Pulmonary infection is a frequent complication among stroke patients and adversely affects clinical outcomes, increases the length of hospitalization stay and costs, and aggravates the financial burden of the national medical health system. Early identification and management of high-risk patients are necessary and imperative to reduce the incidence of stroke-associated pneumonia (SAP).The evidence-based practice project evaluated the effectiveness of a standard care bundle intervention in preventing the occurrence of SAP.The project was conducted in a neurology department of a teaching hospital. Given the variation in assessment and management standards, evidence-based practice (EBP) methodology was used to establish a process for quality improvement. A thorough literature search was conducted to identify evidence-based interventions to manage and prevent SAP. Thorough critiques of the literature and synthesis of the evidence were completed. A systematic management flow and care bundle interventions were established. The care bundle included interventions, such as the utilization of tools for SAP risk screening; dysphagia screening and rehabilitation; feeding modification, oral care, airway management, position management, and the nursing techniques of traditional Chinese medicine.p = 0.025). In addition, significantly lower duration of hospitalization, lower rate of aspiration, and improvements in albumin and oral hygiene were found after the implementation of the care bundle.A significant improvement was observed in preventing SAP in patients in the postimplementation group compared with those in the preimplementation group (14.0% vs. 37.2%, Evidence-based care bundles successfully empower nurses to reduce the incidence of SAP. The management flow of SAP prevention could be promoted to other units of the neurology department in the future. The results of the project reflect positively on the capacity to implement EBP in an acute care setting for stroke. The EBP methodology can be utilized to solve other clinical problems.The online version contains supplementary material available at 10.1186/s12883-022-02826-8. Stroke is a widely prevalent acute cerebrovascular disease with high morbidity and mortality . Acute iStroke-associated pneumonia (SAP) refers to pulmonary infections that develop within the first 7 days of stroke onset among nonventilated patients, affecting 2.3 to 44% of stroke patients , 7. FemaPrevious studies have shown that SAP can be prevented , 15. In Although many scholars have explored and evaluated the effects of different preventive interventions on SAP from different perspectives, systematic prevention recommendations or management flowcharts for SAP have not yet been developed. Effective nursing interventions include feeding management, respiratory tract management, dysphagia rehabilitation, cluster nursing interventions, and traditional Chinese medicine (TCM) nursing , 18, 19.This project was implemented in the Neurology Department of The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, which is a cerebrovascular disease medical center with more than 300 beds. A 28-bed internal medicine unit with more than 1200 annual cerebrovascular disease visits was designated for the project. The prevalence rate of SAP in the unit was 26.5% in 2018.This nurse-led project aimed to institute a best practice bundle and management process to reinforce systematic management of patients with acute stroke, resulting in a decrease in the incidence of SAP.2DS2  score between 5 and 10. The exclusion criteria were: (1) a history of mental diseases; and (2) a history of severe diseases of the heart, liver and kidney .The population involved in the project was a convenience sample from September 2020 to May 2021. The inclusion criteria were as follows: (1) diagnosed with ischaemic stroke by computed tomography (CT) or magnetic resonance imaging (MRI); (2) between 18 and 80 years old; (3) time from symptom onset within 7 days; (4) admission without pulmonary infection; and (5) ASample size estimation was based on a similar study, which adopted an evidence-based care bundle to decrease the incidence of SAP from 43.3 to 16.7% . With a The Iowa Model of Evidence-Based Practice was utilized as a framework for project execution . SAP in The clinical nurse specialist conducted a systematic literature search. The goal was to identify what evidence-based interventions might exist to decrease the incidence of SAP. The Population, Intervention, Comparison, Outcome (PICO) framework was used to develop the search strategy: in patients with acute stroke, how do evidence-based nursing bundle interventions compared to conventional nursing interventions affect SAP rates? A Boolean search was completed using the following terms:  AND . The databases searched included the National Institute for Clinical Excellence (NICE), National Guideline Clearinghouse (NGC), Scottish Intercollegiate Guidelines Network (SING), MEDLINE, PubMed, Embase, Cochrane Library, Joanna Briggs Institute (JBI), EBSCO, Web of Science, Ovid, Chinese National Knowledge Infrastructure (CNKI), Wan Fang Data, VIP, and SinoMed. The inclusion criteria allowed articles about randomized controlled trials, quasi-experimental studies, case-control studies, and cohort studies published between 2009 and 2018. The search yielded 4766 articles and included 16 articles after critical appraisal with tools of Joanna Briggs Institute and AGREE II. These included 4 evidence-based clinical guidelines from America, England and Canada, 3 Chinese clinical guidelines and expert consensus, 3 evidence synthesis, 1 systematic review, 2 cohort trails and 3 random controlled trials. Evidence-based practice interventions were based on high quality clinical evidence and emphasized clinical expertise, patient values and expectations . A gap aThe study was approved by the ethical committee of The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine. Based on a literature review, SAP management recommendations included dysphagia screening and management, feeding management, oral hygiene management, position management, and TCM nursing techniques Figs. .Multiple staff meetings and face-to-face discussions were organized, and electronic materials were provided through the WeChat app to educate nursing staff about the bundle intervention protocol. Nursing education was done during a 2-week period before implementing the bundle nursing practice. The whole training was completed by the first author, and swallowing screening and rehabilitation were trained by senior speech and language therapists specializing in neurological rehabilitation. During the training process, the SAP prevention and management manual was produced based on the evidence, and sought for the support of the department head and rehabilitation therapists. At the end of the study, the nurses received a comprehensive real-situation examination by one senior speech therapist and one head nurse of the unit that included dysphagia screening, formulation and implementation of rehabilitation recommendations, and patient education. Those who passed the examination could implement the evidence-based care bundle in the stroke unit.The impact of the evidence-based care bundle on the rate of SAP and related patient outcomes was evaluated using data collected directly from patients and electronic medical records. In this study, SAP was diagnosed based on the medical documents and re-evaluated by the treating physician according to American CDC’s (Centers for Disease Control and Prevention) diagnostic criteria  for pneu2DS2 score; the results of 30 ml water swallowing test; aspiration  were compared with data from the preimplementation period  .Data analysis included descriptive statistics for all variables. The differences between the preimplementation and postimplementation groups were compared by the χTable p = 0.025). After the evidence-based care bundle implementation, the postimplementation group had lower levels of PCT (p = 0.007) and CRPH (p = 0.013) than the preimplementation group  patients in the postimplementation group were identified as diagnosed SAP, which was significantly lower than that in the preimplementation group (14.0% vs. 37.2%, The mean length of hospital stay decreased from 14.47 ± 6.68 days before implementation to 11.74 ± 5.51 days after implementation. The cost of medical care of the postimplementation group was lower than that of the preimplementation group, but the difference was not statistically significant. The rate of aspiration of the postimplementation group was significantly lower than that of the preimplementation group. In addition, there were significant improvements in ALB, and oral hygiene Table . The nurThis project instituted an evidence-based practice bundle in the management of acute stroke patients to successfully reduce the incidence of SAP. The focus on dysphagia screening and rehabilitation; feeding modification, oral care, airway management, position management, and TCM nursing techniques were strategies introduced through the care bundle.SAP can be prevented in a variety of ways. Many other important factors, such as head position, getting out of bed, continuous tube feeding, caregivers’ feeding experience, aspiration caused by vomiting or gastroesophageal reflux, oral hygiene, immunosuppression after acute stroke, and the lesion location of dysphagia, are also linked to the occurrence of SAP and must be considered in care plans to prevent respiratory infections in patients with acute stroke , 25. ManApplying evidence-based practice methods to our project resulted in a decrease in the incidence of SAP. The infection indicators PCT and CRPH in the postimplementation group were significantly lower than those in the preimplementation group. The care bundle included dysphagia management, feeding management, oral hygiene management, position management, airway management and TCM nursing techniques. The above 6 aspects of the nursing interventions worked together to prevent SAP.After the intervention, the nutrition indicators ALB and oral hygiene were significantly better in the postimplementation group than in the preimplementation group. Early nutritional risk screening, oral care and swallowing rehabilitation training could help patients increase food intake and improve malnutrition. In addition, the significant improvement in aspiration benefited from standard and systematic screening and management. The cost of medical care was lower than before but did not have statistical significance considering complex factors, such as treatment protocols, the severity of stroke and complications. All factors were combined to reduce the length of hospitalization stay.This was a single-center EBP project in an urban level 1 stroke center, and was limited by small sample size and restricted time for project implementation. Furthermore, some blood markers were not tested on the same day that the disease attacked, so bias may exist. Finally, the nurses’ compliance with using the entire care bundle needs to be improved in the future. The stroke center was a teaching hospital that had a frequent turnover of clinical nursing staff because of internship rotations, which required attention to who had been trained and who may have missed meetings or training sessions. Nonetheless, the clinically important findings in the prevention of SAP were promising and warrant further investigation with a larger sample.Given the success of the initial project, the practice changes can be expanded to other neurology units in the clinical facility. This is in line with the guidance provided by the Iowa Model of Evidence-Based Practice for care quality improvement . AccordiSAP has presented challenges to nurses who care for patients with acute ischaemic stroke for a long time. An evidence-based practice project to empower nurses to reduce the incidence of SAP was successfully implemented. The results of the project reflect positively on the capacity to implement evidence-based practice in an acute care setting of stroke. These outcomes support the call to question traditional practice, which is necessary to advance the nursing profession in support of improved patient outcomes.Additional file 1.Additional file 2.Additional file 3.


