Precursory changes in seismic velocity for the spectrum of earthquake failure modes.

Temporal changes in seismic velocity during the earthquake cycle have the potential to illuminate physical processes associated with fault weakening and connections between the range of fault slip behaviors including slow earthquakes, tremor and low frequency earthquakes1. Laboratory and theoretical studies predict changes in seismic velocity prior to earthquake failure2, however tectonic faults fail in a spectrum of modes and little is known about precursors for those modes3. Here we show that precursory changes of wave speed occur in laboratory faults for the complete spectrum of failure modes observed for tectonic faults. We systematically altered the stiffness of the loading system to reproduce the transition from slow to fast stick-slip and monitored ultrasonic wave speed during frictional sliding. We find systematic variations of elastic properties during the seismic cycle for both slow and fast earthquakes indicating similar physical mechanisms during rupture nucleation. Our data show that accelerated fault creep causes reduction of seismic velocity and elastic moduli during the preparatory phase preceding failure, which suggests that real time monitoring of active faults may be a means to detect earthquake precursors.

Laboratory observations of slow earthquakes and the spectrum of tectonic fault slip modes.

Slow earthquakes represent an important conundrum in earthquake physics. While regular earthquakes are catastrophic events with rupture velocities governed by elastic wave speed, the processes that underlie slow fault slip phenomena, including recent discoveries of tremor, slow-slip and low-frequency earthquakes, are less understood. Theoretical models and sparse laboratory observations have provided insights, but the physics of slow fault rupture remain enigmatic. Here we report on laboratory observations that illuminate the mechanics of slow-slip phenomena. We show that a spectrum of slow-slip behaviours arises near the threshold between stable and unstable failure, and is governed by frictional dynamics via the interplay of fault frictional properties, effective normal stress and the elastic stiffness of the surrounding material. This generalizable frictional mechanism may act in concert with other hypothesized processes that damp dynamic ruptures, and is consistent with the broad range of geologic environments where slow earthquakes are observed.

Slow earthquakes, preseismic velocity changes, and the origin of slow frictional stick-slip.

Earthquakes normally occur as frictional stick-slip instabilities, resulting in catastrophic failure and seismic rupture. Tectonic faults also fail in slow earthquakes with rupture durations of months or more, yet their origin is poorly understood. Here, we present laboratory observations of repetitive, slow stick-slip in serpentinite fault zones and mechanical evidence for their origin. We document a transition from unstable to stable frictional behavior with increasing slip velocity, providing a mechanism to limit the speed of slow earthquakes. We also document reduction of P-wave speed within the active shear zone before stick-slip events. If similar mechanisms operate in nature, our results suggest that higher-resolution studies of elastic properties in tectonic fault zones may aid in the search for reliable earthquake precursors.

Influence of vibration amplitude on dynamic triggering of slip in sheared granular layers.

We perform a systematic statistical investigation of the effect of harmonic boundary vibrations on a sheared granular layer undergoing repetitive, fully dynamic stick-slip motion. The investigation is performed using two-dimensional discrete element method simulations. The main objective consists of improving the understanding of dynamic triggering of slip events in the granular layer. Here we focus on how the vibration amplitude affects the statistical properties of the triggered slip events. The results provide insight into the granular physical controls of dynamic triggering of failure in sheared granular layers.

Fluid balance in critically ill patients. Should we really rely on it?

