Advance orders to limit therapy in 67 long-term care facilities in Finland

OBJECTIVE: To assess the documentation of a do-not-attempt-resuscitation (DNAR) or do-not-hospitalize (DNH) orders in the medical record and to determine factors related to these orders. MATERIALS AND METHODS: Five thousand six hundred and fifty four subjects from three different levels of institutional long-term care (LTC), chronic care hospitals (n = 1989), nursing homes (n = 3310), and assisted living (n = 335) in 67 LTC facilities in 19 municipalities were assessed. RESULTS: Out of these patients, 751 (13%) had a DNAR order and only 36 (0.6%) had a DNH order. The variation in DNAR orders between individual LTC institutions was enormous, ranging from 0 to 92%. In logistic regression analysis, individual institutions and their local caring cultures had the strongest explanatory value (R(2) = 0.49) for advance orders to limit therapy. Impaired activity in daily living (ADL) function (R(2) = 0.11), impaired cognition (R(2) = 0.07), level of LTC (R(2) = 0.05), and diagnoses (R(2) = 0.04) did not provide adequate explanations. Terminal prognosis was not significantly associated with advance orders. CONCLUSIONS: We found marked differences in the use of DNAR and DNH orders between caring units. Diseases and ADL status were only weakly significant as background factors. Open discussions, general guidelines, and research about the adequacy of DNAR decisions are needed to improve equality and self-empowerment among the elderly residing in institutions.     

Proinflammatory HLA-DRB1*01-haplotype predisposes to ST-elevation myocardial infarction

BackgroundMajor histocompatibility complex (MHC) gene region harbours haplotypes that associate with coronary artery disease (CAD). Their role in ST-elevation infarction (STEMI) or on the inflammatory level is not known.MethodsFour candidate MHC markers were analyzed by real-time quantitative PCR and constructed into haplotypes from patients with STEMI (n = 162), matched controls with no CAD (n = 319) and general population sample (n = 149). High sensitivity C-reactive protein (hsCRP) was assessed in a follow-up visit from patients (n = 86) and at inclusion from other study subjects.ResultsThe haplotype with one copy of HLA-DRB1*01, C4A, C4B but no HLA-B*35 doubled the risk of STEMI (OR = 2.15, 95%CI = 1.11–4.15, p = 0.020 for patients vs. controls, and OR = 2.26, 95%CI = 0.97–5.24, p = 0.052 for patients vs. population sample). The association between patients and controls persisted in multivariate analyses. The frequency of the haplotype was 5.86% (n = 19/324) in patients, 2.82% (n = 18/638) in controls and 2.68% (n = 8/298) in population sample. None of the individual MHC markers alone showed significant association with STEMI.In multivariate analyses, the haplotype carriers had higher hsCRP levels in patients (median 3.37 mg/L in carriers vs. 1.14 mg/L in non-carriers, p = 0.019) and in controls (median 2.90 mg/L vs. 1.21 mg/L, p = 0.009, respectively).ConclusionThe MHC haplotype associates with STEMI and elevated baseline hsCRP levels. The results are in concordance with previous data on non-STEMI patients, implying that a HLA-DRB1*01 – related haplotype increases the risk of CAD, possibly though increased inflammation.     

Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia — significance for activation of the kynurenine pathway

Background

Accumulating evidence indicates that schizophrenia is associated with brain immune activation. While a number of reports suggest increased cytokine levels in patients with schizophrenia, many of these studies have been limited by their focus on peripheral cytokines or confounded by various antipsychotic treatments. Here, well-characterized patients with schizophrenia, all receiving olanzapine treatment, and healthy volunteers were analyzed with regard to cerebrospinal fluid (CSF) levels of cytokines. We correlated the CSF cytokine levels to previously analyzed metabolites of the kynurenine (KYN) pathway.

