Exploring Relative Preferences for HIV Service Features Using Discrete Choice Experiments: a Synthetic Review.

PURPOSE OF REVIEW: Aligning HIV treatment services with patient preferences can promote long-term engagement. A rising number of studies solicit such preferences using discrete choice experiments, but have not been systematically reviewed to seek generalizable insights. Using a systematic search, we identified eleven choice experiments evaluating preferences for HIV treatment services published between 2004 and 2020. RECENT FINDINGS: Across settings, the strongest preference was for nice, patient-centered providers, for which participants were willing to trade considerable amounts of time, money, and travel distance. In low- and middle-income countries, participants also preferred collecting antiretroviral therapy (ART) less frequently than 1 monthly, but showed no strong preference for 3-compared with 6-month refill frequency. Facility waiting times and travel distances were also important but were frequently outranked by stronger preferences. Health facility-based services were preferred to community- or home-based services, but this preference varied by setting. In high-income countries, the availability of unscheduled appointments was highly valued. Stigma was rarely explored and costs were a ubiquitous driver of preferences. While present improvement efforts have focused on designs to enhance access (reduced waiting time, travel distance, and ART refill frequency), few initiatives focus on the patient-provider interaction, which represents a promising critical area for inquiry and investment. If HIV programs hope to truly deliver patient-centered care, they will need to incorporate patient preferences into service delivery strategies. Discrete choice experiments can not only inform such strategies but also contribute to prioritization efforts for policy-making decisions.

Therapeutic hypothermia for neonatal encephalopathy results in improved microstructure and metabolism in the deep gray nuclei.

BACKGROUND AND PURPOSE: Therapeutic hypothermia has reduced morbidity and mortality and is associated with a lower burden of lesions on conventional imaging in NE. However, its effects on brain microstructure and metabolism have not been fully characterized. We hypothesized that therapeutic hypothermia improves measures of brain microstructure and metabolism. MATERIALS AND METHODS: Forty-one neonates with moderate/severe NE (29 treated with hypothermia, 12 nontreated) and 12 healthy neonates underwent MR imaging, DTI, and (1)H-MR spectroscopy. MR imaging scans were scored by the predominant pattern of brain injury: normal, watershed, and BG/thalamus. ADC, FA, Lac:NAA, and NAA:Cho values from bilateral BG and thalamus ROIs were averaged. T test and linear regression analysis were used to determine the association between hypothermia and MR imaging quantitative measures. RESULTS: Conventional MR imaging findings were normal in 41% of treated neonates; all nontreated neonates had brain injury. Values of MR imaging metrics were closer to normal in treated neonates compared with nontreated neonates: ADC was 63% higher in the BG and 116% higher in the thalamus (both P < .05), and Lac:NAA was 76% lower (P = .04) in the BG. Treated neonates with normal MR imaging findings had normal (1)H-MR spectroscopy metabolites, and ADC was higher by 35% in the thalamus (P = .03) compared with healthy neonates. CONCLUSIONS: Therapeutic hypothermia may reduce disturbances of brain metabolism and preserve its microstructure in the setting of NE, possibly by minimizing cytotoxic edema and cell death. Long-term follow-up studies are required to determine whether early post-treatment DTI and (1)H-MR spectroscopy will be useful biomarkers of treatment response.

Corticosteroids for bacterial corneal ulcers.

AIMS: The aim of the study was to conduct a preliminary clinical trial to assess whether adjunctive topical corticosteroids improve outcomes in bacterial keratitis and, if no difference was found, to determine the feasibility and sample size necessary for conducting a larger trial to answer this question. METHODS: In this single centre, double-masked clinical trial, 42 patients with culture-confirmed bacterial keratitis at Aravind Eye Hospital in India were randomised to receive either topical prednisolone phosphate or placebo. All patients received topical moxifloxacin. The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months, adjusting for enrolment BSCVA and arm. Other pre-specified outcomes included re-epithelialisation time, infiltrate/scar size and adverse events. RESULTS: Compared with placebo, patients in the steroid group re-epithelialised more slowly (hazard ratio 0.47, 95% CI 0.23 to 0.94). There was no significant difference in BSCVA or infiltrate/scar size at 3 weeks or 3 months. To have 80% power to detect a two-line difference in acuity, 360 cases would be required. CONCLUSIONS: Although corticosteroid treatment resulted in a statistically significant delay in re-epithelialisation, this did not translate to a significant difference in visual acuity, infiltrate/scar size or adverse events. To assess the effect of steroids on acuity, a larger trial is warranted and feasible.

