TMEM151A as an alternative to PRRT2 in paroxysmal kinesigenic dyskinesia: About three new cases.

Paroxysmal kinesigenic dyskinesia (PKD) are movement disorders triggered by sudden voluntary movement. Variants in the TMEM151A gene have recently been associated with the development of PKD. We report three patients presenting PKD with different TMEM151A mutations, two of which have not been described yet.

Nicotine in Parkinson's Disease - a Therapeutic Track Gone up in Smoke?

In recent decades, numerous studies have found that smoking or the intake of any form of nicotine, such as smokeless tobacco, exposure to environmental tobacco smoke, or even dietary sources such as peppers, reduces the risk of developing Parkinson's disease.1 Such observations suggest a potential disease-modifying effect of nicotine in Parkinson's disease. Many experimental studies, some of them supported by grants from the tobacco industry, have lent support for such a hypothesis.

Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19.

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are being deployed, but the global need greatly exceeds the supply, and different formulations might be required for specific populations. Here we report Day 42 interim safety and immunogenicity data from an observer-blinded, dose escalation, randomized controlled study of a virus-like particle vaccine candidate produced in plants that displays the SARS-CoV-2 spike glycoprotein (CoVLP: NCT04450004 ). The co-primary outcomes were the short-term tolerability/safety and immunogenicity of CoVLP formulations assessed by neutralizing antibody (NAb) and cellular responses. Secondary outcomes in this ongoing study include safety and immunogenicity assessments up to 12 months after vaccination. Adults (18-55 years, n = 180) were randomized at two sites in Quebec, Canada, to receive two intramuscular doses of CoVLP (3.75 µg, 7.5 µg, and 15 µg) 21 d apart, alone or adjuvanted with AS03 or CpG1018. All formulations were well tolerated, and adverse events after vaccination were generally mild to moderate, transient and highest in the adjuvanted groups. There was no CoVLP dose effect on serum NAbs, but titers increased significantly with both adjuvants. After the second dose, NAbs in the CoVLP + AS03 groups were more than tenfold higher than titers in Coronavirus 2019 convalescent sera. Both spike protein-specific interferon-γ and interleukin-4 cellular responses were also induced. This pre-specified interim analysis supports further evaluation of the CoVLP vaccine candidate.

Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial.

BACKGROUND: Increased rates of sexually transmitted infections (STIs) have been reported among men who have sex with men. We aimed to assess whether post-exposure prophylaxis (PEP) with doxycycline could reduce the incidence of STIs. METHODS: All participants attending their scheduled visit in the open-label extension of the ANRS IPERGAY trial in France (men aged 18 years or older having condomless sex with men and using pre-exposure prophylaxis for HIV with tenofovir disoproxil fumarate plus emtricitabine) were eligible for inclusion in this open-label randomised study. Participants were randomly assigned (1:1) at a central site to take a single oral dose of 200 mg doxycycline PEP within 24 h after sex or no prophylaxis. The primary endpoint was the occurrence of a first STI (gonorrhoea, chlamydia, or syphilis) during the 10-month follow-up. The cumulative probability of occurrence of the primary endpoint was estimated in each group with the Kaplan-Meier method and compared with the log-rank test. The primary efficacy analysis was done on the intention-to-treat population, comprising all randomised participants. All participants received risk-reduction counselling and condoms, and were tested regularly for HIV. This trial is registered with ClinicalTrials.gov number, NCT01473472. FINDINGS: Between July 20, 2015, and Jan 21, 2016, we randomly assigned 232 participants (n=116 in the doxycycline PEP group and n=116 in the no-PEP group) who were followed up for a median of 8·7 months (IQR 7·8-9·7). Participants in the PEP group used a median of 680 mg doxycycline per month (IQR 280-1450). 73 participants presented with a new STI during follow-up, 28 in the PEP group (9-month probability 22%, 95% CI 15-32) and 45 in the no-PEP group (42%, 33-53; log-rank test p=0·007). The occurrence of a first STI in participants taking PEP was lower than in those not taking PEP (hazard ratio [HR] 0·53; 95% CI 0·33-0·85; p=0·008). Similar results were observed for the occurrence of a first episode of chlamydia (HR 0·30; 95% CI 0·13-0·70; p=0·006) and of syphilis (0·27; 0·07-0·98; p=0·047); for a first episode of gonorrhoea the results did not differ significantly (HR 0·83; 0·47-1·47; p=0·52). No HIV seroconversion was observed, and 72 (71%) of all 102 STIs were asymptomatic. Rates of serious adverse events were similar in the two study groups. Gastrointestinal adverse events were reported in 62 (53%) participants in the PEP group and 47 (41%) in the no-PEP group (p=0·05). INTERPRETATION: Doxycycline PEP reduced the occurrence of a first episode of bacterial STI in high-risk men who have sex with men. FUNDING: France Recherche Nord & Sud Sida-HIV Hépatites (ANRS) and Bill & Melinda Gates Foundation.

