The extent of undiagnosed HIV infection among emergency department patients: results of a blinded seroprevalence survey and a pilot HIV testing program

This study was performed to determine the rate of previously undiagnosed HIV infection among patients presenting to an urban emergency department (ED) and to assess the feasibility of routinely offering voluntary HIV testing in this setting. HIV serostatus was determined anonymously among consecutive acute medicine and trauma ED patients (aged 18-55) who had blood drawn as part of their medical care. Excess serum was aliquoted and coded with an anonymous study code. Before performing HIV testing, the number of persons with previously reported HIV infection was determined by linkage with the state HIV/AIDS reporting registry. Concurrent with the blinded HIV serosurvey, ED patients were offered voluntary HIV testing in a pilot program. Overall, 76 of 2,155 (3.5%) adult ED patients in the blinded survey were HIV-seropositive, 15 of whom (0. 7% of those tested, 20% of those HIV-seropositive) had no infection previously reported to the state HIV/AIDS registry. In the pilot program, six of the 156 (3.8%) individuals who underwent voluntary HIV testing were HIV-seropositive, including three of 53 (5.6%) individuals without prior HIV testing. Of the six HIV-seropositive subjects, one was previously diagnosed, while five of the remaining 155 (3.2%) represented previously undiagnosed infections. Overall, 3. 5% of ED patients from whom blood was obtained for other reasons tested positive for HIV antibody, 20% of whom were previously undiagnosed. Implementation of the voluntary testing program uncovered newly diagnosed infection among 3.2% of those tested. An ED may be an important setting for routinely offering HIV testing, especially for patients who have not been previously tested for HIV.     

Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme.

We undertook a Phase I/II trial in patients with apparent recurrent glioblastoma multiforme (GBM) based on imaging studies to determine the safety and tumor response of repetitive intravenous administration of NDV-HUJ, the oncolytic HUJ strain of Newcastle disease virus. The first part of the study utilized an accelerated intrapatient dose-escalation protocol with one-cycle dosage steps of 0.1, 0.32, 0.93, 5.9, and 11 billion infectious units (BIU) of NDV-HUJ (1 BIU = 1 x 10(9) EID(50) 50% egg infectious dose) followed by three cycles of 55 BIU. Virus was administered by intravenous infusion over 15 min. In the second part, patients received three cycles of 11 BIU. All patients without progressive disease were maintained with two doses of 11 BIU iv weekly. Eleven of the 14 enrolled patients (11-58 years, Karnofsky performance scale 50-90%) received treatment. Toxicity was minimal with Grade I/II constitutional fever being seen in 5 patients. Maximum tolerated dose was not achieved. Anti-NDV hemagglutinin antibodies appeared within 5-29 days. NDV-HUJ was recovered from blood, saliva, and urine samples and one tumor biopsy. One patient achieved a complete response. Intravenous NDV-HUJ is well tolerated. The findings of good tolerability and encouraging responses warrant the continued evaluation of NDV-HUJ in GBM, as well as other cancers.     

Immunomodulation by lipid emulsions in pulmonary inflammation: a randomized controlled trial

IntroductionAcute respiratory distress syndrome (ARDS) is a major cause of mortality in intensive care units. As there is rising evidence about immuno-modulatory effects of lipid emulsions required for parenteral nutrition of ARDS patients, we sought to investigate whether infusion of conventional soybean oil (SO)-based or fish oil (FO)-based lipid emulsions rich in either n-6 or n-3 fatty acids, respectively, may influence subsequent pulmonary inflammation.MethodsIn a randomized controlled, single-blinded pilot study, forty-two volunteers received SO, FO, or normal saline for two days. Thereafter, volunteers inhaled pre-defined doses of lipopolysaccharide (LPS) followed by bronchoalveolar lavage (BAL) 8 or 24 h later. In the murine model of LPS-induced lung injury a possible involvement of resolvin E1 (RvE1) receptor ChemR23 was investigated. Wild-type and ChemR23 knockout mice were infused with both lipid emulsions and challenged with LPS intratracheally.ResultsIn volunteers receiving lipid emulsions, the fatty acid profile in the plasma and in isolated neutrophils and monocytes was significantly changed. Adhesion of isolated monocytes to endothelial cells was enhanced after infusion of SO and reduced by FO, however, no difference of infusion on an array of surface adhesion molecules was detected. In neutrophils and monocytes, LPS-elicited generation of pro-inflammatory cytokines increased in the SO and decreased in the FO group. LPS inhalation in volunteers evoked an increase in neutrophils in BAL fluids, which decreased faster in the FO group. While TNF-α in the BAL was increased in the SO group, IL-8 decreased faster in the FO group. In the murine model of lung injury, effects of FO similar to the volunteer group observed in wild-type mice were abrogated in ChemR23 knockout mice.ConclusionsAfter infusion of conventional lipid emulsions, leukocytes exhibited increased adhesive and pro-inflammatory features. In contrast, FO-based lipid emulsions reduced monocyte adhesion, decreased pro-inflammatory cytokines, and neutrophil recruitment into the alveolar space possibly mediated by ChemR23-signaling. Lipid emulsions thus exert differential effects in human volunteers and mice in vivo.

