Series Of Case-control Studies Research Articles

Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol

IntroductionConsidering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk–benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing....

Fathoming the link between anthropogenic chemical contamination and thyroid cancer.

Incidence and mortality of thyroid cancer are increasing, thus making mandatory to improve the knowledge of disease etiology. The hypothesis of a role for anthropogenic chemicals is raising wide consideration. A series of occupational studies revealed that job exposures with high risk of chemical contamination were usually more prone to thyroid cancer development. These include shoe manufacture, preserving industry, building activities, pulp/papermaker industry and the wood processing, agricultural activities, and other work categories characterized by contact with chemicals, such as chemists and pharmacists. However, such epidemiological analyses cannot define a causal relationship. Thyroid-disrupting activity has emerged for a broad set of anthropogenic chemicals, with the best evidence being gained for polychlorinated biphenyls, polybrominated diphenyl ethers, dioxins, bisphenols, phthalates, pesticides, and heavy metals. A series of case-control studies, assessing exposure to thyroid-disrupting agents, as measured on biological matrices, have been recently performed providing the following insights: a) positive relationship with thyroid cancer was found for phthalates, bisphenols, the heavy metals cadmium, copper, and lead; b) polybrominated diphenyl ethers exposure showed no relationship with thyroid cancer c) controversial results were reported for polychlorinated biphenyls and pesticides. However, such studies cannot demonstrate the causal link with disease occurrence, as exposure is assessed after tumour development. Studies with different methodological approach are therefore required for defining the role of anthropogenic environmental chemicals in thyroid carcinogenesis.

Exosome Biomarkers Revolutionize Preclinical Diagnosis of Neurodegenerative Diseases and Assessment of Treatment Responses in Clinical Trials.

Alzheimer's disease and other neurodegenerative diseases have long preclinical phases with active and progressively irreversible pathology. Therefore, biomarkers are essential for identifying patients early in the course of these diseases, when they may benefit the most from disease-modifying interventions. A limitation of biomarkers measured in the soluble phase of blood is their tenuous link to brain pathology. A new approach to biomarker discovery that addresses this limitation is deriving extracellular vesicles (EVs) enriched for neuronal and astrocytic origin from peripheral blood. EVs are membranous particles (subdivided into smaller exosomes and larger microvesicles) that are shed by all cells and found in all biofluids. Neuronal and astrocytic EVs have been implicated in the pathogenesis of several neurodegenerative diseases. Given their origin, neuronal and astrocytic enriched EVs harvested from blood can be used to interrogate brain pathologic processes previously inaccessible in vivo. In a long series of case control studies based on these EV subpopulations, we have identified candidate protein biomarkers for Alzheimer's disease and other neurodegenerative diseases. In GeNeDis 2018, an update of these studies and results from a validation study of these biomarkers in preclinical Alzheimer's disease will be presented. In addition, we will present results from studies demonstrating EV biomarker responses to experimental interventions. EV-based biomarkers are a valuable new tool that will enable researchers to test hypotheses in proof of concept studies with carefully selected participants at the preclinical phase, spearheading therapeutic discovery in neurodegenerative disease.

The neuropsychological deficits and dissociations in Huntington Disease-Like 2: A series of case-control studies

ObjectivesHuntington's Disease Like-2 (HDL2) is a rare autosomal dominant genetic disease caused by a mutation in the JPH3 gene. The Huntington's Disease (HD) phenocopy has the greatest clinical resemblance to HD, but its neurocognitive characterisation is poorly researched. This study reports on the neurocognitive profile of seven HDL2 patients including preserved functions, deficits and dissociations (classical and strong) and provides a general characterisation of the cognitive dysfunction of HDL2 in relation to the progression of the disease. MethodsThe neuropsychological performance of seven HDL2 patients were compared to one of four control groups, matched by age and level of education using a Single Case-Control design. All patients were polyglots and with public education (primary and secondary). Deficits, as well as classical and strong dissociations within each case profile, were identified by implementing Crawford and Howell’s (1998) t-test and the Revised Standardized Difference Test (Crawford and Garthwaite, 2005), respectively. ResultsThe HDL2 neurocognitive syndrome is heterogeneous with a variable rate of progression, with the psychomotor and dexterity domain consistently and severely impaired. ConclusionHDL2 has a heterogeneous impact on cognitive functions from early stages in the disease, which evolve to dementia in a non-uniform manner, in keeping with preferential damage in the cerebrocortical-basal ganglia-thalamus-cerebrocortical circuit.

