Bloodstream Infections in Patients With Pulmonary Arterial Hypertension Treated With Intravenous Prostanoids: Insights From the REVEAL REGISTRY(®)

ObjectiveTo evaluate the rate of and potential risk factors for bloodstream infections (BSIs) using data from the REVEAL (Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension [PAH] Disease Management) REGISTRY^®, which provides current information about patients with PAH.Patients and MethodsPatients were enrolled from March 30, 2006, through December 8, 2009, and data on reported BSIs were collected through the third quarter of 2010. Bloodstream infection rates were calculated per 1000 patient-days of risk.ResultsOf 3518 patients enrolled, 1146 patients received intravenous (IV) prostanoid therapy for more than 1 day (no BSI, n=1023; ≥1 BSI, n=123; total BSI episodes, n=166). Bloodstream infections rates were significantly increased in patients receiving IV treprostinil vs IV epoprostenol (0.36 vs 0.12 per 1000 treatment days; P<.001), primarily due to gram-negative organisms (0.20 vs 0.03 per 1000 treatment days; P<.001). Multivariate analysis adjusting for age, causes of PAH, and year of BSI found that treatment with IV treprostinil was associated with a 3.08-fold increase (95% confidence interval, 2.05-4.62; P<.001) in BSIs of any type and a 6.86-fold increase (95% confidence interval, 3.60-13.07; P<.001) in gram-negative BSIs compared with treatment with IV epoprostenol.ConclusionCompared with IV epoprostenol therapy, treatment with IV treprostinil is associated with a significantly higher rate of gram-negative BSIs; observed differences in BSI rate did not seem to be due to any other analyzed factors.Trial Registrationclinicaltrials.gov Identifier: NCT00370214     

Is the Use of Low-Pressure Pulsatile Lavage for Pressure Ulcer Management Associated With Environmental Contamination With Acinetobacter baumannii?

Ho CH, Johnson T, Miklacic J, Donskey CJ. Is the use of low-pressure pulsatile lavage for pressure ulcer management associated with environmental contamination with Acinetobacter baumannii?

Objective

To determine the extent of environmental contamination associated with low-pressure pulsatile lavage of stage III or IV pressure ulcers in patients with spinal cord injury (SCI) when routine infection control precautions are used for wounds colonized or infected with Acinetobacter baumannii.

Design

Prospective investigation in which pressure ulcer cultures and environmental cultures were obtained before and after low-pressure pulsatile lavage treatment, and before and after regular dressing changes. Environmental cultures included the patient's bedrail and settle plates placed 0.6, 1.5, and 2.4m from the wound to assess airborne spread of A. baumannii.

Setting

SCI inpatient unit in a Department of Veterans Affairs Medical Center.

Participants

Inpatients (N=15) with SCI receiving daily low-pressure pulsatile lavage treatment for stage III or IV pressure ulcers with standard dressing change, as well as regular dressing changes without low-pressure pulsatile lavage at other times of the day.

Interventions

Standard, regular dressing changes and dressing changes with low-pressure pulsatile lavage.

Main Outcome Measures

Comparison of frequency of environmental contamination with A. baumannii associated with low-pressure pulsatile lavage versus regular dressing changes.

Results

Of the 15 SCI inpatients meeting inclusion criteria, 9 (60%) grew A. baumannii from their wounds. Of the 9 patients with wound cultures positive for A. baumannii, only 1 (11%) had environmental contamination with this organism after performance of low-pressure pulsatile lavage, and the same patient had environmental contamination after a standard dressing change. The antibiotic susceptibility patterns of the wound and environmental A. baumannii isolates were identical.

Conclusions

Low-pressure pulsatile lavage using the infection control methods described is not associated with an increased rate of environmental contamination of A. baumannii in comparison with standard dressing changes.     