High-resolution CT imaging of carotid artery atherosclerotic plaques.

BACKGROUND AND PURPOSE: Plaque morphologic features have been suggested as a complement to luminal narrowing measurements for assessing the risk of stroke associated with carotid atherosclerotic disease, giving rise to the concept of "vulnerable plaque." The purpose of this study was to evaluate the ability of multidetector-row CT angiography (CTA) to assess the composition and characteristics of carotid artery atherosclerotic plaques with use of histologic examination as the gold standard. MATERIALS AND METHODS: Eight patients with transient ischemic attacks who underwent carotid CTA and "en bloc" endarterectomy were enrolled in a prospective study. An ex vivo micro-CT study of each endarterectomy specimen was obtained, followed by histologic examination. A systematic comparison of CTA images with histologic sections and micro-CT images was performed to determine the CT attenuation associated with each component of the atherosclerotic plaques. A computer algorithm was subsequently developed that automatically identifies the components of the carotid atherosclerotic plaques, based on the density of each pixel. A neuroradiologist's reading of this computer analysis was compared with the interpretation of the histologic slides by a pathologist with respect to the types and characteristics of the carotid plaques. RESULTS: There was a 72.6% agreement between CTA and histologic examination in carotid plaque characterization. CTA showed perfect concordance for calcifications. A significant overlap between densities associated with lipid-rich necrotic core, connective tissue, and hemorrhage limited the reliability of individual pixel readings to identify these components. However, CTA showed good correlation with histologic examination for large lipid cores (kappa = 0.796; P < .001) and large hemorrhages (kappa = 0.712; P = .102). CTA performed well in detecting ulcerations (kappa = 0.855) and in measuring the fibrous cap thickness (R(2) = 0.77; P < .001). CONCLUSION: The composition of carotid atherosclerotic plaques determined by CTA reflects plaque composition defined by histologic examination.

The lung-to-head ratio and fetoscopic temporary tracheal occlusion: prediction of survival in severe left congenital diaphragmatic hernia.

OBJECTIVES: To evaluate the reliability of sonographic lung-to-head ratio (LHR) measurement as a predictor of survival in fetuses with congenital diaphragmatic hernia (CDH) and to compare the probability of survival in those with temporary tracheal occlusion (TO) or standard care with respect to the LHR. METHODS: Fifty-six fetuses with left CDH with liver herniated into the thorax at complete prenatal evaluation were included in logistic regression analyses of antenatal predictors of survival to hospital discharge. Sixteen subjects underwent TO and 40 received standard care. RESULTS: LHR was a significant predictor of survival, with probability of survival increasing with increasing LHR (odds ratio (OR) 8.5, P = 0.04). When subjects with anomalies were excluded, the LHR effect was similar after adjustment for TO (OR 7.1, P = 0.11). Linear spline models suggested a plateau in survival at an LHR of 1.0 and all models suggested increased odds of survival with TO. Minimum LHR measurements had a high degree of inter- and intraobserver agreement (intraclass correlation coefficients of 0.70 and 0.80, respectively). CONCLUSIONS: Calculation of the LHR in fetuses with CDH is a reliable and powerful predictor of survival to hospital discharge, although improving odds of survival may plateau at an LHR of 1.0. TO may have an independent benefit on survival to hospital discharge.

Seizure-associated brain injury in term newborns with perinatal asphyxia.

