Drivers of and Barriers to COVID-19 Vaccine Booster Dose Acceptance in Indonesia.

Obtaining a booster dose of coronavirus disease 2019 (COVID-19) vaccine is required to maintain the protective level of neutralizing antibodies and therefore herd immunity in the community, and the success of booster dose programs depends on public acceptance. The aim of this study was to determine the acceptance of a booster dose of COVID-19 vaccine and its drivers and barriers in Indonesia. A cross-sectional survey was conducted in the provinces of Indonesia between 1 and 15 August 2022. Individuals who completed the primary series of the COVID-19 vaccine were asked about their acceptance of a booster dose. Those who refused the booster dose were questioned about their reasons. A logistic regression was used to determine the determinants associated with rejection of a booster dose of COVID-19 vaccine. A total of 2935 respondents were included in the final analysis. With no information on the efficacy and safety of the COVID-19 vaccine, 95% of respondents agreed to receive a booster dose if it were provided for free by the government. This acceptance was reduced to only 50.3% if the vaccine had a 75% efficacy with a 20% chance of side effects. The adjusted logistic regression analysis indicated that there were eight factors associated with the rejection of the booster dose: age, marital status, religion, occupation, type of the first two vaccines received, knowledge regarding the importance of the booster dose, belief that natural immunity is sufficient to prevent COVID-19 and disbelief in the effectiveness of the booster dose. In conclusion, the hesitancy toward booster doses in Indonesia is influenced by some intrinsic factors such as lack of knowledge on the benefits of the booster dose, worries regarding the unexpected side effects and concerns about the halal status of the provided vaccines and extrinsic determinants such as the effectiveness and safety of the vaccine. These findings suggest the need for more campaigns and promotions regarding the booster dose benefits to increase its acceptance.

Willingness to Pay (WTP) for COVID-19 Vaccine Booster Dose and Its Determinants in Indonesia.

Willingness to pay (WTP) for booster doses of coronavirus disease 2019 (COVID-19) vaccines is an under studied research topic. Therefore, the current study aimed to investigate the WTP for the booster doses of COVID-19 vaccines and its predictors in Indonesia using an online survey distributed all over the provinces of this low-middle-income country. The WTP was evaluated using a basic dichotomous contingent valuation approach, and its associated determinants were evaluated using a linear regression model. Out of 2935 responders, 66.2% (1942/2935) were willing to pay for a booster dose of the COVID-19 vaccine. The majority of respondents (63.5%) were willing to pay within a price range of 100,000-500,000 Indonesian rupiah (IDR), i.e., USD 6.71-33.57. Being older than 40 years, having a higher educational level, having a higher income, knowing and understanding that booster doses were important, and having a vaccine status that is certified halal (permissible in Islamic law), were all associated with a higher WTP for the booster dose of COVID-19 vaccines. The study findings imply that the WTP for a booster dose of COVID-19 vaccination in Indonesia is lower compared to acceptance of vaccines provided free of charge. This WTP data can be utilized to develop a pricing scheme for the booster doses of COVID-19 vaccination in the country with potential benefits in other low-income countries. The government may be required to provide subsidies for the herd immunity vaccination process to proceed as anticipated. Furthermore, the public community must be educated on the importance of vaccination as well as the fact that the COVID-19 epidemic is far from being over.

Visualising and quantifying microvascular structure and function in patients with heart failure using optical coherence tomography.

