asphyxia, low birth weight and multiple pregnancies increase the, mortality hazard while administering antenatal corticosteroids decreases it. Thus, administering corticosteroids- before giving birth and special emphasis on children with Chorioaminoitis, asphyxia, low birth weight and multiple pregnancies is important for reducing neonatal mortality.

Survival status and predictors of mortality among adult Stroke patients admitted to Jimma University Medical Center, South west Ethiopia: A retrospective Cohort study.

Stroke is the leading cause of cardiovascular disease death in sub-Saharan Africa and the second leading cause of mortality worldwide. In 2016, 6.23% of all fatalities in Ethiopia were stroke-related. To assess survival status and predictors of mortality among adult stroke patients admitted to Jimma University Medical Center from April 1/2017 to March 31/2022. A retrospective cohort study was conducted on 480 adult stroke patients selected by simple random sampling from patients admitted to the Jimma University Medical Center Stroke Unit from April 1, 2017 to March 31, 2022. Data were extracted from May to June 2022 and entered Epi-data v.3.1 and analyzed by R v.4.2. The Kaplan-Meier curve with Log rank test was used to estimate survival time and to compare survival experience between categories of explanatory variables. The Cox regression model was computed to identify predictors of survival status in stroke patients. Then the 95% CI of the hazard ratio was set with corresponding p-value < 0.05 to declare statistical significance. During 4350 person-days of follow-up; 88 (18.33%) patients died; resulting in an incidence mortality of 20.23 per 1000 person-days, with a median survival time of 38 days. Glasgow coma score <8 on admission (AHR = 7.71; 95% CI: 3.78, 15.69), dyslipidemia (AHR = 3.96; 95% CI: 2.04, 7.69), aspiration pneumonia (AHR 2.30; 95% CI: 1.23-4.26), and increased intracranial pressure (AHR = 4.27; 95% CI: 2.33, 7.81), were the independent predictors of the time until death. The incidence of stroke mortality was higher at the seven and fourteen days. Glasgow Coma Scale, increased intracranial pressure, dyslipidemia, and aspiration pneumonia were independent predictors of mortality.