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Background: The third stage of labor is a pivotal phase in obstetric care. Management may be physiological or active. Although the use of prophylactic placental cord drainage has been assessed in prior data, there is still no clear-cut evidence supporting its effectiveness in improving key obstetric outcomes., Objective: The aim of the study was to investigate the impact of placental cord drainage during the third stage of labor on the amount of maternal bleeding, duration of the third stage, and incidence of postpartum hemorrhage., Study Design: A randomized controlled trial was conducted at a high-volume tertiary obstetric center between May 2021 and December 2022. A total of 212 pregnant women with a singleton uncomplicated pregnancy were randomly assigned to undergo placental cord drainage or standard care without drainage. The randomization was manual, using premarked cards drawn by the participants. The power calculation determined a sample size of 92 participants per group to achieve 80% power at a 5% significance level, aiming to detect 20% difference in bleeding amount between the groups. In practice, we included more than 100 women in each group. The primary outcome was the amount of bleeding during the third stage of labor, while secondary outcomes included the duration of the third stage and incidence of postpartum hemorrhage. After delivery, all participants received 10 units of oxytocin via intravenous drip, and delayed cord clamping was performed. In the study group, the maternal umbilical cord was then unclamped. Blood was allowed to drain into a plastic bag placed under the women's buttocks. If an episiotomy or perineal tear was observed, pressure packing was applied to reduce bleeding. The collected blood was measured in milliliters after placental expulsion., Results: A total of 212 women were recruited of whom 104 underwent placental cord drainage and 108 received standard care without drainage. No significant differences were observed between the intervention and control groups in mean duration of the third stage of labor (10.56±6.12 vs 10.95±6.33 minutes, P=.65), incidence of postpartum hemorrhage (3.84% vs 7.41%, P=.38), or mean amount of bleeding during the third stage of labor (292±200 vs 300±242 mL, P=.79). Furthermore, there were no significant between-group differences in the mean amount of bleeding on separate analysis of nulliparous women (356±246 vs 330±240 mL, P=.68), multiparous women (265±171 vs 289±244 mL, P=.50), women who were not exposed to external oxytocin during labor (287±204 vs 317±250 mL, P=.59), and women who were exposed to external oxytocin (296±198 vs 289±238 mL, P=.39)., Conclusion: Placental cord drainage during the third stage of labor showed no statistically significant impact on bleeding amount, third-stage length, or postpartum hemorrhage rate. The findings suggest that placental cord drainage may not offer additional benefits in preventing postpartum hemorrhage in women with uncomplicated pregnancies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The work of midwives is emotionally challenging. Midwives share moments of joy, when a baby is born, and attend complex events of loss and trauma. Exposure to childbirth complications, emergencies, and loss can affect their professional quality of life and functioning. This aspect of midwives' practice has not been sufficiently researched., Aim: To examine the associations between exposures to traumatic events, post-traumatic symptoms, and personal resilience with professional quality of life and organizational commitment among hospital midwives., Methods: Participants in this cross-sectional study conducted in 2020 included 131 midwives from three large hospitals in central Israel. Data were collected using a structured self-administered questionnaire that examined socio-demographic characteristics, exposure to traumatic events during childbirth, personal resilience, post-traumatic symptoms, professional quality of life, and organizational commitment., Results: The three most traumatic events for midwives were: neonatal death or feared death, maternal death or feared death, and stillbirth. The more frequent the exposure to traumatic events, the more numerous and intense the post-traumatic symptoms. The more numerous and intense the post-traumatic symptoms, the higher the level of professional burnout and compassion fatigue and the lower the compassion satisfaction. Higher compassion satisfaction and lower professional burnout were associated with higher organizational commitment. Personal resilience, country of birth, post-traumatic symptoms, and organizational commitment predicted compassion satisfaction., Conclusions: Midwives' exposure to traumatic events is associated with the onset of post-traumatic symptoms, impaired professional quality of life, and reduced organizational commitment, and is accompanied by burnout and compassion fatigue. There is a need to address this issue in training programs and to develop organizational support and policies to improve midwives' well-being and quality of care., (© 2024 Wiley Periodicals LLC.)

