Norovirus outbreaks in a teaching hospital: the role of infection control

In January 2004, 20 patients and 19 staff in one ward became ill in an outbreak of norovirus-related gastroenteritis over a 12-day period. The epidemic curve indicated person-to-person transmission. Infection control measures were instituted in consultation with the government health authorities. A prompt rigorous response may have prevented spread to other wards. In March 2004, 54 staff and 1 member of a patient's family became ill in an outbreak of gastroenteritis. The source of norovirus contamination was associated with food served at the hospital restaurant. Secondary infection was prevented because the outbreak was recognized early and staff members with gastroenteritis symptoms were asked to stay home. Immediate control measures, such as identification and announcement of the outbreak, isolation of symptomatic individuals from others, personal protection, helped control the infection.     

Tobacco use and cancer causation: association by tumour type

In the second part of our review we describe the association between tobacco use and risk of specific cancer types. There is evidence for an established association of tobacco use with cancer of the lung and larynx, head and neck, bladder, oesophagus, pancreas, stomach and kidney. In contrast, endometrial cancer is less common in women who smoke cigarettes. There are some data suggesting that tobacco use increases the risk for myeloid leukaemia, squamous cell sinonasal cancer, liver cancer, cervical cancer, colorectal cancer after an extended latency, childhood cancers and cancer of the gall bladder, adrenal gland and small intestine. Other forms of cancer, including breast, ovarian and prostate cancer, are unlikely to be linked to tobacco use.     

Gout and arrhythmias: In search for causation beyond association

Gout is a systemic disease, characterized by the formation and deposition of crystals in tissues (mainly in and around the joints) of individuals with elevated serum uric acid levels. Lately, a considerable number of reports relating elevated uric acid and/or gout with rhythm disorders, such as atrial fibrillation, have been published. This review summarizes evidence linking common arrhythmias and hyperuricemia/gout and discusses questions or controversies that surround it. Overall, existing evidence may not be overwhelming, but strongly suggests a positive correlation between uric acid levels and common rhythm disorders. Needless to say that such a link – as a univariate association between the two – is to be expected, given the extensive overlap of risk factors and comorbidities of hyperuricemia/gout and arrhythmias. However, the observed associations seem to persist – in most studies – after extensive adjustment for potential confounders. Still, multivariable analyses of epidemiologically collected data cannot substitute for proof coming from basic and clinical studies. There is obviously a need for further basic research to establish a causal relationship between uric acid effects and arrhythmias, as well as translational studies and clinical trials to investigate the therapeutic implications of such a relationship. Simply put, we are fairly certain that there is association, but proof of causation is what we are still in want of.     

Lung surfactant: How it does and does not work

Earlier analyses of the physical chemistry of lung surfactant (LS) are rejected on the grounds that the definition of surface tension is not complied with. Furthermore, with 1 or 2 exceptions the devices used to measure the properties of LS have given misleading information. On the other hand, a protein-free formulation of an artificial lung-expanding compound (ALEC) consisting of a 7:3 mole/mole mixture of dipalmitoylphosphatidylcholine and phosphatidylglycerol seems to function as a reasonably good substitute for natural LS in very premature babies. It has the following necessary properties. It spreads rapidly and spontaneously at an air/water interface at 37°C, reducing the surface tension of water by about 2/3. The unsaturated phosphatidylglycerol (PG) moiety can be squeezed out of the mixed monolayer by rapid overcompression (equivalent to exhalation) and is irreversibly lost to the surface system by reassembly into liposomes. The residual dipalmitoylphosphatidylcholine (DPPC) becomes progressively enriched to the point that, at 37°C, it condenses out as a solid phase so rigid that it prevents the alveolae from collapsing. The preparation is protein-free. It is suggested that this simple mixture of 2 phospholipids exhibits both thermodynamic (equilibrium) forces and the consequences of kinetic forces during the course of a compression/decompression cycle on a trough. Likewise, during a respiratory cycle, the alveolae may be kept open (or more precisely, the liquid lining the alveolae is prevented from filling them up) at full expiration by the presence of a permanent residue of almost pure DPPC which, being condensed (solid) at 37°C, is incompressible. The work of extending the uncovered air/water interface, upon inspiration, is reduced by replenishment from the stockpile of dry surfactant as though from a lamellar body. The respiratory cycle is thus seen as a dynamic sequence of refinement, ablution, and replenishment of phospholipid molecules.     

