COVID-19 vaccine acceptance and hesitancy in low- and middle-income countries

Widespread acceptance of COVID-19 vaccines is crucial for achieving sufficient immunization coverage to end the global pandemic, yet few studies have investigated COVID-19 vaccination attitudes in lower-income countries, where large-scale vaccination is just beginning. We analyze COVID-19 vaccine acceptance across 15 survey samples covering 10 low- and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in our LMIC samples (mean 80.3%; median 78%; range 30.1 percentage points) compared with the United States (mean 64.6%) and Russia (mean 30.4%). Vaccine acceptance in LMICs is primarily explained by an interest in personal protection against COVID-19, while concern about side effects is the most common reason for hesitancy. Health workers are the most trusted sources of guidance about COVID-19 vaccines. Evidence from this sample of LMICs suggests that prioritizing vaccine distribution to the Global South should yield high returns in advancing global immunization coverage. Vaccination campaigns should focus on translating the high levels of stated acceptance into actual uptake. Messages highlighting vaccine efficacy and safety, delivered by healthcare workers, could be effective for addressing any remaining hesitancy in the analyzed LMICs.Publisher PDFPeer reviewe

The role of minimally invasive ablative therapies in the treatment of primary and radio-recurrent prostate cancer

Focal cryotherapy and High Intensity Focused Ultrasound (HIFU) are emerging treatment modalities for men with prostate cancer both as a primary and radiorecurrent treatment. They aim to treat only the cancer within the prostate using minimally invasive surgical techniques whereby either cold or heat is applied in a focal manner to the cancerous areas whilst sparing adjacent structures. This process leads to control of the cancer whilst minimising treatment related side-effects particularly with regard to urinary and sexual function. My aim in primary disease was to assess the oncological and functional outcomes from focal cryotherapy before performing a comparative analysis of the oncological and functional outcomes against an established surgical treatment, radical prostatectomy. My aim in radiorecurrent disease was to assess outcomes from whole-gland salvage therapy, perform a systematic review on focal salvage therapies before presenting results from the FORECAST trial (FOcal RECurrent Assessment and Salvage Treatment, NCT01883128) and present oncological and functional outcomes in men who underwent focal salvage HIFU and Cryotherapy for both localised and metastatic radio-recurrent prostate. Primary Disease: An initial systematic review on focal cryotherapy confirmed good oncological outcomes in the short-medium term. When assessing intra-operative ice ball formation, using data from gel model experiments, I found that the -40oC lethal isotherm is approximately 1cm inside the leading edge of the ice-ball. The optimum distance between cryo-needles was 1.5 – 2 cm’s. At distances further apart the ice-balls had either a central core >-40oC or an hourglass shape. Subsequently analysis of a prospective registry-based case-series of 122 consecutive patients confirmed good early oncological control when treating predominantly anterior primary prostate with a 3-year failure free survival of 90.5% [95%CI 84.2-97.3]. Incontinence defined as any was 0/69 (0%) and erectile dysfunction was 5/31 (16.1%). Finally, a propensity score analysis was constructed using a combined focal cryotherapy and HIFU database versus a prospective radical prostatectomy database. After matching there were 246 patients in each arm with low-intermediate risk localised primary prostate cancer. Failure-free survival (95% CI) in the radical prostatectomy compared to focal therapy groups was 79% (73-86%) vs. 83% (76-90%) at 8 years (adjusted log rank p-value 0.12). Radiorecurrent Disease: Initial analysis of a 50-patient salvage HIFU showed a 5-year progression-free survival of 31% and 5-year overall survival (OS) of 87%. The main limitation was the adverse event profile with 3/50 (6%) developing a fistula, 27/50 (54%) needing further intervention for bladder outlet obstruction and 8/26 (31%) developing incontinence (any pad-use). A systemic review on focal salvage ablation showed that similar or better oncological outcomes could be obtained with focal salvage treatment with a superior side-effect profile. Results from the FORECAST trial showed that mpMRI for the detection of radiorecurrent disease had a sensitivity of 81% (95%CI 73-88%), specificity 88% (95%CI 73-98%), PPV 96% (95%CI 90-99%) and NPV 57% (95%CI 42-70%). Sensitivity of MRI-targeted biopsy in 87 men was 92% (95%CI 83-97%), specificity 75% (95%CI 45-92%), PPV 94% (95%CI 86-98%) and NPV 65% (95%CI 38-86%). Overall, 4/72 (6%) cancers were missed on systematic biopsies alone and 6/72 (8%) were missed on targeted biopsies alone. Subsequently, 93/181 underwent salvage focal therapy: HIFU (64/93) or cryotherapy (29/93). Probability of return of continence was 84% at 12-months. 73 underwent focal therapy for localised disease. Metastases Free Survival was 80% [95% CI 68 – 88] at 2-years. 20 underwent cytoreductive focal ablation in the presence of nodal/metastatic disease. All were alive at last follow-up. 4/20 had evidence of progression on whole-body imaging. The programme of work detailed above confirms both the good oncological and functional outcomes that can be achieved from focal therapy in primary and recurrent disease. This evidence provides the basis for future randomised controlled trials and whilst we await the results from these the presented data can be used to guide patients regarding their treatment options

Numerical Investigation on the Thrust Vectoring Performance of Bypass Dual Throat Nozzle

Modern aircraft and missiles are gradually integrating thrust vector control systems to enhance their military capabilities. Bypass Dual-Throat Nozzle (BDTN) control is a new fluidic thrust vectoring technique capable of achieving superior performance with large vector angles and low thrust loss. In this study, we analyzed the flow characteristics and performance parameters of BDTN by varying the bypass angle, nozzle convergence angle, and bypass width. The flow governing equations are solved according to a finite volume discretization technique of the compressible RANS equations coupled with the Renormalization Group (RNG) k-ϵ turbulence model for Nozzle Pressure Ratio (NPR = 2~10) to capture the significance of under-expanded and over-expanded jets. Results show that by decreasing the bypass angle from 90° to 35°, there is a 6% increase in vectoring angle while the vectoring efficiency is enhanced by 18%. However, a decrease of 3% in the thrust and discharge coefficients is also observed. When the convergence angle was increased from 22° to 37°, vectoring angle, discharge coefficient, and thrust coefficient increased by 2%, 1%, and 0.26%, respectively. Moreover, vectoring efficiency is also enhanced by 8% by reducing the convergence angle from 37° to 22°. Based on the investigated parameters, it is determined that nozzle convergence angle does not significantly influence thrust vectoring performance, however, bypass width and bypass angle have a significant effect on thrust vectoring performance

Additional Treatments to the Local tumour for metastatic prostate cancer - Assessment of Novel Treatment Algorithms (IP2-ATLANTA): Protocol for a multicentre, phase II randomised controlled trial

Introduction Survival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone. Methods A phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. Primary outcome: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024. Ethics and dissemination Approved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals