Incidence and determinants of high-sensitivity troponin and natriuretic peptides elevation at admission in hospitalized COVID-19 pneumonia patients.

BACKGROUND: Myocardial involvement in the course of coronavirus disease 2019 (COVID-19) pneumonia has been reported, though not fully characterized yet. The aim of the present study is to undertake a joint evaluation of hs-Troponin and natriuretic peptides (NP) in patients hospitalized for COVID-19 pneumonia. METHODS: In this multicenter observational study, we analyzed data from n = 111 patients. Cardiac biomarkers subgroups were identified according to values beyond reference range. RESULTS: Increased hs-Troponin and NP were found in 38 and 56% of the cases, respectively. As compared to those with normal cardiac biomarkers, these patients were older, had higher prevalence of cardiovascular diseases (CVD) and had more severe COVID-19 pneumonia by higher CRP and D-dimer and lower PaO2/FIO2. Two-dimensional echocardiography performed in a subset of patients (n = 24) showed significantly reduced left ventricular ejection fraction in patients with elevated NP (p = 0.02), whereas right ventricular systolic function (tricuspid annular plane systolic excursion) was significantly reduced both in patients with high hs-Troponin and NP (p = 0.022 and p = 0.03, respectively). Both hs-Troponin and NP were higher in patients with in-hospital mortality (p = 0.001 and p = 0.002, respectively). On multivariable analysis, independent associations were found of hs-Troponin with age, PaO2/FIO2 and D-dimer (B = 0.419, p = 0.001; B = - 0.212, p = 0.013; and B = 0.179, p = 0.037, respectively) and of NP with age and previous CVD (B = 0.480, p < 0.001; and B = 0.253, p = 0.001, respectively). CONCLUSIONS: Myocardial involvement at admission is common in COVID-19 pneumonia. Independent associations of hs-Troponin with markers of disease severity and of NP with underlying CVD might point toward existing different mechanisms leading to their elevation in this setting.

265 Incidence, determinants and prognostic relevance of HS-troponin and natriuretic peptides elevation at admission in hospitalized COVID-19 pneumonia patients.

Aims: myocardial involvement in the course of Coronavirus disease 2019 (COVID-19) pneumonia has been reported, though not fully characterized yet. Aim of the present study is to undertake a joint evaluation of hs-Troponin and natriuretic peptides (NP) in patients hospitalized for COVID-19 pneumonia. Methods and results: in this multicenter observational study, we analyzed data from n = 111 COVID-19 patients admitted to dedicated "COVID-19" medical units. Hs-Troponin was assessed in n = 103 patients and NP in n = 82 patients on admission; subgroups were identified according to values beyond reference range. increased hs-Troponin and NP were found in 38% and 56% of the cases respectively. As compared to those with normal cardiac biomarkers, these patients were older, had higher prevalence of cardiovascular diseases (CVD) and more severe COVID-19 pneumonia by higher CRP and D-dimer and lower PaO2/FIO2. Two-dimensional echocardiography performed in a subset of patients (n = 24) showed significantly reduced left ventricular ejection fraction in patients with elevated NP only (p = 0.02), whereas right ventricular systolic function (tricuspid annular plane systolic excursion) was significantly reduced both in patients with high hs-Troponin and NP (p = 0.022 and p = 0.03 respectively). On multivariable analysis, independent associations were found of hs-Troponin with age, PaO2/FIO2 and D-dimer (B = 0.419, p = 0.001; B=-0.212, p = 0.013 and B = 0.179, p = 0.037 respectively), and of NP with age and previous CVD (B = 0.480, p < 0.001 and B = 0.253, p = 0.001 respectively). In patients with in-hospital mortality (n = 23, 21%) hs-Troponin and NP were both higher (p = 0.001 and p = 0.002 respectively), while increasing hs-troponin and NP were associated with worse in-hospital prognosis [OR 4.88 (95% CI 1.9-12.2), p = 0.001 (adjusted OR 3.1 (95% CI 1.2-8.5), p = 0.025) and OR 4.67 (95% CI 2-10.8), p < 0.001 (adjusted OR 2.89 (95% CI 1.1-7.9), p = 0.04) respectively]. Receiver operator characteristic curves showed good ability of hs-Troponin and NP in predicting in-hospital mortality (AUC = 0.869 p < 0.001 and AUC = 0.810, p < 0.001 respectively). Conclusion: myocardial involvement at admission is common in COVID-19 pneumonia and associated to worse prognosis, suggesting a role for cardiac biomarkers assessment in COVID-19 risk stratification. Independent associations of hs-Troponin with markers of disease severity and of NP with underlying CVD might point towards existing different mechanisms leading to their elevation in this setting.