Case–Control Estimation of the Impact of Oncolytic Adenovirus on the Survival of Patients With Refractory Solid Tumors

Oncolytic immunotherapy with cytokine armed replication competent viruses is an emerging approach in cancer treatment. In a recent randomized trial, an increase in response rate was seen but the effect on overall survival is not known with any virus. To facilitate randomized trials, we performed a case–control study assessing the survival of 270 patients treated in an Advanced Therapy Access Program (ATAP), in comparison to matched concurrent controls from the same hospital. The overall survival of all virus treated patients was not increased over controls. However, when analysis was restricted to GMCSF-sensitive tumor types treated with GMSCF-coding viruses, a significant improvement in median survival was present (from 170 to 208 days, P = 0.0012, N = 148). An even larger difference was seen when analysis was restricted to good performance score patients (193 versus 292 days, P = 0.034, N = 90). The survival of ovarian cancer patients was especially promising as median survival nearly quadrupled (P = 0.0003, N = 37). These preliminary data lend support to initiation of randomized clinical trials with GMCSF-coding oncolytic adenoviruses.     

What Elements of the Informational,Management, and Relational Continuity Are Associated With Patient Satisfaction With Rehabilitation Care and Global Rating Change?

Objective

To describe the quality of patients' continuity experiences in a population of outpatients receiving postacute rehabilitation care, and to check which elements and types of continuity most strongly determine their satisfaction with care and functional changes.

Design

Cross-sectional self-report survey.

Setting

Three postacute ambulatory centers in metropolitan areas.

Participants

Outpatients (N=218; mean age ± SD, 38.5±11.7y).

Interventions

Not applicable.

Main Outcome Measures

The questionnaire included experiences regarding aspects of informational (transference of information, accumulated knowledge), management (consistency and flexibility of care), and relational (established relation and consistency of provider) continuity, as well as questions concerning patients' sociodemographic characteristics, satisfaction with care, and global rating change.

Results

Respondents indicated more problems in terms of management and relational continuity than in informational continuity. For all patient groups, experiences regarding elements of management continuity (R²=15.3%–22.4%), followed by relational continuity (R²=14.3%–25.2%), explained most of the variance of satisfaction. Consistency and flexibility of care, together with an established relation, were the most determining elements of satisfaction. Experiences regarding elements of management continuity explained most of the variance of change (18.5%), and flexibility was the most decisive element.

Conclusions

Patient satisfaction and functional changes are related with experiences in aspects of management continuity, where there is room for improvement. Measures of management continuity may be promising as indicators of continuity, and they should be prioritized.     

Are Patients' Views on Seclusion Associated With Lack of Privacy in the Ward?

The lack of single-bed rooms in psychiatric wards may reduce the possibility of patients getting sufficient rest and privacy and may increase their risk of being overstimulated. This study explored whether residing in single- versus multiple-bed rooms in a psychiatric ward was associated with psychiatric patients' opinions about seclusion. More specifically, it was studied whether patients who had shared a room with other patients prior to seclusion rated seclusion more favorably. It was thought that they would rate seclusion more favorably due to the lack of rest they previously experienced in their regular room. For this, the Patient View-of-Seclusion Questionnaire of Hammill, McEvoy, Koral, and Schneider [Hammill, K., McEvoy, J., Koral, H., & Schneider, N. (1989). Hospitalized schizophrenic patient views about seclusion. Journal of Clinical Psychiatry, 50, 174-177] was completed by 54 secluded adult patients hospitalized in a locked ward of a Dutch psychiatric hospital. A significant association was found between residing in multiple-bed rooms prior to seclusion and a less negative view on seclusion. This finding suggests that the ward environment may have a rather large impact on how seclusion is perceived. The results underline the need for single-bed rooms in the treatment of psychiatric inpatients.     

Women’s Perceptions of Hospital-Based Breastfeeding Care and the Association With Exclusive Breastfeeding

ObjectiveTo examine the differences in women’s perceptions of hospital-based breastfeeding care and the association of these perceptions with exclusive breastfeeding.DesignObservational, mixed-methods study.Setting/Local ProblemA 932-bed, Baby-Friendly Hospital Initiative–designated, university hospital with approximately 2,000 births per year, where 50% of women who wanted to breastfeed were supplementing with formula before hospital discharge.ParticipantsThirty-four women who gave birth to a term, singleton newborn and had a desire to breastfeed exclusively.MeasurementsWomen’s perceptions were assessed using a modified version of the Questionnaire for the Breastfeeding Mother.ResultsWomen’s perceptions of breastfeeding care were positively associated with exclusive breastfeeding (p = .049). In addition, the influence of how a woman’s own mother fed her as an infant was shown, because women who themselves were breastfed as infants were more likely to exclusively breastfeed their own newborns. Content analysis showed that women appreciated the care received in the hospital from lactation consultants and access to a hospital-administered breastfeeding clinic after discharge.ConclusionCreating a hospital environment supportive of breastfeeding could yield positive breastfeeding outcomes for women and newborns.     

