Cohort Study of Somatostatin-Based Radiopeptide Therapy With [90Y-DOTA]-TOC Versus [90Y-DOTA]-TOC Plus [177Lu-DOTA]-TOC in Neuroendocrine Cancers

Purpose Radiopeptide therapy is commonly performed with a single radioisotope. We aimed to compare the effectiveness of somatostatin-based radiopeptide therapy with a single versus a combination of radioisotopes. Patients and Methods In a cohort study, patients with metastasized neuroendocrine cancer were treated with repeated cycles of 90yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([90Y-DOTA]-TOC) or with cycles alternating between [90Y-DOTA]-TOC and 177lutetium-labeled DOTA-TOC ([177Lu-DOTA]-TOC) until tumor progression or permanent toxicity. Multivariable Cox regression and competing risk regression were used to study predictors of survival and renal toxicity in patients completing three or more treatment cycles. Results A total of 486 patients completed three or more treatment cycles; 237 patients received [90Y-DOTA]-TOC and 249 patients received [90Y-DOTA]-TOC + [177Lu-DOTA]-TOC. Patients receiving [90Y-DOTA]-TOC + [177Lu-DOTA]-TOC had a significantly longer survival than patients receiving [90Y-DOTA]-TOC alone (5.51 v 3.96 years; hazard ratio, 0.64; 95% CI, 0.47 to 0.88; P = .006). The rates of severe hematologic toxicities (6.3% v 4.4%; P = .25) and severe renal toxicity (8.9% v 11.2%; P = .47) were comparable in both groups. Conclusion [90Y-DOTA]-TOC + [177Lu-DOTA]-TOC was associated with improved overall survival compared with [90Y-DOTA]-TOC alone in patients completing three or more cycles of treatment. Contrary to the current practice in radiopeptide therapy, our results suggest an advantage of using a combination of radioisotopes.

Download Full-text

Prognostic impact of elevated lactate levels on mortality in critically ill patients with and without preadmission metformin treatment: a Danish registry-based cohort study

Annals of Intensive Care ◽

10.1186/s13613-020-00652-0 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 3

Author(s):

Rene A. Posma ◽

Trine Frøslev ◽

Bente Jespersen ◽

Iwan C. C. van der Horst ◽

Daan J. Touw ◽

...

Keyword(s):

Cohort Study ◽

Mortality Rate ◽

Critically Ill ◽

Critically Ill Patients ◽

Cox Regression ◽

Lower Mortality ◽

Prognostic Impact ◽

Icu Admission ◽

Lactate Levels ◽

Restricted Cubic Splines

Abstract Background Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers. Methods This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model. Results Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2–3.2) in metformin users and 1.6 (1.0–2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users. Conclusion In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use.

Download Full-text

Metformin use and long-term risk of benign prostatic hyperplasia: a population-based cohort study

BMJ Open ◽

10.1136/bmjopen-2020-041875 ◽

2020 ◽

Vol 10 (12) ◽

pp. e041875

Author(s):

Mette Nørgaard ◽

Bianka Darvalics ◽

Reimar Wernich Thomsen

Keyword(s):

Cohort Study ◽

Benign Prostatic Hyperplasia ◽

Cox Regression ◽

Population Based ◽

Prostatic Hyperplasia ◽

Haemoglobin A1c ◽

First Line ◽

Intention To Treat ◽

Lowering Drug

ObjectiveTo assess whether metformin use affects risk of benign prostatic hyperplasia (BPH) by comparing the risk of BPH in men with type 2 diabetes who initiated first-line treatment with either metformin or sulfonylurea monotherapy between 2000 or 2006 in Northern Denmark. In this period, sulfonylurea and metformin were both frequently used as first-line glucose-lowering drug (GLD) treatment.DesignA population-based cohort study.SettingNorthern Denmark.ParticipantsAll men who filled at least two prescriptions for metformin or for sulfonylurea, respectively, during their first 6 months of GLD treatment. Follow-up started 6 months after treatment start.Primary outcome measuresRates of subsequent BPH, identified based on community prescriptions for BPH-related treatment or hospital BPH diagnoses, and rates of transurethral resection of the prostate (TURP). Rates in metformin and sulfonylurea users were compared overall and stratified by 6-month haemoglobin A1c (HbA1c) using Cox regression and an intention-to-treat (ITT) approach and an as-treated analysis.ResultsDuring follow-up, less than five persons were lost to follow-up due to emigration. In 3953 metformin initiators with a median follow-up of 10 years, the 10-year cumulative BPH incidence was 25.7% (95% CI 24.2 to 27.1). Compared with 5958 sulfonylurea users (median follow-up 8 years, 10-year cumulative incidence 27.4% (95% CI 26.2 to 28.6)), the crude HR for BPH was 0.83 (95% CI 0.77 to 0.89) and adjusted HR in the ITT analyses was 0.97 (95% CI 0.88 to 1.06). For TURP, the adjusted HR was 0.96 (95% CI 0.63 to 1.46). In the as-treated analysis, adjusted HR for BPH was 0.91 (95% CI 0.81 to 1.02).ConclusionsCompared with sulfonylurea, metformin did not substantially reduce the incidence of BPH in men with diabetes.