On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection.

BACKGROUND: Antiretroviral preexposure prophylaxis has been shown to reduce the risk of human immunodeficiency virus type 1 (HIV-1) infection in some studies, but conflicting results have been reported among studies, probably due to challenges of adherence to a daily regimen. METHODS: We conducted a double-blind, randomized trial of antiretroviral therapy for preexposure HIV-1 prophylaxis among men who have unprotected anal sex with men. Participants were randomly assigned to take a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or placebo before and after sexual activity. All participants received risk-reduction counseling and condoms and were regularly tested for HIV-1 and HIV-2 and other sexually transmitted infections. RESULTS: Of the 414 participants who underwent randomization, 400 who did not have HIV infection were enrolled (199 in the TDF-FTC group and 201 in the placebo group). All participants were followed for a median of 9.3 months (interquartile range, 4.9 to 20.6). A total of 16 HIV-1 infections occurred during follow-up, 2 in the TDF-FTC group (incidence, 0.91 per 100 person-years) and 14 in the placebo group (incidence, 6.60 per 100 person-years), a relative reduction in the TDF-FTC group of 86% (95% confidence interval, 40 to 98; P=0.002). Participants took a median of 15 pills of TDF-FTC or placebo per month (P=0.57). The rates of serious adverse events were similar in the two study groups. In the TDF-FTC group, as compared with the placebo group, there were higher rates of gastrointestinal adverse events (14% vs. 5%, P=0.002) and renal adverse events (18% vs. 10%, P=0.03). CONCLUSIONS: The use of TDF-FTC before and after sexual activity provided protection against HIV-1 infection in men who have sex with men. The treatment was associated with increased rates of gastrointestinal and renal adverse events. (Funded by the National Agency of Research on AIDS and Viral Hepatitis [ANRS] and others; ClinicalTrials.gov number, NCT01473472.).

Noninvasive ventilation and breathing-swallowing interplay in chronic obstructive pulmonary disease*.

OBJECTIVES: To investigate breathing-swallowing interactions in patients with chronic obstructive pulmonary disease requiring noninvasive mechanical ventilation and, if needed, to develop a technical modification of the ventilator designed to eliminate ventilator insufflations during swallowing. DESIGN: We conducted a prospective, open-label, interventional study. PATIENTS: Fifteen consecutive chronic obstructive pulmonary disease patients with exacerbations requiring ICU admission and NIV. INTERVENTIONS: Swallowing performance and breathing-swallowing interactions were investigated noninvasively by chin electromyography, cervical piezoelectric sensor, and inductive respiratory plethysmography. Two water-bolus sizes (5 and 10 mL) were tested in random order. Swallowing was tested with and without noninvasive mechanical ventilation, in random order. First, a standard mechanical ventilator capable of delivering noninvasive mechanical ventilation was used. Second, a marketed device was equipped with an off-switch for use during swallowing. MEASUREMENTS AND MAIN RESULTS: Swallowing performance and breathing-swallowing interactions were investigated noninvasively by chin electromyography, cervical piezoelectric sensor, and inductive respiratory plethysmography. Two water bolus sizes (5 and 10 mL) were tested in random order. Swallowing was tested with and without noninvasive mechanical ventilation in random order. First, a standard mechanical ventilator capable of delivering noninvasive mechanical ventilation was used. Swallowing efficiency, breathing-swallowing synchronization, and Borg Scale dyspnea scores improved significantly with noninvasive mechanical ventilation. However, swallowing induced ventilator triggering followed by autotriggering. To improve patient-ventilator synchrony, a marketed device was equipped with an off-switch for use during swallowing. This device completely eliminated swallowing-induced ventilator triggering and postswallow autotriggering. CONCLUSION: Patients with chronic obstructive pulmonary disease admitted to the ICU for acute exacerbations had abnormal breathing-swallowing interactions and dyspnea, which improved with noninvasive mechanical ventilation. Furthermore, a ventilator device with a simple switch-off pushbutton to eliminate insufflations during swallows prevented swallowing-induced ventilator triggering and postswallow autotriggering.

