Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of toxicity after acute accidental methotrexate ingestions in children under 6 years old: a 16-year multi-center review

Abstract Context: There is little data on the frequency of adverse events following acute methotrexate ingestions in pediatric patients. Likewise, recommendations for observation length, site and management strategies in this population are not well established. Therefore, most recommendations are modeled after management of chronic overdose in patients with underlying medical conditions. Objective: The primary objective of this study is to determine the frequency of acute toxicity after acute methotrexate accidental unsupervised ingestions in patients less than six years. In addition, we describe the frequency of late toxicity and characterize the management site and approaches. Materials and Methods: This is a retrospective cohort study of pediatric accidental unsupervised methotrexate ingestions reported to six poison centers in the United States over a 16 year period. Demographic information, exposure details, signs, symptoms, treatments, length and location of observation and outcomes were collected. Results: 103 patients met inclusion criteria. Methotrexate dose was reported in 86 patients (84%) and ranged from 1.3 mg–75 mg. The majority of cases (97%) ingested a dose ≤20 mg. The significant majority of cases experienced no clinical effects (99 of 103 cases; 96%). Three children experienced minor outcome (3%). There were no patients with a major outcome or death. Conclusions: The incidence of toxicity from pediatric single, acute ingestions of methotrexate is rare and when it occurs is generally limited to no or only minimally concerning effects. Because concentrations from single ingestions were consistent with low subtoxic exposures, we believe that home monitoring without hospital referral and without methotrexate specific therapy is reasonable in those with acute ingestions up to 20 mg.
Bacterial Sexually Transmitted Disease Screening Outside the Clinic—Implications for the Modern Sexually Transmitted Disease Program

Background The development of noninvasive nucleic acid amplification tests for chlamydia and gonorrhea has facilitated innovation in moving sexually transmitted disease (STD) screening to nonclinical settings. However, limited data are available to inform local STD programs on evidence-based approaches to STD screening in nonclinical settings in the United States. Methods We conducted a systematic review of the literature published since 2000 related to chlamydia, gonorrhea, and syphilis screening in US correctional settings, bathhouses and sex venues, self-collected at-home testing, and other nonclinical sites. Results Sixty-four articles met eligibility criteria and were reviewed. Although data on testing volume and positivity were available, there were scarce data on the proportion of new positives treated and the programmatic costs for the various screening programs. Screening in correctional settings identified a sizable amount of asymptomatic infections. The value and sustainability of screening in the other nonclinical settings examined was not clear from the published literature. Conclusions Local and state health departments should explore the development of sustainable jail and juvenile detention screening programs for STDs. Furthermore, local programs should pilot outreach and home-based STD screening programs to determine if they are identifying asymptomatic persons who would not have otherwise been found. Local programs are encouraged to present and publish their findings related to non–clinic-based screening to enhance the limited body of literature; data on the proportion of new infections treated and the local program costs are needed. Key Findings: STD screening in correctional settings identifies a sizable amount of undiagnosed chlamydia, gonorrhea, and syphilis. STD screening in other community settings, including sex venues, college campuses, drug treatment, and bars, had variable yield. Self-collected, home-based chlamydia and gonorrhea screening is an exciting innovation; however, limited data are available to assess its population health benefit. Data related to the proportion of new infections that get appropriately treated and the costs of various non–clinic-based screening programs are largely unavailable.
Sex, Illness, Illness Behavior, and the Use of Health Services

Abstract Many investigators of the sex differences in health confound conception with reporting, illness with illness behavior, and symptoms with disability. There is also a tendency to confuse subjects' responses, those attributable to the selective process through which men and women appear at varying sources of help, and those due to the attitudes and the behavior of health personnel. This paper considers a group of alternative hypotheses that attempt to account for sex differences in health. Existing data suggest that women seem to report many more subjective symptoms than men. Also, much of the excess chronic illness reported by women is in part a reflection of how they define and respond to illness and to their life situations. There is a need for developing research designs that test alternative conceptions of the sex differences in health more rigorously.
Significant Reduction in the Incidence of Genital Warts in Young Men 5 Years Into the Danish Human Papillomavirus Vaccination Program for Girls and Women