BACKGROUND: There is controversy over whether seizures, the most common manifestation of neonatal brain injury, may themselves damage the developing brain. OBJECTIVE: To determine if neonatal seizures are independently associated with brain injury in newborns with perinatal asphyxia. METHODS: Ninety term neonates were studied with MRI and single-voxel (1)H-MRS on median day of life 6 (range 1 to 13 days). The severity of MR abnormality in the (1)H-MRS regions of interest was scored using a validated scale. Seizure severity was scored based on seizure frequency and duration, EEG findings, and anticonvulsant administration. Multivariable linear regression tested the independent association of seizure severity with impaired cerebral metabolism measured by lactate/choline and compromised neuronal integrity measured by N-acetylaspartate/choline in both regions. RESULTS: Clinical seizures occurred in 33 of 90 infants (37%). Seizure severity was associated with increased lactate/choline in both the intervascular boundary zone (p < 0.001) and the basal nuclei (p = 0.011) when controlling for potential confounders of MRI abnormalities and amount of resuscitation at birth. Each increase in seizure score was independently associated with a 21% increase in lactate/choline in the intervascular boundary zone (95% CI, 5.1-38.2%) and a 15% increase in the basal nuclei (95% CI, 0.1-31.7%). Seizure severity was independently associated with diminished N-acetylaspartate/choline in the intervascular boundary zone (p = 0.034). CONCLUSION: The severity of seizures in human newborns with perinatal asphyxia is independently associated with brain injury and is not limited to structural damage detectable by MRI.

Correlation of tumor and whole-body dosimetry with tumor response and toxicity in refractory neuroblastoma treated with (131)I-MIBG.

UNLABELLED: The purpose of our study was to determine the effect of tumor-targeted radiation in neuroblastoma by correlating administered (131)I-metaiodobenzylguanidine (MIBG) activity to tumor and whole-body dosimetry, tumor volume change, overall response, and hematologic toxicity. METHODS: Eligible patients had MIBG-positive lesions and tumor-free, cryopreserved hematopoietic stem cells. Activity was administered according to body weight and protocol as part of a phase I and phase II study. The whole-body radiation dose was derived from daily 1-m exposure measurements, the tumor self-absorbed radiation dose (TSARD) was determined from scintillation-camera conjugate views, and the tumor volume was measured using CT or MRI. RESULTS: Forty-two patients with refractory neuroblastoma (16 with prior hematopoietic stem cell transplant) received a median activity of 555 MBq/kg (15 mCi/kg) (range, 93-770 MBq/kg) and a median total activity of 11,470 MBq (310 mCi) (range, 3,330-30,969 MBq). The median whole-body radiation dose was 228 cGy (range, 57-650 cGy) and the median TSARD was 3,300 cGy (range, 312-30,500 cGy). Responses among evaluable patients included 16 partial response, 3 mixed response, 14 stable disease, and 9 progressive disease. Higher TSARD values predicted better overall disease response (P < 0.01). The median decrease in tumor volume was 19%; 18 tumors decreased, 4 remained stable, and 5 increased in size. Correlation was seen between administered activity per kilogram and whole-body dose as well as hematologic toxicity (assessed by blood platelet and neutrophil count nadir) (P < 0.05). The median whole-body dose was higher in the 11 patients who required hematopoietic stem cell infusion for prolonged neutropenia versus the 31 patients who did not (323 vs. 217 cGy; P = 0.03). CONCLUSION: Despite inaccuracies inherent in dosimetry methods, (131)I-MIBG activity per kilogram correlated with whole-body radiation dose and hematologic toxicity. The TSARD by conjugate planar imaging predicted tumor volume decrease and also correlated with overall tumor response.

Identifying pulmonary tuberculosis in patients with negative sputum smear results.

BACKGROUND: Clinicians need to decide whether to begin empiric therapy for patients who are suspected of having tuberculosis (TB) but have negative sputum smear results. Culture results may take weeks, and delaying treatment may allow further transmission of disease. STUDY OBJECTIVE: To identify the clinical, demographic, and radiographic characteristics that identify smear-negative patients who have TB, and to create a TB prediction rule. DESIGN: Retrospective chart review. SETTING: University-affiliated public hospital in San Francisco, CA, between 1993 and 1998. PATIENTS: Forty-seven patients with TB and 141 control patients who were hospitalized with a suspicion of pulmonary TB; all had negative sputum smear results. MEASUREMENTS AND RESULTS: Demographic, clinical, and radiographic variables were determined by chart review. In multivariate analysis, a positive tuberculin skin test result (odds ratio [OR], 4.8; 95% confidence interval [CI], 2.0 to 11.9) was independently associated with an increased risk of a positive TB culture finding. A radiographic pattern not typical of pulmonary tuberculosis (OR, 0.3; 95% CI, 0.1 to 0.7) and expectoration with cough (OR, 0.3; 95% CI, 0.1 to 0.6) were predictive of a decreased risk. An interaction between HIV seropositivity and mediastinal lymphadenopathy on the chest radiograph was also associated with a positive TB culture result (OR, 7.2; 95% CI, 1.4 to 36.0). The TB prediction score (TPS) was created with widely ranging likelihood ratios that could affect the posterior probability of TB by 30-fold. CONCLUSION: The TPS put into context with the overall prevalence of TB in a given area may help clinicians decide if a patient with negative sputum smear results should start empiric antituberculous therapy or wait for culture results. These results need prospective validation.