We believe that the employment of the available results and results of the future large-scale trials into cardiac care guidelines would help reduce the global cost of cardiac care tremendously.Microvascular angina (MVA), historically called cardiac syndrome X, refers to angina with nonobstructive coronary artery disease. This female-predominant cardiovascular disorder adds considerable health-related costs due to repeated diagnostic angiography and frequent hospital admissions. Despite the high prevalence of this diagnosis in patients undergoing coronary angiography, it is still a therapeutic challenge for cardiologists. Unlike obstructive coronary artery disease, with multiple evidence-based therapies and management guidelines, little is known regarding the management of MVA. During the last decade, many therapeutic interventions have been suggested for the treatment of MVA. However, there is a lack of summarization tab and update of current knowledge about pharmacologic management of MVA, mostly due to unclear pathophysiology. In this article, we have reviewed the underlying mechanisms of MVA and the outcomes of various medications in patients with this disease. Contrary to vasospastic angina in which normal angiogram is observed as well, nitrates are not effective in the treatment of MVA. Beta-blockers and calcium channel blockers have the strongest evidence of improving the symptoms. Moreover, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, statins, estrogen, and novel antianginal drugs has had promising outcomes. Investigations are still ongoing for vitamin D, omega-3, incretins, and  Microvascular angina (MVA) was first described by Kemp in 1973 as an angina-like chest pain without any evidence of coronary obstruction in angiogram . AdvanceAlthough earlier MVA was considered a benign condition, the Women's Ischemia Syndrome Evaluation (WISE) study reported the 5-year risk of adverse cardiovascular events 3 to 6 times higher in women with MVA compared to normal asymptomatic women . MoreoveIn the last decade, despite advances in our understanding of MVA, it still remains a therapeutic challenge for physicians. In this review, we primarily focus on the pharmacologic management of MVA.Various anatomic and functional pathophysiologic mechanisms involving coronary microcirculation are proposed to lead to MVA. Of note, MVA must not be confused with vasospastic angina which classically is a disorder of major epicardial coronary arteries.Impaired vasodilation response, either via endothelium-dependent or endothelium-independent mechanisms, is frequently implied in the pathogenesis of MVA . A vasodEndothelial dysfunction in patients with MVA seems to be multifactorial, and it is conceivable that risk factors like hypertension, hypercholesterolemia, smoking, diabetes mellitus, and insulin resistance can contribute to its development . Cosín-SIn addition to functional abnormalities, some studies support the structural abnormalities of coronary microvasculature as a mechanism for MVA , 25. In A number of studies have related the signs and symptoms of MVA patients to neurologic abnormalities including cardiac adrenergic hyperactivity, cardiac neurasthenia, and low threshold of chest pain , 27. IncThe majority of patients with MVA do have some extent of concomitant coronary atherosclerosis as seen in studies using the intravascular ultrasound . Thus, aThe main goal of pharmacologic interventions in patients with MVA is to control symptoms and improve patients' quality of life. Nitrates, statins, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEI), and beta-blockers are the most commonly administered drugs for MVA patients. However, at least in part due to heterogeneous mechanisms of MVA pathophysiology, the mentioned medications have modest efficacies. Hence, the management of MVA remains a significant challenge. In the following section, we will review the mechanisms and outcomes of treatment with conventional and novel drugs in MVA patients.p < 0.0005) [p < 0.01) and improve symptoms, diastolic function, and exercise tolerance in MVA patients [p < 0.0005); however, no significant association was found in the verapamil group (3.4 ± 1.7 vs. 3.9 ± 1.8) [Blocking beta-adrenergic receptors improves myocardial ischemia by lowering heart rate, myocardial contractility, blood pressure, and consequently myocardial oxygen consumption. Additionally, beta-blockers enhance coronary blood flow (CBF) by diastolic time prolongation , 33. Bet 0.0005) . Atenolopatients , 36. Betpatients , 36. In 9 ± 1.8) .p < 0.01), in one-third ST segment shift was less than 1 mm during exercise tolerance test (p < 0.05), and these proportions were significantly higher in carvedilol group than placebo group [3-adrenergic receptor activation [Unlike earlier generations of beta-blockers, third-generation drugs such as nebivolol and carvedilol have more endothelium-dependent vasodilatory effects. Substantial increases in the serum levels of endothelial function markers including plasma NO, L-arginine, and L-arginine/asymmetric dimethylarginine ratio have been reported in the administration of nebivolol compared to metoprolol . In addibo group . To explbo group , overexptivation , and dectivation , 43. Ovetivation  and, if CCBs reduce myocardial oxygen demand through their negative inotropic (nondihydropyridine) and vasodilatory effects and subsequent decrease in heart afterload . MoleculA meta-analysis compared the effects of four CCBs in vasospastic angina patients which suggested that benidipine outperformed amlodipine, nifedipine, and diltiazem in terms of attack suppression . DiffereStatins beyond their lipid-lowering effect by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase have noticeable effects on improving endothelial function through increasing NO bioavailability, antioxidant properties, and suppressing inflammatory responses .A large number of clinical trials have demonstrated statins' effect on improving endothelial dysfunction –60. A syTaking all these lines of evidence together, statins should be regarded as a major drug class in the management of patients with MVA, particularly in combination with CCBs.Angiotensin II is a vasoconstrictor agent which increases superoxide production by its effect on nicotinamide adenine dinucleotide phosphate -NADPH- and nicotinamide adenine dinucleotide –NADH , 65. ACEIn several clinical trials, beneficial effects of an ACEI on forearm blood flow, CBF, and flow-mediated dilation have been demonstrated both in patients with CAD and in those with normal epicardial coronary arteries in the angiography –71. In aTo evaluate the priority of ACEI, beta-blockers, CCBs, and diuretics in MVA treatment, Higashi et al. conducted a clinical trial. In this study, the forearm blood flow response to reactive hyperemia, an index of endothelium-dependent vasodilation, was substantially higher in patients treated with ACEI than in individuals treated with either CCBs, beta-blockers, diuretic agents, or nothing .Accordingly, it seems that ACEIs are highly potent medications in patients with angina and normal epicardial coronary artery angiogram, particularly in the presence of arterial hypertension. Thus overall, the evidence favors the role of ACEI in the management of MVA.In a study using intravascular ultrasound, it was found that there is a high prevalence of atherosclerosis in patients with chest pain and without obstructive CAD . This suDirect relaxant effect of nitrates on vascular smooth muscles results from activation of the guanylyl cyclase signaling pathway by nitrate-released NO. Vasodilation induced by nitrates lowers cardiac preload and afterload and consequently reduces myocardial oxygen consumption , 79. In Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are NO synthase inhibitors that have been shown to be higher in MVA patients who develop adverse events , 88, 89.NO promotes muscle relaxation via the cyclic guanosine monophosphate (cGMP)-dependent mechanism . SildenaThe effect of sildenafil on improving endothelial dysfunction has been demonstrated frequently –100. HowCilostazol as a phosphodiesterase type 3 (PDE-3) inhibitor increases intracellular cyclic adenosine monophosphate with anti-inflammatory, antiplatelet, and vasodilatory effects . The effTetrahydrobiopterin is an essential cofactor of aromatic amino acid hydroxylases used in the biosynthesis of several neurotransmitters such as serotonin and catecholamines; in addition, it plays a critical role in nitric oxide production as a cofactor , 106.Many studies have noted that BH4 causes significant improvement in the NO-mediated endothelial function –109. HigAlpha-blockers have been proposed for MVA treatment due to their sympatholytic capacity which causes a reduction in the microvascular tone . HoweverSixteen patients with MVA underwent a double-blind, placebo-controlled, crossover clinical trial for 10 weeks. Lastly, no difference in exercise duration, time to angina pectoris, and exercise time to 0.1 mV ST-segment depression has been noted between doxazosin-treated patients and placebo group . In anotIn addition to the low efficacy of alpha-blockers, another limitation of their recommendation in MVA is tolerance which occurs in frequent administration .The high prevalence of MVA in postmenopausal women implies that hormonal deficiency may be a critical factor in the development of endothelial dysfunction. Estrogen, by its property for accelerating reendothelialization and inhibiting endothelial cell apoptosis, certifies endothelial integrity , 117. FuReduced number of chest pain episodes was observed in 17-beta-estradiol administration for postmenopausal women with cardiac syndrome X compared to placebo  in a double-blind placebo-controlled study . In anotThus, estrogens are effective drugs in alleviating MVA symptoms; however, some pieces of evidence contradict with long-term prescription of estrogen because of safety concerns and reduction of benefits in long-term administration , 124.The inverse association of vitamin D and the renin-angiotensin-aldosterone system leads to increased vascular inflammation and endothelial dysfunction in vitamin D deficiency . Increasp = 0.003), exercise duration, maximal work capacity (p < 0.001), and maximal ST-segment depression (p = 0.001) [Studies have found significantly lower serum vitamin D levels in patients with MVA in comparison with the control group , 128. Co= 0.001) .Accordingly, recent studies suggest vitamin D as a novel and efficient medication for the treatment of MVA; however, more clinical trials are necessary to confirm the efficacy and safety of vitamin D supplementation therapy.