Nonfocal Symptoms in Patients with Transient Ischemic Attack and Association with Stroke Risk

Background and Objective: Patients with transient ischemic attack（TIA）occasionally showed nonfocal symptoms, such as decreased consciousness, amnesia and non-rotatory dizziness. This study intended to evaluate the effect of nonfocal symptoms on the prognosis of patients with TIA. Methods: Data from the prospective hospital-based TIA database of the First Affiliated Hospital of Zhengzhou University were analyzed. The predictive outcome was stroke occurrence at 1 year. Cumulative risks of stroke in patients with and without nonfocal symptoms were estimated with Kaplan-Meier models. Results: We studied 1384 patients with TIA (842 men; mean age, 56±13 years), including 450 (32.5%) with nonfocal symptoms. In the first year after TIA, stroke occurred in 168（12.1%） patients. There was no difference in the risk of stroke between patients with both focal and nonfocal symptoms and patients with focal symptoms alone (11.8% vs 12.4%, log-rank; P=0.691). Conclusions: The occurrence of nonfocal symptoms did not increase the risk of stroke at one-year follow-up compared to the occurrence of focal symptoms alone.

Postoperative de novo epilepsy after craniotomy: a nationwide register-based cohort study

Background and objectivesThe risks of postoperative risk of epilepsy after a craniotomy is widely believed to be raised. A study is warranted to quantify the risks for any neurosurgical indication. In this unselected register-based nationwide cohort study with virtually complete follow-up, the short-term and long-term cumulative risks of postoperative de novo epilepsy for all major neurosurgical indications were estimated.MethodsThe study was based on 8948 first-time craniotomy patients in Denmark 1 January 2005 to 31 December 2015 with follow-up until 31 December 2016. The patients were classified according to their underlying neurosurgical pathology. Patients with preoperative epilepsy were excluded. The postcraniotomy risks of de novo epilepsy were estimated using the Aalen-Johansen estimator in a multistate model.ResultsThe overall cumulative 1-year risk of postcraniotomy de novo epilepsy was 13.9% (95% CI 13.2 to 14.6). For patients with intracranial tumour the cumulative 1-year risk was 15.4% (95% CI 14.4 to 16.5), for spontaneous intracranial haemorrhage 11.3% (95% CI 10.1 to 12.6), for traumatic intracranial haemorrhage 11.1% (95% CI 9.6 to 12.9), for cerebral abscess 27.6% (95% CI 22.8 to 33.5) and for congenital malformations 3.8% (95% CI 1.3 to 11.7). The 6-month, 1-year and 5-year risks for all major indications by specific subtypes are provided.ConclusionsThe cumulative risk of de novo epilepsy following craniotomy is high for patients with any indication for craniotomy, as compared with the background population. The results provide comprehensive data to support future recommendations regarding prophylactic antiepileptic treatment and driving restrictions.

Instrumental variable estimation for a time-varying treatment and a time-to-event outcome via structural nested cumulative failure time models

Background In many applications of instrumental variable (IV) methods, the treatments of interest are intrinsically time-varying and outcomes of interest are failure time outcomes. A common example is Mendelian randomization (MR), which uses genetic variants as proposed IVs. In this article, we present a novel application of g-estimation of structural nested cumulative failure models (SNCFTMs), which can accommodate multiple measures of a time-varying treatment when modelling a failure time outcome in an IV analysis. Methods A SNCFTM models the ratio of two conditional mean counterfactual outcomes at time k under two treatment strategies which differ only at an earlier time m. These models can be extended to accommodate inverse probability of censoring weights, and can be applied to case-control data. We also describe how the g-estimates of the SNCFTM parameters can be used to calculate marginal cumulative risks under nondynamic treatment strategies. We examine the performance of this method using simulated data, and present an application of these models by conducting an MR study of alcohol intake and endometrial cancer using longitudinal observational data from the Nurses’ Health Study. Results Our simulations found that estimates from SNCFTMs which used an IV approach were similar to those obtained from SNCFTMs which adjusted for confounders, and similar to those obtained from the g-formula approach when the outcome was rare. In our data application, the cumulative risk of endometrial cancer from age 45 to age 72 under the “never drink” strategy (4.0%) was similar to that under the “always ½ drink per day” strategy (4.3%). Conclusions SNCFTMs can be used to conduct MR and other IV analyses with time-varying treatments and failure time outcomes.

Radioactive Iodine Treatment and the Risk of Long-Term Cardiovascular Morbidity and Mortality in Thyroid Cancer Patients: A Nationwide Cohort Study

(1) Background: This study aimed to investigate the association between radioactive iodine (RAI) and long-term cardiovascular disease (CVD) morbidity/mortality in thyroid cancer. (2) Methods: The study was conducted using data from the Taiwan National Health Insurance Database during 2000–2015. Thyroid cancer patients aged ≥20 years were categorized into RAI (thyroidectomy with RAI) and non-RAI (thyroidectomy only) groups. The Cox proportional hazard regression model and Kaplan–Meier method were used for analysis. (3) Results: A total of 13,310 patients were included. Kaplan–Meier analysis demonstrated that the two groups had similar cumulative risks of CVD (log-rank p = 0.72) and CVD-specific mortality (log-rank p = 0.62). On Cox regression analysis of different RAI doses, the risk of CVD was higher in the cumulative dosage >3.7 GBq (hazard ratio = 1.69, 95% confidence interval = 1.24–2.40, p < 0.001). (4) Conclusions: RAI was not associated with an increased risk of CVD in thyroid cancer. However, CVD surveillance is indicated in the patients receiving the cumulative RAI dosage above 3.7 GBq.