Download Full-text

Effect of introducing human papillomavirus genotyping into real-world screening on cervical cancer screening in China: a retrospective population-based cohort study

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211010939 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110109

Author(s):

Binhua Dong ◽

Huachun Zou ◽

Xiaodan Mao ◽

Yingying Su ◽

Hangjing Gao ◽

...

Keyword(s):

Cervical Cancer ◽

Cohort Study ◽

Human Papillomavirus ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Cox Regression ◽

Intraepithelial Neoplasia ◽

Population Based ◽

Hpv Genotyping ◽

Cytology Screening

Background: China’s Fujian Cervical Pilot Project (FCPP) transitioned cervical cancer screening from high-risk human papillomavirus (HR-HPV) nongenotyping to genotyping. We investigated the clinical impact of this introduction, comparing performance indicators between HR-HPV genotyping combined with cytology screening (HR-HPV genotyping period) and the previous HR-HPV nongenotyping combined with cytology screening (HR-HPV nongenotyping period). Methods: A retrospective population-based cohort study was performed using data from the FCPP for China. We obtained data for the HR-HPV nongenotyping period from 1 January 2012 to 31 December 2013, and for the HR-HPV genotyping period from 1 January 2014 to 31 December 2016. Propensity score matching was used to match women from the two periods. Multivariable Cox regression was used to assess factors associated with cervical intraepithelial neoplasia of grade 2 or worse (CIN2+). The primary outcome was the incidence of CIN2+ in women aged ⩾25 years. Performance was assessed and included consistency, reach, effectiveness, adoption, implementation and cost. Results: Compared with HR-HPV nongenotyping period, in the HR-HPV genotyping period, more CIN2+ cases were identified at the initial screening (3.06% versus 2.32%; p < 0.001); the rate of colposcopy referral was higher (10.87% versus 6.64%; p < 0.001); and the hazard ratio of CIN2+ diagnosis was 1.64 (95% confidence interval, 1.43–1.88; p < 0.001) after controlling for health insurance status and age. The total costs of the first round of screening (US$66,609 versus US$65,226; p = 0.293) were similar during the two periods. Higher screening coverage (25.95% versus 25.19%; p = 0.007), higher compliance with age recommendations (92.70% versus 91.69%; p = 0.001), lower over-screening (4.92% versus 10.15%; p < 0.001), and reduced unqualified samples (cytology: 1.48% versus 1.73%, p = 0.099; HR-HPV: 0.57% versus 1.34%, p < 0.001) were observed in the HR-HPV genotyping period. Conclusions: Introduction of an HR-HPV genotyping assay in China could detect more CIN2+ lesions at earlier stages and improve programmatic indicators. Evidence suggests that the introduction of HR-HPV genotyping is likely to accelerate the elimination of cervical cancer in China.

Download Full-text

Gender- and age-related differences of statin use on incident dementia in patients with rheumatoid arthritis: a Nationwide population-based cohort study

Lipids in Health and Disease ◽

10.1186/s12944-021-01465-1 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Tsung-Kun Lin ◽

Jing-Yang Huang ◽

Lung-Fa Pan ◽

Gwo-Ping Jong

Keyword(s):

Rheumatoid Arthritis ◽

Cohort Study ◽

Subgroup Analysis ◽

Cox Regression ◽

Population Based ◽

Age Related ◽

Hazard Ratios ◽

Incident Dementia ◽

Gender And Age ◽

New Onset

Abstract Background Some observational studies have found a significant association between the use of statin and a reduced risk of dementia. However, the results of these studies are unclear in patients with rheumatoid arthritis (RA). This study is to determine the association between the use of statins and the incidence of dementia according to sex and age-related differences in patients with RA. Methods We conducted a nationwide retrospective cohort study using the Taiwan Health Insurance Review and Assessment Service database (2003–2016). The primary outcome assessed was the risk of dementia by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression was used to estimate the adjusted hazard ratio of new-onset dementia. Subgroup analysis was also conducted. Results Among the 264,036 eligible patients with RA aged > 40 years, statin users were compared with non-statin users by propensity score matching at a ratio of 1:1 (25,764 in each group). However, no association was found between the use of statins and the risk of new-onset dementia (NOD) in patients with RA (HR: 1.01; 95% CI: 0.97–1.06). The subgroup analysis identified the use of statin as having a protective effect against developing NOD in male and older patients. Conclusion No association was observed between the use of a statin and the risk of NOD in patients with RA, including patients of both genders and aged 40–60 years, but these parameters were affected by gender and age. The decreased risk of NOD in patients with RA was greater among older male patients. Use of a statin in older male (> 60 years) patients with RA may be needed in clinical practice to prevent dementia.

