Albert M. Vollaard

Self-rated health and physician-rated health as independent predictors of mortality in elderly men

BACKGROUND When assessing health status, physicians may focus on objective symptoms and diagnoses, whereas individuals may focus more on subjective symptoms, functional limitations and quality of life. METHODS In the Zutphen Elderly Study, 710 community-living men (aged 64-84 years) were followed until death for 15 years. Self-rated health was assessed through a single-item question. Physician-rated health was estimated on a Likert scale by physicians after medical history assessment and physical examination. Both health ratings were categorised into three groups. All-cause, cardiovascular and cancer mortality rates were analysed in Cox proportional-hazards models. RESULTS There were 352 (49.6%) men who felt healthy and 225 (31.7%) men with a good physician-rated health. During 15 years of follow-up 503 of 710 men (70.8%) died, of whom 229 (45.5%) from cardiovascular causes and 144 (28.6%) from cancer. Self-rated and physician-rated health both predicted independently all-cause mortality (hazard ratios [HR] for worst vs. best health category: 1.72; 95% confidence interval [CI]: 1.26-2.33, and 1.77; 95% CI: 1.36-2.29; respectively; P-values of <0.005). When self-rated and physician-rated health were discordant, mortality risk was highest when physicians had a less favourable view on the health status than the participant. Self-rated health predicted independently cancer mortality (HR 2.41), whereas physician-rated health cardiovascular mortality (HR 2.13). CONCLUSION Self-rated and physician-rated health status predicted both all-cause mortality, and showed a differential pattern for cancer and cardiovascular diseases mortality.

Susceptibility to typhoid fever is associated with a polymorphism in the cystic fibrosis transmembrane conductance regulator (CFTR)

The cystic fibrosis transmembrane conductance regulator (CFTR) is the affected protein in cystic fibrosis (CF). The high rate of CF carriers has led to speculation that there must be, similar to the sickle cell haemoglobin advantage in malaria, a selective advantage for heterozygotes. Such a selective advantage may be conferred through reduced attachment of Salmonella typhi to intestinal mucosa, thus providing resistance to typhoid fever. We tested this hypothesis by genotyping patients and controls in a typhoid endemic area in Indonesia for two highly polymorphic markers in CFTR and the most common CF mutation. We found an association between genotypes in CFTR and susceptibility to typhoid fever (OR=2.6). These analyses suggest that the role CFTR plays in vitro in S. typhi infection is also important for infection in the human population.

Expression and Function of S100A8/A9 (Calprotectin) in Human Typhoid Fever and the Murine Salmonella Model

Background Typhoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8) and S100A9 (MRP14) form bioactive antimicrobial heterodimers (calprotectin) that can activate Toll-like receptor 4, promoting lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize the expression and function of S100A8/A9 in patients with typhoid fever and in a murine invasive Salmonella model. Methods and principal findings S100A8/A9 protein levels were determined in acute phase plasma or feces from 28 Bangladeshi patients, and convalescent phase plasma from 60 Indonesian patients with blood culture or PCR-confirmed typhoid fever, and compared to 98 healthy control subjects. To functionally characterize the role of S100A8/A9, we challenged wildtype (WT) and S100A9-/- mice with S. Typhimurium and determined bacterial loads and inflammation 2- and 5- days post infection. We further assessed the antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi replication in vitro. Typhoid fever patients demonstrated a marked increase of S100A8/A9 in acute phase plasma and feces and this increases correlated with duration of fever prior to admission. S100A8/A9 directly inhibited the growth of S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both the liver and the systemic compartment but S100A9-/- mice were indistinguishable from WT mice with respect to bacterial growth, survival, and inflammatory responses, as determined by cytokine release, histopathology and organ injury. Conclusion S100A8/A9 is markedly elevated in human typhoid, correlates with duration of fever prior to admission and directly inhibits the growth of S. Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive Salmonella model, S100A8/A9 does not contribute to an effective host response against S. Typhimurium in mice.

Helicobacter pylori infection and typhoid fever in Jakarta, Indonesia.