Trial registration

DRKS00006131 at the German Clinical Trial Registry, 2014/05/14

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-0933-6) contains supplementary material, which is available to authorized users.     

Correlates of fatigue in HIV infection prior to AIDS: a pilot study

Fatigue is widely recognized as a significant source of morbidity in persons with human immunodeficiency virus (HIV) infection, yet there are few data examining fatigue in this population. We present pilot data assessing the relationship between fatigue and various physical and psychosocial measures in 20 men with HIV infection prior to the clinical development of acquired immunodeficiency syndrome (AIDS). Fatigue was measured by a visual analogue scale (VAS) and the Fatigue Assessment Inventory (FAI). No statistically significant associations were found between fatigue measures and physical parameters including haemoglobin, haematocrit, albumin, total protein, and physical dimension score of the Sickness Impact Profile (SIP). The FAI correlated well with Beck's Depression Inventory and SIP — Psychosocial Dimension (r = 0·72 and 0·81, respectively; p < 0·001.) Both the FAI and VAS held moderate associations with the total SIP score. The SIP profile was similar to that observed in a sample of persons with chronic fatigue but without HIV infection, reported previously. Although the sample size is small, our data suggest a stronger association with psychosocial, rather than physical, parameters among persons with HIV infection and fatigue. The implications for clinical management and further research are discussed.     

Phase I/II trial of outpatient PEG-interferon with interleukin-2 in advanced renal cell carcinoma: a cytokine working group study

A phase I/II trial was undertaken to determine the maximum tolerated dose of polyethylene glycol interferon-alpha-2b (PEG-IFN) with interleukin-2 (IL-2), and to evaluate the efficacy and toxicity in patients with metastatic renal cell carcinoma. Patients initially received subcutaneous PEG-IFN, 3.0 mcg/kg/wk, combined with IL-2, but owing to unexpected toxicity a revised phase I schedule ensued. Patients received 1.0, 1.5, 2.0, or 3.0 mcg/kg/wk of PEG-IFN on days 1, 8, 15, and 22; subcutaneous IL-2 was given at a dose of 5 x 10 IU/m2 every 8 hours x 3 on day 1, followed daily at 5 x 10 IU/m2 days 2, 3, 4, and 5 of week 1, then 5 times per week for 3 weeks, followed by 2 weeks off. The maximum tolerated dose of PEG-IFN was 2.0 mcg/kg/wk. Fifty-four patients were enrolled. Frequent grade III/IV cardiac and neurologic toxicities led to an expanded phase I trial. Eleven serious events in 33 patients in the phase II portion led to early termination. No patient died from treatment. The overall response rate in 53 evaluable patients was 30.2% (95% confidence interval 20.5-39.9), with 2 complete responses and 14 partial responses and at least 1 response at each dose level. The median duration of response was 11 months (range, 2 to 65+ mo); median survival was 20 months (range, 2 to 71+ mo); median time to progression was 4 months. Despite clinical efficacy, the study was closed prematurely owing to excess toxicity. Although all serious adverse events resolved, this degree of toxicity is unacceptable for an outpatient treatment regimen.     