BACKGROUND: The computation of fluid balances (FBs) by subtracting fluid outputs from inputs is a common critical care practice. Limited information exists about the accuracy and consistency of nurse-registered cumulative FBs and regarding the value of suggested corrections for non-measurable losses. METHODS: From 147 ICU patients, we prospectively evaluated the cumulative FBs and their relationship to changes in body weight (BW). Standardised measurements of BW were performed on admission and discharge. FB charts were accurately reviewed and arithmetic errors corrected. Net cumulative FBs and adjusted cumulative FBs (considering sensible or insensible fluid losses/fever/liquid faeces) were analysed for all patients and 3 subgroups (cardiac-cerebral, septic, and others). Agreement between FBs and BW changes was calculated according to the defined subgroups and confounding variables. RESULTS: Cumulative FBs were inaccurate in 49 cases (33%) with errors ranging from -3606 mL to +2020 mL. The total (average daily) difference between measured BW and FBs (mean ± SD) was 0.185±1.874 kg (0.101±1.020 kg). Correlation (r(2)) and Bland-Altman agreement was poor between BW changes and net cumulative FBs (0.552 and -1.26±5.41 kg) and slightly better between BW changes and adjusted cumulative FBs (0.714 and +0.18±3.68 kg). Standard deviations of the average daily differences between BW changes and FBs were always >1 L. Correction of the net FBs as suggested in the literature were not useful. New multiple regression models only modestly improved correlation. CONCLUSION: For a large portion of patients nurse-registered cumulative FBs are neither accurate nor do they agree with standardised BW measurements. Patient care and clinical decision-making should be based on more objective techniques.

Eosinophilic vasculitis: an inhabitual and resistant manifestation of a vasculitis.

A 55-year-old woman was referred because of diffuse pruritic erythematous lesions and an ischemic process of the third finger of her right hand. She was known to have anaemia secondary to hypermenorrhea. She presented six months before admission with a cutaneous infiltration on the left cubital cavity after a paravenous leakage of intravenous iron substitution. She then reported a progressive pruritic erythematous swelling of her left arm and lower extremities and trunk. Skin biopsy of a lesion on the right leg revealed a fibrillar, small-vessel vasculitis containing many eosinophils.Two months later she reported Raynaud symptoms in both hands, with a persistent violaceous coloration of the skin and cold sensation of her third digit of the right hand. A round 1.5 cm well-delimited swelling on the medial site of the left elbow was noted. The third digit of her right hand was cold and of violet colour. Eosinophilia (19 % of total leucocytes) was present. Doppler-duplex arterial examination of the upper extremities showed an occlusion of the cubital artery down to the palmar arcade on the right arm. Selective angiography of the right subclavian and brachial arteries showed diffuse alteration of the blood flow in the cubital artery and hand, with fine collateral circulation in the carpal region. Neither secondary causes of hypereosinophilia nor a myeloproliferative process was found. Considering the skin biopsy results and having excluded other causes of eosinophilia, we assumed the diagnosis of an eosinophilic vasculitis. Treatment with tacrolimus and high dose steroids was started, the latter tapered within 12 months and then stopped, but a dramatic flare-up of the vasculitis with Raynaud phenomenon occurred. A new immunosuppressive approach with steroids and methotrexate was then introduced. This case of aggressive eosinophilic vasculitis is difficult to classify into the usual forms of vasculitis and constitutes a therapeutic challenge given the resistance to current immunosuppressive regimens.

Economic burden of unjustified medications at hospital discharge.

QUESTION UNDER STUDY: Medication errors are a major concern for health care since they may cause or lead to inappropriate medication use or patient harm. However, little is known regarding the economic burden of unjustified medications. METHODS: Hospital discharge records of 577 patients were prospectively screened for the presence of unjustified medications. From this sample population, 318 (55%) were eligible and their data were used to assess the monthly costs of unjustified discharge medications, their relationship to the total and each individual's drug expenditure, and the relative cost weights of relevant unjustified drug classes. RESULTS: The results found that 619 out of 3691 prescriptions (16.8%) were unjustified. The mean (median; 95% CI) monthly costs of unjustified discharge medications were 32 euro (27 euro; 29 euro to 35 euro). The percentage of unnecessary treatments was inversely linked to the amount of total individual drug expenditure. For this collective, monthly extra costs due to unjustified medications were 18585 euro, and the relative cost weights of the relevant drug classes were 45.8% for gastrointestinal agents (33.8% for proton pump inhibitors), 17.7% for cardiovascular drugs, and 17.2% for psychiatric drugs. CONCLUSIONS: There is a considerable financial burden imposed by unjustified medications at hospital discharge. Discharge medications not motivated by appropriate diagnoses should be questioned. This study should be repeated in other institutions and in a larger population.

Omitted and unjustified medications in the discharge summary.

