Early versus delayed fixed dose combination abacavir/lamivudine/zidovudine in patients with HIV and tuberculosis in Tanzania.

Fixed dose combination abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) among HIV-1 and tuberculosis (TB)-coinfected patients was evaluated and outcomes between early vs. delayed initiation were compared. In a randomized, pilot study conducted in the Kilimanjaro Region of Tanzania, HIV-infected inpatients with smear-positive TB and total lymphocyte count <1200/mm(3) were randomized to initiate ABC/3TC/ZDV either 2 (early) or 8 (delayed) weeks after commencing antituberculosis therapy and were followed for 104 weeks. Of 94 patients screened, 70 enrolled (41% female, median CD4 count 103 cells/mm(3)), and 33 in each group completed 104 weeks. Two deaths and 12 serious adverse events (SAEs) were observed in the early arm vs. one death, one clinical failure, and seven SAEs in the delayed arm (p = 0.6012 for time to first grade 3/4 event, SAE, or death). CD4 cell increases were +331 and +328 cells/mm(3), respectively. TB-immune reconstitution inflammatory syndromes (TB-IRIS) were not observed in any subject. Using intent-to-treat (ITT), missing = failure analyses, 74% (26/35) vs. 89% (31/35) randomized to early vs. delayed therapy had HIV RNA levels <400 copies/ml at 104 weeks (p = 0.2182) and 66% (23/35) vs. 74% (26/35), respectively, had HIV RNA levels <50 copies/ml (p = 0.6026). In an analysis in which switches from ABC/3TC/ZDV = failure, those receiving early therapy were less likely to be suppressed to <400 copies/ml [60% (21/35) vs. 86% (30/35), p = 0.030]. TB-IRIS was not observed among the 70 coinfected subjects beginning antiretroviral treatment. ABC/3TC/ZDV was well tolerated and resulted in steady immunologic improvement. Rates of virologic suppression were similar between early and delayed treatment strategies with triple nucleoside regimens when substitutions were allowed.

Adenosine-induced flow arrest to facilitate intracranial aneurysm clip ligation: dose-response data and safety profile.

BACKGROUND: Adenosine-induced transient flow arrest has been used to facilitate clip ligation of intracranial aneurysms. However, the starting dose that is most likely to produce an adequate duration of profound hypotension remains unclear. We reviewed our experience to determine the dose-response relationship and apparent perioperative safety profile of adenosine in intracranial aneurysm patients. METHODS: This case series describes 24 aneurysm clip ligation procedures performed under an anesthetic consisting of remifentanil, low-dose volatile anesthetic, and propofol in which adenosine was used. The report focuses on the doses administered; duration of systolic blood pressure <60 mm Hg (SBP(<60 mm Hg)); and any cardiovascular, neurologic, or pulmonary complications observed in the perioperative period. RESULTS: A median dose of 0.34 mg/kg ideal body weight (range: 0.29-0.44 mg/kg) resulted in a SBP(<60 mm Hg) for a median of 57 seconds (range: 26-105 seconds). There was a linear relationship between the log-transformed dose of adenosine and the duration of a SBP(<60 mm Hg) (R(2) = 0.38). Two patients developed transient, hemodynamically stable atrial fibrillation, 2 had postoperative troponin levels >0.03 ng/mL without any evidence of cardiac dysfunction, and 3 had postoperative neurologic changes. CONCLUSIONS: For intracranial aneurysms in which temporary occlusion is impractical or difficult, adenosine is capable of providing brief periods of profound systemic hypotension with low perioperative morbidity. On the basis of these data, a dose of 0.3 to 0.4 mg/kg ideal body weight may be the recommended starting dose to achieve approximately 45 seconds of profound systemic hypotension during a remifentanil/low-dose volatile anesthetic with propofol induced burst suppression.

Spectrotemporal CT data acquisition and reconstruction at low dose.