Can Surface Neuromuscular Electrical Stimulation of the Wrist and Hand Combined With Routine Therapy Facilitate Recovery of Arm Function in Patients With Stroke?

Rosewilliam S, Malhotra S, Roffe C, Jones P, Pandyan AD. Can surface neuromuscular electrical stimulation of the wrist and hand combined with routine therapy facilitate recovery of arm function in patients with stroke?ObjectiveTo investigate whether treatment with surface neuromuscular electrical stimulation to the wrist extensors improves recovery of arm function in severely disabled patients with stroke.DesignSingle blinded randomized controlled trial.SettingAcute stroke unit and stroke rehabilitation wards of a university hospital.ParticipantsPatients with no upper limb function (Action Research Arm Test [ARAT] score 0) (N=90; mean age ± SD, 74±11y; 49% men) were recruited to the study within 6 weeks of stroke. Only 67 participants were alive at the end of the study and data from 66 of these people were analyzed.InterventionsParticipants were randomized to surface neuromuscular electrical stimulation using surface electrical stimulators for 30 minutes, twice in a working day for 6 weeks in addition to standardized upper limb therapy or just standardized upper limb therapy.Main Outcome MeasureThe primary outcome measure was the ARAT score. Assessments were made at baseline and at 6, 12, 24, and 36 weeks after recruitment.ResultsThere were statistically significant improvements in measures of wrist extensor (mean difference 0.5; 95% confidence interval [CI], 0.0–1.0) and grip strength (mean difference 0.9; 95% CI, 0.1–1.7) over the treatment period. Arm function (ARAT score) was not significantly different between the groups over the treatment period at 6 weeks (mean difference 1.9; 95% CI, ?2.9 to 6.8) or over the study period at 36 weeks (mean difference 6.4; 95% CI, ?1.8 to 14.7), and the rate of recovery was not significantly different (mean difference 0.7; 95% CI, ?0.2 to 1.6).ConclusionsIn patients with severe stroke, with no functional arm movement, electrical stimulation of wrist extensors improves muscle strength for wrist extension and grip, and larger studies are required to study its influence on arm function.     

With increasing ageing in Western populations, what are the prospects for lowering the incidence of coronary heart disease?

Coronary heart disease (CHD), rare in the early 1900s, in the 1970s was responsible for almost a third of deaths in Western populations. Although its mortality rate has fallen in the last 20 years, considerably in certain populations, it remains the leading cause of death, and there is little evidence of any fall in its incidence rate. The primary risk factors, which include pattern of diet, smoking practice, and level of physical activity, are well known, but explain only approximately 50% of variation in its occurrence. Despite the numerous health improvement recommendations made, alterations in diet have been relatively slight. Although smoking practice has halved in some populations, its prevalence is now rising in the young. The extent of physical activity is low, compared with that in the past, and may even be decreasing in the young. With the general ageing of populations, the near absence of strong encouragement from the state, and individuals' general failure to reduce risk factors significantly, the chances of decreases in the incidence of CHD appear remote.     

Systemic TNFα Gene Therapy Synergizes With Liposomal Doxorubicine in the Treatment of Metastatic Cancer

Tumor necrosis factor alpha (TNFα) is a potent antitumoral cytokine, either killing tumor cells directly or affecting the tumor vasculature leading to enhanced accumulation of macromolecular drugs. Due to dose limiting side effects systemic administration of TNFα protein at therapeutically active doses is precluded. With gene vectors, tumor restricted TNFα expression can be achieved and in principle synergize with chemotherapy. Synthetic gene carriers based on polyamines were intravenously injected, which either passively accumulate within the tumor or specifically target the epidermal growth factor receptor. A single intravenous injection of TNFα gene vector promoted accumulation of liposomal doxorubicine (Doxil) in murine neuroblastoma and human hepatoma by enhancing tumor endothelium permeability. The expression of transgenic TNFα was restricted to tumor tissue. Three treatment cycles with TNFα gene vectors and Doxil significantly delayed tumor growth in subcutaneous murine Neuro2A neuroblastoma. Also tumors re-growing after initial treatment were successfully treated in a fourth cycle pointing at the absence of resistance mechanisms. Systemic Neuro2A metastases or human LS174T colon carcinoma metastases in liver were also successfully treated with this combined approach. In conclusion, this schedule opens the possibility for the efficient treatment of tumors metastases otherwise not accessible for macromolecular drug carriers.     

