This cohort study assesses receipt of physical therapy and chiropractic care for chronic low back pain among Medicare beneficiaries with opioid use disorder (OUD) from different racial and ethnic groups. Are there racial and ethnic differences in receipt of physical therapy (PT) or chiropractic care for chronic low back pain (CLBP) among people with opioid use disorder (OUD)?In this cohort study of 69 362 Medicare beneficiaries with CLBP and OUD, 10.2% received PT or chiropractic services within 3 months. Black or African American and Hispanic persons had lower odds of chiropractic care compared with non-Hispanic White persons.In this study, PT and chiropractic care use was low overall and racial and ethnic inequities in utilization and time to chiropractic care were observed, underscoring the need for equitable and multimodal pain management among people with OUD. Nonpharmacologic treatments are important for managing chronic pain among persons with opioid use disorder (OUD), for whom opioid and other pharmacologic therapies may be particularly harmful. Racial and ethnic minority individuals with chronic pain and OUD are vulnerable to suboptimal pain management due to systemic inequities and structural racism, highlighting the need to understand their receipt of guideline-recommended nonpharmacologic pain therapies, including physical therapy (PT) and chiropractic care.To assess differences across racial and ethnic groups in receipt of PT or chiropractic care for chronic low back pain (CLBP) among persons with comorbid OUD.This retrospective cohort study used a 20% random sample of national Medicare administrative data from January 1, 2016, to December 31, 2018, to identify fee-for-service community-dwelling beneficiaries with a new episode of CLBP and comorbid OUD. Data were analyzed from March 1, 2022, to July 30, 2023.Race and ethnicity as a social construct, categorized as American Indian or Alaska Native, Asian or Pacific Islander, Black or African American, Hispanic, non-Hispanic White, and unknown or other.The main outcomes were receipt of PT or chiropractic care within 3 months of CLBP diagnosis. The time (in days) to receiving these treatments was also assessed.Among 69 362 Medicare beneficiaries analyzed, the median age was 60.0 years  and 42 042 (60.6%) were female. A total of 745 beneficiaries (1.1%) were American Indian or Alaska Native; 444 (0.6%), Asian or Pacific Islander; 9822 (14.2%), Black or African American; 4124 (5.9%), Hispanic; 53 377 (77.0%); non-Hispanic White; and 850 (1.2%), other or unknown race. Of all beneficiaries, 7104 (10.2%) received any PT or chiropractic care 3 months after a new CLBP episode. After adjustment, Black or African American  and Hispanic  persons had lower odds of receiving chiropractic care within 3 months of CLBP diagnosis compared with non-Hispanic White persons. Median time to chiropractic care was longest for American Indian or Alaska Native  and Black or African American  persons and shortest for Asian or Pacific Islander persons . No significant racial and ethnic differences were observed for PT.In this retrospective cohort study of Medicare beneficiaries with comorbid CLBP and OUD, receipt of PT and chiropractic care was low overall and lower across most racial and ethnic minority groups compared with non-Hispanic White persons. The findings underscore the need to address inequities in guideline-concordant pain management, particularly among Black or African American and Hispanic persons with OUD. While the racial and ethnic gap in pain care has been well documented for pharmacologic therapies, few studies have examined whether racial and ethnic disparities exist in receipt of PT and chiropractic care for chronic pain,21 and, to our knowledge, this question has not been assessed among persons with OUD.Managing chronic pain among persons with OUD, however, is complex as clinicians need to carefully consider guideline-recommended care for both conditions.24 and who had access to Medicare-covered nonpharmacologic treatments, such as PT and chiropractic care. We hypothesized that following a new diagnosis of chronic pain, racial and ethnic minority groups would have lower receipt of PT and chiropractic care compared with non-Hispanic White individuals and that among persons who receive these treatments, racial and ethnic minority groups would have a longer time to receipt of treatment.The objective of this study was to investigate differences in use of PT and chiropractic care among persons diagnosed with chronic pain and OUD across racial and ethnic groups. We analyzed a cohort of Medicare beneficiaries, a population with high reported prevalence of chronic pain among whom rates of OUD are increasingSTROBE) reporting guideline.The Brown University institutional review board determined the study to be exempt from review based on secondary analysis of deidentified data, and informed consent was not required. