Dynamic assessment of prealbumin for nutrition support effectiveness in critically ill patients.

BACKGROUND & AIMS: Serum prealbumin is considered to be a sensitive predictor of clinical outcomes and a quality marker for nutrition support. However, its susceptibility to inflammation restricts its usage in critically ill patients according to current guidelines. We assessed the performance of the initial value of prealbumin and dynamic changes for predicting the ICU mortality and the effectiveness of nutrition support in critically ill patients. METHODS: This monocentric study included patients admitted to the ICU between 2009 and 2016, having at least one initial prealbumin value available. Prospectively recorded data were extracted from the electronic ICU charts. We used both univariable and multivariable logistic regressions to estimate the performance of prealbumin for the prediction of ICU mortality. Additionally, the association between prealbumin dynamic changes and nutrition support was assessed via a multivariable linear mixed-effects model and multivariable linear regression. Performing subgroup analysis assisted in identifying patients for whom prealbumin dynamic assessment holds specific relevance. RESULTS: We included 3136 patients with a total of 4942 prealbumin levels available. Both prealbumin measured at ICU admission (adjusted odds-ratio (aOR) 0.04, confidence interval (CI) 95% 0.01-0.23) and its change over the first week (aOR 0.02, CI 95 0.00-0.19) were negatively associated with ICU mortality. Throughout the entire ICU stay, prealbumin dynamic changes were associated with both cumulative energy (estimate: 33.2, standard error (SE) 0.001, p < 0.01) and protein intakes (1.39, SE 0.001, p < 0.01). During the first week of stay, prealbumin change was independently associated with mean energy (6.03e-04, SE 2.32e-04, p < 0.01) and protein intakes (1.97e-02, SE 5.91e-03, p < 0.01). Notably, the association between prealbumin and energy intake was strongest among older or malnourished patients, those suffering from increased inflammation and those with high disease severity. Finally, prealbumin changes were associated with a positive mean nitrogen balance at day 7 only in patients with SOFA <4 (p = 0.047). CONCLUSION: Prealbumin measured at ICU admission and its change during the first-week serve as an accurate predictor of ICU mortality. Prealbumin dynamic assessment may be a reliable tool to estimate the effectiveness of nutrition support in the ICU, especially among high-risk patients.

Agreement between self-, mother and father proxy-reports on health-related quality of life in adolescents with Tourette syndrome.

This study aimed to investigate agreement and discrepancies between parent proxy- and adolescent self-reports on assessments of adolescents' health-related quality of life (HRQoL), and the role that individual factors may play in parent-adolescent agreement, in a sample of adolescents with Tourette syndrome (TS) compared to a control group of healthy adolescents. Adolescents aged 12-18 years diagnosed with TS were recruited with their parents from primary and secondary referral centres. Adolescent healthy controls were matched for gender and age. Adolescents and each of their parents completed a set of questionnaires including a HRQoL evaluation of adolescent, the 'Vécu et Santé Perçue de l'Adolescent'. Mother-adolescent, father-adolescent and mother-father agreements on adolescents' HRQoL scores were investigated at individual and group level, both in TS and control groups. Data were available for 75 adolescents, 75 mothers and 63 fathers, in the TS group. Agreement between mother, father proxy-reports and TS adolescents self-reports of HRQoL varied from poor to good, without significant difference with the control group. In TS group, mothers and fathers underestimated adolescents' HRQoL in 'Psychological well-being' subscale and mothers underestimated it in 'Physical 'well-being' subscale, while controls overestimated adolescents' HRQoL in these subscales. Larger mother-adolescent discrepancies for 'Psychological well-being' and 'Physical well-being' subscales were associated with internalizing symptoms. Regarding future studies, comprehensive evaluation of the various dimensions of adolescents' HRQoL with TS requires the integration of the perspectives of both adolescents, mothers and fathers. Clinicians should take into account this point to provide comprehensive care and services.

Deep brain stimulation of the subthalamic nucleus in severe Parkinson's disease: relationships between dual-contact topographic setting and 1-year worsening of speech and gait.

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) alleviates severe motor fluctuations and dyskinesia in Parkinson's disease, but may result in speech and gait disorders. Among the suspected or demonstrated causes of these adverse effects, we focused on the topography of contact balance (CB; individual, right and left relative dual positions), a scantly studied topic, analyzing the relationships between symmetric or non-symmetric settings, and the worsening of these signs. METHOD: An observational monocentric study was conducted on a series of 92 patients after ethical approval. CB was specified by longitudinal and transversal positions and relation to the STN (CB sub-aspects) and totalized at the patient level (patient CB). CB was deemed symmetric when the two contacts were at the same locations relative to the STN. CB was deemed asymmetric when at least one sub-aspect differed in the patient CB. Baseline and 1-year characteristics were routinely collected: (i) general, namely, Unified Parkinson's Disease Rating Scores (UPDRS), II, III motor and IV, daily levodopa equivalent doses, and Parkinson's Disease Questionnaire of Quality of Life (PDQ39) scores; (ii) specific, namely scores for speech (II-5 and III-18) and axial signs (II-14, III-28, III-29, and III-30). Only significant correlations were considered (p < 0.05). RESULTS: Baseline characteristics were comparable (symmetric versus asymmetric). CB settings were related to deteriorations of speech and axial signs: communication PDQ39 and UPDRS speech and gait scores worsened exclusively with symmetric settings; the most influential CB sub-aspect was symmetric longitudinal position. CONCLUSION: Our findings suggest that avoiding symmetric CB settings, whether by electrode positioning or shaping of electric fields, could reduce worsening of speech and gait.

Design and Rationale of the Sevoflurane for Sedation in Acute Respiratory Distress Syndrome (SESAR) Randomized Controlled Trial.

Preclinical studies have shown that volatile anesthetics may have beneficial effects on injured lungs, and pilot clinical data support improved arterial oxygenation, attenuated inflammation, and decreased lung epithelial injury in patients with acute respiratory distress syndrome (ARDS) receiving inhaled sevoflurane compared to intravenous midazolam. Whether sevoflurane is effective in improving clinical outcomes among patients with ARDS is unknown, and the benefits and risks of inhaled sedation in ARDS require further evaluation. Here, we describe the SESAR (Sevoflurane for Sedation in ARDS) trial designed to address this question. SESAR is a two-arm, investigator-initiated, multicenter, prospective, randomized, stratified, parallel-group clinical trial with blinded outcome assessment designed to test the efficacy of sedation with sevoflurane compared to intravenous propofol in patients with moderate to severe ARDS. The primary outcome is the number of days alive and off the ventilator at 28 days, considering death as a competing event, and the key secondary outcome is 90 day survival. The planned enrollment is 700 adult participants at 37 French academic and non-academic centers. Safety and long-term outcomes will be evaluated, and biomarker measurements will help better understand mechanisms of action. The trial is funded by the French Ministry of Health, the European Society of Anaesthesiology, and Sedana Medical.

Inhaled Sedation in Patients with COVID-19-Related Acute Respiratory Distress Syndrome: An International Retrospective Study.

BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic and the shortage of intravenous sedatives has led to renewed interest in inhaled sedation for patients with acute respiratory distress syndrome (ARDS). We hypothesized that inhaled sedation would be associated with improved clinical outcomes in COVID-19 ARDS patients. METHODS: Retrospective international study including mechanically ventilated patients with COVID-19 ARDS who required sedation and were admitted to 10 European and US intensive care units. The primary endpoint of ventilator-free days through day 28 was analyzed using zero-inflated negative binomial regression, before and after adjustment for site, clinically relevant covariates determined according to the univariate results, and propensity score matching. RESULTS: A total of 196 patients were enrolled, 78 of whom died within 28 days. The number of ventilator-free days through day 28 did not differ significantly between the patients who received inhaled sedation for at least 24 h (n = 111) and those who received intravenous sedation only (n = 85), with medians of 0 (interquartile range [IQR] 0-8) and 0 (IQR 0-17), respectively (odds ratio for having zero ventilator-free days through day 28, 1.63, 95% confidence interval [CI], 0.91-2.92, p = 0.10). The incidence rate ratio for the number of ventilator-free days through day 28 if not 0 was 1.13 (95% CI, 0.84-1.52, p = 0.40). Similar results were found after multivariable adjustment and propensity matching. CONCLUSION: The use of inhaled sedation in COVID-19 ARDS was not associated with the number of ventilator-free days through day 28.