Challenges and opportunities for oral pre-exposure prophylaxis in the prevention of HIV infection: where are we in Europe?

Following US Food and Drugs Administration approval in July 2012 of daily oral tenofovir and emtricitabine for pre-exposure prophylaxis (PrEP) to prevent HIV infection in high-risk individuals in the USA, there has been much controversy about the implementation of this PrEP regimen in other countries throughout the world, and in Europe in particular. In this review, we focus on the challenges and opportunities of a daily oral PrEP regimen to curb the rising incidence of HIV infection in high-risk groups, and particularly in men who have sex with men. A number of issues would need to be addressed before PrEP could be implemented, including assessing the real effectiveness and cost-effectiveness of daily PrEP, the sustainability of daily adherence, the risk of selecting resistance, the long-term safety, and the risk of change in sexual behavior that might offset the benefit of PrEP. Alternatives to a daily oral PrEP regimen are being explored.

Accuracy of plasma neutrophil gelatinase-associated lipocalin in the early diagnosis of contrast-induced acute kidney injury in critical illness.

PURPOSE: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker for acute kidney injury (AKI). We evaluated the diagnostic and prognostic accuracies of plasma NGAL (pNGAL) for contrast-induced AKI (CI-AKI) in critically ill patients. METHODS: In a prospective observational study in two adult intensive care units in a university hospital, 100 consecutive critically ill patients with stable serum creatinine concentrations up to 48 h before contrast medium (CM) injection were enrolled. Serial blood sampling for pNGAL analysis was performed at enrolment, 2, 6, and 24 h after CM injection. The primary outcome was CI-AKI, defined by AKIN criteria, within the first 72 h following CM injection. Secondary outcomes were the need for renal replacement therapy (RRT) and mortality. RESULTS: Of the 98 patients analyzed, 30 developed CI-AKI. The pNGAL levels did not differ in patients with or without CI-AKI, and were higher in septic patients compared to nonseptic patients, and in patients with AKI preceding CM injection. The discriminative value of pNGAL to predict CI-AKI and mortality was poor; although, it did predict the need for RRT requirement after CM injection (area under receiver-operating characteristic curve, 0.85, 0.80, 0.83 and 0.86 at H0, H2, H6 and H24, respectively). CONCLUSION: CI-AKI was common in critically ill patients. pNGAL levels were higher in patients with sepsis or previous AKI, but did not help to diagnose CI-AKI any earlier than serum creatinine after CM injection. However, pNGAL could be of interest to detect patients at risk of subsequent RRT requirement.

Use of online blood volume and blood temperature monitoring during haemodialysis in critically ill patients with acute kidney injury: a single-centre randomized controlled trial.