Letter re: Evaluating the safety of β-interferons in MS: A series of nested case-control studies.

In a series of case-control studies of patients with multiple sclerosis (MS), de Jong et al.1 found that exposure to β-interferons was associated with a 1.8-fold increased risk of stroke. The authors rightfully state that stroke is not well-recognized as a potential adverse event of β-interferons, referring to cases reported in 2006 and 2008.2,3

Endometrial BCL6 Overexpression in Eutopic Endometrium of Women With Endometriosis.

The objective of this study was to examine B-cell CLL/lymphoma 6 (BCL6) expression in human eutopic endometrium across the menstrual cycle in women with and without endometriosis and to establish a cutoff for future studies. This design was a series of case-control studies in tertiary University teaching hospitals. We examined BCL6 expression by messenger RNA and immunohistochemically in prospectively collected samples in both the proliferative (P) and the secretory phases. BCL6 is minimally increased in the mid-secretory phase of the menstrual cycle compared to the P phase in normal patients. BCL6 protein expression was significantly higher in the secretory phase of patients with endometriosis (n = 29) versus fertile controls without endometriosis at laparoscopy (n = 20; P < .0001). Normal fertile controls (n = 28) recruited for endometrial biopsy also had low levels of secretory phase BCL6 expression compared to women with unexplained infertility (UI; n = 119). A receiving-operator characteristic analysis of these data revealed an area under the curve of 94% (95% confidence interval 85%-100%; P < .0001) with an HSCORE cutoff of 1.4 to differentiate cases with and without endometriosis. Using this cutoff value, BCL6 was positive in 88% of cases with UI. Laparoscopic examination of a subset of 65 patients confirmed abnormalities in 98% of cases; 61 (93.8%) were found to have endometriosis, 3 (4.6%) with hydrosalpinx, and 1 (1.5%) with a normal pelvis. These data suggest that BCL6 is a promising candidate as a single diagnostic biomarker for detection of endometriosis in women with otherwise UI and may be associated with endometrial dysfunction, including progesterone resistance.

Foodborne Bacterial Pathogens Associated with the Risk of Gastroenteritis in the State of Qatar

To assess the risk of gastroenteritis associated with bacterial foodborne pathogens and identify associated factors in a highly diverse population. A series of case-control studies were carried out to address the stated objective. The study population consisted of individuals who were admitted to the Hamad Medical Corporation hospitals and stool analysis indicated positive findings to Campylobacter spp., Escherichia coli, or Salmonella spp. between the period of August 2009 and December 2012. Cases were defined based on positive stool analysis to any of the previously mentioned organisms. Control group was similar to case group but negative in stool analysis to the particular pathogen under study. Association between demographic characteristics and likelihood of pathogen infection were investigated using logistic regression analysis. A total of 423 individuals diagnosed with these bacterial pathogens were randomly enrolled in the study. The majority of cases were infected by E.coli. Age was significantly associated with E.coli and Salmonella spp. E.coli infection is common among young children. The risk of Salmonella increases with age. Campylobacter may affect any age. Further investigation of interaction between foodborne pathogen infection and environmental factors is necessary.

Diet and health. What can you believe: or does bacon kill you?

Diet and health. What can you believe: or does bacon kill you?