+ current which is observed in myocardial ischemia disturbs ion homeostasis through elevation of intracellular Na+ concentration with subsequent elevation of intracellular Ca2+. Ranolazine by inhibiting late sodium current in cardiomyocytes plays a significant role in relieving symptoms of myocardial ischemia [Increased inward late Naischemia . A numbeischemia .Although favorable effects of ranolazine in the management of obstructive CAD were initially hopeful , there iIf current, an important ionic current in charge of pacemaker activity of SA node. Ivabradine as a selective If current blocker lowers heart rate and subsequently reduces myocardial oxygen demand and improves oxygen supply [Funny channels are highly expressed in sinoatrial (SA) node myocytes control n supply .Even though ivabradine's therapeutic effects on obstructive CAD have been demonstrated in several studies , there iThus, ivabradine represents a novel and effective therapeutic modalities for MVA management; however, more clinical trials are warranted to empower such conclusions.Fasudil, HA-1077, is an inhibitor of Rho-kinase, which mediates vascular smooth muscle, endothelial, and inflammatory cell function . Preclinμg/min for 15 min) decreases pacing-induced angina symptoms, the magnitude of ST depression, and the lactate production [p < 0.01) and lactate production (p = 0.0125) in patients with angina and normal coronary angiogram [Even though the major therapeutic use of fasudil is pulmonary arterial hypertension treatment, a few studies report beneficial effects of this drug on vasospastic, microvascular, and stable effort angina. Fasudil therapy administered intracoronary  beta-oxidation leads to greater oxygen consumption, intracellular acidosis, and ROS formation , 146. TrDiscordant results have been reported about the efficacy of trimetazidine in the treatment of MVA. Nalbantgil et al. examined the effect of trimetazidine on 35 patients with nonobstructive CAD in a placebo-controlled, double-blind study. They have found no change in heart rate, blood pressure at rest, peak exercise, and the time of 1 mm ST segment depression by trimetazidine intake; however, prolonged total exercise time and time to 1 mm ST depression have been noted in the trimetazidine-treated group compared with placebo . Also, tAccording to a hypothesis, exposure of distal esophageal mucosa to gastric acid triggers esophagocardiac reflex, leading to coronary vasoconstriction . The devp < 0.001) [Dietrich et al. conducted a study on 72 patients with MVA with gastroesophageal reflux disease (GERD) to assess the effect of proton pump inhibitor (PPI) on relieving angina. After eight weeks of PPI therapy in doubled standard dose, statistically significant improvement has been achieved in intensity, frequency, and duration of symptoms (< 0.001) . AlthougThiazolidinediones, a class of antidiabetic medications used in type-2 diabetes mellitus, have been demonstrated to be efficient in improving endothelial dysfunction through modulation of oxidative processes , 155. A Although positive effects of thiazolidinediones on endothelial dysfunction have been determined in several studies; however, their effects on patients with MVA have not been examined.Metformin as an antidiabetic agent commonly prescribed for type-2 diabetes has been shown to be beneficial in reducing myocardial infarction in diabetic patients . The rolSodium-glucose cotransporter (SGLT) channel 2 inhibitors as an antidiabetic medication have proven to have beneficial effects on cardiovascular outcomes including cardiovascular death and heart failure in people with or without diabetes –162. An A and ETb are two receptors mediating ET-1, from which ETA is involved in the coronary vasoconstriction [Endothelin (ET-1) increases vascular tone and causes vasoconstriction, especially in coronary arteries , 165. ETtriction , 167. Ittriction , 168.Due to the possible effects of endothelin receptors antagonist on MVA, a randomized double-blind controlled trial investigated the effects of ET-1 receptor antagonist atrasentan on patients with multiple cardiovascular risk factors, nonobstructive CAD, and coronary endothelial dysfunction. It concluded that 6-month treatment with atrasentan could enhance coronary microvascular endothelial function . The posAdenosine, besides its role in blood flow regulation through vasodilatory effects, is the major mediator of ischemic pain perception , 172. AsA double-blind crossover study has indicated beneficial effects on exercise-induced angina in MVA patients who had received oral aminophylline for three weeks. However, no difference between aminophylline-treated patients and placebo group in frequency of ST depression and peak exercise ST depression has been noted . AfterwaAllopurinol, a xanthine oxidase inhibitor, has established a positive role in myocardial function improvement in ischemic injury and endothelial dysfunction . The stu+ channels in cell membranes leads to arterioles' smooth muscle relaxation and subsequently blood flow augmentation in ischemic areas [Hyperpolarization induced by the opening of Kic areas . Additioic areas .p = 0.036 and 0.026, respectively) compared with placebo treatment [Nicorandil treatment was significantly associated with longer total exercise time and prolonged time to 1 mm ST depression , has been shown to elevate the pain threshold through the inhibition of serotonin and adrenaline reuptake . Imipramp = 0.03) [p = 0.01). However, 83% of the treated group have shown imipramine side effects including dry mouth, dizziness, nausea, and constipation, and even three patients had to be withdrawn from the study [In a randomized, double-blind, placebo-controlled trial, the effect of imipramine in patients with chest pain and normal coronary angiogram was tested, which resulted in a statistically significant reduction in angina episodes in imipramine-treated patients in comparison with the placebo group  . Cox et he study .Although imipramine causes a significant reduction in chest pain episodes in patients with angina and normal angiogram, especially in whom remain symptomatic despite conventional antianginal therapy, the high incidence of side effects limited its use in MVA management.Omega-3 fatty acids as polyunsaturated fatty acids (PUFAs) have beneficial effects on vascular integrity and endothelial dysfunction by modifying inflammatory cytokine expression and inhibiting oxidative stress , 190.p < 0.05) and nitroglycerin-mediated dilatation , and malondialdehyde, a marker for oxidative stress, significantly decreases  in patients who had received omega-3. Significant improvement in MVA symptoms also has been noted in omega-3-treated group [Bozcali et al. evaluated the effect of 4-month treatment with omega-3 in MVA patients. They have reported a substantial increase in flow-mediated dilation  a GLP-1 receptor agonist-induced endothelial NO synthase phosphorylation and subsequently increased NO production via a 5′AMP-activated protein kinase (AMPK)-dependent pathway [μg/mL glycated bovine serum albumin) [Glucagon-like peptide-1 (GLP-1) is an incretin hormone that improves glycemic control through stimulating insulin secretion, inhibiting glucagon release and appetite suppression , 194. La pathway . Moreovealbumin) .μg/100 mL)-induced forearm blood flow in healthy volunteers (n = 10) undergoing GLP-1 infusion (1.2 pmol/kg/min), whereas GLP-1 did not affect sodium nitroprusside–regulated blood flow (0.5–2 μg/100 mL) [Clinical studies also demonstrated favorable effect of incretin on coronary and forearm blood flow. Basu et al. have shown enhancement in ACh (2–8 /100 mL) . Further/100 mL) . In cont/100 mL) .Although incretin seems to have therapeutic properties for MVA management, clinical studies are warranted to demonstrate its efficacy and safety in patients with MVA.N-acetylcysteine (NAC), a thiol, is a prodrug to L-cysteine, which converts to the biologic antioxidant, and glutathione. Hence, NAC modifies NO half-life and potentiates the activity of NO by forming NO adducts –202.p = 0.02) elevation in coronary and femoral blood flow after NAC administration [Andrews et al. conducted a study on 16 patients undergoing cardiac catheterization  testing the effect of NAC on ACh-mediated coronary vasodilation. They have shown 36 ± 11% (stration .Taken together, NAC potentially is an effective medication to manage MVA, but more pieces of evidence are required to support its efficacy.Besides the mentioned treatments, there are some newly-introduced ones that should be considered and investigated in detail. A summary of treatment type, duration of treatment, and main findings in recently published trials on the management of MVA are available in Although the heterogeneity in the pathophysiology of MVA makes it difficult to control the disease in a fixed pattern, traditional anti-ischemic medications are the first line of MVA pharmacologic management. Beta-blockers, statins, ACEI/ARBs, and CCBs are the most efficient classes of drugs and should still remain the first choice of MVA treatment. If single-drug therapy is not effective, a combination of beta-blockers or statins with CCBs can be proposed . Also, iTo sum up, MVA seems to have received insufficient attention from clinicians and researchers up to now. However, according to our investigations, beta-blockers, statins, ACEI/ARBs, and CCBs in addition to risk factor control may be helpful in the management of MVA. The only way to assess the efficacy and safety of suggested treatments for MVA is through large clinical trials. We hope that future trials on the treatment of this tricky yet burdensome cardiovascular issue will yield definite therapeutic strategies.