BACKGROUND: Little is known about the clinical impact on cardiovascular stability during intermittent haemodialysis (IHD) for acute kidney injury (AKI) of online monitoring devices that control blood volume (BV) and blood temperature in the intensive care unit (ICU) setting. We compared different dialysis treatment modalities with or without these new systems among critically ill patients requiring IHD. METHODS: In a prospective single-centre three-arm randomized controlled trial, 600 dialysis sessions in 74 consecutive AKI critically ill patients were involved to assess intradialytic hypotension. Standard dialysis therapy with constant ultrafiltration (UF) rate, cool dialysate and high sodium conductivity (Treatment A) was compared to regimens with adjunctive interventions including BV control (Treatment B) and the combination of BV and active blood temperature control (Treatment C). Each dialysis session was randomly assigned to one of the three treatment arms and served as statistical unit. RESULTS: Five hundred and seventy-two dialysis sessions were analysed (188, 190 and 194 in Treatments A, B and C, respectively). Hypotension occurred in 16.6% treatments, with similar rates among the arms. Haemodynamic parameters and dialysis-related complications did not differ between therapies. Based on generalized estimating equation adjusted to dialysate sodium conductivity, higher Sequential Organ Failure Assessment the day of dialysis session, the need for vasopressors and lower systolic blood pressure at the onset of the session were identified as independent predictors of hypotensive episodes, whereas regimens containing the new online monitors were not. CONCLUSIONS: These results suggest that both actively controlled body temperature and UF profiled by online monitoring systems have no significant impact on the incidence of intradialytic hypotension in the ICU setting. Further research is needed before the use of these new sophisticated automatic methods can be applied routinely to the ICU setting.

A comparison of survival with and without extracorporeal life support treatment for severe poisoning due to drug intoxication.

BACKGROUND: The use of extracorporeal life support (ECLS) as a treatment for severe cardiovascular impairment due to poisoning is unclear. Therefore, we conducted a retrospective cohort analysis to compare survival among critically ill poisoned patients treated with or without ECLS. METHODS: All consecutive patients admitted into 2 university hospitals in northwestern France over the past decade for persistent cardiac arrest or severe shock following poisoning due to drug intoxication were included. ECLS was preferentially performed in 1 of the 2 centers. RESULTS: Sixty-two patients (39 women, 23 men; mean age 48±17 years) fulfilled inclusion criteria: 10 with persistent cardiac arrest and 42 with severe shock. Fourteen patients were treated with ECLS and 48 patients with conventional therapies. All subjects received vasopressor and fluid loading. Patients treated with or without ECLS at ICU admission had comparable drug ingestion histories, Simplified Acute Physiology Score (SAPS II score) (66±18), Sequential Organ Failure Assessment (SOFA) score (median: 11 [IQR, 9-13]), Glasgow Coma Scale score (median: 3 [IQR, 3-11]), need for ventilator support (n=56) and extra renal support (n=23). Thirty-five (56%) patients survived: 12/14 (86%) ECLS patients and 23/48 (48%) non-ECLS patients (p=0.02, by Fisher exact test). None of the patients with persistent cardiac arrest survived without ECLS support. Based on admission data, beta-blocker intoxication (p=0.02) was also associated with lower mortality. In multivariate analysis, adjusting for SAPS II and beta-blocker intoxication, ECLS support remained associated with lower mortality [Adjusted Odds Ratio, 0.18; 95% CI, 0.03-0.96; p=0.04]. CONCLUSION: In the absence of response to conventional therapies, we consider that ECLS may improve survival in critically ill poisoned patients experiencing cardiac arrest and severe shock.

Overview of adverse events related to invasive procedures in the intensive care unit.

BACKGROUND: This study was conducted to determine the frequency, predictors, and clinical impact of adverse events (AEs) related to invasive procedures in the intensive care unit (ICU). METHODS: This was a prospective observational study of ICUs in a university hospital. RESULTS: A total of 893 patients requiring invasive procedures were admitted over a 1-year period. Among these, 310 patients (34.7%) experienced a total of 505 AEs. The mean number of AEs per patient was 1.6 ± 1.1 (range, 1-7). Infectious AEs were significantly more frequent than mechanical AEs (60.4% vs 39.6%; P = .01). Factors independently associated with AE occurrence were isolation of multidrug-resistant bacteria at ICU admission, >5 invasive procedures, and ICU length of stay >8 days. Thirty-three AEs (6.5%) resulted in severe clinical impact, including 24 deaths. Ventilator-associated pneumonia (VAP) accounted for 62.5% of the deaths related to AEs. CONCLUSIONS: One-third of critically ill patients experienced AEs related to invasive procedures. Severe AEs were associated with 11% of all ICU deaths. VAP was the most frequent AE related to death. An improved assessment of the risk-benefit balance before each invasive procedure and increased efforts to decrease VAP prevalence are needed to reduce AE-related mortality.