The association between blood lipid and phlegm turbidity syndrome of angina pectoris: A systematic review and meta-analysis

A series of case-control studies have been conducted to investigate the association between blood lipid and phlegm turbidity syndrome of angina pectoris, but produced inconsistent results. We performed a meta-analysis to determine the association between blood lipid and phlegm turbidity syndrome of angina pectoris more precisely. Manual screening as well as screening of the China National Knowledge Infrastructure (CNKI), Chinese Journal full-text database (VIP), Wanfang database (WF), ScienceDirect, Pubmed, the Cochrane Library, and Embase were carried out for relevant literature. The formula was translated to calculate the pooled mean value and standard deviation value. The "Newcastle-Ottawa Quality Assessment Scale: Case-Control Studies" (NOS) was taken to assess the quality of the included studies. The Revman 5.2.6 software provided by "The Cochrane Collaboration" was used to analyze the collected data. The subgroup analysis was established according to the sample size proportion between the test group and the control group. Sensitivity analysis was constructed by using two different effect models. Besides, a funnel plot was created to analyze potential publication bias. No statistically meaningful difference existed between the test group and control group of total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) in non-Qi and yin deficiency syndrome (QYDS) and non-Yang deficiency syndrome (YDS) subgroup, whereas the two biotic indicators in the test group were higher than the non-phlegm syndrome group in other subgroups. Triglyceride (TG) in phlegm syndrome group showed superior to non-phlegm syndrome group in the rest subgroups except for the non-CCS (Cold coagulating syndrome)-non-YDS subgroup. High-density lipoprotein-cholesterol (HDL-C) levels of the phlegm group were lower than that of the non-phlegm group in all subgroups. When comparing with Traditional Chinese Medicine (TCM) syndromes of asthenia nature, such as YDS, QYDS, and heart qi deficiency syndrome), the levels of TG, TC, and LDL-C were higher in phlegm turbidity syndrome. However, for sthenia syndromes such as Qi stagnation syndrome (QSS), heart blood stasis syndrome (HBSS), and CCS, there was no obvious difference. Furthermore, HDL-C levels in the phlegm turbidity group were lower than those of the non-phlegm group. Nevertheless, these results should be confirmed with further studies.

Validation of a home safety questionnaire used in a series of case-control studies

ObjectiveTo measure the validity of safety behaviours, safety equipment use and hazards reported on a questionnaire by parents/carers with children aged under 5 years participating in a series of home...

Normal Leptin Expression, Lower Adipogenic Ability, Decreased Leptin Receptor and Hyposensitivity to Leptin in Adolescent Idiopathic Scoliosis

Leptin has been suggested to play a role in the etiology of Adolescent Idiopathic Scoliosis (AIS), however, the leptin levels in AIS girls are still a discrepancy, and no in vitro study of leptin in AIS is reported. We took a series of case-control studies, trying to understand whether Leptin gene polymorphisms are involved in the etiology of the AIS or the change in leptin level is a secondary event, to assess the level of leptin receptor, and to evaluate the differences of response to leptin between AIS cases and controls. We screened all exons of Leptin gene in 45 cases and 45 controls and selected six tag SNPs to cover all the observed variations. Association analysis in 446 AIS patients and 550 healthy controls showed no association between the polymorphisms of Leptin gene and susceptibility/severity to AIS. Moreover, adipogenesis assay of bone mesenchymal stem cells (MSCs) suggested that the adipogenic ability of MSCs from AIS girls was lower than controls. After adjusting the differentiation rate, expressions of leptin and leptin receptor were similar between two groups. Meanwhile, osteogenesis assay of MSC showed the leptin level was similar after adjusting the differentiation rate, but the leptin receptor level was decreased in induced AIS osteoblasts. Immunocytochemistry and western blot analysis showed less leptin receptors expressed in AIS group. Furthermore, factorial designed studies with adipogenesis and osteogenesis revealed that the MSCs from patients have no response to leptin treatment. Our results suggested that Leptin gene variations are not associated with AIS and low serum leptin probably is a secondary outcome which may be related to the low capability of adipogenesis in AIS. The decreased leptin receptor levels may lead to the hyposensitivity to leptin. These findings implied that abnormal peripheral leptin signaling plays an important role in the pathological mechanism of AIS.