Download Full-text

Clinical characteristics and outcome of influenza virus infection among adults hospitalized with severe COVID-19: a retrospective cohort study from Wuhan, China

BMC Infectious Diseases ◽

10.1186/s12879-021-05975-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xunliang Tong ◽

Xiaomao Xu ◽

Guoyue Lv ◽

He Wang ◽

Anqi Cheng ◽

...

Keyword(s):

Influenza Virus ◽

Cohort Study ◽

Clinical Features ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Cox Regression ◽

Influenza Virus Infection ◽

Chronic Respiratory Disease ◽

Hospital Death ◽

New City

Abstract Background Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that rapidly spreads worldwide and co-infection of COVID-19 and influenza may occur in some cases. We aimed to describe clinical features and outcomes of severe COVID-19 patients with co-infection of influenza virus. Methods Retrospective cohort study was performed and a total of 140 patients with severe COVID-19 were enrolled in designated wards of Sino-French New City Branch of Tongji Hospital between Feb 8th and March 15th in Wuhan city, Hubei province, China. The demographic, clinical features, laboratory indices, treatment and outcomes of these patients were collected. Results Of 140 severe COVID-19 hospitalized patients, including 73 patients (52.14%) with median age 62 years were influenza virus IgM-positive and 67 patients (47.86%) with median age 66 years were influenza virus IgM-negative. 76 (54.4%) of severe COVID-19 patients were males. Chronic comorbidities consisting mainly of hypertension (45.3%), diabetes (15.8%), chronic respiratory disease (7.2%), cardiovascular disease (5.8%), malignancy (4.3%) and chronic kidney disease (2.2%). Clinical features, including fever (≥38 °C), chill, cough, chest pain, dyspnea, diarrhea and fatigue or myalgia were collected. Fatigue or myalgia was less found in COVID-19 patients with IgM-positive (33.3% vs 50/7%, P = 0.0375). Higher proportion of prolonged activated partial thromboplastin time (APTT) > 42 s was observed in COVID-19 patients with influenza virus IgM-negative (43.8% vs 23.6%, P = 0.0127). Severe COVID-19 Patients with influenza virus IgM positive have a higher cumulative survivor rate than that of patients with influenza virus IgM negative (Log-rank P = 0.0308). Considering age is a potential confounding variable, difference in age was adjusted between different influenza virus IgM status groups, the HR was 0.29 (95% CI, 0.081–1.100). Similarly, difference in gender was adjusted as above, the HR was 0.262 (95% CI, 0.072–0.952) in the COX regression model. Conclusions Influenza virus IgM positive may be associated with decreasing in-hospital death.

Download Full-text

Sleep duration and all-cause mortality in the elderly in China: a population-based cohort study

BMC Geriatrics ◽

10.1186/s12877-020-01962-5 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Yanfeng Ren ◽

Maohua Miao ◽

Wei Yuan ◽

Jiangwei Sun

Keyword(s):

Cohort Study ◽

Sleep Duration ◽

Dose Response ◽

Cox Regression ◽

Oldest Old ◽

The Elderly ◽

Response Analysis ◽

Short Sleep Duration ◽

All Cause Mortality

Abstract Background Although a U-shaped association between sleep duration and all-cause mortality has been found in general population, its association in the elderly adults, especially in the oldest-old, is rarely explored. Methods In present cohort study, we prospectively explore the association between sleep duration and all-cause mortality among 15,092 participants enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2005 to 2019. Sleep duration and death information was collected by using structured questionnaires. Cox regression model with sleep duration as a time-varying exposure was performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). The dose-response association between them was explored via a restricted cubic spline function. Results During an average follow-up of 4.51 (standard deviation, SD: 3.62) years, 10,768 participants died during the follow-up period. The mean (SD) age of the participants was 89.26 (11.56) years old. Compared to individuals with moderate sleep duration (7–8 hours), individuals with long sleep duration (> 8 hours) had a significantly higher risk of all-cause mortality (HR: 1.13, 95%CI: 1.09–1.18), but not among individuals with short sleep duration (≤ 6 hours) (HR: 1.02, 95%CI: 0.96–1.09). Similar results were observed in subgroup analyses based on age and gender. In the dose-response analysis, a J-shaped association was observed. Conclusions Sleep duration was associated with all-cause mortality in a J-shaped pattern in the elderly population in China.