The impact of electronic health records on healthcare quality: a systematic review and meta-analysis.

OBJECTIVE: To assess the impact of electronic health record (EHR) on healthcare quality, we hence carried out a systematic review and meta-analysis of published studies on this topic. METHODS: PubMed, Web of Knowledge, Scopus and Cochrane Library databases were searched to identify studies that investigated the association between the EHR implementation and process or outcome indicators. Two reviewers screened identified citations and extracted data according to the PRISMA guidelines. Meta-analysis was performed using the random effects model for each indicator. Heterogeneity was quantified using the Cochran Q test and I2 statistics, and publication bias was assessed using the Egger's test. RESULTS: Of the 23 398 citations identified, 47 articles were included in the analysis. Meta-analysis showed an association between EHR use and a reduced documentation time with a difference in mean of -22.4% [95% confidence interval (CI) = -38.8 to -6.0%; P < 0.007]. EHR resulted also associated with a higher guideline adherence with a risk ratio (RR) of 1.33 (95% CI = 1.01 to 1.76; P = 0.049) and a lower number of medication errors with an overall RR of 0.46 (95% CI = 0.38 to 0.55; P < 0.001), and adverse drug effects (ADEs) with an overall RR of 0.66 (95% CI = 0.44 to 0.99; P = 0.045). No association with mortality was evident (P = 0.936). High heterogeneity among the studies was evident. Publication bias was not evident. CONCLUSIONS: EHR system, when properly implemented, can improve the quality of healthcare, increasing time efficiency and guideline adherence and reducing medication errors and ADEs. Strategies for EHR implementation should be therefore recommended and promoted.

Frequency and severity of pain and symptom distress among patients with chronic kidney disease receiving dialysis.

QUESTION UNDER STUDY: Data on pain management in haemodialysis patients with end-stage renal disease are scanty. Our study aimed to collect information on the frequency and severity of pain and symptom distress among long-term dialysis patients in southern Switzerland. METHODS: Patients with chronic kidney disease stage 5, on dialysis, treated in five nephrology units in southern Switzerland, who had given informed consent and were able to complete the survey, were interviewed to assess pain and correlated symptoms using a Visual Analogue Scale (VAS), the Brief Pain Inventory and the Edmonton Symptom Assessment System. To evaluate the impact of symptoms, the Instrumental Activities of Daily Living questionnaire was used. RESULTS: One hundred and twenty-three patients, aged 36-90 years and with a mean time on dialysis of 3.5 years, were interviewed. Pain was experienced by 81 patients during the 4 weeks before the interview: 68 had chronic pain; 66 reported pain intensity higher than 5 on the VAS; 35 identified musculoskeletal pain as the most disturbing pain. Five patients used drugs to cope with pain during the night. Asthenia and fatigue were prevalent concomitant symptoms. Asthenia, fatigue, sleep disturbances, dyspnoea, loss of appetite, nausea/vomiting and anxiety were correlated with pain. The majority of the patients reported that their pain limited their daily life activities. CONCLUSIONS: Pain severity and symptom distress in dialysis patients are important, but underestimated and undertreated. They interfere with sleep quality and daily living. Routine assessment of pain burden, pain management similar to that used in palliative care, and adequate analgesic use to treat specific dialysis-associated pain syndromes should be considered in guidelines.

Outcome of fibrillary glomerulonephritis.

