Juvenile arthritis patients report favorable subjective outcomes of hip arthroplasty despite poor standard outcome scores.

We evaluated midterm patient-reported outcomes and satisfaction with total hip arthroplasty in patients who had severe juvenile idiopathic arthritis. Thirty-one patients (49 hips), with a mean age of 29 years (range, 16-43 years), reported low hip pain and stiffness at follow-up (mean, 7 years; range, 3-17 years). Up to 92% were satisfied with their ability to perform various activities; 96% were satisfied with pain relief. A mean postoperative flexion arc of 96° was observed. Final 36-Item Short Form Health Survey, EuroQol in 5 dimensions, Western Ontario and McMaster Universities Arthritis Index, and Harris Hip scores were lower than reference populations, particularly for mobility, physical functioning, and social functioning subscores. Young adults with end-stage hip involvement and severe longstanding juvenile idiopathic arthritis expressed high satisfaction with total hip arthroplasty, which improved range of motion, pain, and stiffness, despite poor performance on widely used outcome measures.

Nouveautés dans la physiopathologie, le diagnostic et le traitement de la douleur neuropathique [New concepts in the pathophysiology, diagnosis and treatment of neuropathic pain].

We here summarize five articles bringing new advances in our knowledge on neuropathic pain and put them into perspective with our current understanding. The first uses a mechanism-based approach with a capsaicin test to stratify patients suffering from painful diabetic neuropathy before starting a topical clonidine treatment. The second reviews disinhibition as a critical mechanism and a promising target for chronic pain. The third evokes neuroglial interactions and its implication regarding the interplay between injuries in childhood and hypersensitivity in adulthood. The last articles remind us that interventional therapies, not always very invasive, have a future potential in the therapy of frequent conditions such as head pain disorders.

Influence of socioeconomic factors on delays, management and outcome amongst patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

The outcome after primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) is strongly affected by time delays. In this study, we sought to identify the impact of specific socioeconomic factors on time delays, subsequent STEMI management and outcomes in STEMI patients undergoing pPCI, who came from a well-defined region of the French part of Switzerland. A total of 402 consecutive patients undergoing pPCI for STEMI in a large tertiary hospital were retrospectively studied. Symptom-to-first-medical-contact time was analysed for the following socioeconomic factors: level of education, origin and marital status. Main exclusion criteria were: time delay beyond 12 hours, previous treatment with fibrinolytic agents or patients immediately referred for coronary artery bypass graft surgery. Therefore, 222 patients were finally included. At 1 year, there was no difference in mortality between the different socioeconomic groups. Furthermore, there was no difference in management characteristics between them. Symptom-to-first-medical-contact time was significantly longer for patients with a low level of education, Swiss citizens and unmarried patients, with median differences of 23 minutes, 18 minutes and 13 minutes, respectively (p <0.05). Nevertheless, no difference was found regarding in-hospital management and clinical outcome. This study demonstrates that symptom-to-first-medical-contact time is longer amongst people with a lower educational level, Swiss citizens and unmarried people. Because of the low mortality rate in general, these differences in delays did not affect clinical outcomes. Still, tertiary prevention measures should particularly focus on these vulnerable populations.

Measurement of biologically available naphthalene in gas and aqueous phases by use of a Pseudomonas putida biosensor.