Download Full-text

Association between glaucoma surgery and all-cause and cause-specific mortality among elderly patients with glaucoma: a nationwide population-based cohort study

Scientific Reports ◽

10.1038/s41598-021-96063-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sang Yeop Lee ◽

Hun Lee ◽

Ji Sung Lee ◽

Sol Ah Han ◽

Yoon Jeon Kim ◽

...

Keyword(s):

Cohort Study ◽

Elderly Patients ◽

Cox Regression ◽

Open Angle Glaucoma ◽

Glaucoma Surgery ◽

Population Based ◽

Angle Closure ◽

Charlson Comorbidity Index Score ◽

All Cause Mortality ◽

Specific Mortality

AbstractThis population-based, retrospective cohort study aimed to evaluate the association between glaucoma surgery and all-cause and cause-specific mortality among Korean elderly patients with glaucoma. A total of 16210 elderly patients (aged ≥ 60 years) diagnosed with glaucoma between 2003 and 2012 were included, and their insurance data were analyzed. The participants were categorized into a glaucoma surgery cohort (n = 487), which included individuals who had diagnostic codes for open angle glaucoma (OAG) or angle closure glaucoma (ACG) and codes for glaucoma surgery, and a glaucoma diagnosis cohort (n = 15,723), which included patients who had codes for OAG and ACG but not for glaucoma surgery. Sociodemographic factors, Charlson Comorbidity Index score, and ocular comorbidities were included as covariates. Cox regression models were used to assess the association between glaucoma surgery and mortality. The incidence of all-cause mortality was 34.76/1,000 person-years and 27.88/1,000 person-years in the glaucoma surgery and diagnosis groups, respectively. The adjusted hazard ratio (HR) for all-cause mortality associated with glaucoma surgery was 1.31 (95% confidence interval [CI], 1.05–1.62, P = 0.014). The adjusted HR for mortality due to a neurologic cause was significant (HR = 2.66, 95% CI 1.18–6.00, P = 0.018). The adjusted HRs for mortality due to cancer (HR = 2.03, 95% CI 1.07–3.83, P = 0.029) and accident or trauma (HR = 4.00, 95% CI 1.55–10.34, P = 0.004) associated with glaucoma surgery for ACG were significant as well. Glaucoma surgery was associated with an increase of mortality in elderly patients with glaucoma. In particular, the risk of mortality associated with glaucoma surgery due to neurologic causes was significant.

Download Full-text

Survival analysis of time to SARS-CoV-2 PCR negativisation to optimise PCR prescription in health workers: the Henares COVID-19 healthcare workers cohort study

Occupational and Environmental Medicine ◽

10.1136/oemed-2020-106903 ◽

2021 ◽

pp. oemed-2020-106903

Author(s):

Julio González Martin-Moro ◽

Marta Chamorro Gómez ◽

Galicia Dávila Fernández ◽

Ana Elices Apellaniz ◽

Ana Fernández Hortelano ◽

...

Keyword(s):

Cohort Study ◽

Healthcare Workers ◽

Cox Regression ◽

Health Workers ◽

Upper Respiratory Tract ◽

Rt Pcr ◽

Kaplan Meier ◽

Confounding Variables ◽

The Impact ◽

Associated Variables

ObjectivesReverse transcriptase PCR (RT-PCR) is considered the gold standard in diagnosing COVID-19. Infected healthcare workers do not go back to work until RT-PCR has demonstrated that the virus is no longer present in the upper respiratory tract. The aim of this study is to determine the most efficient time to perform RT-PCR prior to healthcare workers’ reincorporation.Materials and methodsThis is a cohort study of healthcare workers with RT-PCR-confirmed COVID-19. Data were collected using the medical charts of healthcare workers and completed with a telephone interview. Kaplan-Meier curves were used to determine the influence of several variables on the time to RT-PCR negativisation. The impact of the variables on survival was assessed using the Breslow test. A Cox regression model was developed including the associated variables.Results159 subjects with a positive RT-PCR out of 374 workers with suspected COVID-19 were included. The median time to negativisation was 25 days from symptom onset (IQR 20–35 days). Presence of IgG, dyspnoea, cough and throat pain were associated with significant longer time to negativisation. Cox logistic regression was used to adjust for confounding variables. Only dyspnoea and cough remained in the model as significant determinants of prolonged negativisation time. Adjusted HRs were 0.68 (0.48–096) for dyspnoea and 0.61 (0.42–0.88) for dry cough.ConclusionsRT-PCR during the first 3 weeks leads to a high percentage of positive results. In the presence of respiratory symptoms, negativisation took nearly 1 week more. Those who developed antibodies needed longer time to negativisate.