QUESTIONS UNDER STUDY: We assessed the long-term follow up of all the patients with fibrillary glomerulonephritis diagnosed since 1992 at our centre of reference for renal pathology in Basel. METHODS: We performed a retrospective surveillance study with mail questionnaire based follow-up of all patients with the diagnosis of fibrillary glomerulonephritis found in the database of the department of renal pathology in Basel from 1992 to 2007. The outcome was assessed in terms of endstage renal disease (ESRD), death, reduction of proteinuria and improvement of estimated glomerular filtration rate (eGFR). RESULTS: We obtained sufficient follow up data from 16 out of 20 identified patients. The mean follow up time was 35 months (1-115.1). Six patients died (37.5%), three without having ESRD. Six patients (37.5%) reached ESRD, five of them went on hemodialysis. Thirteen patients (81.3%) received an immunosuppressive therapy with steroids, five of them in combination with cyclophosphamide. The group without immunosuppressive therapy was too small to compare the two groups. In relation to the histological pattern membranous glomerulonephritis (MGN) had a better outcome as compared to the other histological patterns. CONCLUSIONS: FGN is a heterogeneous disease associated with significant risk of ESRD and mortality. The histological type of the glomerulonephritis may influence the course of the disease.

Comparison of in-hospital secondary prevention for different vascular diseases.

BACKGROUND: Secondary prevention of coronary artery disease is highly effective and implemented on a large scale. However, studies testing adherence to recommended secondary prevention of other vascular diseases are rare. Our goal was to evaluate whether the kind of vascular disease influences prescription practice of secondary drug prophylaxis at hospital discharge and to which extent secondary prevention is actually complete. METHODS: A 3-month prospective observational review of the hospital discharge information of all patients hospitalized because of a vascular disease diagnosis: coronary artery disease (i.e. acute myocardial infarction [AMI] and chronic stable angina [CSA]); peripheral artery disease [PAD] and cerebrovascular disease [CVD]. The analysis was done by board registered internists with a structured form that founded on internationally accepted recommendations. RESULTS: From 271 patients 191 had coronary artery disease (105 AMI and 86 CSA), 88 PAD and 72 CVD. Global prescription rate (mean; 95% CI) of indicated secondary prophylaxis drugs was 74.1% (69.9-78.2) for AMI, 72.4% (67.2-77.5) for CSA, 74.7% (68.8-80.7) for PAD and 72.1% (66.9-77.3) for CVD. The proportion of patients who were prescribed a complete bundle of recommended medications was globally 29.5% (24.1-35.0). CONCLUSIONS: We found similar global prescription rates of secondary prevention for the different vascular diseases. However, only one third of the studied collective gets a complete set of required prophylactic drugs.

Poor oral hygiene enhances gingival overgrowth caused by calcineurin inhibitors.

AIM: To estimate the prevalence of gingival overgrowth in kidney allograft recipients in southern Switzerland and to determine the factors associated with it. We hypothesized that poor oral hygiene was a risk factor. METHODS: We assessed the level of oral hygiene among renal transplant patients and determined whether a good level of information and regular dental checkups in addition to good oral hygiene could prevent gingival hyperplasia. Seventy-six adults who had undergone kidney transplantation were examined. The level of oral hygiene, gender, age, time elapsed from transplantation, medication and dose were recorded. RESULTS: In general the level of oral hygiene was average. We found a significant association between the severity of gingival overgrowth and the level of oral hygiene. No statistical relationship between gingival hyperplasia and the other recorded variables was detected. Patients on tacrolimus had a tendency to have less gingival hyperplasia. Patient education, along with regular dental checkups and a good level of oral hygiene, should prevent gingival hyperplasia or maintain it at an acceptable level. CONCLUSION: Intensive motivation of patients to maintain good oral hygiene is necessary to reduce the incidence of gingival hyperplasia.

Citrate- vs. acetate-based dialysate in bicarbonate haemodialysis: consequences on haemodynamics, coagulation, acid-base status, and electrolytes.