Issues in planning a placebo-controlled trial of manual methods: results of a pilot study

OBJECTIVE: There are fundamental differences between the administration of medications and the application of manual procedures, such as those used by chiropractors. The objective of this study was to gather preliminary information on how to address these differences in the design of a multisite, randomized placebo-controlled trial of chiropractic care for women with chronic pelvic pain (CPP). DESIGN: Pilot study for a multisite, randomized, placebo-controlled clinical trial. SETTING: Three chiropractic research clinics in the midwest United States. SUBJECTS: Thirty-nine (39) women with CPP of at least 6 months' duration, diagnosed by board-certified gynecologists. INTERVENTIONS: The active intervention consisted of the chiropractic technique, lumbar spine flexion-distraction, combined with manual Trigger Point Therapy. The placebo intervention consisted of a sham chiropractic procedure performed with an instrument combined with effleurage (light massage). OUTCOME MEASURES: The primary outcome measure was the change in the Pain Disability Index (PDI) from baseline to the end of treatment (6 weeks), assessed by group and site. If the change score was in the same direction at all sites, the results were to be combined to estimate treatment effect size. RESULTS: Patient characteristics were similar to those of patients with CPP in other studies. Recruitment methods, particularly in respect to the eligibility criteria and screening protocols, would require modification in order to recruit an adequate sample for the planned randomized controlled trial. Clinicians followed standardized procedures with apparently minimal deviation, patients in both groups were satisfied with their care and blinding appeared to be successful. PDI change scores were not consistent across sites and so results were not combined and overall treatment effect sizes were not estimated. CONCLUSIONS: The technical and personnel resources required to achieve adequate standardization of procedures at multiple sites may make a placebo-controlled trial unfeasible, given our current lack of knowledge about the active agent in manual chiropractic procedures.     

Acceptability and feasibility of a randomized clinical trial of oral naltrexone vs. placebo for women living with HIV infection: Study design challenges and pilot study results

BackgroundWomen living with HIV/AIDS who drink alcohol are at increased risk for adverse health outcomes, but there is little evidence on best methods for reducing alcohol consumption in this population. We conducted a pilot study to determine the acceptability and feasibility of conducting a larger randomized clinical trial of naltrexone vs. placebo to reduce alcohol consumption in women living with HIV/AIDS.MethodsWe designed the trial with input from community and scientific review. Women with HIV who reported current hazardous drinking (> 7 drinks/week or ≥ 4 drinks per occasion) were randomly assigned to daily oral naltrexone (50 mg) or placebo for 4 months. We evaluated willingness to enroll, adherence to study medication, treatment side effects, and drinking and HIV-related outcomes.ResultsFrom 2010 to 2012, 17 women enrolled (mean age 49 years, 94% African American). Study participation was higher among women recruited from an existing HIV cohort study compared to women recruited from an outpatient HIV clinic. Participants took 73% of their study medication; 82% completed the final assessment (7-months). Among all participants, mean alcohol consumption declined substantially from baseline to month 4 (39.2 vs. 12.8 drinks/week, p < 0.01) with continued reduction maintained at 7-months. Drinking reductions were similar in both naltrexone and placebo groups.ConclusionsA pharmacologic alcohol intervention was acceptable and feasible in women with HIV, with reduced alcohol consumption noted in women assigned to both treatment and placebo groups. However, several recruitment challenges were identified that should be addressed to enhance recruitment in future alcohol treatment trials.     

Phase I/II trial of formoterol fumarate combined with megestrol acetate in cachectic patients with advanced malignancy

Purpose

The aim of this study was to test the safety, tolerability and efficacy of a novel combination of an anabolic β₂-agonist and an appetite stimulant in patients with cancer cachexia.

Methods

Thirteen patients (M/F 5:8) with advanced malignancy and involuntary weight loss received oral formoterol (80 μg/day) and megestrol acetate (480 mg/day) for up to 8 weeks. Quadriceps size (MRI), quadriceps and hand-grip strength, lower limb extensor power, physical activity and quality of life were measured at baseline and at 8 weeks. Response criteria were specified pre-trial, with a major response defined as an increase in muscle size ≥4 % or function ≥10 %.