Abstract PL01-02: Human papillomavirus in the etiology and prevention of genital cancers

Abstract PL01-02: Human papillomavirus in the etiology and prevention of genital cancers

Role of Thrombophilia in Adverse Obstetric Outcomes and Their Prevention Using Antithrombotic Therapy

A series of case-control studies in the last decade have shown the role of inherited thrombophilia in the occurrence of adverse obstetric outcomes. In small series of cases, it has been proven that rare inherited causes of thrombophilia such as natural anticoagulant deficiencies can be associated with fetal losses. The confirmed presence of antiphospholipid antibodies in plasma, representing an acquired thrombophilic condition, is also an established cause of fetal losses, although other studies with a smaller sample size have found an association with other obstetric complications, namely preeclampsia, fetal growth restriction, and abruption placentae. Case-control studies have been performed regarding the potential association between unexplained fetal losses and mild hyperhomocysteinemia. Although case-control and prospective studies are also available regarding hyperhomocysteinemia and other gestational vascular complications, published data are conflicting. Intervention studies have been performed to prevent adverse obstetric outcomes in women with inherited or acquired thrombophilia and previous adverse outcomes. There is much debate in the literature regarding the need for treatment of women with thrombophilia during pregnancy. Although in most cases these are not randomized controlled trials, all studies found significantly better outcomes in treated pregnancies compared with those of untreated pregnancies.

Diet and cancer in Mediterranean countries: carbohydrates and fats

Several aspects of the diet characteristic of the Mediterranean countries are considered favourable not only on cardiovascular disease, but also on cancer risk. We considered some aspects of the Mediterranean diet (including, in particular, the consumption of olive oil and carbohydrates) on cancer risk. Data were derived from a series of case-control studies, conducted in Italy since the early 1990s, on over 10,000 cases of thirteen cancer sites and over 17,000 controls. Olive oil, and other mono- and unsaturated fats, appear to be favourable indicators of breast, ovarian, colorectal, but mostly of upper aero-digestive tract cancers. Whole grain foods are also related to reduced risk of upper aero-digestive tract and various other cancers. In contrast, refined grain intake and, consequently, glycaemic index and glycaemic load were associated to increased risk for several cancer sites. Fish, and hence a diet rich in n-3 polyunsaturated fatty acids, tended to be another favourable diet indicator, while frequent red meat intake was directly related to some common neoplasms. An a priori defined Mediterranean diet score was inversely related to upper digestive and respiratory tract cancers. These data provide additional evidence that major characteristics of the Mediterranean diet favourably affect cancer risk.

Cyclooxygenase-2 (cox-2) blockade in the chemoprevention of cancers of the colon, breast, prostate, and lung

The existing epidemiologic literature was comprehensively reviewed to retrieve all epidemiologic studies (case control and cohort studies) that examined exposure to traditional over the counter nonsteroidal anti-inflammatory drugs (OTC NSAIDs) and the risk of cancers of the colon, breast, prostate and lung from 1980 forward. These malignancies account for more that half of all cancer deaths in the United States and the United Kingdom. Estimates of effects (relative risks or odds ratios) and 95% confidence intervals were abstracted from these reports for meta-analysis. Regular intake of OTC NSAIDs produced highly significant composite risk reductions of 43% for colon cancer, 25% for breast cancer, 28% for lung cancer, and 27% for prostate cancer. Furthermore, in a series of case control studies, daily use of a selective COX-2 inhibitor, either celecoxib or rofecoxib, significantly reduced the risk for each of these malignancies. The evidence is compelling that anti-inflammatory agents with selective or non-selective activity against cycloooxygenase- 2 (COX-2) have strong potential for the chemoprevention of cancers of the colon, breast, prostate and lung. Results confirming that COX-2 blockade is effective for cancer prevention have been tempered by observations that some selective COX-2 inhibitors pose a risk to the cardiovascular system. Nevertheless, meta-analysis of independent estimates from 72 studies provides no evidence that the selective COX-2 inhibitor, celecoxib, influences the relative risk of cardiovascular disease (composite relative risk = 0.98, 95% CI = 0.88-1.10). Molecular studies reveal that over-expression of COX-2 is a prominent feature of premalignant and malignant neoplasms. Evidence is accumulating that carcinogenesis often evolves as a progressive series of highly specific cellular and molecular changes in response to induction of constitutive over-expression of COX-2 and the prostaglandin cascade in the "inflammogenesis of cancer".