Genetically constructed microbial biosensors for measuring organic pollutants are mostly applied in aqueous samples. Unfortunately, the detection limit of most biosensors is insufficient to detect pollutants at low but environmentally relevant concentrations. However, organic pollutants with low levels of water solubility often have significant gas-water partitioning coefficients, which in principle makes it possible to measure such compounds in the gas rather than the aqueous phase. Here we describe the first use of a microbial biosensor for measuring organic pollutants directly in the gas phase. For this purpose, we reconstructed a bioluminescent Pseudomonas putida naphthalene biosensor strain to carry the NAH7 plasmid and a chromosomally inserted gene fusion between the sal promoter and the luxAB genes. Specific calibration studies were performed with suspended and filter-immobilized biosensor cells, in aqueous solution and in the gas phase. Gas phase measurements with filter-immobilized biosensor cells in closed flasks, with a naphthalene-contaminated aqueous phase, showed that the biosensor cells can measure naphthalene effectively. The biosensor cells on the filter responded with increasing light output proportional to the naphthalene concentration added to the water phase, even though only a small proportion of the naphthalene was present in the gas phase. In fact, the biosensor cells could concentrate a larger proportion of naphthalene through the gas phase than in the aqueous suspension, probably due to faster transport of naphthalene to the cells in the gas phase. This led to a 10-fold lower detectable aqueous naphthalene concentration (50 nM instead of 0.5 micro M). Thus, the use of bacterial biosensors for measuring organic pollutants in the gas phase is a valid method for increasing the sensitivity of these valuable biological devices.

Measurement of immunoreactive angiotensin-(1-7) heptapeptide in human blood.

BACKGROUND: The renal enzyme renin cleaves from the hepatic alpha(2)-globulin angiotensinogen angiotensin-(1-10) decapeptide [Ang-(1-10)], which is further metabolized to smaller peptides that help maintain cardiovascular homeostasis. The Ang-(1-7) heptapeptide has been reported to have several physiological effects, including natriuresis, diuresis, vasodilation, and release of vasopressin and prostaglandins. METHODS: To investigate Ang-(1-7) in clinical settings, we developed a method to measure immunoreactive (ir-) Ang-(1-7) in 2 mL of human blood and to estimate plasma concentrations by correcting for the hematocrit. A sensitive and specific antiserum against Ang-(1-7) was raised in a rabbit. Human blood was collected in the presence of an inhibitor mixture including a renin inhibitor to prevent peptide generation in vitro. Ang-(1-7) was extracted into ethanol and purified on phenylsilylsilica. The peptide was quantified by radioimmunoassay. Increasing doses of Ang-(1-7) were infused into volunteers, and plasma concentrations of the peptide were measured. RESULTS: The detection limit for plasma ir-Ang-(1-7) was 1 pmol/L. CVs for high and low blood concentrations were 4% and 20%, respectively, and between-assay CVs were 8% and 13%, respectively. Reference values for human plasma concentrations of ir-Ang-(1-7) were 1.0-9.5 pmol/L (median, 4.7 pmol/L) and increased linearly during infusion of increasing doses of Ang-(1-7). CONCLUSIONS: Reliable measurement of plasma ir-Ang-(1-7) is achieved with efficient inhibition of enzymes that generate or metabolize Ang-(1-7) after blood sampling, extraction in ethanol, and purification on phenylsilylsilica, and by use of a specific antiserum.

Morbidity and outcome after sentinel lymph node dissection in patients with early-stage malignant cutaneous melanoma.

OBJECTIVE: Prospective analysis of the morbidity and outcome of the sentinel lymph node (SLN) technique in a consecutive series of patients with early-stage melanoma. METHODS: Between 1997 and 1998, 60 patients with stage IB-II malignant melanoma underwent SLN dissection. Preoperative dynamic lymphoscintigraphy with mapping of the lymph vessels and lymph nodes and location of the sentinel node was performed the day before SLN dissection. SLN was identified by use of the blue dye technique. SLN was assessed for histopathological and immunohistochemical examination. Postoperative morbidity and mortality were recorded. Follow-up consisted of repetitive clinical examination with lymph nodes status, laboratory and radiologic findings. RESULTS: Tumor-positive SLN was observed in 18% of the patients and stage II disease was found in 91% of the patients with positive SLN. Breslow thickness was the only significant factor predicting involvement of a SLN (p = 0.02). In 36% of the positive SLN, metastases could be assessed only by immunohistochemical examination. Postoperative complications after SLN dissection were observed in 5% in comparison with 36% after elective lymph node dissection. After a mean follow-up of 32 months, recurrence was observed in 3% with a mean disease-free survival of 8 months. Overall survival was 82% and 90% in patients with positive and negative SLN, respectively. Overall mortality was 15%, due to distant metastases in 78% of the cases. CONCLUSIONS: Staging of early-stage melanoma with the SLN dissection by use of the blue dye technique combined to lymphoscintigraphy and immunohistochemistry is reliable and safe, with less morbidity than elective lymphadenectomy. Long-term follow-up is mandatory to establish the exact reliability of SLN dissection.

