Medical history and risk of lymphoma: results of a European case–control study (EPILYMPH)

Introduction  Lymphomas are a heterogeneous group of immune-cell malignancies. Immunology-related conditions are among the few factors for which consistent evidence exists relating them to lymphoma risk. Materials and methods   We used the data from the European case–control study Epilymph on 2,362 lymphoma cases and 2,458 controls to investigate associations between a medical history of infectious and non-infectious diseases with overall and subentity-specific lymphoma risk. Results   As key results, we observed an increased odds ratio (OR) for self-reported infections with hepatitis B virus (HBV, OR = 1.91, 95% CL = 1.24–2.94) and a null result for rheumatoid arthritis. Additionally, we found an increased OR for infectious mononucleosis (OR = 1.68, 95% CL = 1.14–2.48), an inverse association to frequency of sickness in childhood (OR = 0.68, 95% CL = 0.55–0.84), and—as casual finding—an increased OR with acetaminophen intake (OR = 2.29, 95% CL = 1.49–3.51). Conclusion   Our results are consistent with the current knowledge about the association with mononucleosis as indicator of Epstein–Barr-virus infection, suggest serological study of the association to HBV infection and do not support the view of a positive association between rheumatoid arthritis and lymphoma risk.     

Hepatitis B virus infection and risk of lymphoma: results of a serological analysis within the European case–control study Epilymph

Background

We have recently reported from Epilymph, a multicentre case–control study of lymphoma conducted in six European countries, a significant association between NHL and self-reported history of past or present HBV infection based on questionnaire data from face-to-face interviews.

Methods

To corroborate this observation, we used the data and blood specimen from Epilymph to investigate the associations between serological indicators of HBV infection with risk of Hodgkin lymphoma, non-Hodgkin lymphoma (NHL) and specific lymphoma entities. For 1,518 cases and 1,496 controls with sufficient amount of serum or plasma, we tested HBs-antigen, anti-HBc and anti-HBs to distinguish between current or past infection and immunity by vaccination. Statistical analysis was carried out with unconditional logistic regression.

Results

We found a positive association of a past HBV infection with multiple myeloma (MM, OR?=?1.97, 95?% CL?=?1.16–3.37). Non-significant associations were found between past HBV infection and B-cell chronic lymphocytic leukaemia (B-CLL, OR?=?1.33, 95?% CL?=?0.82–2.16) and T-cell NHL (OR?=?1.59, 95?% CL?=?0.65–3.90), as well as between current HBV infection and NHL (OR?=?1.49, 95?% CL?=?0.65–3.41), B-NHL (OR?=?1.58, 95?% CL?=?0.69–3.64) and diffuse large B-cell lymphoma (DLBCL, OR?=?1.50, 95?% CL?=?0.47–4.82). Subjects having self-reported HBV infection were serological positive in 75?% of cases and 80?% of controls. For vaccination, the corresponding figures were 49 and 54?%, respectively.

Conclusion

The present results support previous reports of an association between a history of HBV infection with an elevated lymphoma risk and add multiple myeloma to the list of potentially virus-associated lymphoma entities.     

Dietary factors and the risk of lumbar spinal stenosis: A case–control analysis from the PREFACE study

Background and aimsThere is a lack of knowledge on the association of dietary factors and Lumbar Spinal Stenosis (LSS). We evaluated the association of a Mediterranean diet (MD), its major food components and ultra-processed food (UPF) with the risk of LSS.Methods and resultsParticipants were recruited from the Neurosurgery Department of the IRCCS Neuromed, Italy. The study sample consisted of 156 cases of LSS, and 312 controls matched 1:2 for sex, age (±6 months) and physical activity, without a history or clinical evidence of LSS who were identified from the general population. Adherence to MD was assessed by the Mediterranean Diet Score based on 9 food groups. UPF was defined according to NOVA classification and calculated as the ratio (%) of UPF (g/d) on total food consumed (g/d). In multivariable-adjusted analysis, a 2-point increase in the MD score was not associated with LSS risk (OR: 1.02, 95% CI: 0.72–1.46). An increment of 10 g/d of fruits and nuts, cereals or fish led to lower odds of LSS (OR: 0.97, 95% CI: 0.95–0.99; OR: 0.88, 95% CI: 0.82–0.94; OR: 0.87, 95% CI: 0.76–0.99, respectively). Additionally, 1% increment in the consumption of UPF in the diet was independently associated with higher LSS risk (OR: 1.09, 95% CI: 1.04–1.14).ConclusionA diet rich in fruits, cereals, fish is associated with lower risk of LSS while a large dietary share of UPF increases the risk of this disease. Further studies with a prospective design and larger sample sizes are warranted.     