Serum neuron-specific enolase as predictor of outcome in comatose cardiac-arrest survivors: a prospective cohort study.

BACKGROUND: The prediction of neurological outcome in comatose patients after cardiac arrest has major ethical and socioeconomic implications. The purpose of this study was to assess the capability of serum neuron-specific enolase (NSE), a biomarker of hypoxic brain damage, to predict death or vegetative state in comatose cardiac-arrest survivors. METHODS: We conducted a prospective observational cohort study in one university hospital and one general hospital Intensive Care Unit (ICU). All consecutive patients who suffered cardiac arrest and were subsequently admitted from June 2007 to February 2009 were considered for inclusion in the study. Patients who died or awoke within the first 48 hours of admission were excluded from the analysis. Patients were followed for 3 months or until death after cardiopulmonary resuscitation. The Cerebral Performance Categories scale (CPC) was used as the outcome measure; a CPC of 4-5 was regarded as a poor outcome, and a CPC of 1-3 a good outcome. Measurement of serum NSE was performed at 24 h and at 72 h after the time of cardiac arrest using an enzyme immunoassay. Clinicians were blinded to NSE results. RESULTS: Ninety-seven patients were included. All patients were actively supported during the first days following cardiac arrest. Sixty-five patients (67%) underwent cooling after resuscitation. At 3 months 72 (74%) patients had a poor outcome (CPC 4-5) and 25 (26%) a good outcome (CPC 1-3). The median and Interquartile Range [IQR] levels of NSE at 24 h and at 72 h were significantly higher in patients with poor outcomes: NSE at 24 h: 59.4 ng/mL [37-106] versus 28.8 ng/mL [18-41] (p < 0.0001); and NSE at 72 h: 129.5 ng/mL [40-247] versus 15.7 ng/mL [12-19] (p < 0.0001). The Receiver Operator Characteristics (ROC) curve for poor outcome for the highest observed NSE value for each patient determined a cut-off value for NSE of 97 ng/mL to predict a poor neurological outcome with a specificity of 100% [95% CI = 87-100] and a sensitivity of 49% [95% CI = 37-60]. However, an approach based on a combination of SSEPs, NSE and clinical-EEG tests allowed to increase the number of patients (63/72 (88%)) identified as having a poor outcome and for whom intensive treatment could be regarded as futile. CONCLUSION: NSE levels measured early in the course of patient care for those who remained comatose after cardiac arrest were significantly higher in patients with outcomes of death or vegetative state. In addition, we provide a cut-off value for NSE (> 97 ng/mL) with 100% positive predictive value of poor outcome. Nevertheless, for decisions concerning the continuation of treatment in this setting, we emphasize that an approach based on a combination of SSEPs, NSE and clinical EEG would be more accurate for identifying patients with a poor neurological outcome.

Predictors of mortality and short-term physical and cognitive dependence in critically ill persons 75 years and older: a prospective cohort study.

BACKGROUND: The purpose of this study was to identify predictors of 3-month mortality in critically ill older persons under medical care and to assess the clinical impact of an ICU stay on physical and cognitive dependence and subjective health status in survivors. METHODS: We conducted a prospective observational cohort study including all older persons 75 years and older consecutively admitted into ICU during a one-year period, except those admitted after cardiac arrest, All patients were followed for 3 months or until death. Comorbidities were assessed using the Charlson index and physical dependence was evaluated using the Katz index of Activity of Daily Living (ADL). Cognitive dependence was determined by a score based on the individual components of the Lawton index of Daily Living and subjective health status was evaluated using the Nottingham Health Profile (NHP) score. RESULTS: One hundred patients were included in the analysis. The mean age was 79.3 ± 3.4 years. The median Charlson index was 6 [IQR, 4 to 7] and the mean ADL and cognitive scores were 5.4 ± 1.1 and 1.2 ± 1.4, respectively, corresponding to a population with a high level of comorbidities but low physical and cognitive dependence. Mortality was 61/100 (61%) at 3 months. In multivariate analysis only comorbidities assessed by the Charlson index [Adjusted Odds Ratio, 1.6; 95% CI, 1.2-2.2; p < 0.003] and the number of organ failures assessed by the SOFA score [Adjusted Odds Ratio, 2.5; 95% CI, 1.1-5.2; p < 0.02] were independently associated with 3-month mortality. All 22 patients needing renal support after Day 3 died. Compared with pre-admission, physical (p = 0.04), and cognitive (p = 0.62) dependence in survivors had changed very little at 3 months. In addition, the mean NHP score was 213.1 ± 132.8 at 3 months, suggesting an acceptable perception of their quality of life. CONCLUSIONS: In a selected population of non surgical patients 75 years and older, admission into the ICU is associated with a 3-month survival rate of 38% with little impact on physical and cognitive dependence and subjective health status. Nevertheless, a high comorbidity level (ie, Charlson index), multi-organ failure, and the need for extra-renal support at the early phase of intensive care could be considered as predictors of death.

