Radiotherapy- and Chemotherapy-Induced Myelodysplasia Syndrome: A Nationwide Population-Based Nested Case–Control Study

This study explored which kinds of cancer are related to a higher incidence of subsequent myelodysplastic syndrome (MDS) after radiotherapy (RT) and chemotherapy (CT).We performed a nested case–control study by using data from the Taiwanese National Health Insurance (NHI) system. The case group included cancer patients who developed MDS. For the control group, 4 cancer patients without MDS were frequency-matched with each MDS case by age, sex, year of cancer diagnosis, and MDS index year. A multivariable logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated.Overall, cancer patients who received RT or CT exhibited secondary MDS more frequently than did those who did not (RT: OR = 1.53; 95% CI = 1.33–1.77; CT: OR = 1.51; 95% CI = 1.25–1.82). Analysis by cancer site showed that RT increased the risk of MDS for patients with stomach, colorectal, liver, breast, endometrial, prostate, and kidney cancers. By contrast, CT was more likely to increase the risk of MDS for patients with lung, endometrial, and cervical cancers. Further analysis revealed that RT and CT seemed to have a positive interaction. The major limitation of this study was the lack of certain essential data in the NHI Research Database, such as data regarding cancer stage and treatment dose details.This population-based nested case–control study determined that RT and CT predisposed patients in Taiwan to the development of MDS. This effect was more prominent when both modalities were used.     

Ischemic Stroke in Young Adults and Preexisting Psychiatric Disorders: A Nationwide Case–Control Study

Previous studies showed that psychiatric disorders such as major depression, bipolar disorders, and alcohol misuse are associated with an increased risk of ischemic stroke. However, the link between psychiatric disorders and stroke in the young population is rarely investigated.Using the Taiwan National Health Insurance Research Database, 2063 young adults aged between 18 and 45 years with ischemic stroke and 8252 age- and sex-matched controls were enrolled in our study between 1998 and 2011. Participants who had preexisting psychiatric disorders were identified.After adjusting for preexisting physical disorders and demographic data, patients with ischemic stroke had an increased risk of having preexisting psychiatric disorders, including bipolar disorder (odds ratio [OR]: 2.23, 95% confidence interval [CI]: 1.06∼4.67), unipolar depression (OR: 2.15, 95% CI: 1.62∼2.86), anxiety disorders (OR: 2.63, 95% CI: 1.87∼3.69), and alcohol use disorders (OR: 2.86, 95% CI: 1.79∼4.57). Young ischemic stroke (age ≥30 years) was related to the risk of preexisting unipolar depression (OR: 1.49, 95% CI: 1.05∼2.11), anxiety disorders (OR: 1.99, 95% CI: 1.33∼2.97), and alcohol use disorders (OR: 2.54, 95% CI: 1.55∼4.14); very young stroke (age <30 years) was only associated with the risk of preexisting unipolar depression (OR: 4.15, 95% CI: 1.47∼11.72).Patients who had experienced ischemic stroke at age younger than 45 years had a higher risk of having pre-existing bipolar disorder, unipolar depression, anxiety disorders, and alcohol use disorders than those who did not after adjusting for demographic data and stroke-related medical comorbidities.Ischemic strokes in adults younger than 45 years of age were regarded as a relatively uncommon event in the proportion of <5% of all ischemic strokes.¹ However, other epidemiological studies have shown a higher proportion of approximately 10% of all ischemic strokes occurring in young adults.^2,3 Compared with stroke in the elderly, stroke in the young adult resulted in a disproportionately great personal, familial, and socioeconomic impacts and consequences by leaving patients disabled before their most productive years.^4,5 The most significantly established risk factors for young ischemic stroke included hypertension, dyslipidemia, diabetes mellitus, and smoking.^5–7The association between psychiatric disorders and stroke has gained the clinical and scientific attention in the past decade.^8–10 For example, Tsai et al¹¹ followed 80,569 patients with schizophrenia for 5 years, and revealed that those with schizophrenia were 1.13 times more likely to have a stroke (95% confidence interval [CI]: 1.05∼1.22). Li et al¹² followed 1003 patients with major depression and 4012 controls for 9 years and found that patients with major depression had a higher risk of stroke (odds ratio [OR]: 1.55, 95% CI: 1.08∼2.211) than the control group during the follow-up. Dong et al⁸ reported a significant positive association between depression and subsequent risk of stroke (relative risk [RR]: 1.34, 95% CI: 1.17∼1.54). Prieto et al''s¹⁰ meta-analysis study composed of 27,092 bipolar patients showed that the risk of stroke in bipolar disorder was significantly increased (RR: 1.74, 95% CI 1.29∼2.35). The First National Health and Nutrition Examination Survey in United States demonstrated that more anxiety symptoms at baseline were associated with increased risk of incident stroke (hazard ratio [HR]: 1.14, 95% CI: 1.03∼1.25).⁹ Following 19,544 men aged 40 to 59 years for 11 years, Iso et al¹³ determined that alcohol consumption was positively associated with the risk of stroke with a 68% excess risk among drinkers of ≥450 g ethanol per week compared with occasional drinkers. However, stroke in the above studies occurred in the late mid-life or in old age but not in the younger age groups. The association between young stroke and psychiatric disorders was less investigated and still unclear.In our study, using the Taiwan National Health Insurance Research Database (NHIRD) with a large sample size and a retrospective study design, we investigated the association between the young ischemic stroke and the risk of preexisting psychiatric disorders, including schizophrenia, bipolar disorder, major depression, anxiety disorders, and alcohol use disorder.     