We evaluated the association between typhoid fever and Helicobacter pylori infection, as the latter microorganism may influence gastric acid secretion and consequently increase susceptibility to Salmonella typhi infection. Anti-H. pylori IgG and IgA antibody titres (ELISA) and gastrin concentration (RIA) were determined in the plasma of 87 blood culture-confirmed typhoid fever cases (collected after clinical recovery) and 232 random healthy controls without a history of typhoid fever, in the Jatinegara district, Jakarta. Patients with typhoid fever more often than controls were seropositive for H. pylori IgG (67% vs. 50%, P<0.008), when antibody titres were dichotomized around median titres observed in controls. H. pylori IgA seropositivity was not associated with typhoid fever. Plasma gastrin concentrations indicative of hypochlorhydria (i.e. gastrin > or =25 or > or =100 ng/l) were not significantly elevated in typhoid fever cases compared to controls (P=0.54 and P=0.27 respectively). In a multivariate analysis, typhoid fever was independently associated with young age (<33 years, median age of the controls) [odds ratio (OR) 7.93, 95% confidence interval (CI) 3.90-16.10], and H. pylori IgG seropositivity (OR 1.93, 95% CI 1.10-3.40). Typhoid fever was independently associated with H. pylori IgG seropositivity, but not with elevated gastrin concentration. Therefore, the association suggests a common risk of environmental exposure to both bacteria, e.g. poor hygiene, rather than a causal relationship via reduced gastric acid production.

Diabetes and the Course of Febrile Urinary Tract Infection

Diabetes is considered a risk factor for acquisition of febrile urinary tract infection (UTI) (1,2), but there is a lack of information on the association of diabetes with the subsequent course of disease and its outcome. We performed a prospective observational multicenter cohort study including consecutive adults with community-onset febrile UTI presenting at 7 emergency departments and 35 primary care centers. The effect of preexisting diabetes on presentation and microbiological and clinical outcome was assessed and multivariable logistic regression performed to establish whether diabetes was an independent risk factor for a complicated course. View this table: Table 1 Baseline characteristics of 858 patients presenting with febrile UTI Of 858 patients, 140 had diabetes (93% type 2 diabetes), of whom 41 (30%) used insulin, 19 (14%) were managed by diet only, and the remaining were managed by a combination of metformin, insulin, and diet. Patients with diabetes were older (median age 73 years [interquartile range {IQR} 46–78] vs. 64 [IQR 42–77], P < 0.001), were more frequently male (48 vs. 35%, P = 0.006), and had a higher …

Clinical use of a prediction rule to guide admission policy in community-acquired invasive urinary tract infection: a randomized clinical trial

A total of 370 patients were included, 237 in the control period and 133 in the intervention period. Use of PRACTICE significantly reduced the primary hospitalization rate (from 92%, in the control group to 72%, in the intervention group, p <0.01). The secondary hospital admission rate after initial outpatient treatment was 6% in control patients and 27% in intervention patients (1/17 and 10/37; p<0.001). In none of these secondary admissions intensive care treatment was required, and no complications were noted. Introduction

Antimicrobiële resistentie – het klinisch perspectief

SamenvattingAntibiotica zijn hulpmiddelen van het afweersysteem. Het is daarom niet verwonderlijk dat antibiotica resistentie van bacteriën in het ziekenhuis vooral een bedreiging vormt voor personen met een ernstig onderliggend lijden dat ook de afweer onderdrukt, zoals bijv. patiënten die op de intensive care afdeling worden verzorgd, chemotherapie voor kanker krijgen, en hen die afweeronderdrukkende geneesmiddelen krijgen zoals orgaantransplantatiepatiënten. Deze vaak zieke patiënten ontberen een normaal afweersysteem en missen de mogelijkheid zich tegen infectieziekten te verdedigen, zodat ze gemakkelijker een infectie oplopen, vaak met laag pathogene micro-organismen, en als dat gebeurt toch ernstig ziek worden. De arts zal ze uit voorzorg vaker antibiotica voorschrijven, al bij vermoeden op een infectie. Doordat vaker antibiotica wordt voorgeschreven is de kans op selectie en kolonisatie, en infectie door resistente bacteriën verhoogd, wat er weer toe leidt dat de gebruikelijke standaard-antibiotica niet langer werken, en lastresort antibiotica voorgeschreven worden. Hiermee is een negatieve spiraal geïnitieerd. De antibiotica die in richtlijnen als eerste keus worden aanbevolen, blijken onwerkzaam, zodat andere antibiotica gebruikt moeten worden die vaak minder effectief zijn, of meer bijwerkingen oproepen. Kortom, de gevolgen van multidrug resistente bacteriën worden vooral gevoeld onder de al kwetsbare ziekenhuispatiënten met onderliggende medische condities. De gevolgen zijn een toegenomen morbiditeit, meer complexe ziekenhuisopnames, en toegenomen sterfte.