Pleuropulmonary localizations of non-typhoid Salmonella infections

Non-typhoid salmonella infections are extremely common, usually taking the form of a benign toxi-infection. In the context of the rare extra-digestive manifestations, the authors report 3 cases of pleuro-pulmonary involvement, in infections due to Salmonella Dublin. In 2 cases, the organism was identified from blood cultures, whilst in the 3rd case it was isolated from pleural fluid. As with other extra-digestive sites, pleuro-pulmonary involvement is favored by underlying pathology, accounting for the grave nature of the problem (amongst the 3 cases, gastrectomy and acute myeloblastic leukemia in one case and obliterative arterial disease in another case). Non-typhoid salmonella infections are sensitive to Sulfamethoxazole-trimethoprim which diffuses well in the respiratory system. They are also sensitive to Amoxicillin and to Chloramphenicol.     

Adiponectin and noncardiovascular death: a nested case-control study

This study is to evaluate the associations between adiponectin level and noncardiovascular death and to test a hypothesis that adiponectin level reflects the degree of systemic wasting that precedes death. A nested case-control study was conducted involving 5243 subjects, drawn from 12490 subjects of the Jichi Medical School Cohort Study, whose blood samples had been drawn between 1992 and 1995. Over an average of 10.8 years of follow-up, 103 cases with noncardiovascular death and 565 controls without history/event/death of any cardiovascular disease were identified. Odds ratios (ORs) were estimated relative to the lowest quintile of adiponectin level. The risks for noncardiovascular death of the second lowest quintile and the highest quintile of adiponectin level were significantly higher than that of the lowest quintile when adjusted for age and sex (model 1) (OR, 2.38 [95% confidence interval (CI), 1.12-5.06] and 2.16 [1.01-4.80]). All the statistical significances disappeared when adjusted further for body mass index and C-reactive protein level (model 2). When excluding cases with cancer death, the odds for death in the highest 2 quintiles were significantly higher than those in the lowest quintile in model 1 (OR, 2.80 [95% CI, 1.04-7.59] and 3.74 [1.38-10.18]). The significant difference between the highest vs the lowest quintile remained significant in model 2 and even after adjusting further for smoking, diabetes, and total cholesterol level (model 3) (OR, 3.28 [95% CI, 1.02-10.51] and 3.98 [1.21-13.13]). Adiponectin levels had linear associations with the risks of noncardiovascular noncancer death in models 1, 2, and 3 (OR per 1 SD increase in log-adiponectin, 1.72 [95% CI, 1.23-2.40], 1.89 [1.23-2.91], and 2.01 [1.29-3.15]). Adiponectin is an independent indicator of noncardiovascular mortality that may relate with systemic wasting.     

Predictors of antiretroviral treatment-associated tuberculosis in Ethiopia: a nested case-control study

Little is known about the predictors of antiretroviral treatment (ART)-associated tuberculosis (TB) in developing nations. The objective of this study was to determine predictors of ART-associated TB in adults with HIV infection at Jimma University Hospital, Ethiopia. A nested case-control study was conducted in October 2009. The study population consisted of adults with HIV infection (aged >14 years) who developed active TB in the first six months since ART initiation and controls that did not develop active TB. Data were collected using a structured and pretested questionnaire. Cox proportions hazards analysis was done to determine predictors of ART-associated TB. A total of 357 patients (119 cases and 238 controls) participated in the study. After six months of follow-up, cumulative incidence of ART-associated TB was 5.2% (123/2355). Forty (33.6%) cases were lost to follow-up after they developed ART-associated TB and 11 (9.2%) died. Fifty-one (21.4%) controls interrupted ART and 11 (4.6%) died. A CD4 lymphocyte count increase >0.5/μL/day (adjusted hazard ratio [AHR] = 19.80, 95% confidence interval [CI]: 9.52, 41.12, P < 0.001), a base-line CD4 lymphocyte count <200 cells/μL (AHR = 9.59, 95% CI: 2.36, 39.04, P = 0.002), World Health Organization (WHO) clinical stage 3 or 4 (AHR = 3.04, 95% CI: 1.62, 5.69, P < 0.001), night sweats during ART initiation (AHR = 1.53, 95% CI: 1.06, 2.21, P < 0.001) and high ART adherence (AHR = 1.30, 95% CI: 1.13, 1.50, P < 0.001) were independent predictors of ART-associated TB. HIV-infected adults with these risk factors should be followed cautiously for the development of ART-associated TB. Good ART adherence and a good immunological response during ART were associated with ART-associated TB, most likely because of an immune reconstitution inflammatory syndrome unmasking the TB.     