Admission of advanced lung cancer patients to intensive care unit: a retrospective study of 76 patients.

BACKGROUND: Criteria for admitting patients with incurable diseases to the medical intensive care unit (MICU) remain unclear and have ethical implications. METHODS: We retrospectively evaluated MICU outcomes and identified risk factors for MICU mortality in consecutive patients with advanced lung cancer admitted to two university-hospital MICUs in France between 1996 and 2006. RESULTS: Of 76 included patients, 49 had non-small cell lung cancer (stage IIIB n = 20; stage IV n = 29). In 60 patients, MICU admission was directly related to the lung cancer (complication of cancer management, n = 30; cancer progression, n = 14; and lung-cancer-induced diseases, n = 17). Mechanical ventilation was required during the MICU stay in 57 patients. Thirty-six (47.4%) patients died in the MICU. Three factors were independently associated with MICU mortality: use of vasoactive agents (odds ratio [OR] 6.81 95% confidence interval [95%CI] [1.77-26.26], p = 0.005), mechanical ventilation (OR 6.61 95%CI [1.44-30.5], p = 0.015) and thrombocytopenia (OR 5.13; 95%CI [1.17-22.5], p = 0.030). In contrast, mortality was lower in patients admitted for a complication of cancer management (OR 0.206; 95%CI [0.058-0.738], p = 0.015). Of the 27 patients who returned home, four received specific lung cancer treatment after the MICU stay. CONCLUSIONS: Patients with acute complications of treatment for advanced lung cancer may benefit from MCIU admission. Further studies are necessary to assess outcomes such as quality of life after MICU discharge.

Neurally adjusted ventilatory assist in patients recovering spontaneous breathing after acute respiratory distress syndrome: physiological evaluation.

OBJECTIVE: Pressure-support ventilation is widely used during the weaning phase in patients with acute respiratory distress syndrome. The pressure-support level is adjusted to prevent ventilator-induced lung injury while limiting the patient's work of breathing. Neurally adjusted ventilatory assist is an assist mode that applies a positive pressure proportional to the integral of the electrical activity of the diaphragm. The objective was to assess the physiologic response to varying pressure-support ventilation and neurally adjusted ventilatory assist levels in selected acute respiratory distress syndrome patients and to evaluate the effect of neural triggering. METHODS: We prospectively assessed 11 consecutive patients with acute respiratory distress syndrome attributable to pulmonary diseases. Pressure-support ventilation and neurally adjusted ventilatory assist were used in random order. Neurally adjusted ventilatory assist was used with a low electrical activity of the diaphragm trigger (neurally adjusted ventilatory assist-electrical activity of the diaphragm) and with a high electrical activity of the diaphragm trigger that led to rescue triggering by inspiratory flow (neurally adjusted ventilatory assist-inspiratory flow). With each ventilation modality, four levels of assistance (100%, 120%, 140%, and 160%) were used in random order. Statistical analysis was performed using analysis of variance for repeated measurements and mixed models. MAIN RESULTS: Contrary to pressure-support ventilation, neurally adjusted ventilatory assist-electrical activity of the diaphragm and neurally adjusted ventilatory assist-inspiratory flow were associated with stable tidal volume levels despite increasing assistance. For the asynchrony index, an interaction was present between ventilation mode and assist level (p = .0076) because asynchrony index increased significantly with the pressure-support ventilation level (p = .004), but not with the neurally adjusted ventilatory assist-electrical activity of the diaphragm or neurally adjusted ventilatory assist-inspiratory flow level. The lowest asynchrony index was obtained with neurally adjusted ventilatory assist-electrical activity of the diaphragm. CONCLUSION: Compared to pressure-support ventilation, neurally adjusted ventilatory assist in acute respiratory distress syndrome patients holds promise for limiting the risk of overassistance, preventing patient-ventilator asynchrony, and improving overall patient-ventilator interactions. Neural triggering (neurally adjusted ventilatory assist-electrical activity of the diaphragm) considerably decreased patient-ventilator asynchrony.