Association Between Benzodiazepine Use and Epilepsy Occurrence: A Nationwide Population-Based Case–Control Study

We conducted a retrospective case–control study to evaluate the association between the risk of benzodiazepine (BZD) use and epilepsy occurrence by using data from the Taiwan National Health Insurance Research Database.We recruited 1065 participants who ages 20 years or older and newly diagnosed with epilepsy (International Classification of Diseases, Ninth Revision, Clinical Modification 345) between 2004 and 2011 and assigned them to the epilepsy group. We subsequently frequency-matched them with participants in a control group (n = 4260) according to sex, age, and index year at a 1:4 ratio. A logistic regression model was employed to calculate the odds ratio (OR) for association of epilepsy with BZD exposure. Multivariate logistic regression was conducted to estimate the dose–response relationship between BZD levels and epilepsy risk.The adjusted OR (aOR) for the association of epilepsy with BZD exposure was 2.02 (95% confidence interval [CI] = 1.68–2.42). The aOR for an average BZD dose increased to 1.26 for the participants on <0.01 defined daily dose (DDD), and increased to 4.32 for those on ≥1.50 DDD. On average, when the DDD of BZD exposure increased by 100 units, the epilepsy risk increase by 1.03-fold (95% CI = 1.01–1.04, P = 0.003). The annual BZD exposure day ranges were significantly associated with epilepsy (2–7 days: aOR = 1.67; 8–35 days: aOR = 3.16; and ≥35 days: aOR = 5.60). Whenever the annual BZD exposure increased by 30 days, the risk of epilepsy notably increased by 1.03-fold (95% CI = 1.01–1.04, P < 0.001). In addition, users who quit BZD for more than 6 months still exhibited a higher risk of epilepsy than did the non-BZD users.A considerable increase in epilepsy occurrence was observed in ones with BZD use, particularly in those with prolonged use, multiple exposure, and high-dose consumption.     