Adolescent girls and young women (AGYW), aged 15–24 years, are disproportionately affected by HIV and other sexual and reproductive health (SRH) risks due to varying social, cultural, and economic factors that affect their choices and shape their knowledge, understanding, and practices with regard to their health. Socio‐Behavioral Change Communication (SBCC) interventions targeted at strengthening the capabilities of individuals and their networks have supported the demand and uptake of prevention services and participation in biomedical research. However, despite growing global recognition of the domain, high‐quality evidence on the effectiveness of SBCC remains scattered. This evidence and gap map (EGM) report characterizes the evidence base on SBCC interventions for strengthening HIV Prevention and Research among AGYW in low‐ and middle‐income countries (LMICs), identifying evidence gaps and outlining the scope of future research and program design.The objectives of the proposed EGM are to: (a) identify and map existing EGMs in the use of diverse SBCC strategies to strengthen the adoption of HIV prevention measures and participation in research among AGYW in LMICs and (b) identify areas where more interventions and evidence are needed to inform the design of future SBCC strategies and programs for AGYW engagement in HIV prevention and research.This EGM is based on a comprehensive search of systematic reviews and impact evaluations corresponding to a range of interventions and outcomes—aimed at engaging AGYW in HIV prevention and research ‐ that were published in LMICs from January 2000 to April 2021. Based on guidance for producing a Campbell Collaboration EGM, the intervention and outcome framework was designed in consultation with a group of experts. These interventions were categorized across four broad intervention themes: mass‐media, community‐based, interpersonal, and Information Communication and Technology (ICT)/Digital Media‐based interventions. They were further sub‐categorized into 15 intervention categories. Included studies looked at 23 unique behavioral and health outcomes such as knowledge attitude and skills, relationship dynamics, household dynamics, health care services, and health outcomes and research engagement. The EGM is presented as a matrix in which the rows are intervention categories/sub‐categories, and the columns are outcome domains/subdomains. Each cell is mapped to an intervention targeted at outcomes. Additional filters like region, country, study design, age group, funding agency, influencers, population group, publication status, study confidence, setting, and year of publication have been added.To be eligible, studies must have tested the effectiveness of SBCC interventions at engaging AGYW in LMICs in HIV prevention and research. The study sample must have consisted of AGYW between the ages of 15–24, as defined by UNAIDS. Both experimental (random assignment) and quasi‐experimental studies that included a comparison group were eligible. Relevant outcomes included those at the individual, influencer, and institutional levels, along with those targeting research engagement and prevention‐related outcomes.This EGM comprises 415 impact evaluations and 43 systematic reviews. Interventions like peer‐led interactions, counseling, and community dialogues were the most dominant intervention sub‐types. Despite increased digital penetration use of media and technology‐driven interventions are relatively less studied. Most of the interventions were delivered by peers, health care providers, and educators, largely in school‐based settings, and in many cases are part of sex‐education curricula. Evidence across geographies was mostly concentrated in Sub‐Saharan Africa (70%). Most measured outcomes focused on disease‐related knowledge dissemination and enhancing awareness of available prevention options/strategies. These included messaging around consistent condom use, limiting sexual partners, routine testing, and awareness. Very few studies were able to include psychographic, social, and contextual factors influencing AGYW health behaviors and decisions, especially those measuring the impact of social and gender norms, relationship dynamics, and household dynamics‐related outcomes. Outcomes related to engagement in the research were least studied.This EGM highlights that evidence is heavily concentrated within the awareness‐intent spectrum of behavior change and gets lean for outcomes situated within the intent‐action and the action‐habit formation spectrum of the behavior change continuum. Most of the evidence was concentrated on increasing awareness, knowledge, and building risk perception around SRH domains, however, fewer studies focused on strengthening the agency and self‐efficacy of individuals. Similarly, evidence on extrinsic factors—such as strengthening social and community norms, relationships, and household dynamics—that determine individual thought and action such as negotiation and life skills were also found to be less populated. Few studies explore the effectiveness of these interventions across diverse AGYW identities, like pregnant women and new mothers, sex workers, and people living with HIV, leading to limited understanding of the use of these interventions across multiple user segments including key influencers such as young men, partners, families, religious leaders, and community elders was relatively low. There is a need for better quality evidence that accounts for the diversity of experiences within these populations to understand what interventions work, for whom, and toward what outcome. Further, the evidence for use of digital and mass‐media tools remains poorly populated. Given the increasing penetration of these tools and growing media literacy on one end, with widening gender‐based gaps on the other, it is imperative to gather more high‐quality evidence on their effectiveness. Timely evidence generation can help leverage these platforms appropriately and enable intervention designs that are responsive to changing communication ecologies of AGYW. SBCC can play a critical role in helping researchers meaningfully engage and collaborate with communities as equal stakeholders, however, this remains poorly evidenced and calls for investigation and investment. A full list of abbreviations and acronyms are available in Supporting Information: Appendix F. Converging social, cultural, and economic factors affect how adolescent girls and young women understand, negotiate and access information and biomedical treatment related to HIV. SBCC interventions form a pivotal part of the comprehensive HIV prevention response as they not only help address aspects of underlying socio‐behavioral barriers that drive the epidemic, but also play a critical role in expanding knowledge of, and access to, quality health services, health equity and participation in research. They also assist in addressing gendered health disparities throughout the continuum of care CDC, . While t1.21Aim of the EGMThe aim of this EGM is to identify, map, and present all the available evidence from systematic reviews and impact evaluations of interventions to strengthen the adoption of HIV prevention measures and participation in research among AGYW in LMICs.AGYW around the world faces serious and multi‐pronged challenges to achieving their sexual and reproductive health rights, including vulnerability to HIV and STIs. To this end, evidence‐informed interventions for HIV prevention, care, and uptake targeting AGYW are critical in addressing these challenges and identifying gaps in programming. This EGM presents a consolidated evidence base of existing SBCC interventions, and the AGYW end‐user behaviors they target, in low‐and‐middle‐income countries. It looks at a range of SBCC strategies including those employing mass media, community‐based interventions, interpersonal interventions, and ICT and digital media‐based interventions.1.3The EGM includes 458 studies: 43 systematic reviews and 415 impact evaluations, published in the English language from 2000 onwards.1.4Evidence remains unevenly distributed across intervention and outcome categories. The most populated interventions include interpersonal communication, followed by community‐based interventions. Most of these interventions were delivered by health care providers and educators. Further, evidence across geographies was mostly concentrated in Sub‐Saharan Africa.Most measured outcomes focused on disease‐related knowledge dissemination and enhancing awareness of available prevention options/strategies. These included messaging around consistent condom use, limiting sexual partners, routine testing, and awareness. Very few studies included psychographic, social, and contextual factors influencing AGYW health behaviors and decisions, especially those measuring the impact of social and gender norms, relationship dynamics, and household dynamics‐related outcomes. Outcomes related to engagement in research were least studied.1.5Behavior change is a dynamic process and is influenced by multiple factors that constantly interact with each other across individual, social and structural levels. Individual behavior is shaped by varying factors that affect their capabilities to make decisions, enable them to translate intent into action and motivate them to make long‐term behavioral shifts , sex workers, and people living with HIV (PLHIV)—leading to a limited understanding of the use of these interventions across critical sub‐populations and multiple user segments. This underscores the need for better quality evidence to understand what interventions work, for whom, and towards what outcome. It is, therefore, important to account for the diversity of experiences within AGYW populations, and better understand behavioral convergences and divergences to inform intervention design and evidence generation.Realizing the value of communication channels in shaping behavior change discourse, this EGM actively looks at evidence across different communication strategies and platforms. However, we found that evidence towards the use of digital media tools such as social media and mobile‐based services remains poorly populated. Studies on the use of popular culture tools—including mass‐media, theatre, and arts‐based approaches—are also relatively low. Given the penetration of digital tools, increased access to mass media and growing media literacy on one end, with ever‐widening gender‐based gaps on the other, it is imperative to gather more high‐quality evidence on the effectiveness of these tools. Timely evidence generation can help leverage this medium appropriately and enable intervention designs that are responsive to the changing communication ecologies