Acute respiratory distress syndrome subphenotypes and therapy responsive traits among preclinical models: protocol for a systematic review and meta-analysis.

BACKGROUND: Subphenotypes were recently reported within clinical acute respiratory distress syndrome (ARDS), with distinct outcomes and therapeutic responses. Experimental models have long been used to mimic features of ARDS pathophysiology, but the presence of distinct subphenotypes among preclinical ARDS remains unknown. This review will investigate whether: 1) subphenotypes can be identified among preclinical ARDS models; 2) such subphenotypes can identify some responsive traits. METHODS: We will include comparative preclinical (in vivo and ex vivo) ARDS studies published between 2009 and 2019 in which pre-specified therapies were assessed (interleukin (IL)-10, IL-2, stem cells, beta-agonists, corticosteroids, fibroblast growth factors, modulators of the receptor for advanced glycation end-products pathway, anticoagulants, and halogenated agents) and outcomes compared to a control condition. The primary outcome will be a composite of the four key features of preclinical ARDS as per the American Thoracic Society consensus conference (histologic evidence of lung injury, altered alveolar-capillary barrier, lung inflammatory response, and physiological dysfunction). Secondary outcomes will include the single components of the primary composite outcome, net alveolar fluid clearance, and death. MEDLINE, Embase, and Cochrane databases will be searched electronically and data from eligible studies will be extracted, pooled, and analyzed using random-effects models. Individual study reporting will be assessed according to the Animal Research: Reporting of In Vivo Experiments guidelines. Meta-regressions will be performed to identify subphenotypes prior to comparing outcomes across subphenotypes and treatment effects. DISCUSSION: This study will inform on the presence and underlying pathophysiological features of subphenotypes among preclinical models of ARDS and should help to determine whether sufficient evidence exists to perform preclinical trials of subphenotype-targeted therapies, prior to potential clinical translation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (ID: CRD42019157236).

Low doses of ketamine reduce delirium but not opiate consumption in mechanically ventilated and sedated ICU patients: A randomised double-blind control trial.

CONTEXT: Low doses of ketamine are commonly used to decrease opiates tolerance, hyperalgesia and delirium in perioperative theatre but these properties have never been studied in intensive care unit (ICU) patients. PURPOSE: To determine the impact of ketamine infusion on opiates consumption when added to standard care in ICU patients requiring sedation for mechanical ventilation. METHODS: Patients admitted in a general ICU of a university hospital and undergoing mechanical ventilation (n = 162) with nurse-driven sedation protocol were randomly assigned into ketamine (2 mg/kg/h) or placebo in a double-blinded control trial. Patients were assessed for sedation and analgesia levels, opiates consumption and delirium (using the Confusion Assessment Method for ICU). RESULTS: Daily consumption of remifentanil (7.9 ± 1.0 vs. 9.3 ± 1.0 µg/kg/h, P = 0.548) and increase in remifentanil doses required for equianalgesia (0.107 ± 0.17 and 0.11 ± 0.18 µg/kg/min, P = 0.78) were not different between ketamine and control groups. The incidence was higher in the placebo group 30/82 (37%) than in the ketamine group 17/80 (21%) (P = 0.03). The duration of delirium was lower in ketamine group (5.3 ± 4.7 vs. 2.8 ± 3 days, P = 0.005). Mortality rates, ventilator-free days and ICU length of stay (LOS) were non-statistically different in both groups. CONCLUSIONS: When the best practices of sedation (nurse-driven sedation, a consistent light-to-moderate sedation level, and delirium monitoring) are used for all patients, the addition of low doses of ketamine does not decrease opiate consumption but reduces delirium incidence and its duration in medico-surgical ICU patients with no effect on mortality rate and ICU LOS.