BACKGROUND: A concentrate for bicarbonate haemodialysis acidified with citrate instead of acetate has been marketed in recent years. The small amount of citrate used (one-fifth of the concentration adopted in regional anticoagulation) protects against intradialyser clotting while minimally affecting the calcium concentration. The aim of this study was to compare the impact of citrate- and acetate-based dialysates on systemic haemodynamics, coagulation, acid-base status, calcium balance and dialysis efficiency. METHODS: In 25 patients who underwent a total of 375 dialysis sessions, an acetate dialysate (A) was compared with a citrate dialysate with (C+) or without (C) calcium supplementation (0.25 mmol/L) in a randomised single-blind cross-over study. Systemic haemodynamics were evaluated using pulse-wave analysis. Coagulation, acid-base status, calcium balance and dialysis efficiency were assessed using standard biochemical markers. RESULTS: Patients receiving the citrate dialysate had significantly lower systolic blood pressure (BP) (-4.3 mmHg, p < 0.01) and peripheral resistances (PR) (-51 dyne.sec.cm-5, p < 0.001) while stroke volume was not increased. In hypertensive patients there was a substantial reduction in BP (-7.8 mmHg, p < 0.01). With the C+ dialysate the BP gap was less pronounced but the reduction in PR was even greater (-226 dyne.sec.cm-5, p < 0.001). Analyses of the fluctuations in PR and of subjective tolerance suggested improved haemodynamic stability with the citrate dialysate. Furthermore, an increase in pre-dialysis bicarbonate and a decrease in pre-dialysis BUN, post-dialysis phosphate and ionised calcium were noted. Systemic coagulation activation was not influenced by citrate. CONCLUSION: The positive impact on dialysis efficiency, acid-base status and haemodynamics, as well as the subjective tolerance, together indicate that citrate dialysate can significantly contribute to improving haemodialysis in selected patients.

Haemodynamic consequences of changing bicarbonate and calcium concentrations in haemodialysis fluids.

BACKGROUND: In a previous study we demonstrated that mild metabolic alkalosis resulting from standard bicarbonate haemodialysis induces hypotension. In this study, we have further investigated the changes in systemic haemodynamics induced by bicarbonate and calcium, using non-invasive procedures. METHODS: In a randomized controlled trial with a single-blind, crossover design, we sequentially changed the dialysate bicarbonate and calcium concentrations (between 26 and 35 mmol/l for bicarbonate and either 1.25 or 1.50 mmol/l for calcium). Twenty-one patients were enrolled for a total of 756 dialysis sessions. Systemic haemodynamics was evaluated using pulse wave analysers. Bioimpedance and BNP were used to compare the fluid status pattern. RESULTS: The haemodynamic parameters and the pre-dialysis BNP using either a high calcium or bicarbonate concentration were as follows: systolic blood pressure (+5.6 and -4.7 mmHg; P < 0.05 for both), stroke volume (+12.3 and +5.2 ml; P < 0.05 and ns), peripheral resistances (-190 and -171 dyne s cm(-5); P < 0.05 for both), central augmentation index (+1.1% and -2.9%; ns and P < 0.05) and BNP (-5 and -170 ng/l; ns and P < 0.05). The need of staff intervention was similar in all modalities. CONCLUSIONS: Both high bicarbonate and calcium concentrations in the dialysate improve the haemodynamic pattern during dialysis. Bicarbonate reduces arterial stiffness and ameliorates the heart tolerance for volume overload in the interdialytic phase, whereas calcium directly increases stroke volume. The slight hypotensive effect of alkalaemia should motivate a probative reduction of bicarbonate concentration in dialysis fluid for haemodynamic reasons, only in the event of failure of classical tools to prevent intradialytic hypotension.

Urinanalysis (UA): a neglected but easy and inexpensive diagnostic tool.