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology  codes for radicular and nonradicular back pain in any position on MedPAR Part A and Part B claims ; in hospice or long-term care facility; 2 or more claims for a cancer diagnosis (treatment for cancer-related chronic pain is distinct from that for noncancer chronic pain and was not the focus of this study)29; younger than 18 years; no OUD claims during study period; residing outside the 50 states and Washington, DC, including Puerto Rico, US Virgin Islands, American Samoa, Marianas Islands, and Guam; or missing Federal Information Processing System Codes for States and Counties.The study population included Medicare fee-for-service beneficiaries with 2 or more diagnoses for chronic low back pain (CLBP) separated by at least 90 daysCurrent Procedural Terminology (CPT) codes from Part B claims  race and ethnicity variable in Medicare enrollment files, which relies on administrative data from the Social Security Administration and an algorithm to impute race and ethnicity from name and geographic location. The validity of the race and ethnicity variables in Medicare data compared with the gold standard of self-report has been evaluated, and findings indicate that the RTI race code is more accurate for Asian or Pacific Islander and Hispanic persons than the Medicare enrollment file beneficiary race code.32 The RTI variable reports race and ethnicity in 7 mutually exclusive groups as American Indian or Alaska Native, Asian or Pacific Islander, Black or African American, Hispanic, non-Hispanic White, other, and unknown. The other category refers to non-Hispanic other race, and a designation of unknown occurs when there are missing data.33 Due to small numbers in the unknown group, we combined it with the group labeled as other, therefore creating a 6-level categorical variable identifying beneficiary race and ethnicity.The primary independent variable was beneficiary race and ethnicity, which we considered as a social rather than a biologic or genetic construct.ICD-10 or CPT codes from MedPAR Part A and Part B claims , current reason for Medicare eligibility, dual eligibility, state and county of residence, and receipt of medication for OUD were measured in the year of CLBP diagnosis from the annual Medicare enrollment file. Comorbidities included cardiovascular conditions, mental health diagnosis, neck pain and fractures, osteoarthritis and joint cartilage conditions, diabetes, chronic obstructive pulmonary disease, obesity, alcohol use disorder, hospitalization, surgery, and the Gagne comorbidity score. All were measured 6 months prior to the CLBP diagnosis date using 38 to create variables for social determinants of health at the county level and the Area Health Resources File39 to determine geographic information and practitioner availability at the state level  and number of chiropractors per 100 000 population in the year of CLBP diagnosis and came from the Area Health Resources File. We linked National Plan and Provider Enumeration System41 data to the billing health care practitioner in the Part B claims using a National Provider Identifier to identify practitioner specialty. Lastly, US region and rural-urban commuting area codes were obtained from the Area Health Resources File at the county level.39 No missing data were observed for individual-level , county-level , or state-level  data.We used the American Community Survey2 test for binary and categorical variables. We calculated the proportions of beneficiaries within each race and ethnicity group who received (1) any PT or chiropractic care, (2) any PT, and (3) any chiropractic care within 3 months of CLBP diagnosis and used Kaplan-Meier curves to visualize the time to receipt of these treatments. Differences across race and ethnicity in the Kaplan-Meier curves were evaluated using log-rank tests. Multilevel logistic regression models separately estimated the association between race and ethnicity and the 3 outcomes, adjusting for all covariates listed in Characteristics of the study population were compared by race and ethnicity using the Kruskal-Wallis test for continuous variables and Pearson χCPT codes for PT evaluations in addition to treatment modalities and therapeutic procedures because of the potential for beneficiaries to obtain clinical benefit through their interaction with a practitioner during the evaluation. Second, to examine the influence of prior PT or chiropractic care on cohort selection, we restricted the study cohort to beneficiaries without any PT or chiropractic care in the 6 months before CLBP diagnosis. Persons with prior use might have different experiences and attitudes toward nonpharmacologic care that increase their continued engagement or disengagement in care; these experiences could also differ by race and ethnicity.We conducted 2 sensitivity analyses. First, we modified the PT outcome to include P < .05 (2-sided test). Data were analyzed from March 1, 2022, to July 30, 2023.All analyses were conducted in SAS, version 9.4 (SAS Institute Inc) and Stata, version 17.0 (StataCorp LLC), and statistical significance was evaluated at Among the 69 362 beneficiaries diagnosed with CLBP and OUD , the medThree months after CLBP diagnosis, the prevalence of PT was low but higher (4358 [6.3%]) compared with chiropractic care (3227 [4.7%]). Use of PT was lowest among American Indian or Alaska Native persons (33 of 745 [4.4%]) and highest among Asian or Pacific Islander persons (47 of 444 [10.6%]) . ChiroprMedian time to PT initiation did not differ substantially across racial and ethnic groups; however, American Indian or Alaska Native persons  and Black or African American persons  had a longer time to receipt of chiropractic care compared with non-Hispanic White persons . Cumulative incidence curves  indicateThe multilevel logistic regression models showed lower odds of any PT or chiropractic care among American Indian or Alaskan Native , Black or African American , and Hispanic  persons compared with non-Hispanic White persons after adjustment . SeparatThe first sensitivity analysis including a broader definition of PT yielded similar results as the main analysis . Compared with other studies evaluating musculoskeletal chronic pain, however, we observed