The effectiveness of screening for prostate cancer: a nested case-control study

BACKGROUND: Screening for prostate cancer is done commonly in clinical practice, using prostate-specific antigen (PSA) tests or digital rectal examination (DRE). Evidence is lacking, however, to confirm a survival benefit among screened patients. We evaluated the effectiveness of PSA, with or without DRE, in reducing mortality. METHODS: We conducted a multicenter nested case-control study at 10 Veterans Affairs medical centers in New England. Among 71 661 patients receiving ambulatory care between 1989 and 1990, 501 case patients were identified as men who were diagnosed as having adenocarcinoma of the prostate from 1991 through 1995 and who died sometime between 1991 and 1999. Control patients were men who were alive at the time the corresponding case patient had died, matched (1:1 ratio) for age and Veterans Affairs facility. The exposure variable (determined blind to case-control status) was whether PSA testing or DRE was performed for screening prior to the diagnosis of prostate cancer among case patients, with the same time interval for control patients. The association of screening and overall or cause-specific (prostate cancer) mortality was adjusted for race and comorbidity. RESULTS: A benefit of screening was not found in our primary analysis assessing PSA screening and all-cause mortality (adjusted odds ratio, 1.08; 95% confidence interval, 0.71-1.64; P=.72), nor in a secondary analysis of PSA and/or DRE screening and cause-specific mortality (adjusted odds ratio, 1.13; 95% confidence interval, 0.63-2.06; P=.68). CONCLUSIONS: These results do not suggest that screening with PSA or DRE is effective in reducing mortality. Recommendations for obtaining "verbal informed consent" from men regarding such screening should continue.     

Psychosocial factors are linked to functional gastrointestinal disorders: a population based nested case-control study

BACKGROUND: It is widely accepted based on volunteer studies that levels of psychological distress are similar in those with functional gastrointestinal (GI) disorders and health in the community, while increased psychological distress in outpatients is largely explained by health-care seeking. AIMS: To determine if psychological distress, life event stress, or social support is associated with functional GI disorders in a population-based study. METHODS: A nested case-control study was performed by first mailing a self-report bowel disease questionnaire to a random sample of Olmsted County, Minnesota, aged 20-50 yr. All persons who reported symptoms of nonulcer dyspepsia (NUD) or irritable bowel syndrome (IBS) (cases), or an absence of GI symptoms (controls), were invited to complete a series of validated questionnaires designed to measure psychological distress, life event stress, social support, current symptoms, and physician visits. RESULTS: 103 subjects with functional GI disorders and 119 controls participated (85% of eligible). Functional GI disorders were more likely to be reported by those with higher scores on each of the nine SCL-90-R scales used to measure psychological distress (except phobic anxiety), and those with more negative and total life event stress. In a multiple logistic regression model (including age and gender), somatization, interpersonal sensitivity, and total life event stress were independently associated with functional GI disorders. Findings were similar when subjects with the IBS and NUD were analyzed separately compared to controls. CONCLUSIONS: Contrary to current dogma, psychosocial factors were significantly associated with functional GI disorders in this community sample. This suggests that these factors may be involved in the etiopathogenesis rather than just driving health-care utilization.     