Colorectal cancer and risk of atrial fibrillation and flutter: a population-based case–control study

Colorectal cancer has recently been associated with an increased atrial fibrillation risk, but evidence is very sparse. So, we conducted a population-based case-control study in northern Denmark (population 1.7 million) during 1998-2006 to estimate the atrial fibrillation/flutter risk in colorectal cancer patients. We identified 28,333 atrial fibrillation/flutter cases and 283,260 sex-, age-, and county-matched population controls. We searched the databases for a prior colorectal cancer diagnosis, a prior cancer diagnosis other than colorectal cancer, and performance of surgery within 30 days prior to atrial fibrillation/flutter. We used conditional logistic regression to estimate the OR of atrial fibrillation/flutter in patients with colorectal cancer, cancers other than colorectal and in patient with surgery. Among cases, 0.59% (n = 168) had a colorectal cancer diagnosis within 90 days before their atrial fibrillation/flutter diagnosis, compared with 0.05% (n = 155) of controls (adjusted OR = 11.8; 95% CI 9.3-14.9). Beyond the first 90 days after a colorectal cancer diagnosis, atrial fibrillation/flutter risk was no longer increased. There was likewise an increased atrial fibrillation/flutter risk in patients diagnosed with another cancer form in the prior 90 days (OR = 7.0, 95% CI 6.3-7.8). Furthermore, the atrial fibrillation/flutter risk was elevated fivefold in patients who had undergone surgery, whether or not cancer-related. We therefore conclude that colorectal cancer patients are at increased atrial fibrillation/flutter risk exclusively in the first 90 days after cancer diagnosis, but to no greater an extent than are patients with other cancers. The performance of surgery probably plays an important role in this association.     

Sulphonylureas and cancer: a case–control study

This study was aimed at the assessment of incidence of malignancies in type 2 diabetic patients treated with different sulphonylureas. A matched case–control study was performed. Cases were 195 diabetic patients aged 69.0 ± 9.2 years who had an incident malignancy. Controls were 195 diabetic patients, unaffected by cancer, who were matched with the corresponding case for age, sex, duration of diabetes, BMI, HbA1_c, comorbidity, smoking and alcohol abuse. Exposure to hypoglycaemic drugs during the 10 years preceding the event (or matching index date) was assessed. After adjusting for concomitant therapies, exposure to metformin and gliclazide for more than 36 months was associated with a significant reduction in the risk of cancer (adj. ORs with 95% CI: 0.28 (0.13–0.57), p < 0.001, and 0.40 (0.21–0.57), p = 0.004, respectively). Conversely, use of glibenclamide for at least 36 months was associated with increased incidence of malignancies (adj. OR 2.62 (1.26–5.42); p = 0.009). Treatment with insulin, thiazolidinediones, or acarbose, was not associated with significant differences in the incidence of cancer. Long-term treatments with individual sulphonylureas could have differential effects on the risk of cancer. In particular, the possible protective effect of gliclazide, as well as the risk associated with glibenclamide, deserves further investigation.     