Devenir à long terme des patients intubés pour état de mal asthmatique [Late outcome after life-threatening asthma]

Pour connaître le devenir à long terme des patients intubés pour état de mal asthmatique, nous avons recontacté en 1990 les 34 patients qui avaient présenté, entre 1978 et 1988, quarante épisodes de détresse respiratoire aiguë. Deux patients sont vivants mais ont été perdus de vue, 3 sont morts dont un seul d'état de mal asthmatique 6 mois après l'épisode initial. Des 29 patients restants (7 hommes et 22 femmes, âge moyen de 48,5 ans) représentant un suivi moyen de 9,6 ans, quinze n'ont jamais été réhospitalisés; des 14 autres, seuls 5 ont requis une intubation et une ventilation mécanique lors d'un épiode ultérieur. La majorité des hospitalisations ultérieures (81%) sont survenues dans les 6 ans suivant l'épiode initial

A comparison of three methods of Mendelian randomization when the genetic instrument, the risk factor and the outcome are all binary.

The method of instrumental variable (referred to as Mendelian randomization when the instrument is a genetic variant) has been initially developed to infer on a causal effect of a risk factor on some outcome of interest in a linear model. Adapting this method to nonlinear models, however, is known to be problematic. In this paper, we consider the simple case when the genetic instrument, the risk factor, and the outcome are all binary. We compare via simulations the usual two-stages estimate of a causal odds-ratio and its adjusted version with a recently proposed estimate in the context of a clinical trial with noncompliance. In contrast to the former two, we confirm that the latter is (under some conditions) a valid estimate of a causal odds-ratio defined in the subpopulation of compliers, and we propose its use in the context of Mendelian randomization. By analogy with a clinical trial with noncompliance, compliers are those individuals for whom the presence/absence of the risk factor X is determined by the presence/absence of the genetic variant Z (i.e., for whom we would observe X = Z whatever the alleles randomly received at conception). We also recall and illustrate the huge variability of instrumental variable estimates when the instrument is weak (i.e., with a low percentage of compliers, as is typically the case with genetic instruments for which this proportion is frequently smaller than 10%) where the inter-quartile range of our simulated estimates was up to 18 times higher compared to a conventional (e.g., intention-to-treat) approach. We thus conclude that the need to find stronger instruments is probably as important as the need to develop a methodology allowing to consistently estimate a causal odds-ratio.

Current practice in neuropsychological outcome reporting after aneurysmal subarachnoid haemorrhage.

BACKGROUND: Neuropsychological deficits (NPD) are common in patients with aneurysmal subarachnoid haemorrhage (aSAH). NPD are one of the major limiting factors for patients with an otherwise acceptable prognosis for sustained quality of life. There are only a few studies reporting outcome after aSAH, which used a standardized neuropsychological test battery as a primary or secondary outcome measure. Aim of this study was to determine the current practice of reporting NPD following aSAH in clinical studies. METHODS: A MEDLINE analysis was performed using the search term "subarachnoid haemorrhage outcome". The latest 1,000 articles were screened. We recorded study design, number of patients, and the presence of neuropsychological outcome report. Additionally, the time of testing after aSAH, the neuropsychological tests administered, as well as the percentage of patients with NPD were analyzed. RESULTS: A total of 324 publications between 2009 and 2012 were selected for further review. Of those, 21 studies (6.5%) reported neuropsychological outcome, in 2,001 of 346,666 patients (0.6%). The assessment of NPD differed broadly using both subjective and objective cognitive evaluation, and a large variety of tests were used. CONCLUSION: Neuropsychological outcome is underreported, and there is great variety in assessment in currently published clinical articles on aSAH. Prospective randomized trials treating aSAH may benefit from implementing more comprehensive and standardized neuropsychological outcome measures. This approach might identify otherwise unnoticed treatment effects in future interventional studies of aSAH patients.