Nicotine withdrawal and agitation in ventilated critically ill patients.

INTRODUCTION: Smoking is highly addictive, and nicotine abstinence is associated with withdrawal syndrome in hospitalized patients. In this study, we aimed to evaluate the impact of sudden nicotine abstinence on the development of agitation and delirium, and on morbidities and outcomes in critically ill patients who required respiratory support, either noninvasive ventilation or intubation, and mechanical ventilation. METHODS: We conducted a prospective, observational study in two intensive care units (ICUs). The 144 consecutive patients admitted to ICUs and requiring mechanical ventilation for >48 hours were included. Smoking status was assessed at ICU admission by using the Fagerström Test of Nicotine Dependence (FTND). Agitation, with the Sedation-Agitation Scale (SAS), and delirium, with the Intensive Care Delirium Screening Checklist (ICDSC), were tested twice daily during the ICU stay. Agitation and delirium were defined by SAS >4 and ICDSC >4, respectively. Nosocomial complications and outcomes were evaluated. RESULTS: Smokers (n = 44) were younger and more frequently male and were more likely to have a history of alcoholism and to have septic shock as the reason for ICU admission than were nonsmokers. The incidence of agitation, but not delirium, increased significantly in the smoker group (64% versus 32%; P = 0.0005). Nicotine abstinence was associated with higher incidences of self-removal of tubes and catheters, and with more interventions, including the need for supplemental sedatives, analgesics, neuroleptics, and physical restraints. Sedation-free days, ventilator-free days, length of stay, and mortality in ICUs did not differ between groups. Multivariate analysis identified active smoking (OR, 3.13; 95% CI, 1.45-6.74; P = 0.003) as an independent risk factor for agitation. Based on a subgroup of 56 patients, analysis of 28 pairs of patients (smokers and nonsmokers in a 1:1 ratio) matched for age, gender, and alcoholism status found similar results regarding the role of nicotine withdrawal in increasing the risk of agitation during an ICU stay. CONCLUSIONS: Nicotine withdrawal was associated with agitation and higher morbidities in critically ill patients. These results suggest the need to look specifically at those patients with tobacco dependency by using the FTND in ICU settings. Identifying patients at risk of behavioral disorders may lead to earlier interventions in routine clinical practice.

Catheter dysfunction and dialysis performance according to vascular access among 736 critically ill adults requiring renal replacement therapy: a randomized controlled study.