Introduction: The Dual Prevention Pill (DPP) combines oral pre-exposure prophylaxis (PrEP) with oral contraception (OC) to prevent HIV and pregnancy. Noting the significant role played by the private sector in delivering family planning (FP) services in countries with high HIV burden, high level of private sector OC uptake, and the recent growth in self-care and technology-based private sector channels, we undertook qualitative research in Kenya, South Africa and Zimbabwe to prioritize private sector service delivery approaches for the introduction of the DPP., Methods: Between March 2022 and February 2023, we conducted a literature review and key informant interviews with 34 donors and implementing partners, 19 government representatives, 17 private sector organizations, 13 pharmacy and drug shop representatives, and 12 telehealth agencies to assess the feasibility of DPP introduction in private sector channels. Channels were analysed thematically based on policies, level of coordination with the public sector, data systems, supply chain, need for subsidy, scalability, sustainability and geographic coverage., Results: Wide geographic reach, ongoing pharmacy-administered PrEP pilots in Kenya and South Africa, and over-the-counter OC availability in Zimbabwe make pharmacies a priority for DPP delivery, in addition to private networked clinics, already trusted for FP and HIV services. In Kenya and South Africa, newer, technology-based channels such as e-pharmacies, telehealth and telemedicine are prioritized as they have rapidly grown in popularity due to nationwide accessibility, convenience and privacy. Findings are limited by a lack of standardized data on service uptake in newer channels and gaps in information on commodity pricing and willingness-to-pay for all channels., Conclusions: The private sector provides a significant proportion of FP services in countries with high HIV burden yet is an untapped delivery source for PrEP. Offering users a range of access options for the DPP in non-traditional channels that minimize stigma, enhance discretion and increase convenience could increase uptake and continuation. Preparing these channels for PrEP provision requires engagement with Ministries of Health and providers and further research on pricing and willingness-to-pay. Aligning FP and PrEP delivery to meet the needs of those who want both HIV and pregnancy prevention will facilitate integrated service delivery and eventual DPP rollout, creating a platform for the private sector introduction of multipurpose prevention technologies., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Introduction: Multipurpose prevention technologies (MPTs) combining contraception with HIV prevention offer a promising solution to uptake and adherence challenges faced with oral pre-exposure prophylaxis (PrEP). The Dual Prevention Pill (DPP), which combines oral PrEP with an oral contraceptive pill (OCP), could address unmet need for family planning (FP) and HIV prevention. This study aimed to identify barriers and motivators for DPP uptake to inform the development of a DPP demand generation strategy and broader introduction efforts for MPTs., Materials and Methods: Qualitative, ethnographic research employing human-centered design techniques was conducted in Kenya, South Africa, and Zimbabwe. A research consortium conducted 45 immersions, 34 key informant interviews, and 12 friendship circles with potential end users, male romantic partners, healthcare providers (HCPs), and cultural commentators. Creative concepts were subsequently co-created and validated in workshops with end users, male partners, and HCPs., Results: Four major themes emerged. Women struggled to balance personal motivations with societal expectations. Relationship goals strongly influenced sexual and reproductive health decisions, particularly related to financial security and social status. Negative experiences, such as untrustworthy partners, were significant triggers for OCP and PrEP use. Lastly, male partners were concerned about the DPP upending gender norms but held more positive individual attitudes. Five initial audience segments for the DPP were identified: women seeking enjoyment outside of their primary relationship; new mothers adhering to social norms; women wanting to maintain romantic relationships; women at risk of unintended pregnancy; and women with unfaithful partners. Segments informed the development of three communication themes, with the preferred route highlighting the DPP as a tool to prepare for life's unpredictability., Discussion: To effectively generate demand for the DPP, several strategies should be considered. Connecting with women's diverse identities and goals and celebrating their individuality is crucial. Linking the DPP to relationship goals reframes it as a means to protect relationships rather than a risk. Leveraging negative triggers through targeted media campaigns empowers women to take control of their sexual health during challenging moments. A balance in channel placement is necessary to raise public awareness while using more discrete channels for potentially controversial messages with male partners and wider communities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Nyagah, Segal, Feltham, Ash, Major and Masani.)