of AGYW.1.6The authors searched for studies published up to April 2021.1.7The lead author, Devi Leena Bose, along with Anhad Hundal and Saif ul Hadi position ourselves as SBCC practitioners from LMIC working towards mainstreaming SBCC practices as an approach to help achieve sustainable development goals. We have been working with IAVI a nonprofit scientific research organization that develops vaccines and antibodies for HIV, tuberculosis, emerging infectious diseases (including COVID‐19), and neglected diseases. Through its various programs spread across India and Africa, IAVI aims to use SBCC strategies towards increasing knowledge, improving attitudes and enhancing practices of individuals and communities towards positive health seeking behavior and reduce barriers of vulnerable populations to contribute more to research and access prevention services. IAVI has co‐created evidence‐driven SBCC interventions for enhancing science literacy, research acceptance, research participation, using human‐centered design and experiential learning. However, these interventions are not evaluated or influence the EGM in any manner. Other co‐authors have no conflict of interest and have contributed to the EGM from a technical and methdolodological perspective.22.1Adolescent girls and young women (AGYW) are disproportionately affected by HIV and other sexual and reproductive health risks. Converging social, cultural, and economic factors affect how AGYW understand, negotiate, and access information and biomedical treatment related to HIV. Persistent gender and age disparities and stigmas around female sexuality faced by this group in the impact of HIV are both exacerbated by, and reinforce, issues such as poverty, lack of access to education  and livelihood opportunities, limited financial autonomy, lack of access to sexual and reproductive healthcare , and the risk of violence, including intimate partner violence (IPV). A UNAIDS report found that nearly 1 in 3 women globally has experienced physical and/or sexual violence by an intimate partner, non‐partner, or both, in their lifetimes , India is committed to achieving the “end of the HIV/AIDS epidemic” as a public health threat by 2030 UNAIDS, . While tThe National Family Health Survey of India (NFHS‐5), 2019–2021  interventions form a pivotal part of the comprehensive HIV prevention response, as they not only help address aspects of underlying behavioral and social barriers that drive the epidemic, but also play a critical role in expanding knowledge of, and access to, quality health services, strengthen equity and participation and assist in addressing gendered health disparities throughout the continuum of care CDC, , thereby2.3This EGM is important to map and consolidate existing evidence on SBCC strategies for HIV prevention and research among AGYW in LMICs. More simply put, this map helps understand what kind of SBCC interventions have been used with which population groups, towards what behavioral and health outcomes and, further, helps identify areas where more evidence and interventions are needed.For socio‐behavioral researchers, this exercise may provide an opportunity to explore the existing evidence base, be better informed about critical research gaps, and, therefore, design future research to address the same.For public health specialists and intervention designers, this EGM may provide a better understanding of the most effective strategies/approaches to engage diverse AGYW populations.For biomedical/public health researchers, this map may provide a preliminary understanding of an array of interventions and outcomes that can inform their methodologies to engage AGYW communities in research.For funders and decision‐makers, this EGM can help to make informed decisions with regard to funding socio‐behavioral research targeting AGYW for HIV prevention and research. This can further inform the development of research agendas and priorities.The knowledge generated through this EGM has the potential to support numerous stakeholders, including intervention designers, policymakers, program managers, community engagement practitioners, socio‐behavioral researchers, donors, and the general public:2.3.1To the best of our knowledge, there are two existing EGMs  in low‐ and middle‐income countries (LMICs) and assess the gaps in the evaluation of these strategies for HIV prevention and research. More specifically, this map seeks to:The map has been produced as per Campbell Collaborations “Guidance for the Production of Evidence and Gap Maps”  such as country, region, population, study confidence, and so forth Figure . The pin44.14.1.1An EGM is a decision‐making and research prioritization tool that highlights research gaps to inform strategic health and social policy, program, and research priorities  of $1035 or less in 2019; lower‐middle‐income economies—those with a GNI per capita between $1036 and $4045; and upper‐middle‐income economies – those with a GNI per capita between $4046 and $12,535 (2020).According to the United Nations Millennium Development Goals Report (2012), formal settings are characterized by adequate spatial planning and utilities . On the other hand, informal settings are defined as those with no urban development , while in rural areas, these settings can encompass tribal areas. Informal settings can also include refugee camps in conflict or disaster‐affected areas in both rural and urban areas.Urban formal—Formal housing settlements, formal institutions like schools/colleges, hospitals, religious places, offices and other areas under the municipality, etc.Urban informal—Slums/unauthorized settlements.Rural formal—Formal settlements and institutions like local governance systems, health centers, hospitals, religious institutions, commercial farms, community‐based organizations (CBOs), schools, etc.Rural informal—Community spaces like market areas, public meeting grounds, tea stalls, community fairgrounds, etc.For this study, we looked at four kinds of settings:In addition to these, this EGM focuses on women living in a high‐risk environment/s, for example, sex workers, etc. Further, the map also includes the influence networks of AGYW, primarily male partners, family elders, peers, key community members, and service providers.The SBCC interventions included in this EGM are divided into four key categories ‐ mass media‐based interventions, community media‐based interventions, interpersonal communication, and Information and Communication Technology (ICT) and digital media‐based interventions. These interventions are further sub‐categorized, the details of which are given in the table below Table .In case the interventions studied did not exactly match the above‐mentioned categories, the team discussed and categorized them to their closest match based on the intervention definition and made a note of the same. Additionally, if a single study covered multiple interventions, the eligible interventions were coded and included.The outcome categories in this EGM include behavioral and health‐related outcomes, outlined along the causal chain based on the conceptual framework presented below Figure . Behavio4.2Table 4.3The studies for this EGM were searched using a comprehensive search strategy . Systematic reviews on the effect of interventions were also included, along with cross‐sectional and panel studiesAs defined by Moher et al. , “A syst1.A clearly stated set of objectives with pre‐defined eligibility criteria for studies.1.An explicit, reproducible search strategy.2.A systematic search that attempts to identify studies that would meet the eligibility criteria.3.A systematic presentation, and synthesis, of the characteristics and findings of the included studies.The key characteristics for a review to be included as a “systematic review”We included impact evaluations that met the following criteria:Studies where participants are randomly assigned to treatment and comparison groups .Studies where assignment to treatment and comparison groups is based on other known allocation rules, including a threshold on a continuous variable (regression discontinuity designs) or exogenous geographical variation in the treatment allocation .Studies with non‐random assignment to treatment and comparison groups that include pre‐and post‐test measures of the outcome variables of interest to ensure equity between groups on the baseline measure, and that use appropriate methods to control for selection bias and confounding. Such methods include statistical matching , regression adjustment .Studies with non‐random assignment to treatment and comparison groups that include post‐test measures of the outcome variables of interest only and use appropriate methods to control for selection bias and confounding, as detailed above. This includes pipeline and cohort studies.Experimental and quasi‐experimental studies:Panel studies: Ferraro and Miranda , 2017 arCross sectional studies: Studies where paricipants are selected on the basis of the inclusion and exclusion criteria, after which the investigator follows the study and measures outcomes and exposures simultaneously Setia, Excluded study designs: Before‐after studies and observational studies without control for selection bias and confounding were excluded. Additionally, modeling‐based studies, commentaries, and literature reviews were excluded.4.5The EGM protocol was published on January 18, 2022 , as well as advocacy and communication professionals—was convened.1.At the inception to assist in defining the scope and review the draft conceptual framework.2.During the review of search methods and strategies.3.During the review of preliminary results where they also provided additional information on how to locate further relevant studies.4.At the time of review of the draft report.Experts were consulted at four key stages during the development of this EGM:A detailed list of the advisors and experts has been included in Supporting Information: Appendix 4.74.7.1This EGM focuses on mapping available evidence about various kinds of SBCC interventions used for engaging AGYW in HIV prevention and research. Further, it helps understand behavioral determinants targeted by these interventions among AGYW towards desired social and health outcomes. The other actors who influence these behavioral determinants (referred to as influencers in this report) were also explored through the EGM.Interventions consisting of SBCC intervention strategies.Outcomes consisting of behavioral, health, and research outcomes. Behavior change dimensions, as mentioned above, were guided by the COM‐B model and The Theoretical Domains Framework (TDF). The health and research outcomes were defined based on programmatic and research priorities, as