Prevalence and Risk Factors of Cognitive Impairment in Parkinson Disease: A Population-Based Case–Control Study in Taiwan

The aim of this study was to evaluate the Parkinson disease (PD) prevalence of cognitive impairment in Taiwan.The case–control study consisted of 6177 cognitive impairment patients and 24,708 noncognitive impairment as controls for the period of 2006 to 2010 and both of the groups aged ≥50 years. The multivariable logistic regression analyses were used to estimate the odds ratio (OR) for cognitive impairment, and the 95% confidence intervals (CIs) among patients with PD were compared with those of non-PD patients.PD (adjusted odds ratio [aOR] is 3.07, 95% CI 2.76–3.41) is the one of the most contributed risk factors for cognitive impairment. Besides, we found a remarkable result of the diagnosed cognitive impairment of PD that was found highest in the first 6 months (aOR 11.98, 95% CI 8.51–16.86) and then decrease the incident year by year. The PD prevalence in a patient with cognitive impairment in our data present is 12.1% lower than those with truly dementia published previously and documented by western studies.We found a remarkable result of the diagnosed cognitive impairment of PD that was found highest in the first 6 months and then decrease the incident year by year.     

Minidose Aspirin and Gastrointestinal Bleeding—A Retrospective,Case–Control Study in Hospitalized Patients

Low or minimal doses of aspirin are widely used for prevention of cardiovascular diseases. Aspirin is known to produce severe adverse gastrointestinal effects, such as bleeding and perforation. Less is known about the risk associated with minidose aspirin. Our aim was to assess the possible association of upper gastrointestinal tract bleeding with minidose aspirin therapy. A retrospective controlled design was used. Patients hospitalized for melena or hematemesis between January 1, 2000, and December 31, 2001, were identified by ICD-9 codes, and their clinical findings were compared to these of patients without upper gastrointestinal bleeding hospitalized during the same period and matched for age and sex. Bleeding was attributed to therapy if patients used a nonsteroidal anti-inflammatory drug or aspirin therapy within 30 days before hospitalization. The study group included 318 patients (59% male), and the control group 141 (65% male). Mean ages were 67 ± 19 and 64 ± 19 years, respectively. Study patients had more accompanying diseases, used more medications, and required more blood transfusions than controls (37%, vs. 2% of controls; P < 0.001). Minidose aspirin was used by 28% of the study group and 18% of the controls (P = 0.03). The average dose was 40 ± 86 and 21 ± 55 mg/day, respectively (P = 0.012). Only 26% of the study patients received a gastric protective agent. On multivariate analysis, aspirin consumption was the only independent risk factor for upper gastrointestinal tract bleeding. There appears to be an association between minidose aspirin treatment and hospitalization for upper gastrointestinal tract bleeding. Despite the advanced age of the patients, only one-quarter were treated with gastric protective agent.     

Incidence and Risks of Congenital Anomalies of Kidney and Urinary Tract in Newborns: A Population-Based Case–Control Study in Taiwan

Congenital anomalies of the kidney and urinary tract (CAKUT) are 1 of the major factors in young adults needing renal replacement therapy, but there is little extensive assessment of their incidence and risk factors. This study aimed to evaluate trends in the incidence of and risk factors for CAKUT among all births in Taiwan.This population-based case–control study design was conducted using the Taiwan national births registry, which contains detailed information about maternal health and characteristics of newborns, supplied by health professionals. Of 1,603,794 newborns registered between 2004 and 2014, 668 infants were reported to have CAKUT. Newborns without congenital anomalies were matched with CAKUT cases by birth year, month, and Apgar score in a ratio of 5:1. Odds ratio (OR) and 95% confidence interval (CI) for developing CAKUT were calculated using a conditional multivariate logistic regression model.The incidence of CAKUT was approximately 4.2 per 10,000 births. The adjusted ORs for CAKUT in newborns associated with maternal age of 20 to 29 (OR, 2.18; 95% CI, 1.11–4.28), or 30 to 39 (OR, 2.29; 95% CI, 1.17–4.51), maternal gestational diabetes (OR, 2.22, 95% CI, 1.06–4.67), maternal thalassemia/hemochromatosis (OR, 2.67; 95% CI, 1.35–5.27), polyhydramnios or oligohydramnios (OR, 9.16; 95% CI, 5.46–15.37), birth parity >1 (OR, 0.27; 95% CI, 0.15–0.50), having a gestational age <37 weeks (OR, 1.48; 95% CI, 1.23–1.78), and being a boy (OR, 1.83; 95% CI, 1.53–2.19). Infants of mother with gestational diabetes were more likely to have congenital anomalies, small gestational age (<37 weeks) and low birth weight.CAKUT are associated with several maternal health risk factors. As Taiwan has the highest prevalence and incidence rates of end-stage renal disease in the world, these findings strongly support the need to develop professional guidelines for prenatal counseling and management of women at risk of adverse birth outcomes, to prevent kidney disease progression and reduce complications.     