Introduction: The pipeline for multi-purpose prevention technologies includes products that simultaneously prevent HIV, pregnancy and/or other sexually transmitted infections. Among these, the Dual Prevention Pill (DPP) is a daily pill co-formulating oral pre-exposure prophylaxis (PrEP), and combined oral contraception (COC). Clinical cross-over acceptability studies for the DPP require training providers to counsel on a combined product. From February 2021-April 2022, a working group of eight HIV and FP experts with clinical and implementation expertise developed counseling recommendations for the DPP based on existing PrEP/COC guidance., Assessment of Policy/guidelines Options and Implications: The working group conducted a mapping of counseling messages from COC and oral PrEP guidance and provider training materials. Six topics were prioritized: uptake, missed pills, side effects, discontinuation and switching, drug interactions and monitoring. Additional evidence and experts were consulted to answer outstanding questions and counseling recommendations for the DPP were developed. Missed pills was the topic with the most complexity, raising questions about whether women could "double up" on missed pills or skip the last week of the pack to recover protection faster. Uptake required aligning the time to reach protective levels for both DPP components and explaining the need to take DPP pills during week 4 of the pack. The potential intensity of DPP side effects , given the combination of oral PrEP with COC, was an important consideration. Discontinuation and switching looked at managing risk of HIV and unintended pregnancy when stopping or switching from the DPP. Guidance on drug interactions contended with differing contraindications for COC and PrEP. Monitoring required balancing clinical requirements with potential user burden., Actionable Recommendations: The working group developed counseling recommendations for the DPP to be tested in clinical acceptability studies. Uptake : Take one pill every day for the DPP until the pack is empty. Days 1-21 contain COC and oral PrEP. Days 22-28 do not contain COC to allow for monthly bleeding, but do contain oral PrEP and pills should be taken to maintain HIV protection. Take the DPP for 7 consecutive days to reach protective levels against pregnancy and HIV. Missed pills : If you miss 1 pill multiple times in a month or 2+ consecutive pills, take the DPP as soon as you remember. Do not take more than 2 pills in a day. If 2+ consecutive pills are missed, only take the last missed pill and discard the other missed pills. Side effects : You may experience side effects when you start using the DPP, including changes to monthly bleeding. Side effects are typically mild and go away without treatment. Discontinuation/switching : If you decide to discontinue use of the DPP, but want to be protected from HIV and/or unintended pregnancy, in most cases, you can begin using PrEP or another contraceptive method right away. Drug interactions : There are no drug-drug interactions from combining oral PrEP and COC in the DPP. Certain medications are not recommended due to their contraindication with oral PrEP or COC. Monitoring : You will need to get an HIV test prior to initiating or restarting the DPP, and every 3 months during DPP use. Your provider may recommend other screening or testing., Discussion: Developing recommendations for the DPP as a novel MPT posed unique challenges, with implications for efficacy, cost, and user and provider comprehension and burden. Incorporating counseling recommendations into clinical cross-over acceptability studies allows for real-time feedback from providers and users. Supporting women with information to use the DPP correctly and confidently is critically important for eventual scale and commercialization., Competing Interests: SH is employed by Viatris, a developer of a DPP. LBH is employed by the Population Council, a non-profit developer of reproductive health products, including a different DPP. The work described in this paper does not specifically pertain to research and development of a DPP product. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Segal, Harris, Carmone, Haddad, Hadigal, Hatzold, Jones, Lathrop, Mason and Mikulich.)