Heart failure (HF) is characterised by abnormal conduit and resistance artery function in humans. Microvascular function in HF is less well characterised, due in part to the lack of tools to image these vessels in vivo. The skin microvasculature is a surrogate for systemic microvascular function and health and plays a key role in thermoregulation, which is dysfunctional in HF. We deployed a novel optical coherence tomography (OCT) technique to visualise and quantify microvascular structure and function in 10 subjects with HF and 10 age- and sex-matched controls. OCT images were obtained from the ventral aspect of the forearm, at baseline (33°C) and after 30 min of localised skin heating. At rest, OCT-derived microvascular density (20.3 ± 8.7%, P = 0.004), diameter (35.1 ± 6.0 µm, P = 0.006) and blood flow (82.9 ± 41.1 pl/s, P = 0.021) were significantly lower in HF than CON (27.2 ± 8.0%, 40.4 ± 5.8 µm, 110.8 ± 41.9 pl/s), whilst blood speed was not significantly lower (74.3 ± 11.0 µm/s vs. 81.3 ± 9.9 µm/s, P = 0.069). After local heating, the OCT-based density, diameter, blood speed and blood flow of HF patients were similar (all P > 0.05) to CON. Although abnormalities exist at rest which may reflect microvascular disease status, patients with HF retain the capacity to dilate cutaneous microvessels in response to localised heat stress. This is a novel in vivo human observation of microvascular dysfunction in HF, illustrating the feasibility of OCT to directly visualise and quantify microvascular responses to physiological stimuli in vivo. KEY POINTS: Microvessels in the skin are critical to human thermoregulation, which is compromised in participants with heart failure (HF). We have developed a powerful new non-invasive optical coherence tomography (OCT)-based approach for the study of microvascular structure and function in vivo. Our approach enabled us to observe and quantify abnormal resting microvascular function in participants with HF. Patients with HF were able to dilate skin microvessels in response to local heat stress, arguing against an underlying structural abnormality. This suggests that microvascular functional regulation is the primary abnormality in HF. OCT can be used to directly visualise and quantify microvascular responses to physiological stimuli in vivo.

Adaptation to Exercise Training in Conduit Arteries and Cutaneous Microvessels in Humans: An Optical Coherence Tomography Study.

INTRODUCTION: Exercise training has antiatherogenic effects on conduit and resistance artery function and structure in humans and induces angiogenic changes in skeletal muscle. However, training-induced adaptation in cutaneous microvessels is poorly understood, partly because of technological limitations. Optical coherence tomography (OCT) is a novel high-resolution imaging technique capable of visualizing cutaneous microvasculature at a resolution of ~30 µm. We utilized OCT to visualize the effects of training on cutaneous microvessels, alongside assessment of conduit artery flow-mediated dilation (FMD). METHODS: We assessed brachial FMD and cutaneous microcirculatory responses at rest and in response to local heating and reactive hyperemia: pretraining and posttraining in eight healthy men compared with age-matched untrained controls (n = 8). Participants in the training group underwent supervised cycling at 80% maximal heart rate three times a week for 8 wk. RESULTS: We found a significant interaction (P = 0.04) whereby an increase in FMD was observed after training (post 9.83% ± 3.27% vs pre 6.97% ± 1.77%, P = 0.01), with this posttraining value higher compared with the control group (6.9% ± 2.87%, P = 0.027). FMD was not altered in the controls (P = 0.894). There was a significant interaction for OCT-derived speed (P = 0.038) whereby a significant decrease in the local disk heating response was observed after training (post 98.6 ± 3.9 µm·s-1 vs pre 102 ± 5 µm·s-1, P = 0.012), whereas no changes were observed for OCT-derived speed in the control group (P = 0.877). Other OCT responses (diameter, flow rate, and density) to local heating and reactive hyperemia were unaffected by training. CONCLUSIONS: Our findings suggest that vascular adaptation to exercise training is not uniform across all levels of the arterial tree; although exercise training improves larger artery function, this was not accompanied by unequivocal evidence for cutaneous microvascular adaptation in young healthy subjects.

Visualizing and quantifying cutaneous microvascular reactivity in humans by use of optical coherence tomography: impaired dilator function in diabetes.