Is Maximal Strength of the Cervical Flexor Muscles Reduced in Patients With Temporomandibular Disorders?

Armijo-Olivo SL, Fuentes JP, Major PW, Warren S, Thie NM, Magee DJ. Is maximal strength of the cervical flexor muscles reduced in patients with temporomandibular disorders?

Objective

To determine whether there was a difference in maximal cervical flexor muscle strength in subjects with temporomandibular disorders (mixed and myogenous) compared with healthy subjects.

Design

Cross-sectional study.

Setting

Orthopedics/sports laboratory at the University of Alberta.

Participants

Subjects (N=149) of whom 50 were healthy, 54 had myogenous temporomandibular disorders (TMD), and 45 had mixed TMD.

Interventions

Not applicable.

Main Outcome Measures

Maximal cervical flexor strength, pain.

Results

There was no statistically significant difference in maximal cervical flexor strength among groups (P>.05). Subjects' body weight was significantly associated with strength. No significant association between jaw disability with maximal cervical flexor strength was found. A significant but weak association between neck disability and maximal cervical flexors strength was found.

Conclusions

These results indicated that strength evaluation is one of several assessment factors that need to be addressed when evaluating musculoskeletal painful conditions such as TMD and neck disorders, but strength evaluation cannot be considered as a direct measure of disability. Future studies should explore evaluation of strength in other muscular groups such as cervical extensors, rotators, and lateral flexors, and also under different conditions such as rapid movements, and in patients with more severe jaw disability.     

Can the Six-Minute Walk Test Predict Peak Oxygen Uptake in Men With Heart Transplant?

Doutreleau S, Di Marco P, Talha S, Charloux A, Piquard F, Geny B. Can the six-minute walk test predict peak oxygen uptake in men with heart transplant?

Objective

To determine whether the six-minute walk test (6MWT) might predict peak oxygen consumption (Vo₂peak) after heart transplantation.

Design

Case-control prospective study.

Setting

Public hospital.

Participants

Patients with heart transplant (n=22) and age-matched sedentary male subjects (n=13).

Interventions

Not applicable.

Main Outcome Measures

Exercise performance using a maximal exercise test, distance walked using the 6MWT, heart rate, and Vo₂peak.

Results

Compared with controls, exercise performance was decreased in patients with heart transplant with less distance ambulated (516±13m vs 592±13m; P<.001) and a decrease in mean Vo₂peak (23.3±1.3 vs 29.6±1mL·min⁻¹·kg⁻¹; P<.001). Patients with heart transplant showed an increased resting heart rate, a response delayed both at the onset of exercise and during recovery. However, the patient's heart rate at the end of the 6MWT was similar to that obtained at the ventilatory threshold. The formula did not predict measured V?o₂, with a weak correlation observed between the six-minute walk distance and both Vo₂peak (r=.53; P<.01) and ventilatory threshold (r=.53; P<.01) after heart transplantation. Interestingly, when body weight was considered, correlations coefficient increased to .74 and .77, respectively (P<.001).

Conclusions

In heart transplant recipients, the 6MWT is a safe, practical, and submaximal functional test. The distance-weight product can be used as an alternative method for assessing the functional capacity after heart transplantation but cannot totally replace maximal V?o₂ determination.     

Genetic Architecture of Plasma Adiponectin Overlaps With the Genetics of Metabolic Syndrome�CRelated Traits

OBJECTIVE

Adiponectin, a hormone secreted by adipose tissue, is of particular interest in metabolic syndrome, because it is inversely correlated with obesity and insulin sensitivity. However, it is not known to what extent the genetics of plasma adiponectin and the genetics of obesity and insulin sensitivity are interrelated. We aimed to evaluate the heritability of plasma adiponectin and its genetic correlation with the metabolic syndrome and metabolic syndrome–related traits and the association between these traits and 10 ADIPOQ single nucleotide polymorphisms (SNPs).