Background: Since oral pre-exposure prophylaxis (PrEP) was approved for HIV prevention in 2012, 78 countries have begun offering PrEP in some form. Measuring progress against global targets and sharing strategies across countries are critical to driving impact. Since 2014, AVAC has collected data from PrEP programs to track and generate insights on PrEP implementation. Methods: The Global PrEP Tracker is a comprehensive database of PrEP projects and national programs. Data are collected through a quarterly survey to 253 programs, and include PrEP initiation numbers, geography, and other indicators. This analysis examined data from Quarter 3 (Q3) 2016 to Q2 2020 to highlight global and regional PrEP initiation trends. Results: Global PrEP uptake has increased six-fold in approximately four years, from 102,446 initiations in 2016 to 651,586 in 2020. Annual growth has slowed over time, from 104% from 2017 to 2018, to 55% from 2018 to 2019, to 18% from 2019 to 2020. At the regional level, Oceania has the highest rate of change, with total PrEP initiations increasing from 318 to 29,093, driven largely by Australia. Sub-Saharan Africa has substantially expanded PrEP access, from 4154 initiations in 2016 to 290,981 by mid-2020, comprising 44% of the global total. South Africa and Kenya have led this growth, counting 69,876 and 63,000 cumulative initiations, respectively. Brazil is leading PrEP uptake in Latin America and the Caribbean, accounting for two-thirds of initiations, and Thailand comprises 51% of initiations in Asia. The United States has the most cumulative initiations at 203,837, about one-third of the global total, but has comparatively modest growth rates. Shared traits in many of these settings are early adoption, national commitment to scale-up, and programs tailored to populations at high risk offering rights-based services and linkages to social support. Conclusions: While PrEP initiations have grown exponentially in several countries, global uptake falls far short of UNAIDS' target of 3 million users, indicating a need for sustained demand creation where PrEP programs exist, and scale-up where PrEP is provided via demonstration projects with limited reach. Countries should replicate successful approaches, including service delivery models that meet end users' needs, to achieve notable reductions in new HIV infections., OA11.01 K. Segal (1); L. Fitch (2); F. Riaz (2); J. Rodrigues (2) and M. Warren (2) (1) AVAC, Product Introduction and Access, Washington, DC, United States, (2) AVAC, New [...]

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a significant impact on hospitals, including the occupational health departments in charge of handling healthcare worker (HCW) staffing during high rates of exposure and infection of HCWs. HCWs who were exposed to a patient or community member infected with SARS-CoV-2 were required to isolate from work for a minimum of 14 days from the date of exposure. Aims This study was aimed to assess the relative risk of SARS-CoV-2 infection following different types of workplace and community exposures. Methods We analyzed the details of workplace and community exposures of HCWs to SARS-CoV-2 at Montefiore Medical Center in New York between 22 June 2020 and 22 November 2020. Results Of 562 HCW SARS-CoV-2 exposures analyzed, 218 were from the community and 345 were from the workplace. Twenty-nine per cent of community exposures resulted in infection, which was significantly greater than workplace exposure infection (2%). Household community exposures resulted in a larger frequency of infection than non-household community exposures. Of the seven infections after workplace exposures, five had qualifying exposures to a co-worker and two were exposed to an infected patient during a non-aerosolized procedure. Conclusions HCW exposure to SARS-CoV-2 continues to present staffing challenges to healthcare systems. Even with deviations from standard personal protective equipment protocol, workplace exposures resulted in low frequencies of infection. In our study, the primary source of HCW infection was exposure in the community. Our findings support investing in efforts to educate around continued masking and social distancing in the community in addition to interventions targeted at addressing vaccine hesitancy. [ABSTRACT FROM AUTHOR]

The HIV pandemic has long revealed the inequities and fault lines in societies, one of the most tenacious being the pandemic's disproportionate impact on adolescent girls and young women. In east and southern Africa, renewed global action is needed to invigorate an effective yet undervalued approach to expanding HIV prevention and improving women's health: integration of quality HIV and sexual and reproductive health (SRH) services. The urgency of advancing effective integration of these services has never been clearer or more pressing. In this piece, national health officials from Kenya, Malawi, and Zimbabwe and global health professionals have joined together in a call to catalyze actions by development partners in support of national strategies to integrate HIV and SRH information and services. This agenda is especially vital now because these adolescent girls and young women are falling through the cracks due to the cascading effects of COVID-19 and disruptions in both SRH and HIV services. In addition, the scale-up of pre-exposure prophylaxis (PrEP) has been anemic for this population. Examining the opportunities and challenges of HIV/SRH integration implemented recently in three countries - Kenya, Malawi, and Zimbabwe - provides lessons to spur integration and investments there and in other nations in the region, aimed at improving health outcomes for adolescent girls and young women and curbing the global HIV epidemic. While gaps remain between strong national integration policies and program implementation, the experiences of these countries show opportunities for expanded, quality integration. This commentary draws on a longer comparative analysis of findings from rapid landscaping analyses in Kenya, Malawi, and Zimbabwe, which highlighted cross-country trends and context-specific realities around HIV/SRH integration.