Salmonella Berta myocarditis: Case report and systematic review of non-typhoid Salmonella myocarditis

AIM: To study trends in the epidemiology, clinical presentation, microbiology and prognosis of non-typhoid Salmonella (NTS) myocarditis.METHODS: We performed a systematic literature search for all reported NTS cases. The search yielded 838 publications. A total of 21 papers were deemed eligible. No language restrictions were enforced. Articles that were not written in English were translated. Pre-specified data such as clinical presentation, electrocardiogram (ECG) changes, transthoracic echocardiographic findings, cardiac magnetic resonance findings, microbiology cultures, Salmonella species, inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), cardiac biomarkers and severity of illness were collected using data extraction sheets. Cases were classified by age into 2 groups; pediatric cases (defined as < 18 years old) and adult cases (defined ≥ 18 years old). The mean age of patients and standard deviations were calculated. The data was analyzed with IBM SPSS Statistics (Windows, Version 20.0. Armonk, NY: IBM Corp.) for demographic characteristics, presenting symptoms, microbiology, diagnostic methods, treatment modalities and outcome.RESULTS: From the selected articles, we identified a total of 24 individual cases with verifiable data. There were 20 males with a male to female ratio of 5:1. The mean age at presentation was 30.8 years (range 1 mo-67 years), 16% of cases were children aged < 18 years. Most patients presented with chest pain, fever, and abdominal pain. The most common ECG finding was ST elevation. Cardiac biomarkers were elevated in around 70% of cases. Salmonella Enteritidis was the most common NTS isolated. Definitive diagnosis was established by blood and stool cultures in most of the cases. The pediatric and adults cases had similar incidence of bacteremia (40% vs 36.8%) while the pediatric group had more stool cultures positive compared to the adult group (100% vs 63.1%). Eighty-three percent of patients received antibiotics and 58% were successfully treated through conservative management. The overall mortality was 24% and 42% of patients required intensive care.CONCLUSION: This systematic review of published cases shows that NTS myocarditis occurs predominantly in young adults and carries a poor prognosis.     

Quinolone antibiotics in the treatment of Salmonella infections

The 4-fluoroquinolones are a new class of antimicrobial agents that possess broad in vitro antibacterial activity, including efficacy against enteric pathogens such as Salmonella, Shigella, Campylobacter, Yersinia, and Vibrio species. These drugs are clinically effective against both drug-sensitive and multiresistant strains of Salmonella typhi and Salmonella paratyphi that cause enteric fever. In salmonella enterocolitis, the quinolones--unlike older antimicrobial agents that may have little impact on the duration of symptomatic illness and can in fact prolong fecal carriage of salmonellae--actually shorten the course of clinical disease and terminate excretion of these organisms in the stool. Similarly, for chronic carriers of both typhoidal and nontyphoidal Salmonella strains, the quinolones are effective in eradicating biliary and fecal reservoirs of infection. Immunosuppressed persons with salmonellosis, such as those with AIDS, may benefit from both short-term treatment and prolonged prophylaxis with a quinolone antibiotic. The optimal agent, dose, and duration of quinolone therapy for all salmonella syndromes remain to be determined by larger controlled trials.     

Bacterial vaginosis and susceptibility to HIV infection in South African women: a nested case-control study

BACKGROUND: Bacterial vaginosis (BV) may increase women's susceptibility to HIV infection, but there are few prospective data. METHODS: During follow-up for up to 36 months, 86 new HIV seroconverters (case patients) were identified among 5110 women enrolled in a cervical cancer screening trial. Nonseroconverting control subjects (n=324) were frequency matched to case patients by age and duration of follow-up. At enrollment, case patients and control subjects were evaluated for clinical signs of BV, and Gram stains of vaginal fluid were scored using Nugent criteria. RESULTS: BV was diagnosed on the basis of clinical criteria at enrollment in 20% of seroconverters and 16% of control subjects (summary odds ratio [OR], 1.31 [95% confidence interval {CI}, 0.71-2.41]). Nugent criteria for BV were met by 74% of seroconverters and 62% of control subjects. Diagnosis of BV on the basis of Nugent criteria was significantly associated with an increased risk of HIV seroconversion, after adjustment for demographic characteristics, other sexually transmitted infections, and sexual behaviors (adjusted OR, 2.01 [95% CI, 1.12-3.62]). CONCLUSIONS: BV may account for a substantial fraction of new HIV infections in this setting. Treatment of BV and other interventions to promote normal vaginal flora warrant attention for HIV prevention.     