lower use of chiropractic care.50 The geographic availability of practitioners may contribute to these differential patterns of PT and chiropractic care.51 It has been reported that labor supply of both PT and chiropractic care is lower in the South and West regions of the US compared with the Northeast and Midwest.53 Variations in local practitioner availability possibly limit access, acceptability, and adoption of these types of pain treatments.53 Limited patient and practitioner knowledge combined with skepticism about the efficacy of nonpharmacologic pain treatment and cultural influences on patient preferences may also impede uptake of these therapies, particularly among patients already receiving opioid therapy.54There is little literature in general regarding nonpharmacologic treatment use and disparities, and the few existing studies indicate wide variations across racial and ethnic subgroups.56 The new clinical practice guidelines for prescribing opioids for pain by the Centers for Disease Control and Prevention recommend that clinicians provide evidence-based medications for persons with OUD.10 Incorporating nonpharmacologic pain therapies along with medication for OUD creates a pain management approach that can minimize safety risks. Accordingly, several trials using behavioral and mind-based therapies to reduce pain and opioid use are currently under way.58 Efforts should also prioritize a multidisciplinary and patient-centered approach that involves cultural competency and understanding of systemic and structural inequities to ensure equal opportunities in pain and OUD care.59 Current health care policies in coverage and financing in Medicare systematically prevent racial and ethnic minority groups from accessing high-quality care.60 Evidence has consistently demonstrated that Black or African American and Hispanic persons are less likely to receive evidence-based care and age-appropriate diagnostic screenings.61 In addition, practitioners that primarily care for low-income minority groups are more likely to receive lower reimbursements from Medicare under value-based payment programs, while pay-for-performance programs reward practitioners caring for high-income and non-Hispanic White individuals.62 To this end, clinical trials assessing nonpharmacologic treatments of chronic pain and OUD can enlist community partnerships to assist in creating effective, safe, and equitable strategies for treatment of both conditions.63 Additionally, current guidelines can prioritize addressing racial and ethnic inequities in treatment of chronic pain and OUD through comprehensive pain clinical care that incorporates factors at the individual, practitioner, and system levels that contribute to the observed disparities.Our findings also call attention to barriers in accessing and using PT and chiropractic care for chronic pain that are compounded by the intersectional nature of racism and OUD-related stigma. Harmful biases about racial and ethnic minority groups with OUD are reinforced in health care settings, resulting in these groups receiving fewer referrals to pain specialists and consequently fewer opportunities to receive nonpharmacologic treatments compared with non-Hispanic White individuals.64 Exclusion of beneficiaries residing in Puerto Rico and the US Virgin Islands also limited the study sample of Hispanic persons. However, as most beneficiaries from these territories are enrolled in Medicare Advantage, they would not have met our inclusion criteria. Second, lack of information on whether practitioners differentially referred beneficiaries to PT or chiropractic care  limits understanding of the underlying mechanisms that explain differences in use of these treatments. Third, due to limited Medicare coverage of nonpharmacologic pain therapies, we could not assess a broader list of treatments aside from PT and chiropractic care. We attempted to characterize cognitive behavioral therapies, but low prevalence limited further assessment by race and ethnicity. Fourth, differential OUD diagnosis by practitioners based on beneficiaries’ racial demographics may contribute to under- or overestimation of the differences in PT or chiropractic care for Black or African American and Hispanic persons, as these groups historically have been underdiagnosed for OUD.65 Fifth, a limitation inherent with administrative claims data is that we could not capture self-paid services for which Medicare did not provide reimbursement, leading to possible underestimation of chronic pain services among beneficiaries.Several limitations of the study should be considered. First, Medicare claims data are limited in their ability to accurately determine race and ethnicity. However, in the absence of self-report, the RTI algorithm used is the best alternative.This cohort study found that receipt of PT and chiropractic care was low overall and lower across most racial and ethnic minority groups compared with non-Hispanic White individuals despite nonpharmacologic approaches to pain management being widely recommended as a strategy to mitigate opioid-related morbidity and mortality. Although there is uncertainty about the individual and practitioner contexts that may explain our findings, historic racial and ethnic disparities in pain treatment appear to persist and are also specifically evident for chiropractic care in persons with OUD. Therefore, efforts are needed to elucidate and address the individual, practitioner, and system-level risk factors that limit racial equity in guideline-recommended pain management in general and for persons with OUD.