Human immunodeficiency virus and acquired immunodeficiency syndrome: correlation but not causation

AIDS is an acquired immunodeficiency syndrome defined by a severe depletion of T cells and over 20 conventional degenerative and neoplastic diseases. In the U.S. and Europe, AIDS correlates to 95% with risk factors, such as about 8 years of promiscuous male homosexuality, intravenous drug use, or hemophilia. Since AIDS also correlates with antibody to a retrovirus, confirmed in about 40% of American cases, it has been hypothesized that this virus causes AIDS by killing T cells. Consequently, the virus was termed human immunodeficiency virus (HIV), and antibody to HIV became part of the definition of AIDS. The hypothesis that HIV causes AIDS is examined in terms of Koch's postulates and epidemiological, biochemical, genetic, and evolutionary conditions of viral pathology. HIV does not fulfill Koch's postulates: (i) free virus is not detectable in most cases of AIDS; (ii) virus can only be isolated by reactivating virus in vitro from a few latently infected lymphocytes among millions of uninfected ones; (iii) pure HIV does not cause AIDS upon experimental infection of chimpanzees or accidental infection of healthy humans. Further, HIV violates classical conditions of viral pathology. (i) Epidemiological surveys indicate that the annual incidence of AIDS among antibody-positive persons varies from nearly 0 to over 10%, depending critically on nonviral risk factors. (ii) HIV is expressed in less than or equal to 1 of every 10(4) T cells it supposedly kills in AIDS, whereas about 5% of all T cells are regenerated during the 2 days it takes the virus to infect a cell. (iii) If HIV were the cause of AIDS, it would be the first virus to cause a disease only after the onset of antiviral immunity, as detected by a positive "AIDS test." (iv) AIDS follows the onset of antiviral immunity only after long and unpredictable asymptomatic intervals averaging 8 years, although HIV replicates within 1 to 2 days and induces immunity within 1 to 2 months. (v) HIV supposedly causes AIDS by killing T cells, although retroviruses can only replicate in viable cells. In fact, infected T cells grown in culture continue to divide. (vi) HIV is isogenic with all other retroviruses and does not express a late, AIDS-specific gene. (vii) If HIV were to cause AIDS, it would have a paradoxical, country-specific pathology, causing over 90% Pneumocystis pneumonia and Kaposi sarcoma in the U.S. but over 90% slim disease, fever, and diarrhea in Africa.(viii) It is highly improbable that within the last few years two viruses (HIV-1 and HIV-2) that are only 40% sequence-related would have evolved that could both cause the newly defined syndrome AIDS. Also, viruses are improbable that kill their only natural host with efficiencies of 50-100%, as is claimed for HIVs. It is concluded that HIV is not sufficient for AIDS and that it may not even be necessary for AIDS because its activity is just as low in symptomatic carriers as in asymptomatic carriers. The correlation between antibody to HIV and AIDS does not prove causation, because otherwise indistinguishable diseases are now set apart only on the basis of this antibody. I propose that AIDS is not a contagious syndrome caused by one conventional virus or microbe. No such virus or microbe would require almost a decade to cause primary disease, nor could it cause the diverse collection of AIDS diseases. Neither would its host range be as selective as that of AIDS, nor could it survive if it were as inefficiently transmitted as AIDS. Since AIDS is defined by new combinations of conventional diseases, it may be caused by new combinations of conventional pathogens, including acute viral or microbial infections and chronic drug use and malnutrition. The long and unpredictable intervals between infection with HIV and AIDS would then reflect the thresholds for these pathogenic factors to cause AIDS diseases, instead of an unlikely mechanism of HIV pathogenesis.     

Adjustment for smoking does not alter the FOXO3A association with longevity

GeroScience - Human longevity is a multifactorial phenotype influenced by both genetic and environmental factors. Despite its heritability of 25–32 %, the genetic background of...     