Hidradenitis suppurativa and inflammatory bowel disease in a nested case-control study

BackgroundAssociation between Hidradenitis Suppurativa (HS) and Inflammatory Bowel Disease (IBD) has been suggested.AimsTo assess characteristics of HS and IBD in patients with or without concomitant IBD.MethodsIn a prospective, nested case-control study, each IBD patient with concomitant HS (Case) was retrospectively matched with 4 patients with HS and no IBD (Controls) for gender and age (±5 years).HS was classified according to the Hurley score and the International Hidradenitis Suppurativa Severity Score System (IHS4). Data were expressed as mean (Standard Deviation). Statistical analysis included Student-t Test or Mann-Whitney Test, χ2 test, univariate and multivariate logistic regression.ResultsThe study population included 125 patients with HS: 25 with IBD, 100 matched Controls with no IBD. IBD group included 19 (76%) Crohn's disease and 6 (24%) Ulcerative Colitis patients. Obesity, familial HS and perianal HS were less frequent in Cases than in Controls (1[4%] vs 25(25%];p = 0.02; 1[4%] vs 21(21%];p = 0.04; 1[4%] vs 31(31%];p = 0.005, respectively).HS was less severe in Cases when assessed by the IHS4 (5.9 ± 4 vs 9 ± 6.7;p = 0.04).Complete drug-induced response for HS was more frequent in IBD (13[53%] vs28 (28%]; p = 0.04).ConclusionClinical characteristics of HS and of patients differed between Cases and Controls. Present findings suggest the need to appropriately search and assess skin lesions compatible with HS in IBD.     

Oral anticoagulation treatment in the elderly: a nested, prospective, case-control study

BACKGROUND: Whether elderly patients are at increased risk of complications during oral anticoagulant treatment (OAT) is still a matter of debate. METHOD: Bleeding and thrombotic events occurring during OAT in 461 patients, aged 75 years or older when they started OAT, and in 461 patients younger than 70 years, matched for sex, OAT indication, and treating center, were examined in a prospective, multicenter, inception-cohort study. RESULTS: Bleeding rate was 9.9% and 6.6% patient-years in elderly and young patients, respectively (P = .07), and 2.1% and 1.1% for major bleeding (P = .19); 6 and 1 events, respectively, were fatal (all intracranial, relative risk, 6.4; P = .05). In the elderly, bleeding rate was lower (4.5%) for international normalized ratios (INRs) between 2.0 and 2.9; it was higher during the first 90 treatment days (P = .05) and when arterial vascular disease was the indication for OAT (P = .03). Thrombosis rate was 4.2% and 2.5% patient-years in elderly and young patients, respectively (P = .10); however, 13 and 5 events were fatal (relative risk, 2.8; P = .04). Thrombosis rate was lower (1.5%) for INRs between 2.0 and 2.9; it was higher during the first 90 treatment days (P<.001) and 6 of 7 venous events occurred at lower than 2.0 INRs. CONCLUSIONS: A nonsignificant trend was noted toward a higher rate of both bleeding and thrombotic complications in elderly vs matched younger patients. Intracranial bleeding and fatal thrombotic events were significantly more frequent in the elderly. Our results also indicate that lower than 2.0 INRs do not preclude bleeding in the elderly nor offer adequate protection from thrombotic events. Moderate anticoagulation (2.0-3.0 INRs) in elderly patients seems the safest and most effective.     

Risk factors for lung cancer in patients with scleroderma: a nested case-control study

OBJECTIVES: To study potential risk factors for the development of lung cancer in patients with scleroderma and explore the chronological relationship between onset of scleroderma symptoms and subtypes of lung cancer. METHOD: Linkage of two population-based registers to identify lung cancer cases and gender-matched controls with scleroderma, followed by retrospective case note review for clinical details. RESULTS: Patients with scleroderma who smoke are seven times more likely to develop lung cancer than non-smokers (p=0.008). Smokers with scleroderma and cancer smoke more than smokers with scleroderma without cancer (p=0.019). Pulmonary fibrosis and anti-topoisomerase antibody do not increase the risk of lung cancer. Peripheral lung tumours occur earlier after the onset of scleroderma symptoms than bronchogenic tumours (p=0.05). CONCLUSIONS: Smokers with scleroderma should be monitored for the presence of lung cancer and counselled to quit smoking. The earlier development of peripheral lung tumours is not consistent, with pulmonary fibrosis being an aetiological factor.     