Henoch–Schonlein Purpura Leads to Functional Gastrointestinal Disorders

Background  

Pain predominant functional gastrointestinal disorders such as irritable bowel syndrome may develop as sequelae to acute infectious gastroenteritis. Henoch–Schonlein purpura is a vaculitis that causes an inflammatory insult to the intestinal mucosa.     

Celiac Disease and Lymphoma Risk: A Multicentric Case–Control Study in Spain

Celiac disease is a highly prevalent condition frequently misdiagnosed because of heterogeneity of the clinical symptoms. It is well recognized that enteropathy-associated T-cell lymphoma is an uncommon lymphoma type linked to celiac disease; it has also been suggested that other types of lymphomas may be associated with celiac disease. Our aim was to estimate the risk of all lymphoma associated with celiac disease. Serological markers and personal interviews were obtained from 298 consecutive lymphoma cases and 251 matched controls recruited in four Spanish hospitals. Celiac disease was detected in two cases (0.67%; n = 298) and in three controls (1.2%; n = 251). Treated celiac disease was observed in one patient with lymphoma and in two control subjects. In our series, there was no evidence that celiac disease was a risk factor for lymphoma (OR = 0.62, 95% CI = 0.10-3.79). Serological screening for CD is not recommended in people with lymphoma.     

Risk Factors Involved in Patients with Bleeding Peptic Ulcers: A Case–Control Study

Our objectives were to (1) identify the risk factors involved in patients with peptic ulcer disease and determine if they predict bleeding in these patients, (2) determine the association between these risk factors, and (3) analyze the cost effectiveness of various tests for Helicobacter pylori (H. pylori). Two-hundred and thirty patients were included in our study between January 2004 and June 2005 (128 bleeding peptic ulcer disease patients constituted the cases, 102 nonbleeding ulcer patients constituted the controls). H. pylori infection was assessed by urease test and biopsy from gastric antrum. There was no statistically significant difference between these groups regarding sex, age, or location of ulcer. Nonsteroidal anti-inflammatory drug (NSAID) use was higher in the case group (P < 0.001), and the rate of H. pylori infection was lower in these patients (P < 0.05). There was no interaction between NSAID use and H. pylori infection in predicting bleeding ulcer risk (P = 0.08). Sensitivity and specificity for urease test in detecting H. pylori was 75% and 99.7%, respectively. So a positive urease test does not need confirmation with biopsy, which is cost effective.     

Functional Inducible Nitric Oxide Synthase Gene Variants Associate With Hypertension: A Case–Control Study in a Finnish Population—The TAMRISK Study