Associations between central obesity and asthma in children and adolescents: a case–control study

Introduction: Evidence supports a significant yet weak association between high-body weight and asthma in children. However, most studies investigating the obesity–asthma link use Body Mass Index (BMI) to evaluate body fatness. The relationship between body fat distribution and asthma remains largely unknown, especially in children. This pediatric case–control investigation examined associations between central obesity/high-body weight and asthma diagnosis. Methods: Five-hundred and fourteen children (217 physician diagnosed asthma cases and 297 healthy controls) of 5–11 years were recruited. Height, weight and waist circumference were measured. Asthma symptoms, past medical history, personal lifestyle, socioeconomic status, diet and physical activity history were also collected. Results: A higher proportion of children with asthma were centrally obese [(≥90th waist percentile) 15.2 vs. 9.4%, p<0.0001; (≥90th waist-to-height ratio percentile) 39.6 vs. 24.2%, p<0.0001)]. Regression analyses revealed that centrally obese children were more likely to have asthma (high-waist circumference (OR?=?1.99, 95% CI: 1.07-3.68) and high-waist circumference to height ratio (OR?=?2.24, 95% CI: 1.47-3.40), following adjustment for various confounders. Overweight/obese participants (BMI defined) were more likely to be asthmatic [odds ratio (OR)?=?1.52, 95% confidence interval (CI): 1.03-2.70)] when compared to controls. Conclusions: Presence of central obesity and high-body weight (at least overweight) as assessed by waist circumference, waist-to-height ratio, and BMI are associated with asthma diagnosis. More studies are needed, especially in children and adolescents, to confirm these findings and better understand how body fat distribution impacts the obesity–asthma relationship.     

Antipsychotics and severe hyponatremia: A Swedish population–based case–control study

BackgroundAntipsychotics have been claimed to cause hyponatremia. The risk associated with individual antipsychotics, or groups (first-generation [FGAs] or second-generation [SGAs] antipsychotics), is not well-documented. The objective of this study was to investigate the association between antipsychotics and hospitalization due to hyponatremia.MethodsThe general Swedish population was the base of this register–based case–control study. Comparisons were made between patients hospitalized with a principal diagnosis of hyponatremia (n = 14,359) and matched controls (n = 57,383). Multivariable logistic regression adjusting for concomitant drugs, medical conditions, previous hospitalizations and socioeconomic factors was performed to investigate the association between hyponatremia and antipsychotic use. In addition newly initiated (≤90 days) or ongoing use was analysed separately.ResultsCompared to controls, the adjusted OR (95%CI) for hospitalization due to hyponatremia was for any antipsychotic 1.67(1.5–1.86). Individuals on FGA were more likely to experience severe hyponatremia (2.12[1.83–2.46]) than those on any SGA (1.32[1.15–1.51]). No increased risks, neither as newly initiated nor ongoing therapy, were found for risperidone (0.86[0.56–1.31] and 0.83[0.67–1.02]) and aripiprazole (1.16[0.30–4.46] and 0.62[0.27–1.34]), respectively.ConclusionsThere was an association between antipsychotic therapy and hospitalization due to hyponatremia. The association was stronger for FGAs than SGAs. Risperidone was not associated with an increased risk.     

Patient risk factors for outer membrane permeability and KPC-producing carbapenem-resistant Klebsiella pneumoniae isolation: results of a double case–control study

Background

In the 1,200-bed university hospital “Umberto I” in Rome, Italy, we observed a dramatic substitution of a precedingly well-documented Klebsiella pneumoniae clone (ST37) with ertapenem resistance by outer membrane permeability modification (Porin-ER-Kp) with a new K. pneumoniae strain expressing carbapenem resistance due to K. pneumoniae carbapenemase production (KPC-CR-Kp). A case–case–control study was carried out to evaluate risk factors for Porin-ER-Kp and KPC-CR-Kp isolation.

Methods

All patients with hospital-acquired K. pneumoniae isolation between July 2008 and June 2011 were included. Two case groups including patients harbouring KPC-CR-Kp and Porin-ER-Kp were analysed, with a third control group from whom carbapenem-susceptible K. pneumoniae (CS-Kp) were isolated.

