Effect of age and care organization on sources of variation in kidney transplant waiting list registration

Despite national guidelines, medical practices and kidney transplant waiting list registration policies may differ from one dialysis/transplant unit to another. Benefit risk assessment variations, especially for elderly patients, have also been described. The aim of this study was to identify sources of variation in early kidney transplant waiting list registration in France. Among 16 842 incident patients during the period 2016–2017, 4386 were registered on the kidney transplant waiting list at the start of, or during the first year after starting, dialysis (26%). We developed various log-linear mixed effect regression models on three levels: patients, dialysis networks, and transplant centers. Variability was expressed as variance from the random intercepts (± standard error). Although patient characteristics have an important impact on the likelihood of registration, the overall magnitude of variability in registration was low and shared by dialysis networks and transplant centers. Between-transplant center variability (0.23 ± 0.08) was 1.8 higher than between-dialysis network variability (0.13 ± 0.004). Older age was associated with a lower probability of registration and greater variability between networks (0.04, 0.20, & 0.93 in the 18–64, 65–74, and 75–84 age groups). Targeted interventions should focus on elderly patients and/or certain regions with greater variability in waiting list access.     

Detection of Mycoplasma pneumoniae in serum specimens from patients with mycoplasma pneumonia by PCR

There are few data on detection of Mycoplasma pneumoniae from blood, serum or plasma, and systematic studies on this diagnostic approach in community-acquired pneumonia (CAP) are scarce. Compared to testing respiratory specimens, this approach has the advantages that it is less dependent on proper specimen collection, serum is easily stored and handled, and the pathogen is detected in a primary sterile site, where colonization can be ruled out. In this study, acute-phase serum specimens from 29 patients of Vienna University Hospital (treated between 11/1994 and 6/2004; female: 14, male: 15; median age: 31 years, range: 15-66 years) with CAP and serologically verified M. pneumoniae infection, who had not received anti-mycoplasma therapy prior to serum collection, were tested for M. pneumoniae by conventional PCR and real-time PCR. Conventional PCR yielded negative results for all specimens, but real-time PCR detected M. pneumoniae in 15/29 patient sera (52%). These findings indicate that M. pneumoniae is present in the bloodstream of a substantial proportion of patients with mycoplasma pneumonia. Despite the possible adherence of M. pneumoniae to human erythrocytes, the pathogen can be detected from serum, if a method with enhanced sensitivity is applied. However, the negative predictive value of PCR from serum with regard to etiological diagnosis is low. With regard to the potential clinical benefit of blood-based PCR diagnosis of mycoplasma pneumonia the diagnostic accuracy of this approach using either serum or whole-blood specimens should be addressed by large-scale studies.     

Characterization of soluble platelet guanylyl cyclase with peptide antibodies

Summary Soluble guanylyl cyclase partially purified from bovine and human platelets was characterized with antibodies raised against synthetic peptides corresponding to different sequences of the ₁- and ₁-subunits of the bovine lung enzyme. On immunoblots, the platelet guanylyl cyclase was recognized by the four antisera used, with the exception of an antiserum against the C-terminus of the ₁-subunit which did not react with the human platelet but with the bovine platelet ₁-subunit. Furthermore the human platelet ₁-subunit exhibited a slightly lower molecular mass than the bovine protein. The C-terminal antibodies precipitated native platelet and lung guanylyl cyclase activity. In contrast an antibody against a peptide out of the putative catalytic domain, which is highly conserved between all guanylyl cyclases sequenced so far, did not precipitate native guanylyl cyclase, although it recognized both subunits on immunoblots, suggesting that the respective amino acid sequence is located in an inner site of the protein.Abbreviations GC_pep2 YGPEVWEDIKKEA (one letter code) - GC_pep3 SRKNTGTEETEQDEN - GC_pep5 VYKVETVGDKYMTVSGLP - GC_pep8 KKDVEEANANFLGKASGID - TBS-T Tris-buffered saline, containing 0.0501o Tween 20 Correspondence to E. Böhme at the above address     

Evaluating thyroid gland function in patients with protein anomalies

The euthyroid hyperthyroxinemia (EHT) is characterized on the one hand by a normal basal THS or TRH-TSH response but also by high plasma values of total thyroxine (TT4) on the other. However if only TT4 is assessed, "hyperthyroidism" may be diagnosed erroneously. EHT may be caused by an increase of specific thyroxine binding proteins which may be hereditary (permanent) or acquired (transient). The most frequent disturbance is due to an estrogen induced increase of thyroxine binding globulin (TBG) in the course of pregnancy, anticonceptive drugs or estrogen treatment. The albumin associated HT (FDH syndrome), first reported in 1979, has autosomal dominant traits. 144 patients with FDH syndrome were observed during the period between 1984 and 1990, i.e. 7% (1986) of all hyperthyroid patients explored. Family screening is required to prevent unjustified treatment. Additionally existing disturbances of thyroid function as well as other protein binding anomalies may both cause problems in differential diagnosis. Prealbumin associated hyperthyroxinemia (PAAH), first published in 1982, may be due to an inherited increase in affinity, but may also be the consequence of a true elevation of prealbumin plasma concentration in the course of an islet cell cancer; both conditions are extremely rare. Nearly as rare are patients with plasma autoantibodies directed against T4 and/or T3 (5 cases); yet, a reverse T3 autoantibody could be observed in merely 1 case. By means of our modified radio-thyroxine-agarosegel-iceelectrophoresis all such protein anomalies may be diagnosed and differentiated in 1 procedure. Moreover, all other types of EHT must be taken into consideration by differential diagnosis.     

Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment.