The case history of a 75-year-old woman, who was hospitalized with the diagnosis of an acute erosive colitis, is presented. The patient was treated with hysterectomy for an endometrial cancer in 2000 and had suffered from multiple sclerosis for 15 years. A persistent non-productive cough with fever requested a pneumological consultation. Multiple small alveolar opacities and cavitating lesions were found at chest imaging, but no precise diagnosis was possible. Only 3 weeks after hospitalization, we noticed that a urine analysis had been forgotten. This additional test clearly demonstrated a nephritic sediment and further analysis confirmed the diagnosis of a ANCA-positive microscopic polyangiitis, which promptly responded to immunosuppressive therapy. The necessity of a routine urine analysis in the majority of internal medicine patients and the possible link between small vessel vasculitis and multiple sclerosis are discussed.

Renal artery assessment with nonenhanced steady-state free precession versus contrast-enhanced MR angiography.

PURPOSE: To prospectively assess the diagnostic accuracy of nonenhanced three-dimensional (3D) steady-state free precession (SSFP) magnetic resonance (MR) angiography for detection of renal artery stenosis (RAS), with breath-hold contrast material-enhanced MR angiography performed as the reference standard. MATERIALS AND METHODS: The study was local ethics committee approved; all patients gave written informed consent. Fifty-three patients (30 male, 23 female; mean age, 58 years) with arterial hypertension and suspected of having RAS were examined with 1.5-T 3D SSFP renal MR angiography. Stenosis grade, maximal visible vessel length, and subjective image quality were compared. Sensitivity, specificity, accuracy, and negative predictive value (NPV) were calculated on artery-by-artery and patient-by-patient bases. The significance of the results was assessed with the paired two-sided t test for continuous variables and with the marginal homogeneity test for categorical variables. Cohen kappa statistics were used to estimate interobserver agreement. RESULTS: One hundred eight renal arteries with 20 significant (>or=50%) stenoses were detected with contrast-enhanced MR angiography. At artery-by-artery analysis, sensitivity, specificity, accuracy, and NPV of nonenhanced SSFP MR angiography for RAS detection were 100%, 93%, 94%, and 100%, respectively, for observer 1 and 95%, 95%, 95%, and 99%, respectively, for observer 2. Corresponding patient-by-patient values were 100%, 92%, 94%, and 100%, respectively, for observer 1 and 100%, 95%, 96%, and 100%, respectively, for observer 2. Overestimation of stenosis grade with SSFP MR angiography resulted in six and four false-positive findings for readers 1 and 2, respectively. Mean maximal visible lengths of the renal arteries were 69.9 mm at contrast-enhanced MR angiography and 61.1 mm at SSFP MR angiography (P<.001). Both techniques yielded good to excellent image quality. CONCLUSION: Slab-selective inversion-prepared 3D SSFP MR angiography had high sensitivity, specificity, accuracy, and NPV for RAS detection, without the need for contrast material. However, RAS severity was overestimated in some patients.

Thrombotic thrombocytopenic purpura associated with renal failure after autologous transplantation for multiple myeloma successfully treated with rituximab.

Thrombotic thrombocytopenic purpura (TTP) is a haematological syndrome characterised by a dramatic onset requiring an urgent treatment with plasma exchange (PE). However, the prognosis is still dismal for PE related complications, a rate of failure and remarkable frequencies of relapse. TTP post transplantation is largely described as an outstanding, unusual complication of allogenic transplantation, but it is rarely mentioned after autologous transplantation. We describe a 62-year-old Caucasian patient who presented with TTP, accompanied by renal failure, after an autologous transplantation for multiple myeloma. PE together with hemodialysis was rapidly initiated but without any benefit. Since empirical administration of Rituximab, anti CD20 monoclonal antibody,was reported to be effective, we administered four courses of Rituximab inducing a complete remission of TTP and subsequently of the renal failure. This response to Rituximab in TTP post transplantation is suggestive of a possible implication of B-lymphocytes in the pathogenesis of TTP and it paves the way for an investigational approach in this settings.

Would artificial neural networks implemented in clinical wards help nephrologists in predicting epoetin responsiveness?