Results

Forty-four KPC-CR-Kp cases, 39 Porin-ER-Kp cases and 60 CS-Kp controls were analysed. During the 3-year study, a specific Porin-ER-Kp endemic clone (ST37) was substituted by a new KPC-CR-Kp clone (ST512). Breakthrough bacteraemias occurred in 21 out of 26 KPC-CR-Kp group bloodstream infections (BSIs); nine of these developed during carbapenem therapy and seven with colistin and/or tigecycline therapy. In 13 Porin-ER-Kp BSIs, breakthrough bacteraemias developed in eight patients and four during carbapenem therapy. In the multivariable analysis, KPC-CR-Kp isolates were associated with carbapenems [odds ratio (OR) 7.74; 95 % confidence interval (CI) 1.70–35.2; p < 0.01) and endoscopy (OR 6.71; 95 % CI 1.25–36.0; p < 0.03). Porin-ER-Kp independent risk factors included second-generation cephalosporins (OR 25.7; 95 % CI 3.20–206.8; p < 0.01), carbapenems (OR 19.1; 95 % CI 4.34–83.9; p < 0.001), acute renal failure (OR 7.17; 95 % CI 1.33–38.6; p < 0.03), endoscopy (OR 6.12; 95 % CI 1.46–25.6; p < 0.02) and third-generation cephalosporins (OR 5.3; 95 % CI 1.34–20.9; p < 0.02).

Conclusions

Porin-ER-Kp strains needed major antimicrobial pressure compared to KPC-CR-Kp to express resistance. KPC-CR-Kp substituted Porin-ER-Kp strains, causing more infections. KPC-CR-Kp breakthrough bacteraemia occurred even under therapy with tigecycline or colistin, underlining that an antibiotic stewardship programme is needed urgently.     

Perception of risk and impact of the COVID-19 pandemic on patients with rheumatic diseases: a case–control study

Clinical Rheumatology - Risk perception of the COVID-19 pandemic may affect chronic disease outcomes among patients with rheumatic diseases (RD). To describe and compare the perception of risk and...     

Red cell distribution width and the risk of cerebral vein thrombosis: A case–control study

BackgroundRed cell distribution width (RDW) is a marker of cardiovascular diseases and venous thromboembolism, but its role in cerebral vein thrombosis (CVT) is unknown.AimsTo investigate whether high values of RDW are associated with an increased risk of CVT.MethodsA case–control study of CVT patients (≥ 18 years-old) referred to our center contrasted with healthy individuals. Odds ratios (ORs) were calculated for RDW values > 90th percentile by multivariable logistic regression and adjusted for demographic characteristics, hemorheological parameters, renal function, fibrinogen and CRP. Quartiles based on the distribution of RDW values were used in an additional model to assess a dose–response relationship. The risk of CVT associated with the combined presence of high RDW and either thrombophilia abnormalities or oral contraceptive use was also estimated.Results143 cases (median age 36 years, 18–79) and 352 controls (42 years, 18–80) were investigated. RDW values > 90th percentile (> 14.6%) were associated with an increased risk of CVT (OR 2.44, 95% CI 1.39–4.28). The association remained after further adjustment for hemorheological parameters (OR 3.73, 95% CI 1.72–8.09), inflammatory markers (OR 3.77, 95% CI 1.72–8.25) and renal function (OR 3.62, 95% CI 1.53–8.55). The risk appeared restricted to these extreme levels (> 14.6%), as there was no graded association between values of RDW and CVT risk over quartiles. There was a synergistic effect on the risk of CVT for the combination of high RDW and thrombophilia abnormalities (OR 33.20, 95% CI 6.95–158.55) or oral contraceptive use (OR 37.99, 95% CI 8.78–164.45).ConclusionsValues of RDW > 90th percentile are associated with CVT.     