Results

Six patients withdrew before 8 weeks, reflecting the frail, comorbid population. In contrast, six out of seven (86 %) patients completing the course achieved a major response for muscle size and/or function. In the six responders, mean quadriceps volume increased significantly (left 0.99 vs. 1.05 L, p?=?0.012; right 1.02 vs. 1.06 L, p?=?0.004). There was a trend towards an increase in quadriceps and handgrip strength (p?>?0.05). The lack of appetite symptom score declined markedly (76.2 vs. 23.8; p?=?0.005), indicating improvement. Adverse reactions were few, the commonest being tremor (eight reports), peripheral oedema (three), tachycardia (two) and dyspepsia (two).

Conclusions

In this frail cohort with advanced cancer cachexia, an 8-week course of megestrol and formoterol in combination was safe and well tolerated. Muscle mass and/or function were improved to a clinically significant extent in most patients completing the course. This combination regimen warrants further investigation in larger, randomized trials.     

Endoscopic ultrasound-guided interstitial brachytherapy of unresectable pancreatic cancer: results of a pilot trial

BACKGROUND AND STUDY AIMS: Intraoperative interstitial brachytherapy has been found to be effective when used during laparotomy to improve local control in patients with locally advanced pancreatic cancer. In this study, we report the results of using endoscopic ultrasound- (EUS-)guided interstitial brachytherapy in patients with advanced pancreatic cancer, with respect to tumor response, clinical response, safety, and complications. PATIENTS AND METHODS: Fifteen patients (eight men, seven women; median age 61 years) with unresectable pancreatic adenocarcinoma were enrolled into the study, eight patients with stage III disease and seven patients with stage IV disease. A mean number of 22 radioactive seeds per patient were implanted into the tumors by EUS-guided needle puncture. The mean total implanted activity was 20 mCi, the minimum peripheral dose was 14,000 cGy, and the mean volume of implants was 52 cm3. Patients were followed-up by examination and by imaging tests every 2-3 months: clinical end points included the Karnofsky performance status and pain responses, tumor response (assessed by computed tomography and/or EUS), and survival. RESULTS: During a median follow-up period of 10.6 months, the objective tumor response was classified as "partial" in 27% of patients (with a median duration of partial response of 4.5 months), "minimal" in 20% patients, and indicative of "stable disease" in 33% of patients. Clinical benefit was shown in 30% of patients, mostly due to reduction in pain, but this lasted for a limited time. Local complications (pancreatitis and pseudocyst formation) occurred in three patients; grade III hematologic toxicity occurred in three patients without serious clinical sequelae. CONCLUSIONS: EUS-guided intraoperative interstitial brachytherapy had a moderate local tumor effect and showed some clinical benefit in 30% of the patients in this study. Combination of this form of treatment with external radiation and/or chemotherapy should be tested in future trials.     

HIV/AIDS and disability: a pilot survey of HIV/AIDS knowledge among a deaf population in Swaziland

This study sought to establish whether there were measurable differences in the level of knowledge about HIV/AIDS between hearing individuals and individuals who identified themselves as deaf sign language users in Swaziland. A cross-sectional survey of 191 rural and urban hearing and deaf adults was undertaken in Swaziland in December 2003. A structured questionnaire was administered, seeking to establish whether there were statistically significant differences between hearing and deaf populations in their level of knowledge about HIV/AIDS symptoms, transmission and prevention, as well as differences in sources of information about HIV/AIDS. Additional questions were asked regarding whether there were differences in accessibility of HIV testing services and HIV/AIDS-related healthcare for the two groups. Significant differences in levels of knowledge about HIV/AIDS were identified between the hearing and deaf respondents. The deaf population was significantly more likely (P<0.05) to believe in incorrect modes of HIV transmission (e.g. hugging and airborne transmission) and HIV prevention (e.g. avoiding sharing utensils and eating healthy foods). Almost all of the deaf respondents (99%) reported difficulties in communicating with healthcare facility staff, which may result in less use of HIV voluntary counseling and testing services. This paper reports the results of this study, and discusses the need for targeted HIV/AIDS education campaigns and improved accessibility in healthcare facilities for deaf sign language users in countries such as Swaziland.     

Homeopathy in HIV infection: a trial report of double-blind placebo controlled study.