Pakistan faces tremendous challenges in providing healthcare due to a lack of consistent policymaking, increasing expenditure and exponential growth in population since its inception in 1947. These challenges are not just driven by politics, policy and allocation of resources but also by healthcare, environment and characteristics of the population biology. Clinical trials provide the best way to find population-specific, cost-effective treatments that do not merely mimic those used in wealthier nations. This article analyzes all clinical studies conducted with at least one site in Pakistan listed on ClinicalTrials.gov, combined with a short overview that considers new therapeutic approaches that can be investigated in future clinical trials. Therapies using repurposed medicines are of particular interest as they use affordable drugs that are already widely available. Since its creation 76 years ago with a nominal infrastructure base, Pakistan has made remarkable progress including improvements in health services. However, it also faces tremendous challenges due to the rapid increase in population since the 1970s, which is currently the fifth largest in the world combined with a modest per capita gross domestic product  .These economics reflect in the poor health outcomes compared to developed nations, but they also compare poorly when compared to other low- and middle-income countries (LMICs) . These cTherefore, there is a specific need for LMICs such as Pakistan to have cost-effective therapies. Coupled with unique cultural, geographic and demographic factors, a critical unmet scientific need is for healthcare treatments that are tested locally for biological and efficiency optimization.We are interested in developing population-specific, cost-effective therapies particularly targeted towards developing nations. Clinical trials, particularly when randomized, are the best way to discover therapies that are safe and efficacious. These are needed to cover the significant gaps in clinical trial research in Pakistan compared to other neighboring LMICs. For example, in an analysis of breast cancer research trials carried out in LMICs, we discovered that of 35 breast cancer research trials carried out in the 3 LMICs of South Asia , only 2 (5%) were located in Pakistan .The ClinicalTrials.gov database is free to use and contains details of more than 460,000 privately and publicly funded clinical studies conducted in 221 countries ; an anal® Excel® for Microsoft 365 and JMP® Pro 17.01.0 running on Windows 10.Specific search terms were used in the query section of ClinicalTrials.gov. The comma-separated values (CSV) file of all studies meeting the query criteria was downloaded and analyzed using MicrosoftA query of [Pakistan] in “location” on 14 August 2023 of 461,791 studies listed on ClinicalTrials.gov found 2564 studies, all of which were then taken forward for analysis. The geographic distribution of the studies is listed in The status of the studies is listed in Only 2.5% (63/2564) of the studies had results available.The start dates of the studies are shown in The phases of the studies are listed in Most studies were categorized as interventional (2210/2564 = 86%), and the majority were categorized as randomized (2021/2564 = 79%). A breakdown by intervention model and masking (blinding) is shown in From the eligibility criteria, the age groups and sex of the participants are tabulated in A histogram of the number of participants in each study is shown in The analysis of clinical trials conducted with at least one site in Pakistan provides evidence of a flourishing and capable infrastructure. Of the 2564 studies identified, 85% had a single site in Pakistan only . The pacEffect of Soleus Pushup Exercise in Type 2 Diabetes Patients (NCT06020846) sponsored by Riphah International University in Rawalpindi. An RCT designed to test whether a simple exercise intervention can lower blood glucose levels in people with Type 2 diabetes.Effects of Prosthesis Training on Pain, Prosthesis Satisfaction and Ambulatory Status of Lower Limb Amputees (NCT06013631) sponsored by the University of Lahore. An RCT assessing the effects of prosthesis training with and without phantom exercises on people who have had a lower-limb amputation.Unified Protocol for Transdiagnostic Treatment for Depression and Anxiety in Adults (NCT06002087) sponsored by the National University of Science and Technology in Islamabad. A pilot RCT of a culturally adapted Unified Protocol for transdiagnostic psychological treatment in adults with anxiety and/or depression to assess the feasibility and acceptability.Effects of Posterior–Anterior Vertebral Mobilization Followed by Prone Press-up Exercise in Nonspecific Low Back Pain (NCT05997069) sponsored by the Sindh Institute of Physical Medicine and Rehabilitation in Karachi. An RCT designed to test a non-pharmacological method to alleviate lower back pain.Effect of Preoperative Tramadol and Naproxen Sodium on Post Operative Pain (ID NCT05982392) sponsored by Dow University of Health Sciences in Karachi. A three-arm RCT comparing a single