Vitamin D deficiency and level of asthma control in women from North of Jordan: a case–control study

Introduction: Reduced vitamin-D levels in patients with asthma have been associated with impaired lung function, increased airway hyper-responsiveness, and reduced glucocorticoid responsiveness. Nationwide studies revealed a considerable prevalence of vitamin-D deficiency (VDD) in Jordanian women. Objective: A case–control study was conducted to determine the relationship between serum vitamin A and D levels and asthma among women in North of Jordan. Methods: Sixty-eight asthmatics, age range between 14 and 65 years and 77 healthy women, age range between 19 and 51 years, were enrolled. Asthma severity was classified using Global Initiative for Asthma (GINA) guidelines and Asthma Control Test (ACT) questionnaire. Serum vitamin-A and 25-hydroxyvitamin-D (25(OH)D3) levels were measured using high-performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods, respectively. Results: The prevalence of VDD (<15?ng/ml) was higher but not statistically significant for women with asthma compared with controls (95.6% vs. 87.0%; p?=?0.070). The severity of VDD correlated with the number of asthma medications (p?=?0.020). 25(OH)-D3 serum levels directly correlated with asthma control level using ACT score (p?=?0.012) and GINA classification (p?=?0.046). After adjusting for age, the odds of having VDD for asthmatic women were 35.9 times higher than that for women with no asthma. There was no difference in serum vitamin-A level between healthy and asthmatic women (p?=?0.214) and none had vitamin-A deficiency (<200?µg/dl). Conclusions: VDD is prevalent in women with asthma in northern Jordan. The severity of VDD correlated with poor asthma control and a need for more medications to control asthma. There was no association between vitamin-A and asthma.     

Maternal obesity as a risk factor for early childhood type 1 diabetes: a nationwide,prospective, population-based case–control study

Aims/hypothesis

Genetic and environmental factors are believed to cause type 1 diabetes. The aim of this study was to investigate the influence of maternal BMI and gestational weight gain on the subsequent risk of childhood type 1 diabetes.

Methods

Children in the Swedish National Quality Register for Diabetes in Children were matched with control children from the Swedish Medical Birth Register. Children were included whose mothers had data available on BMI in early pregnancy and gestational weight gain, giving a total of 16,179 individuals: 3231 children with type 1 diabetes and 12,948 control children.

Results

Mothers of children with type 1 diabetes were more likely to be obese (9% [n = 292/3231] vs 7.7% [n = 991/12,948]; p = 0.02) and/or have diabetes themselves (2.8% [n = 90/3231] vs 0.8% [n = 108/12,948]; p < 0.001) compared with mothers of control children. Gestational weight gain did not differ significantly between the two groups of mothers. In mothers without diabetes, maternal obesity was a significant risk factor for type 1 diabetes in the offspring (p = 0.04). A child had an increased risk of developing type 1 diabetes if the mother had been obese in early pregnancy (crude OR 1.20; 95% CI 1.05, 1.38; adjusted OR 1.18; 95% CI 1.02, 1.36). Among children with type 1 diabetes (n = 3231) there was a difference (p < 0.001) in age at onset in relation to the mother’s BMI. Among children in the oldest age group (15–19 years), there were more mothers who had been underweight during pregnancy, while in the youngest age group (0–4 years) the pattern was reversed.

Conclusions/interpretation

Maternal obesity, in the absence of maternal diabetes, is a risk factor for type 1 diabetes in the offspring, and influences the age of onset of type 1 diabetes. This emphasises the importance of a normal maternal BMI to potentially decrease the incidence of type 1 diabetes.