OBJECTIVE: This study was aimed to evaluate the immuno-modulator role of homeopathic remedies in Human Immunodeficiency Virus (HIV) infection. METHODOLOGY: A randomised double blind clinical trial was conducted to compare the effect of homeopathic remedies with placebo, on CD4+ve T-lymphocytes in HIV infected individuals, conforming to Centres for Disease Control (CDC) stage II & III. 100 HIV+ve individuals between 18-50 y (71% males) were included in the study. 50 cases conformed to CDC stage II--Asymptomatic HIV infection, and 50 cases to CDC stage III--Persistent Generalised Lymphadenopathy (PGL). Cases were stratified according to their clinical status and CD4+ve lymphocyte counts. The randomisation charts were prepared much before the start of the trial by randomly assigning placebo and verum codes to registration numbers from 1 to 50. A single individualised homeopathic remedy was prescribed in each case and was followed up at intervals of 15 d to one month. A six months study was performed for each registered case. Assessment of progress was made by evaluation of CD+ve lymphocyte counts, which was the prospectively-defined main outcome measure of the study; the results were compared with the base line immune status. RESULTS: In PGL, a statistically significant difference was observed in CD+ve T-lymphocyte counts between pre and post trial levels in verum group (P < 0.01). In the placebo group a similar comparison yielded non-significant results. (P = 0.91). Analysis of change in the pre and post trial counts of CD4+ve cells between groups was also statistically significant (P = 0.04). In asymptomatic HIV infection, differences in absolute CD4+ve lymphocyte counts between pre and post trial levels were not significant. Analysis of changes in pre and post trial CD4 levels of placebo and verum groups for combined strata of asymptomatic and PGL groups was also not significant. CONCLUSION: The study suggests a possible role of homeopathic treatment in HIV infection in symptomatic phase, as evidenced by a statistically significant elevation of base line immune status in persistent generalised lymphadenopathy.     

Homeopathy for attention-deficit/hyperactivity disorder: a pilot randomized-controlled trial

OBJECTIVES: The aim of this study was to carry out a preliminary trial evaluating the effectiveness of homeopathy in the treatment of attention-deficit/hyperactivity disorder (ADHD). DESIGN: This work was a randomized, double-blind, placebo-controlled trial. SETTINGS/LOCATION: This study was conducted in a private homeopathic clinic in the Seattle metropolitan area. SUBJECTS: Subjects included children 6-12 years of age meeting Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria for ADHD. INTERVENTIONS: Forty-three subjects were randomized to receive a homeopathic consultation and either an individualized homeopathic remedy or placebo. Patients were seen by homeopathic physicians every 6 weeks for 18 weeks. OUTCOME MEASURES: Outcome measures included the Conner's Global Index-Parent, Conner's Global Index- Teacher, Conner's Parent Rating Scale-Brief, Continuous Performance Test, and the Clinical Global Impression Scale. Results: There were no statistically significant differences between homeopathic remedy and placebo groups on the primary or secondary outcome variables. However, there were statistically and clinically significant improvements in both groups on many of the outcome measures. CONCLUSIONS: This pilot study provides no evidence to support a therapeutic effect of individually selected homeopathic remedies in children with ADHD. A therapeutic effect of the homeopathic encounter is suggested and warrants further evaluation. Future studies should be carried out over a longer period of time and should include a control group that does not receive the homeopathic consultation. Comparison to conventional stimulant medication for ADHD also should be considered.     

96 week results from the MONET trial: a randomized comparison of darunavir/ritonavir with versus without nucleoside analogues, for patients with HIV RNA <50 copies/mL at baseline

BACKGROUND: In virologically suppressed patients, switching to darunavir/ritonavir monotherapy could avoid resistance and adverse events from continuing nucleoside analogues. METHODS: Two hundred and fifty-six patients with HIV RNA <50 copies/mL on current antiretrovirals were switched to darunavir/ritonavir 800/100 mg once daily, either as monotherapy (n = 127) or with two nucleoside analogues (n = 129). Treatment failure was defined as two consecutive HIV RNA levels at least 50 copies/mL by week 96, or discontinuation of study drugs. The trial had 80% power to show non-inferiority (δ = -12%) at week 48. Results Patients were 81% male, 91% Caucasian, and had a median baseline CD4 count of 575 cells/mm(3). There were more patients with hepatitis C co-infection at baseline in the monotherapy arm (18%) compared with the triple therapy arm (12%). In the efficacy analysis, HIV RNA <50 copies/mL by week 96 (per protocol, time to loss of virological response, switch equals failure) was 78% versus 82% in the monotherapy and triple therapy arms [difference -4.2%, 95% confidence interval (CI) -14.3% to +5.8%]; in a switch included analysis, HIV RNA <50 copies/mL was 93% versus 92% (difference +1.6%, 95% CI -5.0% to +8.1%). The percentage of patients with HIV RNA <5 copies/mL (optical density from the sample equal to the negative control) remained constant over time in both treatment arms. Conclusions In the week 96 analysis of the MONotherapy in Europe with TMC114 (MONET) trial, switching to darunavir/ritonavir monotherapy showed non-inferior efficacy to darunavir/ritonavir plus two nucleoside analogues in the switch included and observed failure analyses, but not in the main switch equals failure analysis.     

