A review of the use of inhaled nitric oxide in the PICU at Red Cross War Memorial Children's Hospital, 2011-2015: A retrospective cohort study.

Background: Inhaled nitric oxide (iNO) functions as a selective pulmonary vasodilator. It is an expensive treatment that is often employed as rescue therapy for refractory hypoxaemia in acute respiratory distress syndrome (ARDS) and pulmonary hypertension (PHT) following cardiac surgery. Objectives: To describe the use of iNO and the cost of treatment in our paediatric intensive care unit (PICU). Methods: A retrospective descriptive study of all patients treated with iNO in the PICU at Red Cross War Memorial Children's Hospital (RCWMCH) from 2011 - 2015. Results: We treated 140 patients with iNO, 82 for PHT following cardiac surgery, 53 for ARDS and 5 for persistent pulmonary hypertension of the newborn (PPHN). A response to treatment was observed in 64% of the cohort as a whole, 80% of those with PPHN, 67% of those with PHT post-cardiac surgery, and 64% of those with ARDS. A longer duration of PICU and hospital admission, and higher in-hospital mortality (53%), was seen in the group with ARDS, in particular those with adenoviral infection (63%), when compared with patients treated for PHT post-cardiac surgery (18%) and for PPHN (20%). The total cost of treatment with iNO was ZAR1 441 376 for the 5-year period studied. There are no protocols guiding the use of iNO in our unit, and it was found that response to treatment was not being objectively measured and documented, and that practice varied between clinicians. Conclusion: Considering the cost of treatment and lack of evidence showing improved outcomes with iNO therapy, its continued use in our resource-limited setting should be guided by protocol. Contributions of the study: There is a paucity of data regarding the indications for use, and outcomes of patients treated with iNO in resource-limited settings. We did not find evidence of improved outcomes in patients treated with iNO despite the high costs of the therapy. Protocols should be developed to guide the use of iNO in resource-limited settings.

Setting up pharmacovigilance based on available endTB Project data for bedaquiline.

SETTING: Active pharmacovigilance (PV) is recommended for TB programmes, notably for multidrug-resistant TB (MDR-TB) patients treated with new drugs. Launched with the support of UNITAID in April 2015, endTB (Expand New Drug markets for TB) facilitated treatment with bedaquiline (BDQ) and/or delamanid of >2600 patients in 17 countries, and contributed to the creation of a central PV unit (PVU).OBJECTIVE: To explain the endTB PVU process by describing the serious adverse events (SAEs) experienced by patients who received BDQ-containing regimens.DESIGN: The overall PV strategy was in line with the 'advanced´ WHO active TB drug safety monitoring and management (aDSM) system. All adverse events (AEs) of clinical significance were followed up; the PVU focused on signal detection from SAEs.RESULTS and CONCLUSION: Between 1 April 2015 and 31 March 2019, the PVU received and assessed 626 SAEs experienced by 417 BDQ patients. A board of MDR-TB/PV experts reviewed unexpected and possibly drug-related SAEs to detect safety signals. The experts communicated on clusters of risks factors, notably polypharmacy and off-label drug use, encouraging a patient-centred approach of care. Organising advanced PV in routine care is possible but demanding. It is reasonable to expect local/national programmes to focus on clinical management, and to limit reporting to aDSM systems to key data, such as the SAEs.

Paclitaxel-coated balloons for failing peripheral bypass grafts: the BYPACS study.

AIM: Aim of the present study was to report the imaging and clinical outcomes of a prospective single-center study investigating paclitaxel-coated balloons (PCB) for the treatment of failing peripheral bypass grafts (BYPACS study). METHODS: In total, 32 patients had their failing peripheral native or synthetic bypass graft treated with PCB angioplasty (Group PCB). Basic inclusion criteria were any significant proximal or distal anastomotic stenosis confirmed by Duplex ultrasound (DUS; PSVR>2.5) associated with significantly reduced in-graft velocities (<45 cm/s) putting the graft at risk of thrombosis. Results were compared with a similar historical control group of 24 patients who had their failing peripheral bypass treated with plain uncoated balloon angioplasty (Group PTA). Primary endpoint was binary lesion restenosis defined as >50% stenosis of the treated lesion on DUS. Secondary endpoints included freedom from target lesion revascularization (TLR) defined as a patent peripheral bypass graft regardless of restenosis but without any repeat intervention (driven by reduced in-graft velocities <45 cm/s), major amputations and graft thrombosis. Multivariable Cox proportional hazards regression analysis was applied to adjust for confounding factors of heterogeneity. Results are reported as Cox-adjusted hazard ratios (HR and 95% CI). RESULTS: Baseline variables were equally distributed between the two groups. Median follow-up was 7 months in group PCB and 8 months in group PTA. Rates of binary restenosis were similar between the 2 groups (HR=1.08, 95% CI=0.49-2.40; P=0.84). Freedom from TLR was also similar (HR=0.97, 95% CI=0.36-2.66; P=0.88). One amputation occurred in the PCB group and 2 in the PTA (P=0.58). Four events of bypass thrombosis occurred in each group (P=0.71). CONCLUSION: PCB does not significantly inhibit restenosis or improve freedom from repeat angioplasty after treatment of failing peripheral arterial vein or synthetic bypass grafts.

An objective method for grading ultrasound images of carotid artery plaques.