Background Denmark introduced the quadrivalent human papillomavirus vaccine into the vaccination program for 12- to 15-year-old girls in 2008 to 2009. In 2012, the program was supplemented with a catch-up program for women aged up to 27 years. We evaluated the effectiveness of the Danish vaccination program on the nationwide incidence of genital warts (GWs), after the second catch-up by including information on both hospital treatments and on self-administered treatment with podophyllotoxin. Genital wart incidence was investigated in both sexes; however, the main focus was on potential herd protection of men. Methods Incident cases of GWs were identified from the Danish National Patient Register and through redemptions of prescription for podophyllotoxin in the Danish National Prescription Registry in 2006 to 2013. Age-specific incidence rates (IRs) were assessed, and estimated annual percentage change (EAPC) was calculated by Poisson regression. Results Genital wart incidence was either stable or increased in both sexes in 2006 to 2008. After introduction of the vaccination program, GW incidence decreased significantly in women aged 12 to 35 years and men aged 12 to 29 years, with rapid decrease among 16- to 17-year-olds (IRwomen, from 1071 to 58 per 100,000 person-years [EAPC, −55.1%; 95% confidence interval, −58.7 to−51.2]; IRmen, from 365 to 77 per 100,000 person-years [EAPC, −36.6%; 95% confidence interval, −40.5 to −32.5] in 2008–2013). Conclusions We found a significantly decreasing incidence of GWs in women up to 35 years of age after the start of the human papillomavirus vaccination program. A similar pattern was observed for men aged 12 to 29 years, indicating substantial herd protection.
Inhibition of epoxyeicosatrienoic acid production in rats with cirrhosis has beneficial effects on portal hypertension by reducing splanchnic vasodilation

In cirrhosis, 11,12‐epoxyeicosatrienoic acid (EET) induces mesenteric arterial vasodilation, which contributes to the onset of portal hypertension. We evaluated the hemodynamic effects of in vivo inhibition of EET production in experimental cirrhosis. Sixteen control rats and 16 rats with carbon tetrachloride‐induced cirrhosis were studied. Eight controls and eight rats with cirrhosis were treated with the specific epoxygenase inhibitor N‐(methylsulfonyl)‐2‐(2‐propynyloxy)‐benzenehexanamide (MS‐PPOH; 20 mg/kg/day) for 3 consecutive days. Portal blood flow and renal and splenic resistive indexes were calculated through echographic measurements, while portal and systemic pressures were measured through polyethylene−50 catheters. Small resistance mesenteric arteries were connected to a pressure servo controller in a video‐monitored perfusion system, and concentration‐response curves to phenylephrine and acetylcholine were evaluated. EET levels were measured in tissue homogenates of rat liver, kidney, and aorta, using an enzyme‐linked immunosorbent assay. Urinary Na+ excretion function was also evaluated. In rats with cirrhosis, treatment with MS‐PPOH significantly reduced portal blood flow and portal pressure compared to vehicle (13.6 ± 5.7 versus 25.3 ± 7.1 mL/min/100 g body weight, P < 0.05; 9.6 ± 1.1 versus 12.2 ± 2.3 mm Hg, P < 0.05; respectively) without effects on systemic pressure. An increased response to acetylcholine of mesenteric arteries from rats with cirrhosis (50% effect concentration ‐7.083 ± 0.197 versus ‐6.517 ± 0.73 in control rats, P < 0.05) was reversed after inhibition of EET production (‐6.388 ± 0.263, P < 0.05). In liver, kidney, and aorta from animals with cirrhosis, treatment with MS‐PPOH reversed the increase in EET levels. In both controls and rats with cirrhosis, MS‐PPOH increased urinary Na+ excretion. Conclusion: In rats with cirrhosis, in vivo inhibition of EET production normalizes the response of mesenteric arteries to vasodilators, with beneficial effects on portal hypertension. (Hepatology 2016;64:923‐930)
Generalized anxiety disorder in China: prevalence, sociodemographic correlates, comorbidity, and suicide attempts.