Increased inducible nitric oxide synthase (iNOS) activity and expression has been associated with hypertension, but less is known whether the 2 known functional polymorphic sites in the iNOS gene (g.–1026 C/A (rs2779249), g.2087 G/A (rs2297518)) affect susceptibility to hypertension. The objective of this study was to investigate the association between the genetic variants of iNOS and diagnosed hypertension in a Finnish cohort.This study included 320 hypertensive cases and 439 healthy controls. All participants were 50-year-old men and women and the data were collected from the Tampere adult population cardiovascular risk study (TAMRISK). DNA was extracted from buccal swabs and iNOS single nucleotide polymorphisms (SNPs) were analyzed using KASP genotyping PCR. Data analysis was done by logistic regression.At the age of 50 years, the SNP rs2779249 (C/A) associated significantly with hypertension (P = 0.009); specifically, subjects carrying the A-allele had higher risk of hypertension compared to those carrying the CC genotype (OR = 1.47; CI = 1.08–2.01; P = 0.015). In addition, a 15-year follow-up period (35, 40, and 45 years) of the same individuals showed that carriers of the A-allele had more often hypertension in all of the studied age-groups. The highest risk for developing hypertension was obtained among 35-year-old subjects (odds ratio [OR] 3.83; confidence interval [CI] = 1.20–12.27; P = 0.024). Those carrying variant A had also significantly higher readings of both systolic (P = 0.047) and diastolic (P = 0.048) blood pressure during the follow-up. No significant associations between rs2297518 (G/A) variants alone and hypertension were found. However, haplotype analysis of rs2779249 and rs2297518 revealed that individuals having haplotype H3 which combines both A alleles (CA–GA, 19.7% of individuals) was more commonly found in the hypertensive group than in the normotensive group (OR = 2.01; CI = 1.29–3.12; P = 0.002).In conclusion, there was a significant association between iNOS genetic variant (rs2779249) and hypertension in the genetically homogenous Finnish population. Those who carried the rare A-allele of the gene had higher risk for hypertension already at the age of 35 years.     

Association Between Vascular Access Dysfunction and Subsequent Major Adverse Cardiovascular Events in Patients on Hemodialysis: A Population-Based Nested Case–Control Study

The association between dialysis vascular access dysfunction and the risk of developing major adverse cardiovascular events (MACE) in hemodialysis patients is unclear and has not yet been investigated. We analyzed data from the National Health Insurance Research Database of Taiwan to quantify this association. Adopting a case–control design nested within a cohort of patients who received hemodialysis from 2001 to 2010, we identified 9711 incident cases of MACE during the stage of stable maintenance dialysis and 19,422 randomly selected controls matched to cases on age, gender, and duration of dialysis. Events of vascular access dysfunction in the 6-month period before the date of MACE onset (ie, index date) for cases and before index dates for controls were evaluated retrospectively. The presence of vascular access dysfunction was associated with a 1.385-fold higher odds of developing MACE as estimated from the logistic regression analysis. This represents a significantly increased adjusted odds ratio (OR) at 1.268 (95% confidence interval [CI] = 1.186–1.355) after adjustment for comorbidities and calendar years of initiating dialysis. We also noted a significant exposure–response trend (P < 0.001) between the frequency of vascular access dysfunction and MACE, with the greatest risk (adjusted OR = 1.840, 95% CI = 1.549–2.186) noted in patients with ≥3 vascular access events. We concluded that dialysis vascular access dysfunction was significantly associated with an increased risk of MACE. Hence, vascular access failure can be an early sign for MACE in patients receiving maintenance hemodialysis. Active monitoring and treatment of cardiovascular risk factors and related diseases, not merely managing vascular access dysfunction, would be required to reduce the risk of MACE.     