intervention of oral tramadol, oral naproxen or placebo with a primary outcome of pain after dental treatment. To reduce bias, the trial is quadruple-blinded (masked) to the participant, care provider, investigator and outcomes assessor.Bifidobacterium longum on weight gain in underweight infants between 30 and 120 days of age.Impact of Bi-26 Supplementation on Weight Gain in Underweight Infants (NCT05952076) sponsored by the Bill and Melinda Gates Medical Research Institute. A placebo-controlled RCT conducted in three sites in Pakistan evaluated the effect of supplementation with a strain of a gut microbe As an illustration of the diversity of clinical trials, here is a brief description of six of the studies currently recruiting or about to open:Our study builds upon and extends previous work in this area. A study of 508 clinical trials conducted in Pakistan registered on clinicaltrials.gov from 1992 to 2019 found an increase in the number of studies registered over time . AnalysiThe 2018 healthcare expenditure for Pakistan’s estimated 250 million populace was $4.5 billion ; for comThe healthcare system in Pakistan is a blend of public and private sectors, with a vast majority of the population relying on public healthcare services that are largely not fit for purpose. Healthcare delivery is jointly administered by the federal and provincial governments. The system can be divided into three tiers: primary, secondary and tertiary care. Primary healthcare facilities are the first point of contact for most patients and are designed to provide basic healthcare services. Secondary care facilities offer more specialized services and are generally located in larger cities. Tertiary care facilities, such as teaching hospitals, provide advanced medical care and training for healthcare professionals .Challenges facing the health system include :Inadequate Funding: One of the most significant challenges is the insufficient allocation of funds to the healthcare sector. Pakistan’s expenditure on healthcare is well below the recommended levels set by international organizations, resulting in a lack of resources for infrastructure development, medical equipment and training of healthcare professionals.Limited Access to Quality Healthcare: Access to quality healthcare services is a major concern, especially in rural and remote areas. Most healthcare facilities are concentrated in urban centers, leaving a significant portion of the population underserved. Healthcare disparities due to geographic location are a problem in many countries, including high-income countries, although there is evidence that Canada, Norway and the Netherlands have managed to reduce these disparities . ClinicaShortage of Healthcare Professionals: Pakistan faces a shortage of trained healthcare professionals, including doctors, nurses and paramedics. This shortage is particularly severe in rural areas, where healthcare professionals are often reluctant to work due to inadequate facilities and security concerns.High Disease Burden: Pakistan has a high burden of communicable diseases, such as malaria, tuberculosis and hepatitis, as well as non-communicable diseases, including cardiovascular diseases and diabetes. Controlling these diseases requires a robust public health infrastructure and preventive measures.Maternal and Child Health: Maternal and child health indicators remain concerning, with high maternal mortality rates and under-five mortality rates. The lack of access to prenatal and postnatal care, skilled birth attendants and appropriate healthcare for children contribute to these issues.Sanitation and Hygiene: Poor sanitation and hygiene practices in many parts of the country exacerbate health issues, leading to preventable diseases like diarrhea and cholera.Despite these challenges, Pakistan has made some strides in recent years to improve its healthcare system.National Health Vision 2025: The government launched the National Health Vision 2016–2025, which aims to revamp the healthcare system by improving infrastructure, increasing human resource capacity and enhancing access to quality healthcare services .Universal Health Coverage Program: Pakistan introduced the Sehat Sahulat Program to provide health coverage to low-income families, offering financial protection against high medical costs .Expanded Immunization Programs: The country has expanded its immunization programs to reach more children, increasing vaccination rates against preventable diseases .Polio Eradication Efforts: Pakistan has made significant progress in eradicating polio, with a considerable decline in cases in recent years. However, challenges remain due to security issues in certain regions and vaccine hesitancy .Digital Health Initiatives: The adoption of digital health initiatives, such as telemedicine and electronic health records, has shown promise in increasing healthcare access and efficiency, especially in remote areas .To build a more robust and equitable healthcare system, Pakistan needs to implement strategic measures and reforms. Some key recommendations include:Increased Funding: A key future