Download Full-text

Adherence to the Mediterranean diet and risk of lung cancer in the Netherlands Cohort Study

British Journal Of Nutrition ◽

10.1017/s0007114517003737 ◽

2018 ◽

Vol 119 (6) ◽

pp. 674-684 ◽

Cited By ~ 12

Author(s):

Maya Schulpen ◽

Piet A. van den Brandt

Keyword(s):

Lung Cancer ◽

Cancer Research ◽

Cohort Study ◽

Cancer Risk ◽

The Netherlands ◽

Mediterranean Diet ◽

Dietary Habits ◽

Lung Cancer Risk ◽

Cox Regression ◽

The Mediterranean

AbstractThe evidence on a cancer-protective effect of the Mediterranean diet (MD) is still limited. Therefore, we investigated the association between MD adherence and lung cancer risk. Data were used from 120 852 participants of the Netherlands Cohort Study (NLCS), aged 55–69 years. Dietary habits were assessed at baseline (1986) using a validated FFQ and alternate and modified Mediterranean diet scores (aMED and mMED, respectively), including and excluding alcohol, were calculated. After 20·3 years of follow-up, 2861 lung cancer cases and 3720 subcohort members (case-cohort design) could be included in multivariable Cox regression analyses. High (6–8) v. low (0–3) aMED excluding alcohol was associated with non-significantly reduced lung cancer risks in men and women with hazard ratios of 0·91 (95 % CI 0·72, 1·15) and 0·73 (95 % CI 0·49, 1·09), respectively. aMED-containing models generally fitted better than mMED-containing models. In never smokers, a borderline significant decreasing trend in lung cancer risk was observed with increasing aMED excluding alcohol. Analyses stratified by the histological lung cancer subtypes did not identify subtypes with a particularly strong inverse relation with MD adherence. Generally, the performance of aMED and World Cancer Research Fund/American Institute for Cancer Research dietary score variants without alcohol was comparable. In conclusion, MD adherence was non-significantly inversely associated with lung cancer risk in the NLCS. Future studies should focus on differences in associations across the sexes and histological subtypes. Furthermore, exclusion of alcohol from MD scores should be investigated more extensively, primarily with respect to a potential role of the MD in cancer prevention.

Download Full-text

Coeliac disease and invasive pneumococcal disease: a population-based cohort study

Epidemiology and Infection ◽

10.1017/s0950268816003204 ◽

2017 ◽

Vol 145 (6) ◽

pp. 1203-1209 ◽

Cited By ~ 9

Author(s):

A. RÖCKERT TJERNBERG ◽

J. BONNEDAHL ◽

M. INGHAMMAR ◽

A. EGESTEN ◽

G. KAHLMETER ◽

...

Keyword(s):

Cohort Study ◽

Coeliac Disease ◽

Invasive Pneumococcal Disease ◽

Pneumococcal Disease ◽

Cox Regression ◽

Statistical Significance ◽

Pneumococcal Vaccination ◽

Population Based ◽

Increased Risk ◽

Severe Infections

SUMMARYSevere infections are recognized complications of coeliac disease (CD). In the present study we aimed to examine whether individuals with CD are at increased risk of invasive pneumococcal disease (IPD). To do so, we performed a population-based cohort study including 29 012 individuals with biopsy-proven CD identified through biopsy reports from all pathology departments in Sweden. Each individual with CD was matched with up to five controls (n = 144 257). IPD events were identified through regional and national microbiological databases, including the National Surveillance System for Infectious Diseases. We used Cox regression analyses to estimate hazard ratios (HRs) for diagnosed IPD. A total of 207 individuals had a record of IPD whereas 45/29 012 had CD (0·15%) and 162/144 257 were controls (0·11%). This corresponded to a 46% increased risk for IPD [HR 1·46, 95% confidence interval (CI) 1·05–2·03]. The risk estimate was similar after adjustment for socioeconomic status, educational level and comorbidities, but then failed to attain statistical significance (adjusted HR 1·40, 95% CI 0·99–1·97). Nonetheless, our study shows a trend towards an increased risk for IPD in CD patients. The findings support results seen in earlier research and taking that into consideration individuals with CD may be considered for pneumococcal vaccination.

Download Full-text