PURPOSE: X-ray computed tomography (CT) is widely used, both clinically and preclinically, for fast, high-resolution anatomic imaging; however, compelling opportunities exist to expand its use in functional imaging applications. For instance, spectral information combined with nanoparticle contrast agents enables quantification of tissue perfusion levels, while temporal information details cardiac and respiratory dynamics. The authors propose and demonstrate a projection acquisition and reconstruction strategy for 5D CT (3D+dual energy+time) which recovers spectral and temporal information without substantially increasing radiation dose or sampling time relative to anatomic imaging protocols. METHODS: The authors approach the 5D reconstruction problem within the framework of low-rank and sparse matrix decomposition. Unlike previous work on rank-sparsity constrained CT reconstruction, the authors establish an explicit rank-sparse signal model to describe the spectral and temporal dimensions. The spectral dimension is represented as a well-sampled time and energy averaged image plus regularly undersampled principal components describing the spectral contrast. The temporal dimension is represented as the same time and energy averaged reconstruction plus contiguous, spatially sparse, and irregularly sampled temporal contrast images. Using a nonlinear, image domain filtration approach, the authors refer to as rank-sparse kernel regression, the authors transfer image structure from the well-sampled time and energy averaged reconstruction to the spectral and temporal contrast images. This regularization strategy strictly constrains the reconstruction problem while approximately separating the temporal and spectral dimensions. Separability results in a highly compressed representation for the 5D data in which projections are shared between the temporal and spectral reconstruction subproblems, enabling substantial undersampling. The authors solved the 5D reconstruction problem using the split Bregman method and GPU-based implementations of backprojection, reprojection, and kernel regression. Using a preclinical mouse model, the authors apply the proposed algorithm to study myocardial injury following radiation treatment of breast cancer. RESULTS: Quantitative 5D simulations are performed using the MOBY mouse phantom. Twenty data sets (ten cardiac phases, two energies) are reconstructed with 88 μm, isotropic voxels from 450 total projections acquired over a single 360° rotation. In vivo 5D myocardial injury data sets acquired in two mice injected with gold and iodine nanoparticles are also reconstructed with 20 data sets per mouse using the same acquisition parameters (dose: ∼60 mGy). For both the simulations and the in vivo data, the reconstruction quality is sufficient to perform material decomposition into gold and iodine maps to localize the extent of myocardial injury (gold accumulation) and to measure cardiac functional metrics (vascular iodine). Their 5D CT imaging protocol represents a 95% reduction in radiation dose per cardiac phase and energy and a 40-fold decrease in projection sampling time relative to their standard imaging protocol. CONCLUSIONS: Their 5D CT data acquisition and reconstruction protocol efficiently exploits the rank-sparse nature of spectral and temporal CT data to provide high-fidelity reconstruction results without increased radiation dose or sampling time.

Future requirements for and supply of ophthalmologists for an aging population in Singapore.

BACKGROUND: Singapore's population, as that of many other countries, is aging; this is likely to lead to an increase in eye diseases and the demand for eye care. Since ophthalmologist training is long and expensive, early planning is essential. This paper forecasts workforce and training requirements for Singapore up to the year 2040 under several plausible future scenarios. METHODS: The Singapore Eye Care Workforce Model was created as a continuous time compartment model with explicit workforce stocks using system dynamics. The model has three modules: prevalence of eye disease, demand, and workforce requirements. The model is used to simulate the prevalence of eye diseases, patient visits, and workforce requirements for the public sector under different scenarios in order to determine training requirements. RESULTS: Four scenarios were constructed. Under the baseline business-as-usual scenario, the required number of ophthalmologists is projected to increase by 117% from 2015 to 2040. Under the current policy scenario (assuming an increase of service uptake due to increased awareness, availability, and accessibility of eye care services), the increase will be 175%, while under the new model of care scenario (considering the additional effect of providing some services by non-ophthalmologists) the increase will only be 150%. The moderated workload scenario (assuming in addition a reduction of the clinical workload) projects an increase in the required number of ophthalmologists of 192% by 2040. Considering the uncertainties in the projected demand for eye care services, under the business-as-usual scenario, a residency intake of 8-22 residents per year is required, 17-21 under the current policy scenario, 14-18 under the new model of care scenario, and, under the moderated workload scenario, an intake of 18-23 residents per year is required. CONCLUSIONS: The results show that under all scenarios considered, Singapore's aging and growing population will result in an almost doubling of the number of Singaporeans with eye conditions, a significant increase in public sector eye care demand and, consequently, a greater requirement for ophthalmologists.

CT Scan Dosimetric Parameters Routine Monitoring: First Results of Radiation Dose Optimization Strategies Promptly Provided by a Multidisciplinary Team

CONCLUSION Radiation dose reduction, while saving image quality could be easily implemented with this approach. Furthermore, the availability of a dosimetric data archive provides immediate feedbacks, related to the implemented optimization strategies. Background JCI Standards and European Legislation (EURATOM 59/2013) require the implementation of patient radiation protection programs in diagnostic radiology. Aim of this study is to demonstrate the possibility to reduce patients radiation exposure without decreasing image quality, through a multidisciplinary team (MT), which analyzes dosimetric data of diagnostic examinations. Evaluation Data from CT examinations performed with two different scanners (Siemens DefinitionTM and GE LightSpeed UltraTM) between November and December 2013 are considered. CT scanners are configured to automatically send images to DoseWatch© software, which is able to store output parameters (e.g. kVp, mAs, pitch ) and exposure data (e.g. CTDIvol, DLP, SSDE). Data are analyzed and discussed by a MT composed by Medical Physicists and Radiologists, to identify protocols which show critical dosimetric values, then suggest possible improvement actions to be implemented. Furthermore, the large amount of data available allows to monitor diagnostic protocols currently in use and to identify different statistic populations for each of them. Discussion We identified critical values of average CTDIvol for head and facial bones examinations (respectively 61.8 mGy, 151 scans; 61.6 mGy, 72 scans), performed with the GE LightSpeed CTTM. Statistic analysis allowed us to identify the presence of two different populations for head scan, one of which was only 10% of the total number of scans and corresponded to lower exposure values. The MT adopted this protocol as standard. Moreover, the constant output parameters monitoring allowed us to identify unusual values in facial bones exams, due to changes during maintenance service, which the team promptly suggested to correct. This resulted in a substantial dose saving in CTDIvol average values of approximately 15% and 50% for head and facial bones exams, respectively. Diagnostic image quality was deemed suitable for clinical use by radiologists.