BACKGROUND: Limited information exists in regard to drug omissions and unjustified medications in the hospital discharge summary (DS). OBJECTIVE: To evaluate the incidence and types of drug omissions and unjustified medications in the DS, and to assess their potential impact on patient health. METHODS: A prospective observational review of the DSs of all patients discharged from our Internal Medicine Department over a 3-month period. Data assessment was made by internists using a structured form. RESULTS: Of the 577 evaluated DSs, 66% contained at least one inconsistency accounting for a total of 1012 irregularities. There were 393 drug omissions affecting 251 patients, 32% of which were potentially harmful. Seventeen per cent of all medications (619/3691) were unjustified, affecting 318 patients. The unjustified medication was potentially harmful in 16% of cases, occurred significantly more frequent in women than in men (61% vs 50%; p = 0.008) and increased linearly with the number of drugs prescribed (p<0.001). Drug omission had a twofold higher potential to cause harm than unjustified medication. CONCLUSIONS: Drug omissions and unjustified medications are frequent, and systemic changes are required to substantially reduce these inconsistencies.

Transition from rolling to jamming in thin granular layers.

We study the granular jamming transition for sheared layers of spherical beads ranging in thickness from 1 to 3 times the grain diameter d. As the layer thickness increases slightly above d, the measured friction jumps discontinuously from 0.02 to >0.1, marking the transition from rolling to jamming. Above a critical layer thickness for jamming, the effective granular pressure displays a power law increase with thickness. For thin layers, friction and P increases as the packing fraction decreases near the jamming transition, in contrast to expectations for bulk granular matter.

BM-derived cells randomly contribute to neoplastic and non-neoplastic epithelial tissues at low rates.

Epithelial cancers can arise from BM-derived cells (BMCs) in animal models. We studied whether the same phenomenon can occur in humans. Biopsy specimens from carcinomas and healthy adjacent tissues were obtained from three women who had undergone allogeneic BMT from an HLA-matched brother. Complete donor hematopoietic chimerism was verified by cytogenetic analysis, RFLP analysis or by reverse transcription-PCR analysis. Biopsies were studied for the presence of the Y chromosome derived from BM-derived cells by combined FISH and immunohistochemical staining. In our studies, we showed that human epithelial neoplastic and adjacent non-neoplastic tissues incorporate the Y chromosome at low and comparable rates. The lack of enrichment in malignancies argues against the possibility that BM-derived cells represent a direct source of carcinomas, and we suggest that these cells randomly contribute to neoplastic and non-neoplastic epithelial cells. On the basis of the absence of a fusion karyotype, we favor a model in which the differentiation of BM-derived cells is largely determined by the microenvironment encountered.

Diagnostic value of serum chromogranin-A combined with MIBG scintigraphy inpatients with adrenal incidentalomas.

AIM: Adrenal incidentalomas (AI) are defined as asymptomatic adrenal masses occasionally discovered during high-resolution imaging procedures, as computed tomography or magnetic resonance. Pheochromocytoma, a chromaffin tumour, must be excluded before any invasive diagnostic or therapeutic procedure, in order to avoid dangerous acute catecholamines-release into blood stream. Chromogranin-A (CgA) is a member of the granin family contained in secretory vesicles of chromaffin system. This study investigated the performance of serum CgA in detecting or excluding pheochromocytoma among patients with AI. METHODS: We enrolled 348 patients by AI > 20 mm without clinical or biochemical signs for corticosteroids overproduction. Serum CgA was assayed by a specific immunoradiometric method and a [123I] metaiodobenzylguanidine (MIBG) scan was performed in the 39 CgA-positive patients. RESULTS: Eighteen out of these patients showed a positive scan and were submitted to laparoscopic adrenalectomy. Pheochromocytoma was histologically confirmed in all cases . The patients with positive serum CgA, were reassessed 1 year later by clinical examination and serum CgA assay. None of patients developed clinical symptoms of chromaffin-tissue hyperactivity , nor showed a serum CgA increase. Serum levels of CgA were significantly higher inpatients with pheochromocytoma than inpatients without (P<0.0001). CONCLUSION: We concluded that serum CgA assay is effective as a single marker to detect or exclude sporadic pheochromocytoma among patients with AI > 20mm. Particularly, a negative serum CgA assay may be used to rule out [123I] MIBG imaging and /or other diagnostic procedures.

Predicting intradialytic hypotension from experience, statistical models and artificial neural networks.

BACKGROUND: Symptomatic intradialytic hypotension (IDH) associated with increased mortality in hemodialysis patients is difficult to predict and hence prevent. Artificial Neural Networks (ANNs) are promising tools to solve multidimensional non-linear problems. The aim of the study was to verify in which way mathematical models, statistics or knowledge of patients influence the ability of the nephrologists to predict IDH. METHODS: The performance of ANNs was compared with that of independent nephrologists supported by a logistic regression giving odds ratio for each studied variable (NEPHiS) or of nephrologists in charge of the patients without (NEPHc) or with statistical support as for NEPHiS (NEPHcS). Data from 98 hemodialysis patients were analysed in order to select patients with frequent IDH (>10% of the dialysis sessions). Complete data on 1979 dialysis sessions from 7 patients were retrieved. The ability to predict the occurrence of hypotension episodes was compared (ROC curves) between ANNs, NEPHc/S (N=7) in Switzerland and NEPHiS from independent dialysis centers in Western Australia (N=10). RESULTS: ANN gave the most accurate correlation between estimated and observed IHD episodes compared to NEPHc (p<0.001), but a similar performance was attained by NEPHcS (p<0.001). NEPHiS were superior to NEPHc (P<0.05), but inferior to ANN (P<0.01). For a sensitivity of 80%, specificity was 44% for ANNs, 33% for NEPHcS and 20% for NEPHc. CONCLUSIONS: ANNs are superior to nephrologists in predicting IDH episodes; however when supported by a statistical analysis, nephrologists reach ANNs in their prediction ability. IDH still remains difficult to predict even with mathematical models.

Vancomycin-induced hypersensitivity reaction with acute renal failure: resolution following cyclosporine treatment.

Drug rash with eosinophilia and systemic symptoms or DRESS syndrome is a distinct severe drug-induced hypersensitivity reaction characterized by skin rash, fever, eosinophilia and visceral involvement. The latter leads to a 10% mortality rate, with interstitial nephritis occurring in about 10% of the cases. The outcome is usually favorable after withdrawal of drug therapy; systemic corticosteroid therapy may hasten the recovery, although there are no data from prospective, randomized trials evaluating the efficacy of this approach. Administration of other immunosuppressive agents (cyclophosphamide, cyclosporine) has also been suggested. We report on a patient with vancomycin-induced DRESS syndrome with acute interstitial nephritis and hepatitis. There was no improvement after withdrawal of the offending agent and empiric corticosteroid use. After tapering the steroids, a five-day course of cyclosporine was followed by quick resolution of the skin rash and recovery of renal function. Cyclosporine could represent a treatment option in cases of severe visceral involvement such as persistent renal insufficiency that do not improve after discontinuation of the offending agent and administration of high doses of steroids.

[Adverse internal medicine drug effects at hospital admission]. / Unerwünschte internmedizinische Arzneimittelwirkungen bei Spitaleintritt.

Hospital admissions due to adverse drug reactions are an important concern, but there are few data concerning the specific situation in Switzerland. During one year we therefore prospectively studied all admissions to our medical department to determine the profile. 138 of 2168 patients presented a total of 150 adverse drug reactions at hospitalisation (6.4%) and among them 65% of the admissions were directly related to adverse drug reaction. Age stratification revealed that with each decade of age there was an increasing risk of adverse drug reactions and that the patients were sicker (more diagnoses), were consuming more drugs and had longer stays. The majority of adverse drug reactions were type A reactions and therefore potentially preventable. Cardio- and cerebrovascular drugs (diuretics, ACE-inhibitors, platelet aggregation inhibiting therapy) accounted for 65% of the side effects. Analysed by affected organ system, the most frequent adverse drug reactions were gastrointestinal complications followed by dehydration (contracted extracellular fluid volume) and hypo-/hyperkalaemia. Non-compliance by the patients was less frequently at the origin of the admission than iatrogenic causes related to physician errors. The patients generally did not know the reasons, details and side effects of their medical treatment. Based on our data, we estimate that the national number of drug-related hospital admissions caused by inappropriate or unnecessary treatment is 12,000-16,000, with direct annual extra costs of 70-100 million Swiss francs. Adverse drug reactions therefore represent a serious medical and financial problem. Specialised computing systems designed to reduce these events should be introduced in hospitals and ambulatory care.