Effects of dexmedetomidine on delirium duration of non-intubated ICU patients (4D trial): study protocol for a randomized trial.

BACKGROUND: Delirium during intensive care unit (ICU) stay is frequent and associated with significant morbidity, mortality and healthcare-related costs. International guidelines suggest its prevention. However, curative treatment remains unclearly established. Despite contradictory and ambiguous academic literature, international guidelines suggest the use of second-generation (atypical) antipsychotics over haloperidol. However, haloperidol remains the most widely used neuroleptic worldwide as a first-line treatment of agitation and/or delirium. Dexmedetomidine, an alpha2-adrenergic receptors agonist, has shown its efficiency in the treatment of delirium in intubated patients but also in its prevention. Dexmedetomidine represents a widely used alternative to haloperidol. Only few studies have compared the efficacy of dexmedetomidine in non-intubated ICU patients as a first-line curative treatment of delirium. The main objective of the 4D trial is to demonstrate that dexmedetomidine decreases delirium duration compared to placebo. METHODS/DESIGN: The 4D trial is an investigator-initiated, prospective, multicenter, randomized, double-blinded, two-arm trial, randomizing 300 non-intubated ICU patients with a diagnosis of agitated delirium to receive dexmedetomidine or placebo as a cure. In case of agitation (RASS≥ + 2), immediate haloperidol administration will be allowed, to protect patient and staff in charge, while waiting for study treatment action. The primary outcome measure is a composite of duration of agitation or delirium or the use of intubation with deep sedation and mechanical ventilation. Secondary outcomes include mortalities at 7 and 30 days, ICU length of stay and occurrence of adverse effects related to dexmedetomidine use (bradycardia or hypotension requesting any treatment; or haloperidol use (neuroleptic malignant syndrome, extrapyramidal syndrome, prolonged QTc). The sample size will allow the detection of a 50% decrease of agitation duration (120 min), of an absolute reduction of delirium duration (1 day) and of a 50% relative decrease of intubation and mechanical ventilation, with a type 1 error rate of 1.8% (error risk inflation due to components of composite) and power of 90%, assuming a 15% incidence of intubation and mechanical ventilation requirements, an agitation duration of 240 min and a delirium duration of 3 days. One hundred and ten patients by group will be needed. An intermediate analysis is scheduled and requires the inclusion of 150 patients. DISCUSSION: The 4D trial may provide important data on the safety of commonly used sedative dexmedetomidine and could have a significant impact on future treatment of non-intubated ICU patients presenting with agitated delirium. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT 03317067 . Registered on 23 October 2017.

Anatomical predictors of cognitive decline after subthalamic stimulation in Parkinson's disease.

We investigated whether pre-operative MRI measures of focal brain atrophy could predict cognitive decline occurring after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). For that purpose, we prospectively collected data of 42 consecutive patients with PD who underwent bilateral STN-DBS. Normalized brain structure volumes and cortical thicknesses were measured on pre-operative T1-weighted MRI. Patients were tested for their cognitive performances before surgery and 1 year after. After controlling for age, gender, pre-operative disease severity, change in dopaminomimetic dose after surgery and contact location, we found correlations: (1) between the variation of the total Mattis dementia rating scale (MDRS) score and left lateral ventricle volume (p = 0.032), (2) between the variation of the initiation/perseveration subscore of the MDRS and the left nucleus accumbens volume (p = 0.042) and the left lateral ventricle volume (p = 0.017) and (3) between the variation of the backward digit-span task and the right and left superior frontal gyrus thickness (p = 0.004 and p = 0.007, respectively). Left nucleus accumbens atrophy was associated with decline in the initiation/perseveration subscore with the largest effect size (d = - 1.64). Pre-operative left nucleus accumbens volume strongly predicted postoperative decline in the initiation/attention subscore (AUC = 0.92, p < 0.001, 96.3% sensitivity, 80.0% specificity, 92.9% PPV and 92.9% NPV). We conclude that the morphometric measures of brain atrophy usually associated with cognitive impairment in PD can also explain or predict a part of cognitive decline after bilateral STN-DBS. In particular, the left accumbens nucleus volume could be considered as a promising marker for guiding surgical decisions.

Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) for the prevention of surgical site infection in elective colorectal surgery: study protocol for a multicentre, double-blind, randomised controlled clinical trial.

INTRODUCTION: Surgical site infections (SSIs) account for 30% of all healthcare-associated infections, with reported rates ranging from 8% and 30% after colorectal surgery and are associated with increased morbidity and mortality rates, length of hospital stay and costs in healthcare. Administration of systemic antimicrobial prophylaxis before surgery is recommended to reduce the risk of SSI, but the optimal regimen remains unclear. We aim to evaluate whether a combined oral and intravenous antimicrobial prophylaxis could be more effective to reduce the incidence of SSI after colorectal surgery, as compared with the standard practice of intravenous antimicrobial prophylaxis alone. METHODS AND ANALYSIS: Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) trial is a randomised, placebo-controlled, parallel, double-blind, multicentre study of 960 patients undergoing elective colorectal surgery. Patients will be randomly allocated in a 1:1 ratio to receive either combined oral and intravenous antimicrobial prophylaxis or intravenous antibiotic prophylaxis alone, stratified by centre, the surgical procedure (laparoscopic or open surgery) and according to the surgical skin antisepsis (chlorexidine-alcohol or povidione-iodine alcoholic solution). The primary endpoint is the rate of SSI by day 30 following surgery, with SSI defined by the criteria developed by the Centers for Disease Control and Prevention. Data will be analysed on the intention-to-treat principle and a per-protocol basis. ETHICS AND DISSEMINATION: COMBINE trial has been approved by an independent ethics committee for all study centres. Participant recruitment began in May 2016. Results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: EudraCT 2015-002559-84; NCT02618720.

Epidural analgesia in critically ill patients with acute pancreatitis: the multicentre randomised controlled EPIPAN study protocol.

BACKGROUND: Acute pancreatitis (AP) is associated with high morbidity and mortality in its most severe forms. Most patients with severe AP require intubation and invasive mechanical ventilation, frequently for more than 7 days, which is associated with the worst outcome. Recent increasing evidence from preclinical and clinical studies support the beneficial effects of epidural analgesia (EA) in AP, such as increased gut barrier function and splanchnic, pancreatic and renal perfusion, decreased liver damage and inflammatory response, and reduced mortality. Because recent studies suggest that EA might be a safe procedure in the critically ill, we sought to determine whether EA reduced AP-associated respiratory failure and other major clinical outcomes in patients with AP. METHODS AND ANALYSIS: The Epidural Analgesia for Pancreatitis (EPIPAN) trial is an investigator-initiated, prospective, multicentre, randomised controlled two-arm trial with assessor-blinded outcome assessment. The EPIPAN trial will randomise 148 patients with AP requiring admission to an intensive care unit (ICU) to receive EA (with patient-controlled epidural administration of ropivacaine and sufentanil) combined with standard care based on current recommendations on the treatment of AP (interventional group), or standard care alone (reference group). The primary outcome is the number of ventilator-free days at day 30. Secondary outcomes include main complications of AP (eg, organ failure and mortality, among others), levels of biological markers of systemic inflammation, epithelial lung injury, renal failure, and healthcare-associated costs. ETHICS AND DISSEMINATION: The study was approved by the appropriate ethics committee (CPP Sud-Est VI). Informed consent is required. If the combined application of EA and standard care proves superior to standard care alone in patients with AP in the ICU, the use of EA may become standard practice in experienced centres, thereby decreasing potential complications related to AP and its burden in critically ill patients. The results will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02126332.

Subthalamus stimulation in Parkinson disease: Accounting for the bilaterality of contacts.