The pathophysiology and time course of impairment in cutaneous microcirculatory function and structure remain poorly understood in people with diabetes, partly due to the lack of investigational tools capable of directly imaging and quantifying the microvasculature in vivo. We applied a new optical coherence tomography (OCT) technique, at rest and during reactive hyperemia (RH), to assess the skin microvasculature in people with diabetes with foot ulcers (DFU, n = 13), those with diabetes without ulcers (DNU, n = 9), and matched healthy controls (CON, n = 13). OCT images were obtained from the dorsal part of the foot at rest and following 5 min of local ischemia induced by inflating a cuff around the thigh at suprasystolic level (220 mmHg). One-way ANOVA was used to compare the OCT-derived parameters (diameter, speed, flow rate, and density) at rest and in response to RH, with repeated-measures two-way ANOVA performed to analyze main and interaction effects between groups. Data are means ± SD. At rest, microvascular diameter in the DFU (84.89 ± 14.84 µm) group was higher than CON (71.25 ± 7.6 µm, P = 0.012) and DNU (71.33 ± 12.04 µm, P = 0.019) group. Speed in DFU (65.56 ± 4.80 µm/s, P = 0.002) and DNU (63.22 ± 4.35 µm/s, P = 0.050) were higher than CON (59.58 ± 3.02 µm/s). Microvascular density in DFU (22.23 ± 13.8%) was higher than in CON (9.83 ± 2.94%, P = 0.008), but not than in the DNU group (14.8 ± 10.98%, P = 0.119). All OCT-derived parameters were significantly increased in response to RH in the CON group (all P < 0.01) and DNU group (all P < 0.05). Significant increase in the DFU group was observed in speed (P = 0.031) and density (P = 0.018). The change in density was lowest in the DFU group (44 ± 34.1%) compared with CON (199.2 ± 117.5%, P = 0.005) and DNU (148.1 ± 98.4, P = 0.054). This study proves that noninvasive OCT microvascular imaging is feasible in people with diabetes, provides powerful new physiological insights, and can distinguish between healthy individuals and patients with diabetes with distinct disease severity.

Optical coherence tomography: a novel imaging approach to visualize and quantify cutaneous microvascular structure and function in patients with diabetes.

INTRODUCTION: The pathophysiology of microvascular disease is poorly understood, partly due to the lack of tools to directly image microvessels in vivo. RESEARCH DESIGN AND METHODS: In this study, we deployed a novel optical coherence tomography (OCT) technique during local skin heating to assess microvascular structure and function in diabetics with (DFU group, n=13) and without (DNU group, n=10) foot ulceration, and healthy controls (CON group, n=13). OCT images were obtained from the dorsal foot, at baseline (33°C) and 30 min following skin heating. RESULTS: At baseline, microvascular density was higher in DFU compared with CON (21.9%±11.5% vs 14.3%±5.6%, p=0.048). Local heating induced significant increases in diameter, speed, flow rate and density in all groups (all p<0.001), with smaller changes in diameter for the DFU group (94.3±13.4 µm), compared with CON group (115.5±11.7 µm, p<0.001) and DNU group (106.7±12.1 µm, p=0.014). Heating-induced flow rate was lower in the DFU group (584.3±217.0 pL/s) compared with the CON group (908.8±228.2 pL/s, p<0.001) and DNU group (768.8±198.4 pL/s, p=0.014), with changes in density also lower in the DFU group than CON group (44.7%±15.0% vs 56.5%±9.1%, p=0.005). CONCLUSIONS: This proof of principle study indicates that it is feasible to directly visualize and quantify microvascular function in people with diabetes; and distinguish microvascular disease severity between patients.

Assessment of the human cutaneous microvasculature using optical coherence tomography: Proving Harvey's proof.

William Harvey proved the circulation of blood 400 years ago using a combination of ligature application and astute observation that presaged the existence of capillaries. Here we report findings, based on our development of a novel application of optical coherence tomography (OCT), that directly confirm the impact of cuff inflation on microvessels as small as ~30µm. By emulating Harvey's proofs, using cuff inflation at low pressure in the presence and absence of skin heating, we have imaged and quantified significant effects on microvascular diameter and density in humans in vivo. The application of cuff pressure significantly increased microvascular diameter (40.5 ± 4.6 vs 47.1 ± 3.9 µm, P = .01) and density (8.33 ± 4.3 vs 15.1 ± 4.9%, P < .01). These impacts were reversed by cuff deflation. Our study also showed the profound impacts of skin heating on microvessel diameter (46.7 ± 5.8 vs 70.6 ± 7.8 µm, P < .01) and density (14.2 ± 6.5 vs 43.2 ± 9%, P < .01) in vivo, which were further exacerbated by cuff inflation. Our approach to the direct visualization of the human skin microvasculature is non-invasive, safe, and easily applied. Future experiments might be directed at questions of microvascular physiology and pathophysiology, such as how different mammals thermoregulate and what impacts cardiovascular disease and diabetes have on microvascular structure and function.

Visualizing and quantifying the impact of reactive hyperemia on cutaneous microvessels in humans.