Policies facilitating access to HIV prevention services, specifically for pre-exposure prophylaxis (PrEP), can foster enabling environments for service uptake. This analysis aims to establish whether policies enabling broad PrEP eligibility, HIV self-testing, and lowered age of consent to HIV testing and treatment services are correlated with PrEP uptake. Ages of consent vary by country, therefore this analysis focused on how age of consent policies, in general, affect adolescent PrEP uptake. Data was collected from the HIV Policy Lab and AVAC's Global PrEP Tracker, a database of approximately 334 PrEP projects operating across 95 countries, and linear regression and correlation analyses were conducted via STATA to examine relationships amongst national oral PrEP eligibility, HIV self-testing, lowered age of consent, and national cumulative oral PrEP initiations, as of December 2021. Of all 194 countries tracked by the HIV Policy Lab, only about 7% have adopted all three policies (HIV self-testing, lowered age of consent, and PrEP eligibility policies). Less than 50% have adopted have adopted at least one of these policies. Of the 54 countries that have fully adopted PrEP eligibility policies, less than 30% have co-adopted HIV self-testing or lowered age of consent policies. About 30% of these 194 countries have yet to adopt any of these policies, of which about 14% have indicated information is "unavailable" for at least one of the policies. Analyses conducted for the 91 countries tracked by both the HIV Policy Lab and the Global PrEP Tracker revealed a significant and positive relationship between cumulative individuals initiated on oral PrEP and adoption of HIV self-testing policies (p = 0.01, r = 0.26), lowered age of consent policies (p = 0.01, r = 0.25), and PrEP eligibility policies (p = 0.01, r = 0.26). Stronger advocacy efforts towards approving public health policies, such as those outlined in our analysis, that enshrine and enable access to HIV prevention are necessary., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Tailor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background:  Though substantial progress has helped curb the HIV epidemic, high rates of new HIV infections persist among adolescent girls and young women (AGYW) in sub-Saharan Africa, reflecting critical gaps in reaching them with integrated HIV prevention and sexual and reproductive health (SRH) services. The scale-up of oral pre-exposure prophylaxis (PrEP) and multiple novel HIV prevention products on the horizon offer countries a unique opportunity to expand innovative approaches to deliver comprehensive, integrated HIV prevention/SRH services. Methods:  This article comparatively analyzes findings from rapid assessments in Kenya, Malawi and Zimbabwe across key themes to highlight cross-country trends and contextual realities around HIV prevention/SRH integration, with a focus on oral PrEP and contraception. In Kenya and Zimbabwe, assessments were completed by Ministries of Health (MOH) and the HIV Prevention Market Manager and include 20 health facility assessments, 73 key informant interviews (KIIs) and six community dialogues. In Malawi, the assessment was completed by the MOH and Georgetown University Center for Innovation in Global Health and includes 70 KIIs and a review of national policies and program implementation in Blantyre. Findings were contextualized through a review of literature and policies in each country. Results:  Across countries, the policy environment is conducive to HIV prevention/SRH integration, though operationalization presents ongoing challenges, with most policies preceding and not accounting for oral PrEP rollout. National coordination mechanisms, youth-friendly health services and prevention of mother-to-child transmission programs are promising practices, while siloed and resource-constrained health systems, limited provider capacity, underfunded demand generation and structural factors exacerbate barriers to achieving integration. Conclusions:  As new HIV prevention products are introduced, demand for integrated HIV prevention/SRH services is likely to grow. Investing in HIV prevention/SRH integration can help to ensure a sustainable response to the HIV epidemic, streamline service delivery and improve the health outcomes and lives of AGYW., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Kachale F et al.)