BACKGROUND: Deep brain stimulation (DBS) in Parkinson's disease uses bi-hemispheric high-frequency stimulation within the subthalamus, however, the specific impacts of bilaterality of DBS are still not clear. Thus, we aimed to study the individual-level clinical impact of locations of right-left contact pair-up accounting for each subthalamic nucleus (STN) anatomy. METHODS: Contact locations and effects at 1 year were studied retrospectively in an unselected series of 53 patients operated between 2004 and 2010. Location of contacts was defined relatively to the main axis of STN used to map longitudinal and transversal positions, and STN membership (out meaning out-of-STN). Contact pairings were described via three methods: (i) Unified contact location (UCL) collapsing DBS into an all-in-one contact; (ii) balance of contact pair-up (BCPU), defined as symmetric or asymmetric regardless of laterality; (iii) hemisphere-wise most frequent contact pair-up (MFCP) regardless of BCPU. Clinical data were: mean levodopa equivalent dose, Unified Parkinson's Disease Rating Scale (UPDRS) motor score III without medication, UPDRS II and III speech sub-scores, UPDRS II freezing sub-score, 1 year versus preoperative values, with and without levodopa. Ad-hoc two-sided tests were used for statistical analysis. RESULTS: Worsening speech, was more frequent for UCL_out patients and when the left MFCP contact was rear and/or superolateral, however, it less frequent for BCPU-asymmetric patients. Worsening freezing was more frequent when the right MFCP contact was rear and superolateral. CONCLUSIONS: These results point to strategies for minimizing dysarthria and freezing as adverse effects of DBS.

Fluid loading in abdominal surgery - saline versus hydroxyethyl starch (FLASH Trial): study protocol for a randomized controlled trial.

BACKGROUND: Inappropriate fluid therapy during surgery is associated with significant morbidity and mortality. Few studies have examined the effects of particular types of fluids (crystalloid or colloid solutions) in surgical patients, especially with the goal of hemodynamic optimization. Isotonic saline is the most commonly used fluid worldwide but may be associated with potential nephrotoxicity. Hydroxyethyl starch (HES) solutions are widely used in surgical patients as a component of goal-directed fluid optimization strategies, but several large multicenter studies have suggested increased rates of acute kidney injury and adverse events with the use of HES in ICU patients. Despite what may be inferred from physiological studies, the benefit and harm of 0.9 % saline and HES during hemodynamic therapy have not been clearly established in surgical patients. METHODS/DESIGN: The FLASH trial is an investigator-initiated, prospective, multicenter, randomized, double-blinded, two-arm trial, randomizing 826 patients with moderate-to-high risk of postoperative complications to receive 6 % HES 130/0.4 or 0.9 % saline during individualized goal-directed fluid optimization. The primary outcome measure is a composite of death or major postoperative complications within 14 days following surgery. The sample size will allow the detection of a 10 % absolute between-group difference in the primary outcome measure with a type 1 error rate of 5 % and power of 95 %, assuming a 5 % mortality rate and 20 % morbidity (thus 25 % for the composite endpoint). DISCUSSION: The FLASH trial may provide important data on the efficacy and safety of commonly used fluid solutions and could have a significant impact on future treatment of surgical patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02502773 . Registered 16 June 2015.

Emergence of restless legs syndrome after subthalamic stimulation in Parkinson's disease: a dopaminergic overstimulation?

OBJECTIVE: Studies investigating the effects of subthalamic deep-brain stimulation (DBS-STN) on restless legs syndrome (RLS) in Parkinson's disease (PD) are limited and report conflicting results, with some describing the emergence of RLS after DBS-STN, while others report postoperative improvement of this disorder. Severe decrease in postoperative dopaminergic medications dose, which may unmask RLS symptoms, has been proposed to explain the emergence of RLS after surgery. We aimed to specifically identify factors associated with the risk of developing RLS after DBS-STN in order to enhance our comprehension of the underlying mechanisms contributing to the development of RLS in PD. PATIENTS: In this observational prospective study, we evaluated the occurrence of RLS in 31 patients with PD originally free from RLS symptoms, six months after bilateral chronic DBS-STN, and compared clinical and treatment parameters of patients who developed postoperative RLS with those of patients without postoperative RLS. RESULTS: Six patients out of 31 reported post-operative emergence of RLS. There was no between-group difference in demographic data, pre-operative treatment parameters or clinical improvement measures after DBS-STN. However, PD patients with emergence of RLS after DBS-STN had a higher dose of dopamine agonists at postoperative evaluation compared to PD patients without emergence of RLS (p = 0.040) and a lower percentage of decrease in dopamine agonists (p = 0.043). CONCLUSION: Overstimulation resulting from cumulative effects of dopamine agonists and STN-DBS may induce changes in excitability of the dopaminergic system, leading to an emergence of RLS. Clinicians should take into account this phenomenon while adjusting pharmacological treatment after surgery.