Methods

We analyzed the CSF from patients and controls using electrochemiluminescence detection with regard to cytokines. Cell culture media from human cortical astrocytes were analyzed for KYN and kynurenic acid (KYNA) using high-pressure liquid chromatography or liquid chromatography/mass spectrometry.

Results

We included 23 patients and 37 controls in our study. Patients with schizophrenia had increased CSF levels of interleukin (IL)-6 compared with healthy volunteers. In patients, we also observed a positive correlation between IL-6 and the tryptophan:KYNA ratio, indicating that IL-6 activates the KYN pathway. In line with this, application of IL-6 to cultured human astrocytes increased cell medium concentration of KYNA.

Limitations

The CSF samples had been frozen and thawed twice before analysis of cytokines. Median age differed between patients and controls. When appropriate, all present analyses were adjusted for age.

Conclusion

We have shown that IL-6, KYN and KYNA are elevated in patients with chronic schizophrenia, strengthening the idea of brain immune activation in patients with this disease. Our concurrent cell culture and clinical findings suggest that IL-6 induces the KYN pathway, leading to increased production of the N-methyl-d-aspartate receptor antagonist KYNA in patients with schizophrenia.     

Psychotropic drug use in non-psychiatric departments of three European university hospitals

The use of psychotropic drugs in the university hospitals in Tartu, Estonia; Huddinge, Sweden; and Badajoz, Spain, were studied, using the defined daily doses per 100 bed-days (DDD/100 bed-days) method. The total amount of drugs used in the surgical and medical departments was 50 DDD/100 bed-days in Huddinge, versus 33 and 14 DDD/100 bed-days in Tartu and Badajoz, respectively. Barbiturates accounted for 35% of all psychotropics in Tartu but were practically not used in Huddinge. In contrast, antidepressants were practically not used in Tartu. The use of psychotropic drugs in the intensive care units was highest in Huddinge (320 DDD/100 bed-days), compared with Tartu and Badajoz (177 and 96 DDD/100 bed-days, respectively). The frequency of psychotropic drug use were strikingly different in the three hospitals studied.     

Spontaneous mutation frequency and emergence of ciprofloxacin resistance in Campylobacter jejuni and Campylobacter coli

OBJECTIVES: We analysed the contribution of spontaneous mutation frequency to the evolution of ciprofloxacin resistance and the diversity of mutations in the quinolone resistance-determining region (QRDR) of gyrA and in the intergenic region, cmeR-cmeA, of the CmeABC efflux pump in Campylobacter jejuni and Campylobacter coli. METHODS: The mutation frequency was measured in 11 quinolone-susceptible C. jejuni and 5 C. coli strains, with and without ox bile. MICs and target-specific and efflux-associated mutations were studied for a number of colonies of each strain selected from plates containing 1 mg/L ciprofloxacin. RESULTS: The spontaneous mutation frequency level among susceptible C. jejuni and C. coli strains ranged from hypomutable (approximately 4 x 10(-9)) to strongly mutable (approximately 7 x 10(-3)). Ox bile had no effect on mutation frequency. Pre-existing ampicillin and tetracycline resistance increased the MICs of ciprofloxacin for two strains from 0.032-0.125 to 0.5 mg/L. MICs of ciprofloxacin for the colonies selected from plates containing 1 mg/L ciprofloxacin varied from 1 to 16 mg/L, with the Thr-86-->Ile or Asp-90-->Asn mutation detected in the QRDR of gyrA. In 21.5% (14/65) of the selected colonies, no specific mutations existed. Two types of mutations in CmeR promoter-binding inverted sequences were identified both in the parent strains and in the colonies selected from ciprofloxacin plates. CONCLUSIONS: The variation in mutation frequencies between most C. jejuni and C. coli strains was up to 700-fold. Mutation in the QRDR of gyrA or in the intergenic region was not associated with differences in spontaneous mutation frequencies. Previously acquired resistance to tetracycline and ampicillin predisposed strains to high-level ciprofloxacin resistance and to multiple antibiotic resistance.