Trends in tuberculosis and the influence of HIV infection in northern Malawi, 1988-2001.

To document the changing incidence and patterns of tuberculosis (TB) in rural Africa and the extent to which they are influenced by HIV. As part of longstanding epidemiological studies in Karonga District, Malawi, a series of case control studies of TB and HIV were conducted from 1988 onwards. Data from these studies, from a total population survey, and from the Malawi national census have been used to reconstruct the changes in the TB epidemic in the area from 1988 to 2001, examining the role of HIV. The incidence of all confirmed TB, and of new smear-positive TB, in adults increased to peak in the late 1990s but appears to have decreased since. Two-thirds of cases are now HIV positive. The rise in incidence was greatest in the 30-44-year-old age group and was particularly marked for women, leading to a decrease in the male : female ratio for TB incidence from 1.3 to 0.8. The proportion of new smear-positive TB cases attributable to HIV increased from 17% in 1988-1990 to 57% in 2000-2001, but the estimated rate of smear-positive TB in the absence of HIV decreased from 0.78/1000 to 0.45/1000. Without HIV the incidence of smear-positive TB would have fallen in this population. Instead it has risen and is predominantly affecting young adults and women. There is some evidence that the HIV-associated TB epidemic may have passed its peak.

Prospective study of transfusion history and thyroid cancer incidence among females in Japan.

A link between hepatitis C virus (HCV) infection and thyroid cancer was recently reported in a series of case-control studies in southern Italy. A prospective study could reinforce these findings. However, cohort studies that began before 1990 rarely assessed serological HCV infection. In addition, thyroid cancer is rare and generally has a good prognosis. Therefore, incidence outcome data are required, rather than mortality data, to evaluate the risk of thyroid cancer. Blood transfusion history might be a possible substitute measure to evaluate the cancer risks associated with HCV infection because blood transfusions were the major HCV transmission route in Japan until 1992. The purpose of our study was therefore to examine the association between transfusion history and thyroid cancer. A baseline survey of members of the JACC Study was conducted from 1988 until 1990, which involved 110,792 participants from 45 areas throughout Japan. Data were collected from a total of 37,983 women with no history of cancer at the baseline (337,906 person-years) and 79 cases of thyroid cancer were identified among this group. A history of blood transfusion marginally increased the risk of thyroid cancer [risk ratio (RR)=1.77, 95% confidence interval (CI)=0.95-3.30], and a history of transfusion and/or liver disease significantly increased the thyroid cancer risk (RR=1.84, 95% CI=1.07-3.16). These results indirectly support an association between HCV and thyroid cancer. In addition, our data reveal an association between blood transfusion and thyroid cancer, which might be facilitated by transfusion-associated immunomodulation.

N-3 polyunsaturated fatty acid intake and cancer risk in Italy and Switzerland.

Data from a series of case-control studies, conducted in Italy and Switzerland between 1991 and 2001, have been analyzed to evaluate the role of n-3 polyunsaturated fatty acid (PUFA) intake in the etiology of cancer of oral cavity and pharynx (736 cases, 1772 controls), esophagus (395 cases, 1066 controls), large bowel (1394 colon, 886 rectum, 4765 controls), breast (2900 cases, 3122 controls) and ovary (1031 cases, 2411 controls). Controls were patients admitted to hospital for acute, non-neoplastic conditions, unrelated to modifications in diet. The multivariate odds ratios (OR) for the highest quintile of n-3 PUFAs compared to the lowest one were 0.5 for oral and pharyngeal cancer, 0.5 for oesophageal cancer, 0.7 for colon cancer, 0.8 for rectal and breast cancer and 0.6 for ovarian cancer; the estimates and the trends in risk were significant for all cancer sites, excluding rectal and breast cancer. The estimates for an increase in n-3 PUFAs of 1 g/week were 0.70 for oral and pharyngeal cancer, 0.71 for oesophageal, 0.88 for colon, 0.91 for rectal, 0.90 for breast and 0.85 for ovarian cancer. All the estimates were statistically significant, excluding that for rectal cancer, and consistent across strata of age and gender. These results suggest that n-3 PUFAs decrease the risk of several cancers.