Central pain modulation after subthalamic nucleus stimulation: A crossover randomized trial.

OBJECTIVE: To investigate the acute effect of subthalamic nuclei deep brain stimulation (STN-DBS) and levodopa on pain and tolerance thresholds in patients with Parkinson disease. We hypothesized that a modification of pain threshold after STN-DBS would suggest a central modification of pain perception, whereas the absence of pain threshold change after STN-DBS would correspond to a peripheral mechanism via a decrease of painful stimuli. METHODS: Nineteen patients with Parkinson disease were included in this double-blind, randomized, crossover study. Postoperatively, we evaluated pain thresholds (thermal and mechanical) and motor symptoms under 3 acute conditions: stimulation on/medication off; stimulation off/medication on; and stimulation off/medication off. We also conducted a retrospective analysis of the data prospectively recorded during the follow-up of the cohort pre- and postoperatively (Unified Parkinson's Disease Rating Scale [UPDRS] score, Hoehn and Yahr stage, equivalent levodopa daily dose, and tapping test score). RESULTS: We found a significant increase of pain and tolerance mechanical thresholds not only after acute STN-DBS but also after acute levodopa administration. We did not find any significant correlation between postoperative clinical pain improvement and UPDRS-III improvement after acute levodopa or STN-DBS, nor with motor complications improvement assessed with UPDRS-IV after chronic STN-DBS. No correlation was found between postoperative clinical pain improvement and mechanical pain threshold modification. CONCLUSION: Clinical pain alleviation after STN-DBS cannot be considered merely as a consequence of motor complications improvement and could be attributable to a direct central modulation of pain perception, via increased mechanical pain and tolerance thresholds.

Quality of life in adults with Gilles de la Tourette Syndrome.

BACKGROUND: Few studies have used standardized QOL instruments to assess the quality of life (QOL) in Gilles de la Tourette Syndrome (GTS) patients. This work investigates the QOL of adult GTS patients and examines the relationships between physical and psychological variables and QOL. METHODS: Epidemiological investigation by anonymous national postal survey of QOL of patients of the French Association of Gilles de la Tourette Syndrome (AFGTS) aged 16 years or older. The clinical and QOL measures were collected by four questionnaires: a sociodemographic and GTS-related symptoms questionnaire, the World Health Organization Quality Of Life questionnaire (WHOQOL-26), the Functional Status Questionnaire (FSQ), and a self-rating questionnaire on psychiatric symptoms (SCL-90), all validated in French. We used stepwise regression analysis to explicitly investigate the relationships between physical and psychological variables and QOL domains in GTS. RESULTS: Questionnaires were posted to 303 patients, of whom 167 (55%) completed and returned them. Our results, adjusted for age and gender, show that patients with GTS have a worse QOL than the general healthy population. In particular, the "Depression" psychological variable was a significant predictor of impairment in all WHOQOL-26 domains, psychological but also physical and social. CONCLUSIONS: The present study demonstrates a strong relationship between QOL in GTS and psychiatric symptoms, in particular those of depression.

Characteristics of the neuropathy induced by thoracotomy: a 4-month follow-up study with psychophysical examination.