objective should be an increase in healthcare expenditure, prioritizing healthcare and allocating adequate funds to strengthen the infrastructure, procure modern medical equipment and support research and development. For example, the economic burden of mental illness in Pakistan was estimated to be £2.97 billion ($3.74 billion) in 2020, highlighting the need to develop a cost-effective national model for mental healthcare .Human Resource Development: Invest in training and retaining healthcare professionals, especially in underserved areas, by offering incentives, such as better salaries, improved working conditions and career development opportunities. For example, a study exploring the facilitators and barriers to the acceptability of volunteer laywomen from the community as delivery agents of a psychosocial intervention for perinatal depression in a rural area of Pakistan found that this could be a way of delivering an effective intervention in relatively low cost .Addressing Inequalities: Address regional disparities by focusing on expanding healthcare facilities and services in rural and remote areas, where access is limited. A study of women seeking surgical care found evidence for gender disparity , particuPublic Health Interventions: Prioritize preventive healthcare measures, such as promoting hygiene and sanitation, expanding immunization coverage and the education of ordinary citizens. For example, the Pakistan Life Savers Programme aims to empower people with the skills needed to save lives and has trained over 225,000 life savers .Maternal and Child Health: Strengthen maternal and child health programs by increasing access to skilled birth attendants, improving prenatal and postnatal care and promoting community-based interventions. For example, the implementation of pulse oximetry might improve child morbidity and mortality from pneumonia but requires improved access to pulse oximeters and oxygen supplies .Health Awareness Campaigns: Launch public health awareness campaigns to educate the population about preventive measures, healthy lifestyles and disease management. For example, mass gatherings such as the Hajj pilgrimage may facilitate the spread of infectious diseases and antimicrobial resistance ; health Public–Private Partnerships: Foster collaboration between the public and private sectors to leverage resources and expertise for improving healthcare delivery. For example, Punjab (the most populous region of Pakistan) has the most developed healthcare infrastructure in the country, due in no small part to the implementation of public–private partnerships .Technology Integration: Continue to embrace digital health technologies to enhance healthcare access and efficiency, particularly in remote and underserved areas. For example, the use of remote health monitoring systems for elderly people could make use of data from wearable sensors collected through cloud servers and analyzed by AI to flag potential issues and alert their families to take preventive action ,28. IdeaAs outlined above, the healthcare system in Pakistan suffers from chronic and deeply entrenched economic, infrastructure and medical personnel crises. The structural problems are complex and deep-seated, and it is beyond the scope of this analysis and the expertise of the authors to propose any meaningful solutions. Even with determination, increased resources and concerted effort by its government, these problems will take many decades to resolve. We do, however, suggest that there may be one avenue, namely, drug repurposing, that could be pursued to address both the problems of population-tailored small molecule therapy and healthcare accessibility for a population in the short to medium term.Drug repurposing  has the potential to provide a cost-effective means of developing new therapies. This approach has numerous advantages in relation to LMICs in general and Pakistan in particular: (i) While de novo drug discovery is an expensive and time-consuming process, taking up to 15 years from concept to translation with a very high rate of attrition , DR can Notably, none of the 2564 studies we analyzed was investigating repurposed medications. This could be due to a lack of economic incentives, but “social finance” might be a way to solve this problem . We propPakistan’s health system has undergone significant progress in recent years despite multiple challenges. The COVID-19 pandemic clearly illustrated the need for high-quality healthcare evidence, and the government’s commitment to healthcare reform and strategic initiatives are encouraging signs that Pakistan sees the need to invest in high-quality randomized clinical trials to ensure that the limited resources available are used most efficiently to find effective health interventions that are suitable for its unique circumstances. With a concerted effort to address funding gaps, improve access to quality healthcare including preventive measures and strengthen the healthcare workforce, Pakistan can achieve a more equitable and effective healthcare system, ultimately improving the well-being of its citizens.