BACKGROUND: Due to its strong intra- and inter-individual variability, predicting the ideal erythropoietin dose is a difficult task. The aim of this study was to re-evaluate the impact of the main parameters known to influence the responsiveness to epoetin beta and to test the performance of artificial neural networks (ANNs) in predicting the dose required to reach the haemoglobin target and the monthly dose adjustments. METHODS: We did a secondary analysis of the survey on Anaemia Management in dialysis patients in Switzerland; a prospective, non-randomized observational study, enrolling 340 patients of 26 centres and in order to have additional information about erythropoietin responsiveness, we included a further 92 patients from the Renal Services of the Ente Ospedaliero Cantonale, Bellinzona, Switzerland. The performance of ANNs in predicting the epoetin dose was compared with that of linear regressions and of nephrologists in charge of the patients. RESULTS: For a specificity of 50%, the sensitivity of ANNs compared with linear regressions in predicting the erythropoietin dose to reach the haemoglobin target was 78 vs. 44% (P < 0.001). The ANN built to predict the monthly adaptations in erythropoietin dose, compared with the nephrologists' opinion, allowed to detect 48 vs. 25% (P < 0.05) of the patients treated with an insufficient dose with a specificity of 92 vs. 83% (P < 0.05). CONCLUSION: In predicting the erythropoietin dose required for an individual patient and the monthly dose adjustments ANNs are superior to nephrologists' opinion. Thus, ANN may be a useful and promising tool that could be implemented in clinical wards to help nephrologists in prescribing erythropoietin.

Chronic and acute consequences of a post-dialysis urokinase lock on permanent hemodialysis catheter function.

BACKGROUND: To treat permanent hemodialysis (HD) catheter dysfunctions due to thrombosis, as an alternative to pre- and intradialytic instillations/infusions of fibrinolytic agents, for practical reasons, a post-dialysis urokinase lock is often preferred. This study aimed to analyze the consequences on catheter function and the cost/effectiveness of an intermittent post-dialysis urokinase lock. METHODS: A prospective open experimental study enrolling 10 dialysis patients with a Tesio twin catheter locked with either heparin 5,000 IU/mL or escalating urokinase doses. Catheter function was monitored measuring the blood flow obtained with an aspiration pressure of -180 mmHg for 28 consecutive HD sessions. RESULTS: No differences were noticed between the blood flow obtained before and after the lock of the catheter with 5000 U/lumen of urokinase (phase 1), but also with 10,000 U/lumen (phase 2) of urokinase. The incidence of catheter dysfunction episodes in the wash-out in the 1st and in the 2nd urokinase phases were, respectively: 13, 6 and 3% (p<0.05 for both 13 vs. 6% and 13 vs. 3%). 47,000 U of urokinase were necessary to avoid one dysfunction episode potentially treatable with an intradialytic urokinase lock of 10,000 U. Between the average blood flow measured in the initial wash out (230 +/- 27 ml/min) and in the 1st (236 +/- 32 ml/min) and also in the 2nd (247 +/- 34 ml/min) urokinase phases significant differences were noticed (p<0.01 and p<0.05, respectively). CONCLUSIONS: The post-dialysis lock with urokinase is associated with an increase in the catheter blood flow and a re-duction in the occurrence of dysfunction episodes. However, the modest impact on dialysis quality and the apparent unfavorable cost/effectiveness of the prophylactic treatment, call for an investigation of its potential advantages in a larger study.

Remember 'a posteriori diagnosis' of carbon monoxide poisoning.

OBJECTIVES: To raise awareness of the possibility of carbon monoxide poisoning as a diagnosis in the emergency department and to present the little known fact that it is possible to diagnose carbon monoxide poisoning retrospectively. METHOD: Presentation of a case report, review of the literature. RESULTS: Persistence of elevated carboxyhaemoglobin levels in a stored vacutainer blood sample. CONCLUSION: Carbon monoxide poisoning is common but often goes unrecognized. This method may help to decrease the number of overlooked cases and thereby possibly prevent further exposure and acute or chronic sequelae.

Does bicarbonate transfer have relevant hemodynamic consequences in standard hemodialysis?