PURPOSE This study aims to determine the 12-month and lifetime prevalence of generalized anxiety disorder (GAD) and its sociodemographic correlates. DESIGN AND METHODS A total of 5,926 subjects were randomly selected and interviewed. FINDINGS The overall 12-month and lifetime prevalence of GAD was 0.8%, and 1.2%, respectively. Being older than 25 years and female, lower education level, unemployed status, and lower (RMB2000/month) monthly income were associated with increased risk of GAD. PRACTICE IMPLICATIONS The low percentage of subjects treated for GAD indicates a major public health problem that should be addressed.
G‐protein‐coupled bile acid receptor plays a key role in bile acid metabolism and fasting‐induced hepatic steatosis in mice

Bile acids are signaling molecules that play a critical role in regulation of hepatic metabolic homeostasis by activating nuclear farnesoid X receptor (Fxr) and membrane G‐protein‐coupled receptor (Takeda G‐protein‐coupled receptor 5; Tgr5). The role of FXR in regulation of bile acid synthesis and hepatic metabolism has been studied extensively. However, the role of TGR5 in hepatic metabolism has not been explored. The liver plays a central role in lipid metabolism, and impaired response to fasting and feeding contributes to steatosis and nonalcoholic fatty liver and obesity. We have performed a detailed analysis of gallbladder bile acid and lipid metabolism in Tgr5−/− mice in both free‐fed and fasted conditions. Lipid profiles of serum, liver and adipose tissues, bile acid composition, energy metabolism, and messenger RNA and protein expression of the genes involved in lipid metabolism were analyzed. Results showed that deficiency of the Tgr5 gene in mice alleviated fasting‐induced hepatic lipid accumulation. Expression of liver oxysterol 7α‐hydroxylase in the alternative bile acid synthesis pathway was reduced. Analysis of gallbladder bile acid composition showed marked increase of taurocholic acid and decrease of tauro‐α and β‐muricholic acid in Tgr5−/− mice. Tgr5−/− mice had increased hepatic fatty acid oxidation rate and decreased hepatic fatty acid uptake. Interestingly, fasting induction of fibroblast growth factor 21 in liver was attenuated. In addition, fasted Tgr5−/− mice had increased activation of hepatic growth hormone‐signal transducer and activator of transcription 5 (GH‐Stat5) signaling compared to wild‐type mice. Conclusion: TGR5 may play a role in determining bile acid composition and in fasting‐induced hepatic steatosis through a novel mechanism involving activation of the GH‐Stat5 signaling pathway. (Hepatology 2017;65:813‐827)
PD-L1 expression in hepatocellular carcinoma: Relationship with clinical and pathological features

The prognosis of hepatocellular carcinoma (HCC) remains poor, with only one third of patients eligible to curative treatments and very limited survival benefits with the use of sorafenib, the current standard-of-care for advanced disease. Recently, agents targeting the PD-L1/PD-1 immune checkpoint were shown to display impressive antitumor activity in various solid or hematological malignancies, including HCC. PD-L1 immunohistochemical expression is thought to represent a biomarker predictive of drug sensitivity. Here, we investigated PD-L1 expression in a series of 217 HCCs and correlated our results with clinical and histological features, and immunohistochemical markers (PD-1, cytokeratin 19, glutamine synthetase, and β-catenin expression). PD-L1 expression by neoplastic cells was significantly associated with common markers of tumor aggressiveness (high serum alpha-foetoprotein (AFP) levels, p=0.038; satellite nodules, p<0.001; macrovascular invasion, p<0.001; microvascular invasion, p<0.001; poor differentiation, p<0.001) and with the progenitor subtype of HCC (cytokeratin 19 expression, p=0.031). High PD-L1 expression by inflammatory cells from the tumor microenvironment also correlated with high serum AFP levels (p<0.001), macrovascular invasion (p=0.001), poor differentiation (p=0.001), high PD-1 expression (p<0.001), and with the so called “lymphoepithelioma-like” histological subtype of HCC (p=0.003). Conclusion: Our study demonstrates that PD-L1 expression by either neoplastic or intratumoral inflammatory cells is related to tumor aggressiveness. It suggests that the response to treatments targeting the PD-L1/PD-1 immune checkpoint could be restricted to particular HCC variants. Thus, enrichment of these tumor subtypes in future clinical trials should be considered. This article is protected by copyright. All rights reserved.
A case series of accidental ingestion of hand warmer