PURPOSE: To evaluate the time course of therapy-induced changes in tumor glucose use during chemoradiotherapy of esophageal squamous cell carcinoma (ESCC) and to correlate the reduction of metabolic activity with histopathologic tumor response and patient survival. PATIENTS AND METHODS: Thirty-eight patients with histologically proven intrathoracic ESCC (cT3, cN0/+, cM0) scheduled to undergo a 4-week course of preoperative simultaneous chemoradiotherapy followed by esophagectomy were included. Patients underwent positron emission tomography with the glucose analog fluorodeoxyglucose (FDG-PET) before therapy (n = 38), after 2 weeks of initiation of therapy (n = 27), and preoperatively (3 to 4 weeks after chemoradiotherapy; n = 38). Tumor metabolic activity was quantitatively assessed by standardized uptake values (SUVs). Results Mean tumor FDG uptake before therapy was 9.3 +/- 2.8 SUV and decreased to 5.7 +/- 1.9 SUV 14 days after initiation of chemoradiotherapy (-38% +/- 18%; P <.0001). The preoperative scan showed an additional decrease of metabolic activity to 3.3 +/- 1.1 SUV (P <.0001). In histopathologic responders (< 10% viable cells in the resected specimen), the decrease in SUV from baseline to day 14 was 44% +/- 15%, whereas it was only 21% +/- 14% in nonresponders (P =.0055). Metabolic changes at this time point were also correlated with patient survival (P =.011). In the preoperative scan, tumor metabolic activity had decreased by 70% +/- 11% in histopathologic responders and 51% +/- 21% in histopathologic nonresponders. CONCLUSION: Changes in tumor metabolic activity after 14 days of preoperative chemoradiotherapy are significantly correlated with tumor response and patient survival. This suggests that FDG-PET might be used to identify nonresponders early during neoadjuvant chemoradiotherapy, allowing for early modifications of the treatment protocol.     

Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study.

PURPOSE: To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain. PATIENTS AND METHODS: Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks. RESULTS: A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups. CONCLUSION: Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.     

Glutathione S-transferases M1, T1, and P1 and breast cancer: a pooled analysis.

The glutathione S-transferase (GST) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the genes GSTM1 and GSTT1 and a base transition polymorphism at codon 105 (Ile-->Val) in GSTP1 were investigated in relation to breast cancer risk. Tobacco smoking and reproductive factors were examined as potential effect modifiers. Individual data from seven case-control studies were pooled within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens. To measure the effect of GSTs on breast cancer risk, odds ratios and 95% confidence intervals were computed adjusting for study center and age. The modifying effect was investigated by stratification on variables of smoking habits and reproductive history. A total of 2,048 cases with breast cancer and 1,969 controls were analyzed. The relative odds ratio (95% confidence interval) of breast cancer was 0.98 (0.86-1.12) with the GSTM1 null, 1.11 (0.87-1.41) with the GSTT1 null, 1.01 (0.79-1.28) with GSTP1 heterozygous mutants, and 0.93 (0.62-1.38) with GSTP1 homozygous mutants. Stratification by smoking or reproductive factors did not reveal a modifying effect of these variables, nor was there any association between GSTM1 and age at diagnosis of breast cancer. This is the largest study investigating susceptibility to breast cancer due to polymorphisms in the GST genes. The results conclusively show that single gene GST polymorphisms do not confer a substantial risk of breast cancer to its carriers. Furthermore, GSTs did not interact with smoking or reproductive history to modify cancer risk.     

Urinary pharmacokinetics of betalains following consumption of red beet juice in healthy humans.

The aim of the present pilot study was to characterise the renal elimination of betalains after consumption of red beet juice (RBJ). Six healthy, non-smoking female volunteers were given a single oral dose of either 500 mL of a commercial RBJ containing 362.7 mg of betalains and 500 mL of tap water, respectively, in a sequential manner. Urine was collected in intervals up to 24 h post-dose. Renal excretion of betalains was determined spectrophotometrically and quantified as betanin-equivalents. In addition, the identity of individual compounds was confirmed by HPLC coupled with diode-array detection and positive ion electrospray mass spectrometry, respectively. The amount (mean+/-S.D.) of intact betalains (betanin and isobetanin) recovered in urine was 1001+/-273 microg corresponding to 0.28+/-0.08% of the administered dose. Maximum excretion rates were observed after a median tmax,R of 3.0 h (range 2.5-8.0 h) amounting to 91.7+/-30.1 microg/h. The terminal elimination rate constant (lambdaz) and the corresponding half-life were 0.097+/-0.021 h(-1) and 7.43+/-1.47 h, respectively. Using the lambdaz estimates obtained the expected total betalain amount excreted in urine was 1228+/-291 microg. Based on the results obtained it is assumed that either the bioavailability of the betalains is low or that renal clearance is a minor route of systemic elimination for these compounds. The urinary excretion rates of unmetabolised betalains were fast and appeared to be monoexponential suggesting a one-compartment model. In order to get a more complete picture of the pharmacokinetics and health-promoting properties of red beet betalains, quantitative data on betalain bioavailability should include measurements of unchanged compounds and their corresponding metabolites in plasma, urine and bile.     

Evolution and conservation of microsatellite markers for Leishmania tropica.

Sixteen polymorphic microsatellite markers were developed for phylogenetic analysis of Leishmania tropica. The phylogenetic tests done demonstrated that they do provide a powerful tool for epidemiological studies. They were also tested for their ability to differentiate strains of other species of Leishmania, confirming that microsatellite markers developed for one leishmanial species cannot generally be used for other leishmanial species. In addition to length variation, a high degree of allelic heterozygosity was seen among the strains investigated, suggestive of sexual recombination within the species L. tropica.