Plaque composition may improve identification of patients at risk of stroke. A new method of grading ultrasound (US) images to assess plaque composition is described. B-mode US images were obtained from 50 carotid specimens. Image analysis parameters were entered into a discriminant analysis package and compared retrospectively with histology. Discriminant functions were derived and then applied prospectively to image-analysis data obtained from a further 50 plaque specimens. For the prospective analysis, US images were graded according to the relative contribution of calcium, fibrous tissue, haemorrhage and lipid. The accuracy for retrospective classification of calcium was 100%, for fibrous tissue 97%, for lipid 76% and 68% for haemorrhage (kappa = 0.81). Prospective classification showed an overall agreement of 65% (kappa = 0.47). Significant intraplaque haemorrhage was identified with an 81% sensitivity and 83% specificity. The US method described demonstrated improved accuracy compared to previous studies. Further study is required to establish the use of this method for in vivo images and its correlation with patient symptoms.

The use of the wavelet transform to describe embolic signals.

A number of methods to detect cerebral emboli and differentiate them from artefacts using Doppler ultrasound have been described in the literature. In most, Fourier transform-based (FT) spectral analysis has been used. The FT is not ideally suited to analysis of short-duration embolic signals due to an inherent trade-off between temporal and frequency resolution. An alternative approach that might be expected to describe embolic signals well is the wavelet transform. Wavelets are ideally suited for the analysis of sudden short-duration signal changes. Therefore, we have implemented a wavelet-based analysis and compared the results of this with a conventional FFT-based analysis. The temporal resolution, as measured by the half-width maximum, was significantly better for the continuous wavelet transform (CWT), mean (SD) 8.40 (8.82) ms, compared with the 128-point FFT, 12.92 (9.70) ms, and 64-point FFT, 10.80 (5.69) ms. Time localization of the CWT for the embolic signal was also significantly better than the FFT. The wavelet transform appears well suited to the analysis of embolic signals offering superior time resolution and time localization to the FFT.

Cerebral blood flow is proportional to cardiac index in patients with septic shock.

PURPOSE: In patients with septic shock, the cardiac index is often increased. Maldistribution of blood flow and regional hypoperfusion has been implicated as a key factor in the pathogenesis of organ dysfunction in these patients. We have investigated the relationship between cerebral blood flow and cardiac index in patients with septic shock. MATERIALS AND METHODS: We used Doppler ultrasound techniques to investigate limb and carotid blood flow in 15 patients with septic shock and 9 nonseptic controls. RESULTS: In the nonseptic control patients, common femoral and brachial blood flow were proportional to cardiac index (r=0.73 and 0.76; P=.038 and .017, respectively) reflecting a protective redistribution of flow to more vital organs. However, this relationship was absent in patients with septic shock (r=0.23 and 0.21). Furthermore, in the septic patients but not the nonseptic controls, cerebral blood flow was correlated with the cardiac index (r=0.66, P < .05 vs r=-0.36, NS in nonseptic controls). Carotid flow was independent of mean arterial pressure, PaCO2 and PaO2 in patients with septic shock. CONCLUSIONS: These data are consistent with a loss of autoregulation of cerebral blood flow and a change in the control of limb blood flow in humans with septic shock.

The changing indications for carotid endarterectomy in the UK.

In early series the majority of carotid endarterectomies were performed in patients with amaurosis fugax (AFx) or transient ischaemic attacks (TIAs) who were thought to have atheromatous ulcers of the carotid bifurcation or the internal carotid artery (ICA). The degree of stenosis was considered to be of secondary importance. We compared our own data with two British series undertaken in the early and late 80s/early 90s. This reflects the broadening of indications and the change of practice for carotid endarterectomy over the years, on the one hand towards including patients who are at greater risk of perioperative stroke (previous CVAs vs TIAs, crescendo TIAs and stroke in evolution), and on the other towards patients who have had no symptoms attributable to the carotid lesion (asymptomatic cases, combined carotid and cardiac procedures).

Surgery for asymptomatic carotid artery stenosis.

The recent European Carotid Surgery Trial (ECST) and North American Symptomatic Carotid Endarterectomy Trial (NASCET) have clearly defined a population who benefit from carotid artery endarterectomy (CAE). However these trials used different criteria to identify > 70% stenosis of the internal carotid artery (ICA). The role of CAE in asymptomatic ICA stenosis has been investigated by the Carotid Artery Stenosis with Asymptomatic Narrowing Operation Versus Aspirin (CASANOVA) study, the Veterans Administration Asymptomatic Carotid Study (VAACS) and the Asymptomatic Carotid Artery Stenosis (ACAS) trials, all of which have design limitations. The Asymptomatic Carotid Stenosis Trial (ACST) is still recruiting patients but until the natural history of asymptomatic ICA disease is understood, the role of surgical intervention will continue to be controversial.

The measurement of time-averaged flow by magnetic resonance imaging using continuous acquisition in the carotid arteries and its comparison with Doppler ultrasound.

A continuous acquisition method was used to measure the time-averaged flow in the carotid arteries of 10 normal volunteers, using an interleaved flow-sensitive and flow-compensated field echo sequence on a 1.5 T magnetic resonance (MR) system. Validation of the sequence and technique was performed using a pulsatile rotating phantom. The measured flow rates for the common carotid arteries were compared with Doppler ultrasound values obtained immediately after the MR measurement using a Duplex scanner. The correlation (r = 0.52, P less than 0.01) was significant with data spread accounted for by the inherent errors of both techniques. The difference between time-averaged flow measured by MR and Doppler ultrasound was 1.9%. Short-term reproducibility of each technique was assessed by consecutive measurements with values of 6.8% and 6.6% respectively for MR and Doppler; measurements after a 2 - 4 week interval gave a long-term reproducibility of 11.8% and 9.8% respectively. The advantages of continuous acquisition make the method suitable for non-invasive flow measurements, particularly for vessels that are not accessible to ultrasound.