designated by UNAIDS ; 2020b, Based on the framework mentioned below, the substantive scope of the EGM was delineated along the following key categories:Testing and uptake of prevention options including condoms, PrEP (pre‐exposure prophylaxis), PEP (post‐exposure prophylaxis), and long‐acting antiretroviral (ARV) drugs and other available or upcoming prevention options.Consistent uptake of Antiretroviral Therapy (ART).Participation in biomedical research.Intimate partner violence, sexual violence, or gender‐based violence affecting HIV and SRH‐related health outcomes.Behavioral factors affecting access to sexual and reproductive health services, such as relationship goals, sexual negotiations, gaps in knowledge, self‐efficacy, and risk perception.Stigma and discrimination related barriers.Collective action, community support, community‐driven action, and social and gender norms affecting SRH and HIV‐related behaviors.To keep the scope manageable, the EGM focused on the following topics of interest around HIV/AIDS and other STIs:This EGM does not focus on other structural factors affecting HIV acquisition in the AGYW population, such as school attendance, labor migration, child sexual abuse, lack of economic empowerment, structural barriers to accessing sexual and reproductive health services, marriage patterns, etc. Other factors impacting adolescent health such as mental health, smoking, alcoholism, drug addiction, nutrition, maternal health, and childcare are also outside of the purview of this EGM. Additionally, topics related to pregnancy, family planning, and abortions were not included in this study if they did not measure the effects of HIV and SRH‐related outcomes.The interventions and outcomes along with their sub‐categories have been outlined in detail in Section 4.7.2SBCC uses behavior‐centered communication approaches to help inform, persuade and provide support to individuals, households, peers, and communities towards creating an enabling environment across the continuum of HIV care, starting with prevention  proposed by Michie et al.  and the Given the complex systems within which behavior change happens, we identified four key target groups that can have a direct or indirect influence on an individual's agency and decision‐making power for adopting behavior changes or their willingness for change. These include AGYW as individuals, their immediate relations , actors who might be outside the immediate circle of influence and yet significantly influence decision making .Lastly, the framework focuses on SBCC delivery strategies, which are a mix of community mobilization, behavior change communication, and advocacy strategies. While other non‐communication strategies such as delivery and access to services are also critical for behavior change, the focus of this EGM remains on SBCC‐based delivery strategies.4.8Table 4.9This study focuses on “Adolescent Girls and Young Women” as defined by UNAIDS , between4.10As mentioned above, this EGM focuses on AGYW populations in low‐income and lower‐ and middle‐income countries, as defined by the World Bank4.11This map looks at four kinds of settings—urban formal, urban informal, rural formal, and rural informal. Informal settings may also include refugee camps in conflict or disaster‐affected areas in both urban and rural contexts.55.1Two researchers independently coded the studies. Any discrepancies in the decision of the two researchers were resolved through discussion. If the disagreements persisted, a third researcher intervened. A piloted coding form with information necessary to generate the EGM, such as intervention strategies, outcome categories, and other filters, was used to code the studies. The full bibliographic information of the included studies is recorded in reference section.5.1.1The screening of the studies was done at the title and abstract level, as well as at the full‐text level, based on intervention, study design, and population. Two researchers independently screened the studies at both stages (title and abstract screening stage). Outcomes were not included in this process. Subsequently, full texts of eligible studies were retrieved and screened, and the reviewers compared the results. The authors of the studies were not contacted at any point for missing information.5.1.2Two people independently screened the records at the title and abstract stage and the full‐text stage using a screening tool containing inclusion and exclusion criteria. Screening decisions were matched, and in case of any disagreements, an arbitrator resolved these issues at the level of screening.5.1.3Two reviewers extracted data on both published and ongoing randomized trials related to population, interventions, comparisons, and outcomes. Coding categories  and HIVR4P (2014 onwards).Of the total 2502 records, 89 duplicates were further removed and a total of 2413 records were included for title and abstract screening.Of these 2413 records, 904 reports were screened for full text. A total of 431 reports were excluded at the full‐text screening stage. Screening at the full‐text stage resulted in the inclusion of 473 records. The reasons for the exclusion of records are given in the PRISMA flowchart  as seen in Figure n = 71) along with ICT and digital media‐based interventions (n = 28)  was the most dominant intervention type, followed by counseling (n = 153). However, very few studies focused on home‐visit‐based intervention methods (n = 35). In the community‐based interventions category, most of the studies focused on community dialogues (n = 173), while emphasis on other sub‐categories—community media (n = 54), gamification and experiential learning (n = 39), theatre and arts‐based approaches (n = 34), capacity strengthening (n = 25), folk media (n = 12)—was comparatively lowerFigure n = 53) and print media (n = 43)—were comparatively better studied than other intervention sub‐categories like folk media, gamification, and experiential learning, theatre, and arts‐based approaches, among others.While the mass‐media intervention category was comparatively less evidenced than other intervention categories, its sub‐categories—electronic media (n = 15), interactive app‐based services (n = 10), social media (n = 8), and digital games and learning tools (n = 4).ICT and digital media‐based interventions were least evidenced among all intervention categories. Subsequently, most of its sub‐categories remain poorly studied, including mobile‐based services  had the highest number of studies among all outcome categories, followed by studies on knowledge, attitude, and skills (n = 311). Studies with a focus on strengthening partner/relationship dynamics (n = 92) and addressing social and community norms (n = 83) were relatively lower. The least evidenced outcome categories included household dynamics (n = 29), healthcare services (n = 24), and research engagement (n = 5).As seen in Figure 6.2.4n = 296) remains a densely studied sub‐category, along with limiting sexual partners (n = 162), as seen in Figure n = 92) being relatively better studied, while outcomes related to strengthening uptake of newer prevention approaches like PrEP and other biomedical prevention options (n = 13) have been less studied within this category.Given that SBCC interventions have been mostly targeted toward strengthening prevention‐related outcomes, it is not surprising to see that correct and consistent condom use n = 29 remains n = 280) and HIV/STI Risk Perception (n = 144). However, only 79 studies focused on strengthening individual agency and self‐efficacy. Further, while interventions focused on knowledge and attitude are better populated, those targeting outcomes like negotiation and life skills (n = 9) and trust in healthcare providers/services (n = 4) are sparsely populated.Knowledge attitude and skills remain the second most evidence outcome category, with a bulk of evidence concentrated on interventions targeting outcomes related to knowledge and awareness about HIV/STIs (n = 48), power equity and role in decision making (n = 34), and partner's HIV/STI awareness (n = 32).Outcomes aimed at addressing partner and relationship dynamics remain comparatively less studied. A deep dive into its sub‐categories highlights the need for more substantiated evidence in this category—addressing sexual and intimate partner violence (n = 41), community support systems (n = 35), gender norms (n = 13), HIV/STIs myths, and misconceptions (n = 5). Outcomes targeted at healthcare services were also minimal—quality of care/satisfaction with services had 16 studies while provider sensitization and engagement skills had 12.Outcomes related to social and community norms were also relatively less studied—stigma and discrimination  of all the included studies, followed by East Asia and Pacific with 15% of studies (n = 70), and South Asia with 13% of studies (n = 61). Included studies from the Latin America and Caribbean region constituted about 11% (n = 52) of the total included studies, while the Middle East and North America (MENA) region had the lowest number of included studies (n = 6). The distribution of included studies across various regions and study designs, from 2000 till April 2021 has been represented in Figure Sub‐Saharan Africa is the most well‐represented region, constituting about 70% , followed by randomized controlled trials (RCTs) (n = 142) and cross‐sectional or panel study design (n = 138). However, trends vary across region—in Sub‐Saharan Africa, the most used study design is RCTs, in South Asia, most studies use cross‐sectional or panel study design, in East Asia and the Pacific a majority of studies use quasi‐experimental study designs, and, in Latin America systematic reviews are the predominant study design.Additionally, distribution of evidence across study design Figure  suggestsn = 81) among all countries, as highlighted in Figure n = 36), Uganda (n = 36), Tanzania (n = 24), Nigeria (n = 22), Zimbabwe (n = 21), and Zambia (15). In the East Asia and Pacific region, China and Thailand have 28 and 13 impact evaluations, respectively. India has the highest number of studies (n = 37) in the South Asia region.South Africa has the highest number of impact evaluations , after which a slight dip in evidence generation is witnessed between 2015 and 2019. While the graph below shows a further decrease in the number of studies following the 2015–2019 period, this is a 2‐year interval which cannot be compared to the rest of the evidence timeline reporting a 5‐year period.The evidence base for these studies seems to significantly increase from 2005 to 2014. The graph  in 2005–2009, over the years a lesser number of studies have adopted this design. The number of cross‐sectional or panel