Tomatoes, lycopene intake, and digestive tract and female hormone-related neoplasms.

Tomato consumption showed a consistent inverse relation with the risk of digestive tract neoplasms in Italy in an integrated series of studies conducted in the 1980s. Another series of case-control studies was conducted between 1992 and 1999 in different areas of Italy. Cases were patients below age 80 with incident, histologically confirmed cancer of the oral cavity and pharynx (n = 754), esophagus (n = 304), colorectum (n = 1953), breast (n = 2529), and ovary (n = 1031). The comparison group involved, overall, over 5000 patients below age 80 with acute, non-neoplastic, nonhormone-related diseases, unrelated to long-term diet modifications and admitted to the same network of hospitals. Information was collected in hospital by trained interviewers using a validated food frequency questionnaire, including 78 foods or groups of foods, various alcoholic beverage, and fat-intake pattern. The multivariate relative risk (RR) of oral, pharyngeal, and esophageal cancer decreased across subsequent levels of lycopene intake to reach 0.7 (95% confidence interval [CI] 0.4-1.0) for oral and pharyngeal, and 0.7 (95% CI 0.4-1.1) for esophageal cancer in the highest quintile of intake. Both trends in risk were of borderline statistical significance. With reference to colorectal, breast, and ovarian cancer, although no consistent association was observed for lycopene (RR = 1.0 for colorectal, 1.2 for breast, and 1.1 for ovary in the highest quintile), tomato intake was inversely and significantly related with colorectal cancer (RR = 0.8). The inverse relation between lycopene and upper digestive tract neoplasms was not explained by alcohol or tobacco, sociodemographic factors, or total energy intake. The interpretation of such an inverse relation, however, remains open to discussion because it may be related to an effect of lycopene due to its antioxidant effect and/or a potential role of lycopene in decreasing insulin growth factor I, which is a promoter in the process of carcinogenesis.

Efficacy of therapeutic drug monitoring in prevention of hypoglycemia caused by cibenzoline.

The purpose of this study was to evaluate the efficacy of our therapeutic drug monitoring (TDM) services in cibenzoline therapy using the risk of hypoglycemia as an end point. The TDM services of cibenzoline were introduced in March 1998. If the serum concentrations of cibenzoline deviated from the therapeutic range, adjustment of dosage was recommended. In addition, the physicians were recommended to pay attention to the hypoglycemia induced by cibenzoline. A series of case-control studies were performed before and after introduction of TDM services. After introduction of TDM services of cibenzoline, four case-control studies were performed every 6 months between March 1998 and February 2000 (stage 2 between March 1998 and August 1998; stage 3 between September 1998 and February 1999; stage 4 between March 1999 and August 1999; stage 5 between September 1999 and February 2000) using the same method as in the previous study which had been performed between September 1997 and February 1998 (stage 1). The TDM data of inpatients and outpatients between March 1998 and February 2000 were reviewed. A significantly increased risk of hypoglycemia was observed for users of cibenzoline during stage 1 [crude odds ratio (OR) 10.4; 95% confidence interval (CI) 2.7-40.3], stage 2 (crude OR 3.1; 95% CI 1.0-9.0), and stage 3 (crude OR 3.8; 95% CI 1.2-12.7). However, during stage 4 and stage 5, no significantly increased risk of hypoglycemia was observed. There was no significant difference between the mean doses during stage 1 and stage 5. However, there was a significant difference in the distributions of the trough levels among the four stages. During stage 4 and stage 5, the percentage of samples with a trough level of 200-400 ng/ml was higher than during stage 2 and stage 3. During stage 2, the percentage of samples with a trough level over 400 ng/ml was 42.9%. Furthermore, the risk of hypoglycemia associated with cibenzoline use decreased together with the increase in the percentage of outpatients whose serum concentrations of cibenzoline had been measured in the past. The risk of hypoglycemia associated with cibenzoline use decreased after introduction of TDM of cibenzoline. Dose adjustment based on TDM and the physicians' increased recognition of hypoglycemia associated with cibenzoline use were beneficial for those patients treated with cibenzoline in order to prevent hypoglycemia.