Parasite Infection and Tuberculosis Disease among Children: A Case–Control Study

We conducted a case–control study to examine associations between parasite infection, including protozoa infection, and tuberculosis (TB) in children in Lima, Peru. We enrolled 189 matched-pairs. In multivariable conditional logistic regression analyses, Blastocystis hominis infection (rate ratio = 0.30, 95% confidence interval = 0.14–0.64, P = 0.002) was strongly associated with a lower risk of TB. We observed a statistically significant inverse linear dose-response relationship between Blastocystis hominis infection and TB. These findings should be confirmed in future prospective studies.Globally, infectious diseases account for more than half of deaths among children less than five years of age.¹ Studies examining the ways in which some infectious diseases interact identify worrisome synergistic relationships in which infection with one disease increases susceptibility to or worsens the prognosis of another.^2–4 The relationship between parasite infection and tuberculosis (TB) has gained increasing attention over the past decade: both animal studies and epidemiologic studies in humans have found evidence indicating that chronic helminth infection may increase the risk of TB and reduce the effectiveness of the Bacillus Calmette–Guérin vaccine.^5,6Protozoa infection, another type of parasitic infection, is common in urban areas lacking clean water access and may result in severe malnutrition as a consequence of chronic diarrhea or anorexia. Protozoa infection can be asymptomatic and may result in elevated levels of cytokines such as interferon-γ (IFN-γ),^7,8 a critical mediator in the host immune response to Mycobacterium tuberculosis. We report on the relationship between various parasite infections, including protozoa infection, and TB among children in Lima, Peru.We conducted this case–control study in two of five health regions in the Lima metropolitan area as described.⁹ Parasite infestation, with protozoa pathogens in particular, is common in Lima, with more than 40% of adults and children infected.^10,11 Eligible cases were children < 15 years of age who received an initial TB diagnosis at the Instituto Nacional de Salud del Niño, the main pediatric tuberculosis referral center in Peru, or a participating health clinic during the study period of February 2010–September 2011. Healthy controls (i.e., no chronic cough or fever) without a history of TB were identified by using a random walk or friend referral and matched to cases by neighborhood, age, and enrollment date. Ethical approval for this study protocol was granted by the Office of Human Research Administration at the Harvard School of Public Health in Boston, Massachusetts and the Instituto Nacional de Salud del Niño in Lima, Peru. Guardians provided informed consent, and children ≥ 8 years of age provided informed assent.To assess parasite infection, we requested that children provide two scotch-tape specimens applied to the anal area for identification of Enterobius vermicularis¹² and three stool samples: the first two samples were preserved with 10% formalin and the third was a fresh sample. An accredited laboratory (Blufstein Laboratorio Clínico, S.A.) in Lima examined stool samples by using direct smear microscopy and spontaneous sedimentation methods and scotch tape specimens by using the Graham method.¹² Laboratory personnel were blinded to the case status of participants. We excluded pairs in which either the case or control did not contribute ≥ 1 stool and scotch tape specimen. Children and their guardians were asked to respond to an interview related to sociodemographic, clinical, and lifestyle factors.We conducted conditional logistic regression analyses, stratified by each matched pair. To create the final multivariable model, we included binary variables for the presence of infection with any parasite species that was found in at least 5% of controls; we also included variables that were identified a priori as potential confounders (

Comparison of UHPLC and HPLC in Benzodiazepines Analysis of Postmortem Samples: A Case–Control Study

The aim of this study was to compare system efficiency and analysis duration regarding the solvent consumption and system maintenance in high-pressure liquid chromatography (HPLC) and ultra high-pressure liquid chromatography (UHPLC).In a case–control study, standard solutions of 7 benzodiazepines (BZs) and 73 biological samples such as urine, tissue, stomach content, and bile that screened positive for BZs were analyzed by HPLC and UHPLC in laboratory of forensic toxicology during 2012 to 2013. HPLC analysis was performed using a Knauer by 100-5 C-18 column (250 mm × 4.6 mm) and Knauer photodiode array detector (PAD). UHPLC analysis was performed using Knauer PAD detector with cooling autosampler and Eurospher II 100-3 C-18 column (100 mm × 3 mm) and also 2 pumps. The mean retention time, standard deviation, flow rate, and repeatability of analytical results were compared by using 2 methods.Routine runtimes in HPLC and UHPLC took 40 and 15 minutes, respectively. Changes in mobile phase composition of the 2 methods were not required. Flow rate and solvent consumption in UHPLC decreased. Diazepam and flurazepam were detected more frequently in biological samples.In UHPLC, small particle size and short length of column cause effective separation of BZs in a very short time. Reduced flow rate, solvent consumption, and injection volume cause more efficiency and less analysis costs. Thus, in the detection of BZs, UHPLC is an accurate, sensitive, and fast method with less cost of analysis.     