studies published was highest from 2010 to 2014 (n = 63), however, we see a sharp decline in the use of this design between 2015 and 2019 (n = 29). The highest number of systematic reviews (n = 20) was published between 2010 and 2014, a significant jump from 2000 to 2004 and 2005–2009 when an equal number of systematic reviews (n = 3) were published. However, between 2015 and 2019 only 11 systematic reviews were produced.In terms of study design, we see a growing trend for RCTs; in 2000–2004, only five studies were using the RCT technique, however, between 2015 and 2019, the total number of studies using RCT grew to 55  of all included studies in this EGM are from Sub‐Saharan Africa , South Asia  followed by Latin America and the Caribbean . The least populated regions include LMICs in Europe and Central Asia  and the Middle East and North Africa region .More than 60%  and young women (n = 299), as seen in Figure n = 56) and people living with HIV (PLHIV) (n = 55) were low, while only 27 studies focused on pregnant women and new mothers (PWNM).A majority of impact evaluations focused on interventions targeted at adolescent girls (n = 251) and/or urban settings (n = 265), as seen in the graph below  and informal (n = 104) settings was relatively lower. It may be noted here, however, that in some of the studies, interventions were conducted in more than one setting. For example, an intervention conducted in a school in a rural area was coded under the categories rural and formal  followed by young women (n = 465). However, very few studies focused on population sub‐categories like sex workers (n = 89) and PLHIV (n = 82). Pregnant women and new mothers (n = 32) emerged as one of the least evidenced population sub‐categories. Figure Most interventions were targeted at adolescent girls (n = 208), educators (n = 184), and health care providers (n = 183) were the most studied influencers. A fewer number of studies included young men (n = 36), community elders (n = 32), partners (n = 19), religious leaders (n = 17), and family (n = 12).The distribution of included studies across intervention strategies and influencers Figure  suggestsn = 8) and educators (n = 9).Interpersonal communication was the most used intervention technique across all sub‐populations, apart from community leaders, religious leaders, and family, where more community‐based interventions were utilized. ICT and digital media‐based tools were most employed for healthcare providers . This was mainly on account of some critical flaws, such as no assessment for risk of bias in primary studies, not using satisfactory techniques for assessing the risk of bias, or not providing the source of funding for the studies included in the review. Of all included systematic reviews, four were found to be of medium confidence (9%) and only one of high confidence (2%)  are rated as being low confidence  Figure .6.3.4n = 68), National Institute of Mental Health (NIMH) (n = 56), the United States Agency for International Development (USAID) (52), the Bill & Melinda Gates Foundation (BMGF) (n = 39), and The Department for International Development  (n = 26). The full list of funding sources is available in Supporting Information: Appendix Most included studies reported Figure  receivin7Key findingsThis EGM includes studies that employ the use of SBCC interventions targeted towards AGYW and their influencers for HIV prevention and engagement in research. We summarize some of the emerging findings and lessons in this section.7.1Evidence is unevenly distributed across different intervention types. While there is a huge focus on interpersonal communication‐based interventions, followed by community‐based interventions, the use of media and technology‐driven interventions are relatively less studied. These include the use of mass‐media and ICT and digital media‐based interventions.Despite increased digital penetration of ICT and digital media‐based interventions Raftree, , evaluatLikewise, despite the global recognition of the effectiveness of mass‐media‐based interventions in supporting efforts to reduce the HIV/AIDS burden, the evaluation of these interventions is comparatively lesser. It is important to note here that multiple studies used media‐based interventions along with other intervention types/sub‐types like community‐based interventions and interpersonal communication‐based interventions.n = 120), interventions are delivered by educators, largely in school‐based settings and, in many cases, are part of sex‐education curricula. While the dominant engagement of peers is understandable given they are key influencers within AGYW networks, the lack of engagement of other key influencers such as partners highlights a gap in intervention design. Further, while educators and healthcare providers can play a critical role in knowledge dissemination, their role in creating enabling ecosystems for behavior change is limited without the engagement of key influencers like family, community elders, religious leaders, etc., who can play a direct role in facilitating the uptake of safe and positive sexual health behaviors.Even within the highly concentrated categories, we see a predominance of certain intervention sub‐types such as peer‐led interactions, facilitated community dialogues and counseling. It is interesting to note that the roll‐out of these interventions among AGYW is heavily dependent on peers, educators, and healthcare providers who are key actors in delivering them. In 26% of included studies , while life skills, joint decision making in households, etc., were sparsely evidenced. Very few studies measured outcomes addressing aspects of opportunity‐related barriers. These included outcomes related to social and community norms, household dynamics, and health care services, among others.Research engagement outcomes remain poorly measured.The role of SBCC interventions in supporting research engagement‐related outcomes was poorly evidenced. Of the five studies that measured outcomes related to participation in biomedical research, four were from Sub‐Saharan Africa and the remaining study was from India. Further, only one study measured outcomes related to research awareness and benefit perception.7.3We find that geographical coverage of evidence remains concentrated in a few Sub‐Saharan African countries, including South Africa, Uganda, Kenya, Tanzania, Zimbabwe, and Nigeria. Subsequently, evidence largely remains unevenly scattered across different regions and countries—in East Asia and the Pacific, evidence remains concentrated within countries like China and Thailand, while in South Asia, India is the only country with a considerable evidence base. There is hardly any evidence from countries like Indonesia, Mozambique, Pakistan, Ukraine, Argentina, Colombia, the Democratic Republic of Congo, etc., despite the high burden of HIV in these countries . The MENA region reported the lowest number of studies, which corresponds to the low HIV burden in the region.n = 5), leaving room for more RCTs and other experimental study designs. There is also an urgent need for better use of high‐quality systematic reviews and implementation research to complement more rigorous evaluations across many components of intervention categories. Currently, most of the systematic reviews included are ranging from low to moderate quality.There is a clear need for more impact evaluations across many of the intervention and outcome categories, with more even distribution across regions and study design. Currently, RCT‐based studies are mostly done in a few countries in Sub‐Saharan Africa, while China and Thailand are the only countries in East Asia and the Pacific region with RCT‐based studies. In South Asia, India emerges as the only country with RCT‐ based studies , of varying sexualities were not explored in the evidence base. Additionally, studies exploring the aspirations, desires, and life and relationship goals of AGYW were found to be largely missing.All this calls for a behavioral and psychographic segmentation of the AGYW population along with better quality evidence to understand what interventions work, for whom, and towards what outcome. It is important that—going forward—program designers, implementers, and policymakers consider the diversity of this group and better understand behavioral convergences and divergences. There is, therefore, a need to reframe the narrative in a manner that is not solely focused on disease knowledge‐centered outcomes and which suits the needs of the AGYW.This EGM highlights that evidence is heavily concentrated within the awareness‐intent spectrum of behavior change and gets lean for outcomes situated within the intent‐action and the action‐habit formation spectrum of the behavior change continuum. In line with this, we find that studies mostly measure outcomes around the domains of knowledge, attitude, and skills, but get sparse around pathways enabling change, such as partner and relationship dynamics, household dynamics, and social and community norms, among others. While there is a lot of emphasis on building disease knowledge, improving risk perception, and increasing knowledge about a few prevention options, there is not enough emphasis on developing skills that can help translate intent into action and further habit formation.We also witness that, within the category of influencers, peers, educators, and healthcare providers were most engaged. While the dominant engagement of peers is understandable given, they are key influencers within AGYW networks, the lack of engagement of other key influencers such as partners highlights a gap in intervention design. Hence, intervention strategies that will create an enabling environment for promoting safe and positive sexual health behaviors are necessary. To achieve this, an ecosystem‐based approach that involves other influencers from their family/community, etc., and creates “safe spaces” for AGYW to openly share and discuss such intimate details of their life can be valuable.The EGM reveals that most of the SBCC work done in the past is through the medium of interpersonal counseling or community‐based engagements. Despite the penetration and influence of mass media and digital media‐based tools, evidence for the utilization of the same for engaging AGYW remains limited. These media forms have the ability to shape and control “the scale and form of human association and action”  program at IAVI, funded by a cooperative agreement through 2026 with the U.S. Agency for International Development (USAID) through the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), aims to work works safe, effective and affordable solutions for HIV.Supporting information.Click here for additional data file.