BACKGROUND: In a previous study we demonstrated that mild metabolic alkalosis resulting from standard bicarbonate hemodialysis induces hypotension. This study aimed to compare hemodynamic consequences of either a decrease in the dialysate bicarbonate from 32 to 26 mmol/l or an increase in the dialysate calcium of 0.25 mmol/l and to verify whether the calcium shift secondary to alkalemia explains the consequences on blood pressure. METHODS: In this randomized controlled trial with a single-blind, cross-over design, we used dialysis liquids with two different bicarbonate (32 mmol/l in modalities A and C, and 26 mmol/l in modality B) and calcium (1.25 mmol/l in modalities A and B, and 1.50 mmol/l in modality C) concentrations, and in 27 patients, 243 dialysis sessions, compared blood pressure, heart rate and the incidence of hypotension. RESULTS: No significant differences were seen between A and B while an increase in systolic and diastolic blood pressures and a decrease in the incidence of hypotension (10.5 vs. 1.2%, p < 0.05) were documented in C. The subgroup of patients who with A showed a lower mean systolic blood pressure received more angiotensin-converting enzyme inhibitors or angiotensin II type-1 receptor blockers (36 vs. 0%, p<0.05) and in C showed a less important increase in systolic and diastolic pressures, but the incidence of hypotensive episodes between A and B was not significantly different (9.1 vs. 15.1%). CONCLUSIONS: In the present study it was not possible to demonstrate hemo dynamic instability associated with mild metabolic alkalosis. Even in the subgroup showing a lower blood pressure with a higher dialysate bicarbonate, significant hemodynamic or clinical consequences were not noticed. The calcium shift (0.05 mmol/l) related to alkalemia would justify a mean decrease in systolic blood pressure of only about 1 mm Hg.

A new job: research volunteer?

We report three years of experience with a newly introduced register for healthy research volunteers in Canton Ticino, Southern Switzerland. The aim of the register was to encourage responsible participation in medical research, and to detect fraud due to volunteers taking part in more than one study at the same time. All healthy volunteers participating in drug studies approved by the Research Ethics Committee were included in the register and given a special code. During three years, in a population of 1436 volunteers involved in 152 studies, 192 subjects (13.4%) were identified as habitual or regular volunteers (they participated regularly, limiting the pause between studies to the minimum of three months as required by the regulations of the Research Ethics Committee). Among them, only three subjects gave false information and were identified. Most volunteers participated in studies only sporadically (54% in one, 21% in two over three years) and 82.4% of the volunteers were involved, on average, in only one study per year. Our register permits fraud detection as well as analysis of the research population from an epidemiological point of view. It has been well accepted from both volunteers and research organisations. It is simple and represents a substantial contribution especially for organisations, which need to recruit a large number of subjects for their research.

Pharmacokinetics of N-acetylcysteine following repeated intravenous infusion in haemodialysed patients.

OBJECTIVE: N-acetylcysteine (NAC) is a mucolytic agent with anti-oxidant properties. It might have potential positive effects in renal patients and, therefore, its pharmacokinetics and safety in haemodialysis was investigated. METHODS: Twelve dialysis patients received 2 g NAC (10 ml NAC 20% solution i.v.) mixed with 500 ml saline during the first 3 h of the session for six dialysis sessions. A bolus of heparin was injected intravenously as LWH-heparin. In six patients, one session was repeated with NAC mixed with heparin and infused through the heparin pump. RESULTS: Baseline NAC was on average 454 ng ml(-1); its concentration increased to 9,253 ng ml(-1) at the second infusion and attained a steady state between 14,000 ng ml(-1) and 17,000 ng ml(-1) at the fourth dose. We observed a C (max) of 53,458 ng ml(-1) with a t (max) of 3.0 h. Plasma clearance was 1.25 l h(-1) and dialytic clearance 5.52 l h(-1). No side effects were observed. CONCLUSION: In the case of repeated doses, the NAC pre-dose concentration after repeated infusion of 2 g of the drug during the first 3 h of a dialysis session reached the steady state at the fourth infusion, without further accumulation. The dialytic clearance is effective, the total body clearance being reduced to 1.25 l h(-1). In dialysis patients, 2 g NAC given intravenously over 3 h is a safe dosage, with no short-term side effects.