Cumulative Risks of Excipients in Pediatric Phytomucolytic Syrups: The Implications for Pharmacy Practice

Expectorant phytomucolytic syrups are widely used pediatric OTC-medicines. Physicians, pediatricians, and pharmacists are traditionally concerned with the efficacy of the active ingredients in cough syrups, and rarely consider the safety aspects of excipients that however are not absolutely “inactive” and are proved to initiate some negative reactions and interactions with other drugs. This paper presents a review, categorization, and comparative analysis of the safety profile of excipients contained in the 22 best-selling OTC pediatric phytomucolytic syrups available in pharmaceutical markets in Ukraine and Germany and proposes an approach to the consideration of the excipients’ safety risks for a pharmacist in the process of pharmaceutical care. The study has revealed that only one of the twenty-two analyzed syrups does not contain any potentially harmful excipients. The results of this analysis were used for developing a specific decision tool for pharmacists that can be used for minimizing excipient-initiated reactions when delivering OTC phytomucolytic syrups for children.

Dietary Risk Assessment and Ranking of Multipesticides in Dendrobium officinale

The presence of pesticide residues in Dendrobium officinale (D. officinale), a commonly used herbal medicine, has attracted much attention in recent years. Therefore, this study presents the levels of 141 pesticide residues in forty D. officinale samples, which were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). And we used a deterministic estimate model to assess chronic and acute dietary exposure risk, as well as the cumulative risks for adults, children, and specific groups of consumers. Furthermore, the residual risk of individual pesticides was sorted by adapting the matrix-ranking scheme. In 92.5% of the samples, 43 pesticides were detected, of which difenoconazole had the highest detection frequency. Multiple residues were detected in 85.0% of the samples, and one sample contained even up to 17 pesticides. The chronic hazard quotient (HQc) and the acute hazard quotient (HQa) were far below 100%, and both cumulative chronic and acute hazard indices (HI) did not exceed 100%. The risk scoring scheme showed that four pesticides were considered to pose a comparatively potential high risk, including difenoconazole, carbofuran, fipronil, and emamectin benzoate. The results indicated that the occurrence of pesticide residues in D. officinale could not pose a serious health problem to the public.

For evidence-based clinical long-term follow-up of childhood cancer survivors, risk stratification is required

The National Cancer Survivorship Initiative (NCSI) advocated reorganizing clinical follow-up care in England depending on cancer type and therapy, with levels ranging from Level 1 (assisted self-management) to Level 3 (intensive follow-up) (consultant-led care). The goal of this research was to use a large population-based cohort of pediatric cancer survivors to investigate the risks of major adverse health outcomes related with NCSI Levels of clinical treatment. SPNs—5 percent (two-fold expected), 14 percent (four-fold expected), and 21 percent (eight-fold expected) by 45 years from diagnosis among non-leukaemic survivors assigned to NCSI Levels 1, 2, and 3; non-neoplastic death—2 percent (two-fold expected), 4 percent (three-fold expected), and 8 percent (seven-fold expected); non-fatal infections—2 percent (two-fold expected), 4 percent (three-fold expected); non- As a result, the total cumulative risks of any negative health outcome were 21%, 45%, and 69%, respectively. Despite its simplicity, the risk stratification tool offers evident and substantial discrimination in terms of long-term cumulative and excess risks of major unfavorable outcomes between survivors allocated to various NCSI Levels.

Cumulative risks of colorectal cancer in Han Chinese patients with Lynch syndrome in Taiwan

Patients with Lynch syndrome have a high risk of colorectal cancer (CRC). In this study, we estimated the age- and sex-specific cumulative risks of CRC in Han Chinese patients with Lynch syndrome caused by the pathogenic germline mutations in MLH1 or MSH2 in Taiwan. Based on 321 mutation carriers and 419 non-mutation carriers from 75 pedigrees collected in an Amsterdam criteria family registry in Taiwan, the age- and sex-specific cumulative risks of CRC in male carriers of mutation in MLH1 and MSH2 at the age of 70 years were 60.3% (95% confidence interval (CI) = 31.1%–89.9%) and 76.7% (95% CI = 37.2%–99.0%), respectively. For females, the cumulative risks of CRC at the age of 70 were estimated to be 30.6% (95% CI = 14.3%–57.7%) and 49.3% (95% CI = 21.9%–84.5%) in the carriers of MLH1 and MSH2 germline mutations, respectively. In conclusion, the cumulative risks of CRC at the age of 70 in the Han Chinese patients is higher in mutation carriers than non-mutation carriers and male mutation carriers have a higher cumulative risk of developing CRC than the female mutation carriers.