Dempster–Shafer evidence theory is an effective way to solve multi-sensor data fusion problems. After developing many improved combination rules, Dempster–Shafer evidence theory can also yield excellent results when fusing highly conflicting evidence. However, these approaches still have deficiencies if the conflicting evidence is due to sensor malfunction. This work presents a combination method by integrating information interaction graph and Dempster–Shafer evidence theory; thus, the multiple evidence fusion process is expressed as a network. In particular, the credibility of each piece of evidence is obtained by measuring the distance between the evidence first. After that, the credibility of the evidence is evaluated, keeping the unreliable evidence out of the information interaction network. With the fusion of connected evidence, the accuracy of the fusion result is improved. Finally, application results show that the presented method is effective. With the advancement of science and technology in recent years, information analysis has gained popularity as a research topic. Applying multi-sensor data fusion techniques will enable the creation of the consolidated view within this process. Therefore, by utilizing multi-sensor data fusion technology in various decision-making applications, such as risk analysis ,2, faultNumerous theories have been put forth up to this point in order to model and handle uncertain and imprecise information, such as rough sets theory ,9, fuzzyDST undoubtedly has some drawbacks. Different degrees of conflicts are generated by the sensors due to different types, tasks, and precision. However, it is usually less likely to produce utterly different evidence if the sensor works normally. In most cases, the evidence obtained is relevant to a certain extent and contains complementary information. However, when strongly conflicting information due to malfunction is combined, the results might be unexpected . There aAs a complex combination problem involving multiple sensors, it makes sense to think about a connection between multi-sensor data fusion and multi-agent systems. Artificial intelligence has long been interested in multi-agent systems, which have solved a number of issues that were too complex for a single agent . CommuniAs a result of the discussion above, a networked approach is used in this paper by connecting graph theory and evidence theory. A newly developed credibility test rule is used to weed out implausible evidence based on the credibility degree of the evidence. The effect of fault information is therefore eliminated due to the faulty sensor’s information being cut off from the communication network. It is worth noting that we assume the evidence used for fusion is already output by each sensor, but how the sensor obtains the output is not within the scope of this manuscript.The main contributions of this study are as follows: (1) A networked information fusion method is proposed to solve the conflict evidence fusion problem. Inspired by the knowledge of graph theory in multi-agent systems, the proposed method takes the information interaction between evidence into account, which makes multi-data fusion problems closer to multi-agent systems. (2) Rather than exclude the evidence with the lowest credibility simply, a credibility degree test rule is defined for the purpose of checking whether the evidence contains enough valid information to participate in the fusion. In this way, accidents where credible evidence is omitted due to the order of credibility are avoided as much as possible. (3) According to the isolated node mechanism of the proposed method, the highly conflicting evidence provided by the faulty sensor can be distinguished as an isolated node. Furthermore, since the isolated node is not involved in the fusion process, the negative impact caused by the fault information can be reduced effectively.The rest of this paper is organized as follows. DST was named by Dempster  and ShafDefinition 1 .Assume U is a set consisting of mutually exclusive and collectively exhaustive events; the set U is called a frame of discernment, which indicted by((Frame of discernment (FOD)) ).Assumeand ⌀ is an empty set.Definition 2 .A FOD U is based on the concept of mass function, which is a mapping ((Mass function) ).A FOD In DST, mass function is also known as basic belief assignment (BBA). If Definition 3 .The belief function and plausibility function of a proposition where ((Belief function) ).The beDefinition 4 .Dempster’s combination rule uses the orthogonal sum of two BBAs. Assume two independent BBAs where B and C are also propositions in ((Dempster’s combination rule) ).DempstGraphs have been used to model information exchange between agents in cooperative multi-agent systems for years ,37. A grThe measure of similarity between BBAs is a natural consideration. The distance measure between BBAs can tell us whether two pieces of evidence are close or distant. In this regard, Jousselme’s distance  is a appDefinition 5 .The distance between where ((Jousselme Distance) ).The diHow to deal with the conflict between evidence in DST has been a problem bothering researchers for a long time. Jousselme’s distance provides an easy and effective way to compare evidence. For instance, a small distance implies the support from other evidence, which means this evidence should play a more important role in fusion. Conversely, a large distance means this evidence is not supported by other evidence, that is to say, an insignificant role should be distributed to this evidence. However, only the similarity measure is still not enough to generate an accurate fusion result.In order to better utilize the accurate information provided by the evidence, the credibility of the evidence is necessary. Furthermore, the case where the sensor failure happened is unavoidable. How can we know a sensor is malfunctioning or functioning normally? Assuming a sensor does fail, how can we know how badly it has failed? Can the information provided by the faulty sensor still be used for fusion? To answer these questions, the graph theory is leveraged to describe the interaction between the evidence in this section. According to the Jousselme distance, the credibility degree is obtained to measure the relative importance of evidence. What is more, the credibility is utilized to determine whether evidence obtained by a faulty sensor should be involved in the fusion process or not.Definition 6 .Through Jousselme’s distance, the divergence measure matrix, denoted as where ((Divergence Measure) ).ThrougDefinition 7 .Let ((Support Degree) ).Let m1The support degree is the reciprocal of the average distance between Definition 8 .The credibility degree of BBA ((Credibility Degree) ).The crDefinition 9 Let a fully connected undirected graph G represent the initial topology of BBAs; the element of the initial adjacency matrix A is defined as(Evidence Connection). To determine whether BBA Once the BBA The previous descriptions provided sufficient theoretical preparation for the fusion problem considered in this paper. Thus, a new networked method is presented to process the fusion problems in this section, which contains the following procedures. Firstly, the credibility degree of evidence can be measured via Jousselme’s distance. Secondly, by means of the relative significance hidden in the credibility, the transmission relationship between evidence can be generated, in which the impact of faulty information is reduced. Lastly, following the evidence interaction flows, the fusion result can be obtained through Dempster’s combination rules by two rounds. The procedures of the proposed approach are depicted in Step 1-1: By mean of Jousselme’s distance, the divergence measure matrix DMM can be constructed as .Step 1-2: For Step 1-3: The support degree Step 1-4: The credibility degree As mentioned above, it is necessary to take advantage of the signals provided by credibility degree. Hence, the credibility degree of the evidence will be obtained via the following steps.Step 2-1: For each evidence, the credibility degree is tested by .Step 2-2: For evidence tisfying , replace(j≠i) in  by 0.Step 2-3: In accordance with the modified adjacency matrix Now, we obtained the credibility of the evidence. According to the conception of the proposed method, the transmission relationship between evidence can be established as follows.Step 3-1: For each evidence ion rule ; the fusStep 3-2: All process evidence obtained in the previous step are fused via Dempster’s combination rule . Hence, The interaction graph between the evidence is now generated; it is time to fuse the evidence and obtain the combination result via the steps below.As explained above, the proposed method still belongs to the second scheme introduced in In order to demonstrate the effectiveness of the proposed method, two application cases from ,39 are iProblem statementU that consists of three potential objects is given by Consider a target recognition problem associated with sensor reports collected from five different types of sensors. It should be noted that this is a fictitious example, and target A is supposed as the real target. These sensor reports, which are modeled as the BBAs, are given in The fusion approachStep 1-1: Construct the divergence measure matrix Step 1-2: Obtain the average evidence distance Step 1-3: Calculate the support degree of Step 1-4: Compute the credibility degree of Step 2-1: Calculate the test value A to Step 2-2: Modify the adjacency matrix Step 2-3: Generate the interaction graph Step 3-1: Fuse the connected evidence via the Dempster’s rule of combination; the process evidence Step 3-2: Fuse the process evidence via Dempster’s combination rule; the fusion results are shown in The more precise results of the proposed method are exhibited bellow.DiscussionA, which demonstrates the proposed method is effective when conflicting evidence exists. In fact, by excluding the untrustworthy evidence from the connection graph, the adverse effects are greatly eliminated, so that the fusion of reliable evidence is reinforced from the other side.From Case 1, we notice that The decision-making applicationIn this subsection, an application case from  is consiThe fusion approachStep 1-1: Construct the divergence measure matrix Step 1-2: Obtain the average evidence distance Step 1-3: Calculate the support degree of Step 1-4: Compute the credibility degree of Step 2-1: Calculate the test value A to Step 2-2: Modify the adjacency matrix Step 2-3: Generate the interaction graph Step 3-1: Fuse the connected evidence via the Dempster’s rule of combination; the process evidence Step 3-2: Fuse the process evidence via Dempster’s combination rule; the fusion results are shown in The more precise results of the proposed method are exhibited bellow.DiscussionFrom case 2, we notice that there is low conflict between the evidence. As shown in In this paper, a networked method to handle information fusion problems was proposed by taking the evidence interaction graph and DST into account. The original purpose is twofold. One is to reduce the impact of conflicting evidence on fusion, and the other is to realize information fusion in the way of multi-agent systems achieving consensus. However, even if the communication topology is established, the difference between evidence and the relative neighboring error between multi-agents is not the same, and the fusion between evidence and the collaborative control of multi-agent systems cannot be carried out in the same way. As a result, only the first goal was achieved, i.e., the influence of conflicting evidence generated by various reasons on fusion was reduced, but the collaborative method between evidence still needs to be explored. In summary, the proposed fusion method is an attempt to bring information fusion into a part of networked systems, which provides a new inspiration for information fusion and networked systems. However, while the fusion performance is satisfactory, the amount of calculation is also significantly increased. In the future, we intend to develop some new rules for modifying evidence connections. In particular, by reducing the number of connected edges or making the connection weights of the edges more refined, we will try to achieve the purpose of reducing computation.