RESEARCH DESIGN AND METHODS

We made use of a family-based population, the Erasmus Rucphen Family study (1,258 women and 967 men). Heritability analysis was performed using a polygenic model. Genetic correlations were estimated using bivariate heritability analyses. Genetic association analysis was performed using a mixed model.

RESULTS

Plasma adiponectin showed a heritability of 55.1%. Genetic correlations between plasma adiponectin HDL cholesterol and plasma insulin ranged from 15 to 24% but were not significant for fasting glucose, triglycerides, blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR), and C-reactive protein. A significant association with plasma adiponectin was found for ADIPOQ variants rs17300539 and rs182052. A nominally significant association was found with plasma insulin and HOMA-IR and ADIPOQ variant rs17300539 after adjustment for plasma adiponectin.

CONCLUSIONS

The significant genetic correlation between plasma adiponectin and HDL cholesterol and plasma insulin should be taken into account in the interpretation of genome-wide association studies. Association of ADIPOQ SNPs with plasma adiponectin was replicated, and we showed association between one ADIPOQ SNP and plasma insulin and HOMA-IR.The dramatic increase in the prevalence of the metabolic syndrome in countries with a western lifestyle is precipitated by environmental variables. However, the individual susceptibility to the obesogenic environment is largely determined by genetic susceptibility (1). Central obesity, dyslipidemia, impaired glucose metabolism, and hypertension are the key elements determining the expression of the metabolic syndrome (2), which is associated with an increased risk for type 2 diabetes and cardiovascular disease (2).Adipose tissue is an active endocrine tissue that can respond to changes in metabolic conditions by secreting biologically active substances (adipokines). The adipokine family can be divided into two overlapping sets of signaling molecules, namely those with metabolic/immunological function, which include interleukins 1β, 6, 8, 10, or 18, tumor necrosis factor-α and transforming growth factor-β, and those with endocrine function, which include leptin, retinol-binding protein 4, adiponectin, and resistin (3). Human adiponectin is a protein of 247 amino acids (30-kDa), encoded by a gene (ADIPOQ) located on chromosome 3q27 (4). Adiponectin is secreted and present in plasma in various multimeric forms, for which the biological significance remains to be determined. Rasmussen-Torvik et al. (5) showed that binding of adiponectin to adiponectin receptors (ADIPOR1 and ADIPOR2) in mice results in increased AMP-activated protein kinase activity and peroxisome proliferator–activated receptor-α activity. In humans, both receptors are expressed mainly in skeletal muscle and adiponectin could thus play a role in energy metabolism.The role of adiponectin in energy metabolism is confirmed by its inverse correlation with body weight, metabolic syndrome, metabolic syndrome–related traits, and type 2 diabetes (6). In mouse models, adiponectin has been shown to play a role in energy homeostasis by regulating insulin sensitivity of the liver (7). In addition, adiponectin is suggested to exhibit anti-inflammatory properties (8). Thus, adiponectin could play a role in obesity–induced impairment of the metabolic state, systemic inflammation, and the corresponding risk for cardiovascular disease.Limited data on the overall heritability of plasma adiponectin are available. Furthermore, it is not known whether the genetics of plasma adiponectin overlap with the genetics of body weight and insulin sensitivity/diabetes or other individual components of the metabolic syndrome. Several studies showed convincing association of genetic variants near and in the promoter region of the ADIPOQ gene with plasma adiponectin and type 2 diabetes or type 2 diabetes–related traits (5,9,10).In the present study, we set out to evaluate the heritability of plasma adiponectin and its genetic correlation with the metabolic syndrome and metabolic syndrome–related traits (BMI, insulin, homeostasis model assessment of insulin resistance [HOMA-IR], and plasma C-reactive protein [CRP]).     

Acute Respiratory Compromise in the Emergency Department: A Description and Analysis of 3571 Events from the Get With the Guidelines–Resuscitation® Registry

Background

Respiratory events requiring the use of assisted ventilation are relatively common in the emergency department (ED), and can be associated with substantial morbidity and mortality.