The mechanisms underlying reactive hyperemia (RH) responses in microvessels are poorly understood. Previous assessment tools have not been capable of directly visualizing microvessels during physiological stimulation in humans. Optical coherence tomography (OCT) is capable of imaging and quantifying subcutaneous microvessels as small as ~30 µm. In this study we use OCT to visualize and quantify skin microvascular changes in response to RH for the first time in humans. We also assessed the reproducibility of this technique. OCT and laser Doppler flowmetry (LDF) were used simultaneously to scan cutaneous microvessels in 10 young healthy subjects on 2 days. We applied a speckle decorrelation algorithm to assess OCT images and calculated flow rate, speed, diameter, and density parameters. Measures were obtained at rest (baseline) and 30-s following a 5-min cuff inflation (RH). All data were compared between days. The RH stimulus significantly increased (P < 0.0001) OCT-derived microvascular diameter (37.6 ± 3.4 vs. 44.5 ± 5.2 µm), flow rate (82.4 ± 23.4 vs. 240.1 ± 58.6 pl/s), speed (48 ± 5.7 vs. 101.5 ± 17.1 µm/s), density (5.1 ± 1.7 vs. 14.6 ± 2.6%), and also LDF-derived flux (12.3 ± 5.7 vs. 31.6 ± 9.1 perfusion units). At baseline, OCT-derived diameter (r = 0.55), flow rate (r = 0.64), speed (r = 0.55), and density (r = 0.75) showed significant between-day correlations (P < 0.05), as did LDF results (r = 0.74). In response to RH, OCT-derived diameter (r = 0.63) and density (r = 0.64) showed significant correlations (P < 0.05), whereas flow rate (r = 0.45), speed (r = 0.43), and LDF (r = 0.26) were less reproducible. Our study is novel in that it establishes the feasibility of using OCT to visualize and quantify microvascular structure and function responses to RH in humans.NEW & NOTEWORTHY This study describes the first evidence in humans that optical coherence tomography provides direct visualization and comprehensive quantification of cutaneous microvascular hemodynamics as a response to reactive hyperemia. This imaging technique will greatly improve human cutaneous microvascular assessment in physiological and clinical settings.

Novel Noninvasive Assessment of Microvascular Structure and Function in Humans.

INTRODUCTION: Optical coherence tomography (OCT) is a novel high-resolution imaging technique capable of visualizing in vivo structures at a resolution of ~10 µm. We have developed specialized OCT-based approaches that quantify diameter, speed, and flow rate in human cutaneous microvessels. In this study, we hypothesized that OCT-based microvascular assessments would possess comparable levels of reliability when compared with those derived using conventional laser Doppler flowmetry (LDF). METHODS: Speckle decorrelation images (OCT) and red blood cell flux (LDF) measures were collected from adjacent forearm skin locations on 2 d (48 h apart), at baseline, and after a 30-min rapid local heating protocol (30°C-44°C) in eight healthy young individuals. OCT postprocessing quantified cutaneous microvascular diameter, speed, flow rate, and density (vessel recruitment) within a region of interest, and data were compared between days. RESULTS: Forearm skin LDF (13 ± 4 to 182 ± 31 AU, P < 0.05) and OCT-derived diameter (41.8 ± 6.6 vs 64.5 ± 6.9 µm), speed (68.4 ± 9.5 vs 89.0 ± 7.3 µm·s), flow rate (145.0 ± 60.6 vs 485 ± 132 pL·s), and density (9.9% ± 4.9% vs 45.4% ± 5.9%) increased in response to local heating. The average OCT-derived microvascular flow response (pL·s) to heating (234% increase) was lower (P < 0.05) than the LDF-derived change (AU) (1360% increase). Pearson correlation was significant for between-day local heating responses in terms of OCT flow (r = 0.93, P < 0.01), but not LDF (P = 0.49). Bland-Altman analysis revealed that between-day baseline OCT-derived flow rates were less variable than LDF-derived flux. CONCLUSIONS: Our findings indicate that OCT, which directly visualizes human microvessels, not only allows microvascular quantification of diameter, speed, flow rate, and vessel recruitment but also provides outputs that are highly reproducible. OCT is a promising novel approach that enables a comprehensive assessment of cutaneous microvascular structure and function in humans.