Oral vs intravenous ciprofloxacin in the initial empirical management of severe pyelonephritis or complicated urinary tract infections: a prospective randomized clinical trial.

BACKGROUND: There are few data on the efficacy of oral antibiotics in the initial empirical management of severe forms of urinary tract infection (UTI). METHODS: In a multicenter, prospective, randomized trial we compared oral (500 mg twice daily) vs intravenous ciprofloxacin (200 mg twice daily) in the initial empirical management of hospitalized patients with serious forms of UTI. Exclusion criteria were severe sepsis, inability to take oral medication, or the presence of obstruction or renal foci of suppuration. The study population included 66 women with pyelonephritis, 43 patients with community-acquired UTIs, and 32 patients with hospital-acquired UTIs. The frequency of bacteremia was 28 (42%) of 66 in the patients with pyelonephritis and 25 (33%) of 75 in those with complicated UTIs. Seventy-two patients were randomized to treatment with oral and 69 to intravenous ciprofloxacin. RESULTS: There were no infection-related deaths and no patients required an early change of antibiotics because of worsening clinical status during the initial empirical phase of treatment. The mean duration of fever was 1.7 days in patients treated by the oral vs 1.9 days in patients treated by the intravenous route (P = .15). The rates of microbiological failure (3% in the oral vs 2% in the intravenous treatment group) and of unsatisfactory clinical response (4% oral vs 3% intravenous) were low. A treatment change was eventually required in 14% of the patients assigned to the oral and 7% of the patients assigned to the intravenous regimen, mainly because of the isolation of enterococci or ciprofloxacin-resistant organisms in pretherapy urine specimens. CONCLUSIONS: In the hospital setting, oral ciprofloxacin is as effective as the intravenous regimen in the initial empirical management of serious UTIs, including bacteremic forms, in patients without severe sepsis, obstruction, or renal foci of suppuration. The efficacy of the oral regimen indicates a potential use for ciprofloxacin in outpatient treatment of a subset of patients currently hospitalized on account of disease severity.

Intracavitary chemotherapy with thiotepa in malignant pericardial effusions: an active and well-tolerated regimen.

PURPOSE: Malignant pericardial effusion, although highly variable, is an uncommon complication of cancer. It is often associated with symptoms like dyspnea, chest pain, and cough, which may be severe and disabling. We analyzed the results of our current treatment policy to evaluate the effectiveness and tolerance of a new approach for this disorder. PATIENTS AND METHODS: Patients with malignant pericardial effusions were treated with intracavitary thiotepa (15 mg on days 1, 3, and 5) through an indwelling pericardial cannula after extraction of as much pericardial fluid as possible on day 0. Responses were assessed by clinical examination, computed tomographic (CT) scan, and echocardiography before treatment, 1 month after treatment, and every 2 months thereafter. Twenty-three patients with malignant symptomatic pericardial effusion were treated and all were assessable for effectiveness and tolerance of the procedure. RESULTS: Nine patients with breast cancer, 11 with lung cancer, two with an unknown primary tumor, and one with metastatic melanoma were treated. In all but three patients, systemic medical treatment was started after completion of intracavitary therapy. Nineteen patients responded to treatment (83%; 95% confidence interval, 61% to 95%) with a rapid improvement of symptoms. The median time to pericardial effusion progression was 8.9 months (range, 1 to 26). No significant side effects were registered, except one patient who had transient grade III thrombocytopenia and leukopenia and one patient who had grade I leukopenia. CONCLUSION: A short course of intracavitary treatment with thiotepa is highly effective and well tolerated in the treatment of malignant pericardial effusion.