Outcome of long-axis percutaneous sacroplasty for the treatment of sacral insufficiency fractures.

Our aim was to assess the clinical outcome of patients who were subjected to long-axis sacroplasty for the treatment of sacral insufficiency fractures. Nineteen patients with unilateral (n = 3) or bilateral (n = 16) sacral fractures were involved. Under local anaesthesia, each patient was subjected to CT-guided sacroplasty using the long-axis approach through a single entry point. An average of 6 ml of polymethylmethacrylate (PMMA) was delivered along the path of each sacral fracture. For each individual patient, the Visual Analogue pain Scale (VAS) before sacroplasty and at 1, 4, 24 and 48 weeks after the procedure was obtained. Furthermore, the use of analgesics (narcotic/non-narcotic) along with the evolution of post-interventional patient mobility before and after sacroplasty was also recorded. The mean pre-procedure VAS was 8 +/- 1.9 (range, 2 to 10). This rapidly and significantly (P < 0.001) declined in the first week after the procedure (mean 4 +/- 1.4; range, 1 to 7) followed by a gradual and significant (P < 0.001) decrease along the rest of the follow-up period at 4 weeks (mean 3 +/- 1.1; range, 1 to 5), 24 weeks (mean 2.2 +/- 1.1; range, 1 to 5) and 48 weeks (mean 1.6 +/- 1.1; range, 1 to 5). Eleven (58%) patients were under narcotic analgesia before sacroplasty, whereas 8 (42%) patients were using non-narcotics. Corresponding values after the procedure were 2/19 (10%; narcotic, one of them was on reserve) and 10/19 (53%; non-narcotic). The remaining 7 (37%) patients did not address post-procedure analgesic use. The evolution of post-interventional mobility was favourable in the study group as they revealed a significant improvement in their mobility point scale (P < 0.001). Long-axis percutaneous sacroplasty is a suitable, minimally invasive treatment option for patients who present with sacral insufficiency fractures. More studies with larger patient numbers are needed to explore any unrecognised limitations of this therapeutic approach.

Single-step extraction of fluconazole from plasma by ultra-filtration for the measurement of its free concentration by high performance liquid chromatography.

High performance liquid chromatography (HPLC) is the reference method for measuring concentrations of antimicrobials in blood. This technique requires careful sample preparation. Protocols using organic solvents and/or solid extraction phases are time consuming and entail several manipulations, which can lead to partial loss of the determined compound and increased analytical variability. Moreover, to obtain sufficient material for analysis, at least 1 ml of plasma is required. This constraint makes it difficult to determine drug levels when blood sample volumes are limited. However, drugs with low plasma-protein binding can be reliably extracted from plasma by ultra-filtration with a minimal loss due to the protein-bound fraction. This study validated a single-step ultra-filtration method for extracting fluconazole (FLC), a first-line antifungal agent with a weak plasma-protein binding, from plasma to determine its concentration by HPLC. Spiked FLC standards and unknowns were prepared in human and rat plasma. Samples (240 microl) were transferred into disposable microtube filtration units containing cellulose or polysulfone filters with a 5 kDa cut-off. After centrifugation for 60 min at 15000g, FLC concentrations were measured by direct injection of the filtrate into the HPLC. Using cellulose filters, low molecular weight proteins were eluted early in the chromatogram and well separated from FLC that eluted at 8.40 min as a sharp single peak. In contrast, with polysulfone filters several additional peaks interfering with the FLC peak were observed. Moreover, the FLC recovery using cellulose filters compared to polysulfone filters was higher and had a better reproducibility. Cellulose filters were therefore used for the subsequent validation procedure. The quantification limit was 0.195 mgl(-1). Standard curves with a quadratic regression coefficient &gt; or = 0.9999 were obtained in the concentration range of 0.195-100 mgl(-1). The inter and intra-run accuracies and precisions over the clinically relevant concentration range, 1.875-60 mgl(-1), fell well within the +/-15% variation recommended by the current guidelines for the validation of analytical methods. Furthermore, no analytical interference was observed with commonly used antibiotics, antifungals, antivirals and immunosuppressive agents. Ultra-filtration of plasma with cellulose filters permits the extraction of FLC from small volumes (240 microl). The determination of FLC concentrations by HPLC after this single-step procedure is selective, precise and accurate.