Sporadic Duodenal Adenoma and Association with Colorectal Neoplasia: A Case–Control Study

Background

Sporadic duodenal adenomas are uncommon. Prior studies show that patients with sporadic duodenal adenoma have increased risk of colorectal neoplasia and should undergo colorectal screening. However, the nature of the risk, location, and type of colorectal neoplasia are not well studied.

Aim

We aimed to identify the risk of colorectal neoplasia in patients who have duodenal adenomas.

Methods

A retrospective case–control study was conducted to identify sporadic duodenal adenoma patients using the databases at one academic center. Colonoscopic findings including histology and location of colorectal cancer neoplasia in sporadic duodenal adenoma patients were compared with a control group of patients without duodenal adenomas who underwent both gastroduodenoscopy and colonoscopy.

Results

Hundred and two patients with sporadic duodenal adenomas or adenocarcinomas were identified. Colonoscopy was performed in 47 patients (46 %), and colorectal neoplasia was present in 22 (46 %). There was a significantly higher rate of colorectal neoplasia in patients with sporadic duodenal adenoma (43 %) compared to the control group (24 %) odds ratio 4.8, 95 % confidence interval (1.7–7.4), but not for advanced colorectal adenoma (9 vs. 26 %, p = 0.17). Case patients had significantly more right-sided lesions than matched controls (p = 0.02).

Limitations

Single-center, retrospective study.

Conclusions

Individuals with sporadic duodenal adenomas have a significantly higher risk of colorectal neoplasia and proximal location of neoplasia. Therefore, these patients should undergo colonoscopy with particular attention to the right colon.     

Aspirin May Prevent Cholangiocarcinoma: A Case–Control Study from the United Kingdom

Background

The proliferation of cholangiocarcinoma cells is suppressed in cell culture by nonsteroidal antiinflammatory drugs (NSAIDs) through the inhibition of cyclo-oxygenase-2 enzyme and also by statins which decrease the production of mediators of the cell cycle.

Aims

To investigate whether there is an inverse association between NSAIDs, including aspirin, and the development of cholangiocarcinoma and, for the first time in a Western population, between statin use and the development of cholangiocarcinoma.

Methods

This epidemiological study had a case–control design in which cases of cholangiocarcinoma diagnosed in Norwich between 2004 and 2010 and in Leicester in 2007 were identified from clinical databases. Controls were patients with basal cell carcinomas treated in the respective dermatology departments. The case notes of all subjects were reviewed to confirm diagnoses and obtain information on medication use. The data were analyzed using unconditional logistic regression to calculate odds ratios (OR) with 95 % confidence intervals (CI).

Results

In total, 81 cases of cholangiocarcinoma and 275 controls were identified. For all cases there was radiological evidence of cancer and 86 % of the cases involved the extrahepatic biliary system. Aspirin use was inversely associated with the development of cholangiocarcinoma (OR 0.45, 95 % CI 0.22–0.92), but there were no significant associations between the development of cholangiocarcinoma and NSAIDs (OR 0.39; 95 % CI 0.11–1.42) or statins (OR 0.58; 95 % CI 0.28–1.19).

Conclusions

The epidemiological data from this study support the biological evidence for aspirin having a protective effect against the development of cholangiocarcinoma. Aspirin use should be measured in future etiological studies and assessed as a chemoprevention agent in those at high risk of developing this type of cancer.     

Pain Hypersensitivity in Patients with Functional Gastrointestinal Disorders: A Gastrointestinal-Specific Defect or a General Systemic Condition?