OBJECTIVES: To explore the role of neuropathy in persistent pain after thoracotomy, combining a clinical follow-up and a psychophysical examination of the operated area. METHODS: Seventy-three patients were followed and examined at their discharge from hospital, 6 weeks and 4 months after pneumonectomy under thoracotomy. Spontaneous and evoked pain was assessed by clinical examination, a 7-day pain score, and the Neuropathic Pain Symptom Inventory. At the fourth month follow-up, pain and tolerance thresholds to pinprick, heat, and warm sensation threshold were measured on both sides of the thorax. RESULTS: The rate of spontaneous pain was 40% at discharge and went up to 59% at the sixth week follow-up. Evoked pain was rare at discharge (11%), most cases appearing at the sixth week follow-up (47%). The evolution profiles of pain between the sixth week and the fourth month follow-up were heterogeneous with a tendency to decrease. Young age, female sex, and spontaneous pain observed at discharge from hospital were identified as early predictive factors of spontaneous pain persisting at the fourth month follow-up. On the side of operation, thresholds tended to increase for warm and hot stimuli, and to decrease for mechanical stimuli. At the fourth month follow-up, spontaneous pain and evoked pain were associated to static hyperalgesia, persisting hypoesthesia, low mechanical thresholds, altered sensation of heat, and impaired quality of life. DISCUSSION: Peripheral neuropathy is common after thoracotomy, with variant characteristics, ranging from subclinical disturbances to severe pain. The process seems to develop between the discharge from hospital and the sixth week after thoracotomy.

Early improvement in peripheral vascular tone following smoking cessation using nicotine replacement therapy: aortic wave reflection analysis.

OBJECTIVES: Cigarette smoking induces cardiovascular pathology and worsens arterial stiffness. Arterial stiffness can be assessed noninvasively based on 2 indices: pulse-wave velocity (PWV), indicating aortic stiffness, and the augmentation index (AIx), indicating aortic wave reflection. The impact of smoking cessation (SC) with nicotine replacement therapies (NRT) on arterial stiffness remains unknown. METHODS: AIx and PWV were studied prospectively (using a SphygmoCor system) in 26 long-term smokers (>10 cigarettes/day; mean age 43 ± 6 years) before (visit 1) and 28 and 56 days (visit 2 and visit 3) after SC supported by NRT. Abstinence was ascertained when exhaled carbon monoxide (CO) was <10 ppm; the quantity of NRT absorbed was assessed based on the serum cotinine level. RESULTS: Sixteen of 24 patients (67%) were abstinent at the end of the study; 8/24 had cut down on smoking, and 2 were lost to follow-up. CO and serum cotinine levels fell after SC. The mean AIx for the population as a whole was 23.4% at visit 1, with a significant early reduction by visit 2 (16.2%) and visit 3 (13.9%) (ANOVA, p < 0.001). The PWV, peripheral blood pressure, and heart rate were unchanged. CONCLUSIONS: The improvement in AIx and the stability of PWV after SC with NRT indicate improved peripheral vascular tone. This impact may account for the early clinical benefit of SC observed even when associated with NRT.

Rest and low-dose dobutamine Tc-99m-mibi gated-SPECT for early prediction of left ventricular remodeling after a first reperfused myocardial infarction.

BACKGROUND: Left ventricular (LV) remodeling after myocardial infarction (MI) occurs frequently despite successful percutaneaous coronary intervention (PCI) but cannot be predicted by simple clinical parameters. METHODS AND RESULTS: This prospective study tested the value of rest and low-dose dobutamine (LDD) Tc-99m-mibi gated-SPECT for early prediction of LV remodeling in patients treated by PCI in the acute phase of a first MI. Infarct size, infarct severity, regional wall motion abnormality (RWMA), and wall thickening score (WTs) were assessed at rest and on LDD by SPECT 6 +/- 2 days after MI in 40 patients. LV remodeling was defined as 20% increase at 6 months in LV end-diastolic volume assessed by MRI. Infarct severity at rest showed the best predictive values for left remodeling (PPV: 86%, NPV: 88%, accuracy: 88%; AUC: 0.750). Functional parameters at neither rest nor LDD study further improved predictive values of the SPECT imaging. CONCLUSIONS: Infarct severity assessed by Tc-99m-sestamibi gated-SPECT performed in the subacute phase of a first STEMI predicts LV remodeling with high accuracy without incremental value nor of functional parameters nor of LDD. Therefore, our results suggest that LDD should not be used in this setting.