Introduction. The use of hand warmers in Hong Kong during cold weather has become increasingly popular. Iron powder is one of the ingredients. We report the first cases of ingestion of hand warmer contents. Care reports. Four elderly patients ingested the contents of hand warmers. All had no or mild symptoms, one had radiopaque particles in the stomach, two showed transiently increased serum iron concentrations (within the reference range), and all recovered with only supportive care. Discussion. These hand warmers contain a mixture of iron powder, activated charcoal, vermiculite, sodium chloride, and water. Iron powder accounts for about 50% of the weight (range 95–120 g). There are no reports of elemental iron or iron oxides ingestion causing iron toxicity and no published data on the absorption, elimination, adverse effects, or toxicities in humans after unintentional ingestion of hand warmer contents. A single oral dose toxicity test of hand warmer contents (2 g/kg) resulted in no toxicity or deaths in ten rats. Ingestions of one hand warmer packet or less can be treated with observation and supportive care as needed. Conclusions. Although this case series is small, the lack of toxicity is consistent with animal studies. It appears unlikely that significant toxicity will occur after the ingestion of one hand warmer packet. The ingestion of larger amounts might lead to iron-related toxicity and may justify more aggressive management. Proper labeling by local distributors may prevent further unintentional ingestions of these non-food products.
Acute tacrolimus toxicity in a non-transplant patient

Introduction. Tacrolimus is an immunosuppressant widely used in recipients of solid organ transplants to prevent rejection. Toxicity is usually reported in transplant patients. We report the first case of tacrolimus toxicity in a non-transplant patient. Case report. A 42 year-old, 48 kg woman complained of neck pain following a motor vehicle collision and was admitted for observation. On examination, her pulse was 112 beats/minute and her blood pressure 188/134 mmHg. Because the hypertension and tachycardia might be ethanol withdrawal, she was admitted and treated with multivitamins, folate, and thiamine in her maintenance fluids. She was discharged after 4 days in hospital. The day after her discharge, she was asked to return after it was discovered that she had inadvertently received tacrolimus (total of 400 mg) instead of thiamine. She was admitted with non-oliguric renal failure and metabolic acidosis. A tacrolimus concentration 27 hours after her last exposure was 96.8 ng/mL (therapeutic 5 to 20 ng/mL). Treatment was supportive and she was discharged after 4 days without sequellae. Discussion. Our patient's tacrolimus dose was 2.1 mg/kg/day for 4 days (therapeutic 0.03 to 0.05 mg/kg/day). Her tacrolimus elimination half-life was 16.5 hours, compared to a mean half-life in healthy volunteers of 34.2 ± 7.7 hours. Conclusion. Clinical toxicity, similar to that seen in transplant patients, can develop in non-transplant patients following intravenous administration of supra-therapeutic doses of tacrolimus.
Controversies in the management of organophosphate pesticide poisoning

Acute poisoning with organophosphorous (OP) pesticides frequently causes ill-health and death all over the world. The treatment of OP poisoning is primarily aimed at reversing the effects of the compound by administration of atropine. A second class of compounds-oximes, capable of regenerating the active enzyme from the OP-cholinesterase complex, is also available to treat OP poisoning. Pralidoxime is the oxime most often used worldwide. The low propensity to aging with diethyl organophosphorous poisoning may allow reactivation of the acetylcholinesterase after several days, when the poison concentration drops. The usefulness of oximes has however been challenged over the past 20 years by physicians in many parts of the world who have failed to see any benefit in their clinical practice. We have carried out a systematic search to find clinical trials, both randomized and nonrandomized involving the management of OP poisoning. The clinical benefits of oximes in OP poisoning is not clear, being limited by the type of OP, poison load, time to start therapy and dose of oximes. Hence, one is left with a doubt as to whether one could use oximes at all in OP poisoning? A high-quality randomized clinical trial on a large number of subjects comparing the current World Health Organization-recommended regimen with a placebo to assess the value of pralidoxime in acute OP poisoning, may answer the above question.
Exposure to bitumen fumes and genotoxic effects on Turkish asphalt workers