Target dose adjustment of busulfan in pediatric patients undergoing bone marrow transplantation.

Published data suggest that the average concentration of busulfan at steady state (Bu Css) is critical for successful engraftment in children receiving busulfan as a conditioning agent for bone marrow transplantation (BMT). We previously found in children that a Bu Css <600 ng/ml correlated with autologous recovery/mixed chimerism; there was no correlation between Bu Css and regimen-related toxicity (RRT). In a cohort continuous with the previous trial, we prospectively evaluated targeted busulfan concentrations in 32 pediatric patients (age 0.6-18.5 years) with AML (n = 6), CML (n = 6) and non-malignant disorders (n = 20) receiving HLA-closely matched donor grafts. In this trial, individual busulfan pharmacokinetics were performed prior to admission. Busulfan doses were then adjusted to achieve a Bu Css target range of 600-900 ng/ml +/- 10% depending on donor source and disease. A repeat study was done following dose 1 of the conditioning regimen. Thirty of thirty-two (94%) patients achieved target concentrations. Total busulfan doses ranged from 10.9 to 29 mg/kg. Thirty of thirty-two patients (94%) have durably engrafted. Grade 3/4 RRT occurred in seven patients (21%). Targeting Bu Css ranges of 600-900 ng/ml significantly improved our rate of successful engraftment from 74% to 94% (P = 0.043). These results indicate that targeted busulfan dosing optimizes allogeneic engraftment in children.

Baseline human immunodeficiency virus type 1 phenotype, genotype, and RNA response after switching from long-term hard-capsule saquinavir to indinavir or soft-gel-capsule saquinavir in AIDS clinical trials group protocol 333.

AIDS Clinical Trials Group protocol 333 was an open-label trial of a switch from saquinavir (SQV) hard capsules (SQVhc) to indinavir (IDV) or saquinavir soft-gel capsules (SQVsgc) after >48 weeks of prior treatment with SQVhc. Eighty-nine subjects received IDV or SQVsgc or continued to receive SQVhc and continued unchanged treatment with non-protease-inhibitor antivirals for 8 weeks. Subjects receiving SQVhc then switched treatment to IDV. Baseline drug susceptibility and protease gene sequencing were done; 12 codons related to IDV and SQV resistance were analyzed. After 112 weeks (median) of SQVhc, the fall in human immunodeficiency virus (HIV) type 1 RNA level from baseline was significantly greater with IDV and was inversely correlated with the number of protease substitutions. The number of substitutions also correlated with baseline CD4 cell count, HIV-1 RNA level, SQV experience, and drug susceptibility. Substitution at codon 10, which occurred only in isolates with >/=2 substitutions, was associated with blunted RNA response. IDV IC(50) correlated with HIV-1 RNA response after the switch to IDV but added little predictive power once the genotype was considered.

A two-stage estimator of the dependence parameter for the Clayton-Oakes model.

This paper describes the properties of a two-stage estimator of the dependence parameter in the Clayton-Oakes multivariate failure time model. The parameter is estimated from a likelihood function in which the marginal hazard functions are replaced by estimates. The method extends the approach of Shih and Louis (1995) and Genest, Ghoudi and Rivest (1995) to allow the marginal hazard for failure times to follow a stratified Cox (1972) model. The method is computationally simple and under mild regularity conditions produces a consistent, asymptotically normal estimator.

An overview of statistical methods for multiple failure time data in clinical trials.

In a long term clinical trial to evaluate a new treatment, quite often each study subject may experience a number of 'failures' that correspond to repeated occurrences of the same type of event or events of entirely different natures during his/her follow-up period. To obtain efficient inference procedures for the therapeutic effect over time, it is desirable to utilize those multiple event times in the analysis. In this article, we review some useful procedures for analysing different kinds of multivariate failure time data. Specifically, we discuss the two-sample problems and the general regression problems with various survival models. We also give some recommendations of appropriate procedures for each type of multiple event data structure for practical usage.