Flecainide for the treatment of chronic neuropathic pain: a Phase II trial

BACKGROUND: Management of neuropathic pain is challenging. Medications that interfere with sodium channel transport, such as lidocaine, mexilitene and flecainide, are promising as analgesics. OBJECTIVE: In a general population of patients with a working diagnosis of neuropathic pain, whether if flecainide produces enough of an improvement in pain to warrant further clinical study is determined. DESIGN: Phase I/II prospective exploratory clinical trial. Eligible patients were observed for week 1, then 50 mg flecainide was administered twice daily for week 2 and then administered 100 mg twice daily for week 3. SETTING/ SUBJECTS: Multi-institutional members of the Eastern Co-operative Oncology Group. Patients had neuropathic pain diagnosed by their oncologists as defined by the International Association for the Study of Pain and a diagnosis of cancer or AIDS. MEASUREMENTS: The Wisconsin Brief Pain Inventory was used. The primary endpoint was a decrease of 3 points (0-10 numerical scale) or a decrease of 50% in the worst pain rating at either day 15 or day 22 relative to the average of days 1 and 8 ratings. RESULTS: Nineteen patients were registered for the study. Four patients were ineligible. Of the remaining 15, one was unevaluable due to incomplete pain rating. Four out of 14 patients had an average drop of 5 points or 53% in their worst pain ratings on a 0-10 numerical scale of pain. No patients withdrew from study because of toxicity. There were no life-threatening or lethal toxicities. All patients were alive at the time of the analysis. CONCLUSIONS: Flecainide produced a 30% response rate. Response in this study was defined to be highly relevant and clinically significant reduction in pain. The drug merits study in a randomized placebo-controlled trial.     

Acupuncture for low back pain: results of a pilot study for a randomized controlled trial.

OBJECTIVES: To pilot procedures to be used in a randomized controlled trial of acupuncture for low back pain. DESIGN: Uncontrolled clinical trial. SETTING: Primary care and acupuncture clinics in York, England. SUBJECTS: 20 patients with low back pain lasting 1 month or more. INTERVENTIONS: 10 sessions of individualized acupuncture from a traditional acupuncturist. MAIN OUTCOME MEASURES: Change in Oswestry low back pain disability questionnaire; present pain intensity scale; effect on daily living scale, and SF-36 general health questionnaire at post-treatment and 6 months after the end of treatment. RESULTS: 14 patients completed follow-up. Patients had similar severity scores at baseline to those referred to an NHS outpatient clinic. Post-treatment, there were statistically significant improvements in Oswestry, present pain intensity, effect on daily living and the physical functioning, social functioning, bodily pain, vitality and mental health sub-scales of the SF36. Similar results were found at the six month follow-up. Oswestry scores showed reduced levels of pain at 6 months compared to than at post-treatment, falling approximately 40% from baseline. CONCLUSIONS: Though the improvements in pain and quality in life may be due to the natural course of back pain, the promising responses justify further research. The procedures used in the study are appropriate for a randomized controlled trial. Drop-out could be reduced by more careful patient monitoring.     

Vertical transmission in HIV infection/AIDS: a feminist perspective

HIV infection and AIDS create a unique dilemma for women in their potential for vertical transmission of these conditions. Selected feminist perspectives in ontology, epistemology, and axiology are reviewed to illuminate possible social, cultural, and political circumstances of these women. Drawing both on these perspectives and various sources of data about women with HIVIAIDS, some implications for nursing complete this discussion.