Use of oral bisphosphonates and the risk of aseptic osteonecrosis: a nested case-control study

OBJECTIVE: To determine whether use of oral bisphosphonates is associated with an increased risk of aseptic osteonecrosis (AON) among a cohort of elderly cardiovascular patients. METHODS: We conducted a nested case-control study within a previously defined cardiovascular cohort of elderly Quebec patients using linked administrative health databases. Cases were defined as those with the diagnosis of hospitalization secondary to AON at a nonspecified site. For each case, 10 controls were randomly selected and matched to the cases by age, calendar time, and length of followup. The main outcome measure was the risk ratio (RR) of AON among ever-users of oral bisphosphonates compared to that among nonusers. As a quality measure, RR for AON among users of statin and angiotensin-converting enzyme inhibitors (ACE-I) compared to nonusers were also calculated. RESULTS: The initial cohort consisted of 87,837 subjects. In the primary analysis, the adjusted RR for AON among bisphosphonate users was 2.87 (95% CI 1.71-5.05). The adjusted RR for alendronate, etidronate, and risedronate were 2.87 (95% CI 1.46-5.67), 2.43 (95% CI 1.05-5.62), and 3.34 (95% CI 1.04-10.67), respectively. There were no significant differences in RR for AON among current users (most recent drug exposure within 90 days of diagnosis) and past users (drug exposure between 91 and 365 days before diagnosis) of bisphosphonates. The adjusted RR for both statins and ACE-I were 0.79 (95% CI 0.49-1.07) and 1.16 (95% CI 0.79-1.70), respectively. CONCLUSION: In this cohort of elderly cardiovascular patients, an association was observed between oral bisphosphonate use and aseptic osteonecrosis. Further research into this putative association is required.     

Serum antibodies to periodontal pathogens prior to rheumatoid arthritis diagnosis: A case-control study

Objectives1) To quantify the association between anti-Porphyromonas gingivalis serum antibody concentrations and the risk of developing rheumatoid arthritis (RA), and 2) to quantify the associations among RA cases between anti-P. gingivalis serum antibody concentrations and RA-specific autoantibodies. Additional anti-bacterial antibodies evaluated included anti-Fusobacterium nucleatum and anti-Prevotella intermedia.MethodsSerum samples were acquired pre- and post- RA diagnosis from the U.S. Department of Defense Serum Repository (n = 214 cases, 210 matched controls). Using separate mixed-models, the timing of elevations of anti-P. gingivalis, anti-P. intermedia, and anti-F. nucleatum antibody concentrations relative to RA diagnosis were compared in RA cases versus controls. Associations were determined between serum anti-CCP2, ACPA fine specificities (vimentin, histone, and alpha-enolase), and IgA, IgG, and IgM RF in pre-RA diagnosis samples and anti-bacterial antibodies using mixed-effects linear regression models.ResultsNo compelling evidence of case-control divergence in serum anti-P. gingivalis, anti-F. nucleatum, and anti-P. intermedia was observed. Among RA cases, including all pre-diagnosis serum samples, anti-P. intermedia was significantly positively associated with anti-CCP2, ACPA fine specificities targeting vimentin, histone, alpha-enolase, and IgA RF (p<0.001), IgG RF (p = 0.049), and IgM RF (p = 0.004), while anti-P. gingivalis and anti-F. nucleatum were not.ConclusionsNo longitudinal elevations of anti-bacterial serum antibody concentrations were observed in RA patients prior to RA diagnosis compared to controls. However, anti-P. intermedia displayed significant associations with RA autoantibody concentrations prior to RA diagnosis, suggesting a potential role of this organism in progression towards clinically-detectable RA.