Simpson's paradox and clinical trials: what you find is not necessarily what you prove.

Expensive clinical trials have become the gold standard for evaluating the efficacy of promising new therapeutic agents. Full exploration of the collected data is routine to maximize the yield of the information available. However, potential methodologic flaws in these extensive analyses may not be appreciated by investigators or readers. One such problem with subgroup analyses is discussed, using hypothetical examples and data from a recently completed clinical trial of brain resuscitation as illustrations.     

The association of autoimmune diseases with pediatric ulcerative colitis does not influence its disease course

Objective. Ulcerative colitis (UC) is a chronic inflammatory condition. Previous reports suggested that UC may have a worse prognosis when associated with auto-immune diseases. We compared characteristics at diagnosis and natural history of the disease between classical ulcerative colitis (CUC) and UC associated with auto-immune diseases (CAI) in children. Material and methods. In this study, 67 children followed for UC at Nancy University Hospital between 1993 and 2012 were included: 45 patients in the CUC group and 22 in the CAI group. Results. Median follow-up was 4.8 years. Median age at diagnosis was 11.6 years in the CAI group and 9.8 years in the CUC group. Time between symptoms onset and diagnosis was broadly similar in the two groups (<3 months) and there were no significant differences regarding biological and histological findings. At 5 years, the need for corticosteroids and azathioprine did not differ between the CAI and the CUC groups. There was also no significant difference between the two groups regarding infliximab use at 1 and 5 years. Conclusions. In this pediatric study, CAI had similar characteristics at baseline as CUC. The course of CAI does not seem to be influenced by the presence of concomitant auto-immune diseases.     

Renoprotective RAAS inhibition does not affect the association between worse renal function and higher plasma aldosterone levels

Background

Aldosterone is elevated in chronic kidney disease (CKD) and may be involved in hypertension. Surprisingly, the determinants of the plasma aldosterone concentration (PAC) and its role in hypertension are not well studied in CKD. Therefore, we studied the determinants of aldosterone and its association with blood pressure in CKD patients. We also studied this during renin-angiotensin-aldosterone system inhibition (RAASi) to establish clinical relevance, as RAASi is the treatment of choice in CKD with albuminuria.

Methods

We performed a post-hoc analysis on data from a randomized controlled double blind cross-over trial in non-diabetic CKD patients (n =?33, creatinine clearance (CrCl) 85 (75–95) ml/min, proteinuria 3.2 (2.5–4.0) g/day). Patients were treated with losartan 100 mg (ARB), and ARB?+?hydrochlorothiazide 25 mg (HCT), during both a regular (200?±?10 mmol Na⁺/day) and low (89?±?8 mmol Na⁺/day) dietary sodium intake, in 6-week study periods. PAC data at the end of each study period were analyzed. The association between PAC and blood pressure was analyzed continuously, and according to PAC above or below the median.

Results

Lower CrCl was correlated with higher PAC during placebo as well as during ARB (β?=??1.213, P =?0.008 and β?=??1.090, P =?0.010). Higher PAC was not explained by high renin, illustrated by a comparable association between CrCl and the aldosterone-to-renin ratio. The association between lower CrCl and higher PAC was also found in a second study with single RAASi with ACE inhibition (ACEi; lisinopril 40 mg/day), and dual RAASi (lisinopril 40 mg/day + valsartan 320 mg/day). Higher PAC was associated with a higher systolic blood pressure (P?=?0.010) during different study periods. Only during maximal treatment with ARB?+?HCT?+?dietary sodium restriction, blood pressure was no longer different in subjects with a PAC above and below the median.

Conclusions

In CKD patients with a standardized regular sodium intake, worse renal function is associated with a higher aldosterone, untreated and during RAASi with either ARB, ACEi, or both. Furthermore, higher aldosterone is associated with higher blood pressure, which can be treated with the combination of RAASi, HCT and dietary sodium restriction.The first study was performed before it was standard to register trials and the study was not retrospectively registered. The second study was registered in the Netherlands Trial Register on the 5th of May 2006 (NTR675).