Visceral hypersensitivity was shown in patients with functional gastrointestinal disorders (FGID). The mechanisms underlying this sensory dysfunction remain undetermined. The initial hypothesis of a generalized reduction in pain tolerance was rejected by further studies that suggested a normal tolerance to somatic stimuli and led to the generally accepted assumption that pain intolerance is specific and exclusive for visceral stimuli in these patients. We wanted to revisit this theory by examining whether patients with FGID reported perception and tolerance to somatic pain differently from normal subjects and whether the response to somatic pain stimulus was correlated to gastrointestinal symptoms or psychological status or distress. Thirty-three patients with FGID (Rome II criteria)(F/M: 26/7; mean age 48 ± 9.9) and 33 normal controls (F/M: 24/9; mean age 44.1 ± 6.8) were asked to immerse their nondominant hand into 4°C water for as long as possible (maximum 120 sec). Time before appearance of: (1) discomfort, (2) pain, and (3) withdrawing of the hand were noted. The intensity of pain was rated on a visual analog scale from 0 to 100. Self-report questionnaires were used to assess the severity of gastrointestinal symptoms (St-Luc GI index) and the psychological distress (SCL-90) in the patient group. Data are expressed in seconds as mean ± sem. Discomfort sensory thresholds were similar in controls and FGID patients (28 ± 3 and 24 ± 2, respectively; NS) whereas pain and withdrawing were significantly lower in FGID (41 ± 3 and 76 ± 6 sec) than in controls (62 ± 6 and 102 ± 4; P < 0.05). Pain intensity was similar in both groups (64 ± 4 vs 67 ± 3; NS). Female patients showed lower sensory thresholds than male patients and control females (pain thresholds: 39.8 ± 3.4 vs 67.8 ± 16.7 and vs 56.8 ± 8.7; P < 0.05). Sensory thresholds were not different in subgroups of patients with FGID (irritable bowel syndrome and functional dyspepsia). No correlation was shown between sensory thresholds and gastrointestinal index or SCL 90-test. In conclusion, FGID patients showed a threshold to painful somatic stimulus that was lower than in normal subjects. These findings suggest that patients with FGID may have hyperalgesia and low pain tolerance that is not limited to the viscera, but that is part of a systemic general condition.     

Recognizing Rheumatoid Arthritis: Oncoprotein Survivin Opens New Possibilities: A Population-based Case–Control Study

Survivin is a biomarker of cancer known for its anti-apoptotic and cell-cycle regulating properties. In the context of non-cancer pathology, high levels of survivin may be measured in blood and synovial fluid of patients with rheumatoid arthritis (RA) and associate with early joint damage and poor therapy response.The aim of the study was to investigate the value of survivin measurements in blood for diagnosis of RA in the frame of the Malaysian epidemiological investigation of rheumatoid arthritis (MyEIRA) study. The study enrolled RA patients from eight rheumatology centres in Peninsular Malaysia. The healthy controls matched by age, gender and ethnicity were recruited on the community basis from the residential area of the patients. Levels of survivin were measured in blood of RA patients (n = 1233) and controls (n = 1566) by an enzyme-linked immuno-sorbent assay (ELISA). The risk for RA was calculated as odds ratio (OR) and 95% confidence intervals in the individuals with high levels of survivin. The risk was calculated in relation to antibodies against cyclic citrullinated peptides (ACPA), detected by ELISA and HLA-DRB1 shared epitope (SE) alleles, identified by the polymerase chain reaction using sequence specific oligonucleotide method.High levels of survivin were detected in 625 of 1233 (50.7%) RA cases and in 85 of 1566 (5.4%) controls, indicating its high specificity for RA. Survivin was association with an increase in RA risk in the patients having neither SE-alleles nor ACPA (OR = 5.40, 95% CI 3.81–7.66). For the patients combining survivin, SE, and ACPA, the estimated risk for RA was 16-folds higher compared to the survivin negative patients with SE and ACPA(OR = 16.21, 95% CI 5.70–46.18).To conclude, detection of survivin in blood provides a simple test to improve diagnostic and to increase predictability for RA.