Objective. Bitumen fumes consist essentially of polycyclic aromatic hydrocarbons (PAHs) and their derivatives, some of which are known to be carcinogenic or cocarcinogenic in humans. The aim of this study was to investigate exposure to asphalt fumes among Turkish asphalt workers and determine whether any effects could be detected with genotoxic tests. Study Design. The study included 26 asphalt workers and 24 control subjects. Sister chromatid exchange (SCE) and micronucleus (MN) were determined in peripheral lymphocytes. Urinary 1‐hydroxypyrene (1-OHP) excretion was used as a biomarker of occupational exposure to PAHs. Results. The asphalt workers had a significant increase in SCEs and MN (for each, p < 0.001). A positive correlation existed between the duration of exposure and rates of SCE or MN frequencies (r = 0.49, p < 0.05; r = 0.53, p < 0.05, respectively). The concentration of 1-OHP in urine was higher for the asphalt workers than for the controls (p < 0.001). However, we found that there was no statistically significant correlation between the urinary 1‐OHP concentration and SCEs or MN frequencies (r = 0.25, p > 0.5; r = 0.17, p > 0.5, respectively). Conclusions. This study shows that Turkish asphalt workers have an increased exposure to PAHs from bitumen fumes, and genotoxic effects could be detected by SCEs and MN tests.
Evaluation of proton pump inhibitor use on treatment outcomes with ledipasvir and sofosbuvir in a real‐world cohort study

Many patients with chronic hepatitis C virus (HCV) are on prolonged proton‐pump inhibitor (PPI) therapy and wish to remain on PPI therapy once treatment for HCV starts. A preliminary report recently suggested decrease rates of sustained virological response (SVR) for patients taking concomitant PPI and ledipasvir/sofosbuvir (LDV/SOF). We sought to determine the effect of PPI use on the rate of SVR in a real‐world cohort of 1,979 patients with chronic HCV treated with LDV/SOF. We collected clinical data and pharmacy dispensing records on patients taking 8, 12, or 24 weeks of LDV/SOF ± ribavirin (RBV). The primary outcome was sustained virological response at 12 weeks after treatment completion (SVR12) in a per‐protocol analysis in order to determine the effect of PPI use adjusted for confounders. Statistical adjustment was performed in propensity‐matched analysis. Among treatment completers, SVR12 was achieved in 441 (97.1%) of PPI recipients compared with 1,497 (98.2%) in PPI nonrecipients (P = 0.19). Neither low‐ nor high‐dose PPI was associated with decreased SVR, although patients taking twice‐daily PPI achieved a lower SVR12 rate (91.2%; 95% confidence interval [CI], 77.0‐97.0; P = 0.046). After propensity matching for PPI use, there were no significant associations between SVR12 and any dose or frequency of PPI use. However, in a sensitivity analysis focusing on patients with cirrhosis, twice‐daily PPI use was associated with lower odds ratio for SVR12 (0.11; 95% CI, 0.02‐0.59). Conclusion: These data from a cohort of real‐world patients receiving hepatitis C antibody therapy with LDF/SOF ± RBV support the prescription labeling suggesting that patients take no more than low‐dose (20‐mg omeprazole equivalents) PPI daily. (Hepatology 2016;64:1893‐1899).
What is History

Among the many things which distinguish man from the lower animals and perhaps in a more spectacular but less extensive way distinguish man at an advanced level of culture from primitive man is the capacity to use the recorded experience of the past. This can help determine his actions in the present and thus determine in part what kind of future the world will see. The codification of knowledge of the past and its interpretation constitute the material of history. Doctrines and beliefs, various schools, and ideological sets about history determine each period's interpretation of what has gone on in the past. For instance, how may one reconcile the doctrinal myth of progress with the fix that the world is in now? In the light of contemporary ideas about causation, determinism, accident, objectivity, and the function and role, if any, of the individual person in history, ideas thin out. Professor
The impact of childhood sexual abuse on psychological distress among women in New Zealand.

PROBLEMS In order to better understand the long-term impact of child sex abuse, this study examined the association between women's experience of abuse, health symptoms, and psychological distress in adulthood. There is limited information about child abuse outside the United States. METHODS Nine hundred sixty-one women participated in a structured interview. RESULTS Participants who had experienced abuse (13%) were significantly more vulnerable to psychological distress in adulthood if they were younger, less satisfied with their standard of living, and resided in urban areas. CONCLUSION Dissemination and evaluation of therapies for the treatment of sex abuse in the New Zealand context is warranted.