OBJECTIVE: To compare dialysis catheter function according to catheter site. DESIGN: Multicenter, open, randomized controlled trial. SETTING: Nine university-affiliated hospitals and three general hospitals in France. PATIENTS: Seven hundred thirty-six patients in intensive care units who required a first venous catheterization to perform either intermittent hemodialysis (470 patients with 1275 sessions) or continuous renal replacement therapy (266 patients with 1003 days). INTERVENTION: Patients randomly received either femoral (n = 370) or jugular (n = 366) catheterization. For the jugular site, right-side position (n = 252) was recommended. MEASUREMENTS AND MAIN RESULTS: Time to catheter ablation for dysfunction, urea reduction ratio (intermittent hemodialysis), and downtime (continuous renal replacement therapy) were assessed for all participants and evaluated by randomly assigned catheterization site (femoral or jugular). Baseline demography and dialysis prescriptions were similar between the site arms. In modified intent-to-treat, catheter dysfunction occurred in 36 of 348 (10.3%) and 38 of 342 (11.1%) patients in the femoral and jugular groups, respectively. The risk of catheter dysfunction did not significantly differ between randomized groups (hazard ratio, 1.06; 95% confidence interval, 0.67-1.68; p = .80). Compared to the femoral site, the observed risk of dysfunction decreased in the right jugular position (15 of 226; 6.6%; adjusted hazard ratio, 0.58; 95% confidence interval, 0.31-1.07; p = .09) and significantly increased in the left jugular position (23 of 118; 19.5%; adjusted hazard ratio, 1.89; 95% confidence interval, 1.12-3.21; p < .02). The postintermittent hemodialysis mean urea reduction ratio per session was 50.8% (standard deviation, 16.1) for femoral vs. 52.8% (standard deviation, 15.8) for jugular (p = .30) sites, and the median continuous renal replacement therapy downtime per patient-day was 1.17 hrs (interquartile range, 0.75-1.50) for both sites (p = .98). CONCLUSIONS: In terms of catheter dysfunction and dialysis performance among critically ill adults requiring acute renal replacement therapy, jugular site did not significantly outperform femoral site placement.

Blood volume- and blood temperature-controlled hemodialysis in critically ill patients: a 6-month, case-matched, open-label study.

BACKGROUND/AIMS: Online monitoring devices for intermittent hemodialysis have been developed to improve intradialytic cardiovascular stability in chronic dialysis patients. We propose to test blood volume and blood temperature biofeedback control systems in critically ill patients with acute kidney injury (AKI). METHODS: Twenty patients were prospectively dialyzed with machines equipped with online monitoring new devices and compared with 42 historical controls. In addition to feasibility and safety appraisals, efficacy was assessed by the intradialytic hypotension rate. RESULTS: During the study period, controlled temperature was assessed by a mean Delta(max) body temperature of -0.3 +/- 0.2 degrees C, and all but 7% of dialysis sessions achieved relative blood volume-guided ultrafiltration profiling without increased dialysis-related complications. This was associated with decreased intradialytic hypotension rate. CONCLUSION: The combination of active controlled body temperature and profiled ultrafiltration by online monitoring systems is feasible and safe in critically ill AKI patients, and suggests possibilities for improvement in intradialytic hemodynamic stability.

Procalcitonin levels and bacterial aetiology among COPD patients admitted to the ICU with severe pneumonia: a prospective cohort study.

BACKGROUND: Serum procalcitonin (PCT) is considered useful in predicting the likeliness of developing bacterial infections in emergency setting. In this study, we describe PCT levels overtime and their relationship with bacterial infection in chronic obstructive pulmonary disease (COPD) critically ill patients with pneumonia. METHODS: We conducted a prospective cohort study in an ICU of a University Hospital. All consecutive COPD patients admitted for pneumonia between September 2005 and September 2006 were included. Respiratory samples were tested for the presence of bacteria and viruses. Procalcitonin was sequentially assessed and patients classified according to the probability of the presence of a bacterial infection. RESULTS: Thirty four patients were included. The PCT levels were assessed in 32/34 patients, median values were: 0.493 microg/L [IQR, 0.131 to 1.471] at the time of admission, 0.724 microg/L [IQR, 0.167 to 2.646] at six hours, and 0.557 microg/L [IQR, 0.123 to 3.4] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 microg/L in 3/32 (9%) patients and greater than 0.25 microg/L in 22/32 (69%) patients, suggesting low and high probability of bacterial infection, respectively. Fifteen bacteria and five viruses were detected in 15/34 (44%) patients. Bacteria were not detected in patients with PCTmax levels < 0.1 microg/L. In contrast, bacteria were detected in 4/7 (57%) patients estimated unlikely to have a bacterial infection by PCT levels (PCTmax > 0.1 and < 0.25 microg/L). CONCLUSION: Based on these results we suggest that a PCT level cut off > 0.1 microg/L may be more appropriate than 0.25 microg/L (previously proposed for non severe lower respiratory tract infection) to predict the probability of a bacterial infection in severe COPD patients with pneumonia. Further studies testing procalcitonin-based antibiotic strategies are needed in COPD patients with severe pneumonia.