     

Treatment with octreotide LAR in clinically non-functioning pituitary adenoma: results from a case–control study

Surgical cure cannot be achieved in most patients with invasive non-functioning pituitary macroadenoma (NFPA). Short-term residual tumor treatment with somatostatin analogs has produced disappointing results. This prospective case?Ccontrol study assessed the efficacy of chronic treatment with long acting octreotide (octreotide LAR) on tumor volume in patients harboring post-surgical NFPA residue. The study population comprised 39 patients with NFPAs not cured by surgery. All patients underwent somatostatin receptor scintigraphy at least 6?months after the last surgery. Patients with a positive pituitary level octreoscan at (n?=?26) received octreotide LAR (20?mg every 28?days) for ??12?months (mean follow-up 37?±?18?months) (Treated group). Moreover, a fragment of tumor tissue from patients in the treated group was retrospectively collected to assess the immunohistochemical expression of somatostatin receptor subtypes (SSTRs). The patients with a negative octreoscan (n?=?13) formed the control group (mean follow-up 37?±?16?months). Hormonal, radiological and visual field parameters were periodically assessed. In the treated group, all tumors expressed at least one SSTR subtype. The SSTR5 subtype was the most abundant, followed by SSTR3. The tumor residue increased in five of 26 patients (19%) in the treated group and in seven of 13 controls (53%). Visual field and pituitary function did not change in any patient. This study indicates that SSTR5 and SSTR3 are the most frequently expressed SSTR subtypes in NFPAs and supports a potential role of SSTR subtypes in stabilization of tumor remnant from NFPAs.     

Predictors of coronary stent thrombosis: a case–control study

Journal of Thrombosis and Thrombolysis - To verify the frequency and predictors associated with stent thrombosis (ST) in a developing country. Observational, case–control study including 2535...     

Socioeconomic status and the risk for being diagnosed with spondyloarthritis and chronic pain: a nested case–control study

Socioeconomic status could potentially impact on which type of rheumatic diagnosis a patient receives. We determined whether different socioeconomic status is a risk factor for being diagnosed with spondyloarthritis (SpA) or chronic pain. In a nested case–control study, we identified two sets of adult cases diagnosed with (i) SpA (n = 1,194) and (ii) chronic pain (n = 3,730) during 2010–2012 in Skåne region, Sweden. We randomly sampled controls matched for age and sex. Level of education, marital status, and income were identified in national registers 4 years before inclusion. We also studied health-care utilization, prescribed pharmaceuticals, and work status. We used conditional logistic regressions and included socioeconomic variables and geographic area in the models. Low (odds ratio [OR] 1.69 95 % CI 1.50–1.91) or moderate education (OR 1.43 95 % CI 1.30–1.57), and low (OR 1.40 95 % CI 1.25–1.57) or moderate income (OR 1.24 95 % CI 1.10–1.38) were associated with a chronic pain diagnosis. For a SpA diagnosis, moderate income (OR 1.25 95 % CI 1.04–1.50) was the only significant factor identified. Both case groups had a larger proportion that did not work (P < 0.001), used more health care (P < 0.001), and were more frequently prescribed NSAIDs (P < 0.001) 4 years before diagnosis than controls. We confirmed that lower levels of education and income are associated with a chronic pain diagnosis. This association may reflect a true higher incidence of chronic pain and/or increased consultation propensity for such pain in people with socioeconomic status. We found no such association for SpA.     

A case–control study of rheumatoid arthritis revealed abdominal obesity and environmental risk factor interactions in northern China

Background: The aim of this study was to evaluate new and previously hypothesized environmental risk factors and their interaction with rheumatoid arthritis (RA).

Methods: Four hundred patients recently diagnosed with RA and 400 controls frequency-matched by gender and birth year using Propensity Score Matching (PSM) were selected from northern China. Investigation was performed using self-reported data from interviewer-administered surveys. Associations between exposure variables and risk of RA were evaluated using multifactor non-conditional logistic regression.

Results: It showed that damp localities, draft indoor, abdominal obesity (AO), and family history of RA among first-degree relatives were independent risk factors and drinking of milk was independent protective factors for RA. Besides these risk factors, in women, infrequent delivery times, early age at menopause, and late age at menarche were also independent risk factors for RA. Both the additive model and the multiplication model suggested that there was an interaction relationship between AO and damp localities (p?p?p?p?Conclusions: In northern China, damp localities, draft indoor, AO, family history of RA among first-degree relatives, and no milk drinking may be important risk factors of RA patients.