Background: We previously reported a Phase 1/2 randomized placebo-controlled trial of systemic administration of bone marrow-derived allogeneic MSCs (remestemcel-L) in COPD. While safety profile was good, no functional efficacy was observed. However, in view of growing recognition of effects of inflammatory environments on MSC actions we conducted a post-hoc analysis with stratification by baseline levels of a circulating inflammatory marker, C-reactive protein (CRP) to determine the effects of MSC administration in COPD patients with varying circulating CRP levels., Methods: Time course of lung function, exercise performance, patient reported responses, and exacerbation frequency following four monthly infusions of remestemcel-L vs. placebo were re-assessed in subgroups based on baseline circulating CRP levels., Results: In COPD patients with baseline CRP ≥ 4 mg/L, compared to COPD patients receiving placebo (N = 17), those treated with remestemcel-L (N = 12), demonstrated significant improvements from baseline in forced expiratory volume in one second, forced vital capacity, and six minute walk distance at 120 days with treatment differences evident as early as 10 days after the first infusion. Significant although smaller benefits were also detected in those with CRP levels ≥ 2 or ≥ 3 mg/L. These improvements persisted variably over the 2-year observational period. No significant benefits were observed in patient reported responses or number of COPD exacerbations between treatment groups., Conclusion: In an inflammatory environment, defined by elevated circulating CRP, remestemcel-L administration yielded at least transient meaningful pulmonary and functional improvements. These findings warrant further investigation of potential MSC-based therapies in COPD and other inflammatory pulmonary diseases., Trial Registration: Clinicaltrials.gov NCT00683722.

Objectives: Differentiated thyroid cancer (DTC) is rare in the pediatric population. It remains unclear whether younger children are at greater risk of more aggressive disease. We aimed to identify prognostic factors for aggressive pediatric DTC and to define an appropriate age stratification., Methods: This retrospective cohort study included all patients aged 18 years or less who were treated for DTC between 1985 and 2021 in a tertiary medical center and were followed up for a minimum of 1.5 years after treatment., Results: Seventy-eight patients were included, all diagnosed with papillary thyroid carcinoma: 30 (38.5%) low-risk, 21 (26.9%) intermediate-risk, and 27 (34.6%) high-risk according to the American Thyroid Association (ATA) risk stratification. The mean duration of follow-up was 11.8 ± 7.8 years. No evidence of disease was documented in 52 patients (66.7%) at 1-year post-treatment and 64 patients (82.1%) at the end of follow-up. On analysis by age, evidence of disease at 1-year post-treatment was found in 66.7% of children younger than 11 years, compared to 25.4% of older children (p = 0.002). There was no significant difference by age in evidence of disease at the last follow-up (p = 0.453). Patients aged <11 years at diagnosis were associated with more aggressive disease features on histopathologic examination, metastatic disease, and high ATA risk level. Patients aged <8 years were associated with more frequent bilateral disease and extrathyroidal extension., Conclusion: Pediatric DTC patients who are younger than 11 years at diagnosis have more aggressive disease features and a lower early remission rate than older patients. Nevertheless, their long-term outcome is satisfactory., Level of Evidence: 4-retrospective cohort study Laryngoscope, 134:4818-4825, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background and Purpose: Botulinum neurotoxin type A1 (BoNT/A) is one of the most potent neurotoxins known. At the same time, it is also one of the safest therapeutic agents used for the treatment of several human disorders and in aesthetic medicine. Notwithstanding great effectiveness, strategies to accelerate the onset and prolong BoNT/A action would significantly ameliorate its pharmacological effects with beneficial outcomes for clinical use., Experimental Approach: Here, we combined BoNT/A with two fast-acting inhibitors of excitation-contraction coupling inhibitors (ECCI), either the μ-conotoxin CnIIIC or dantrolene, and tested the effect of their co-injection on a model of hind-limb paralysis in rodents using behavioural, biochemical, imaging and electrophysiological assays., Key Results: The BoNT/A-ECCI combinations accelerated the onset of muscle relaxation. Surprisingly, they also potentiated the peak effect and extended the duration of the three BoNT/A commercial preparations OnabotulinumtoxinA, AbobotulinumtoxinA and IncobotulinumtoxinA. ECCI co-injection increased the number of BoNT/A molecules entering motoneuron terminals, which induced a faster and greater cleavage of SNAP-25 during the onset and peak phases, and prolonged the attenuation of nerve-muscle neurotransmission during the recovery phase. We estimate that ECCI co-injection yields a threefold potentiation in BoNT/A pharmacological activity., Conclusions and Implications: Overall, our results show that the pharmacological activity of BoNT/A can be combined and synergized with other bioactive molecules and uncover a novel strategy to enhance the neuromuscular effects of BoNT/A without altering the neurotoxin moiety or intrinsic activity, thus maintaining its exceptional safety profile., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)