Acute multivessel revascularization improves 1-year outcome in ST-elevation myocardial infarction: a nationwide study cohort from the AMIS Plus registry.

BACKGROUND: The optimal strategy for percutaneous coronary intervention (PCI) of ST-segment elevation myocardial infarction (STEMI) in multi-vessel disease (MVD), i.e., multi-vessel PCI (MV-PCI) vs. PCI of the infarct-related artery only (IRA-PCI), still remains unknown. METHODS: Patients of the AMIS Plus registry admitted with an acute coronary syndrome were contacted after a median of 378 days (interquartile range 371-409). The primary end-point was all-cause death. The secondary end-point included all major adverse cardiovascular and cerebrovascular events (MACCE) including death, re-infarction, re-hospitalization for cardiac causes, any cardiac re-intervention, and stroke. RESULTS: Between 2005 and 2012, 8330 STEMI patients were identified, of whom 1909 (24%) had MVD. Of these, 442 (23%) received MV-PCI and 1467 (77%) IRA-PCI. While all-cause mortality was similar in both groups (2.7% both, p>0.99), MACCE was significantly lower after MV-PCI vs. IRA-PCI (15.6% vs. 20.0%, p=0.038), mainly driven by lower rates of cardiac re-hospitalization and cardiac re-intervention. Patients undergoing MV-PCI with drug-eluting stents had lower rates of all-cause mortality (2.1% vs. 7.4%, p=0.026) and MACCE (14.1% vs. 25.9%, p=0.042) compared with those receiving bare metal stents (BMS). In multivariate analysis, MV-PCI (odds ratio, OR 0.69, 95% CI 0.51-0.93, p=0.017) and comorbidities (Charlson index ≥ 2; OR 1.42, 95% CI 1.05-1.92, p=0.025) were independent predictors for 1-year MACCE. CONCLUSION: In an unselected nationwide real-world cohort, an approach using immediate complete revascularization may be beneficial in STEMI patients with MVD regarding MACCE, specifically when drug-eluting stents are used, but not regarding mortality. This has to be tested in a randomized controlled trial.

Recurrence of status epilepticus: Prognostic role and outcome predictors.

OBJECTIVE: Predictors of morbidity and mortality after status epilepticus (SE) have been studied extensively in hospital- and population-based cohorts. However, little attention has been directed toward SE recurrence after an incident episode. We investigated clinical and demographic characteristics of patients presenting SE recurrence and its specific prognostic role. METHODS: In this observational cohort study, we screened our prospective registry of consecutive adults with SE between April 2006 and February 2014. Demographic and clinical data were compared between incident and recurrent SE episodes; risk of SE recurrence was assessed through survival analysis, and the prognostic role of SE recurrence with multivariable logistic regressions. RESULTS: Of the incident cohort (509 patients), 68 (13%) experienced recurrent SE. The cumulative recurrence rate over 4 years was 32%. Recurrence risk was significantly reduced after an acute SE etiology (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.31-0.82; p = 0.005), and was borderline increased in women (HR 1.59, 95% CI 0.97-2.65; p = 0.06). Although recurrent SE episodes showed lower morbidity and mortality, prognosis was independently related to Status Epilepticus Severity Score (STESS) and potentially fatal etiology, but not to SE recurrence. SIGNIFICANCE: This study provides class III evidence that SE recurrence involves a significant proportion of patients, and that recurrence risk is independently associated with chronic etiology and to a lesser extent with female gender. However, contrary to underlying cause and SE severity, SE recurrence per se does not independently correlate with outcome. Early identification of patients at higher risk of SE recurrence may influence their management during follow-up.