The aim of this review was to map evidence of integrating pre-exposure prophylaxis (PrEP) for HIV prevention into family planning services. A comprehensive package, using a combination of PrEP and contraceptive delivery, could reduce the number of new HIV infections and/or unintended pregnancies for at-risk women and adolescent girls.A scoping literature search was conducted between August 2020 and October 2020. After developing the review question, electronic databases  were systematically reviewed. All types of articles published from 2012 to August 2020 in English were included. The intended outcome was to identify barriers and enablers of integrating services at the client-level and provider-level.38 articles met inclusion criteria, with 16 from low-and middle-income countries and 22 from high-income countries. Barriers at the client-level included a lack of risk perception associated with low uptake and continuation of PrEP and pill burden; and at the provider-level, barriers included a lack of studies on cost-effectiveness of integrating services and provider training and knowledge. Facilitators included the initiation of PrEP and contraception at the same time and by the same provider or HIV self-testing.Mapping and synthesising current evidence, this review identified key barriers and facilitators for the integration of PrEP into family planning services for women and adolescent girls. In order to address these factors, more implementation research in a variety of settings is needed to meet women’s sexual and reproductive health needs globally. Pre-exposureprophylaxis (PrEP) inwomen is an effective HIV prevention option when taken regularly. Providing PrEP in family planning services could contribute to PrEP uptake globally. Understanding how PrEP could be delivered in these services has to be further investigated.Multi-level barriers were identified at client level , and at provider-level . Facilitating factors such as HIV self-testing were identified which should be implemented to improve the integration of both services.More implementation of research studies are needed from diverse settings on how best to integrate PrEP into family planning services, with current evidence mainly from pilot studies in Kenya and the USA.Integrating pre-exposure prophylaxis (PrEP) for HIV prevention within family planning (FP) services is an area of emerging interest to researchers and policymakers. Where women and adolescent girls are at increased risk for HIV infection, offering HIV prevention services during visits to FP services provides an important opportunity to reduce both the risk of HIV infection and unplanned pregnancy during clinic visits.Integration is defined as combining different types of services to maximise outcomes and can be bi-directional, with sexual and reproductive health (SRH) services integrated into HIV services and HIV services integrated into SRH services.This review was informed by Arksey and O'Malley’s (2005)10.1136/bmjsrh-2021-201356.supp1Supplementary dataBetween August 2020 and September 2020, five peer reviewed electronic databases were systematically reviewed comprising MEDLINE, Embase, Cochrane Library, Global Health, and Web of Science. To include grey literature the search was also run in Google Scholar. Potential ongoing studies were searched for in PROSPERO  as well as the Australian New Zealand Clinical Trial Registry (ANZCTR)  The timeThe search and selection found that 38 articles met the inclusion criteria and were included in the review; 33 of the articles provided primary data . Sixteen articles referred to low- and middle-income countries (LMICs) (13/16 in Kenya) and 22 in high-income countries (HICs) (22/22 in the USA). Studies from LMICs on the integration of PrEP into FP services were primarily published since 2018, studies from the USA primarily since 2016. Box 1PrEP Implementation in Young Women and Adolescents (PrIYA) programme (n=6) is an implementation programme in Kisumu, Kenya which delivered PrEP to young women at substantial risk of HIV.Zimbabwe National Family Planning Council (ZNFPC) (n=2) coordinates, takes leadership and supports implementation of integrated FP and related SRH services in Zimbabwe.Prevention Options for Women Evaluation Research (POWER) study (n=3) intends to understand PrEP use and uptake among women attending FP clinics in Kenya and youth friendly clinics in South Africa.This review identified multiple inhibiting and facilitating factors when PrEP services were accessed through FP services. Furthermore, when available, characteristics of implementation strategies were specified in the results section.Themes that arose from the dataset included client-level and provider-level barriers and facilitators of delivering PrEP in settings where FP services were provided.et al found that awareness of PrEP (89%) was high among high-risk adolescent girls and young women (AGYW) (n=470) attending four FP services in Kisumu, Kenya.A survey conducted by Sila et alet al found that delivering PrEP through FP services, which are already trusted by black adolescent and young adult women, can have a positive impact on drug adherence and uptake and therefore act as an enabler of uptake.et alet alet al piloted PrEP integration in an urban FP clinic in Zimbabwe in 2018, and found an uptake of 4.1% that was influenced by partners’ or families’ support, by healthcare workers’ knowledge and attitudes, as well as participants’ awareness of PrEP.et alet al integrated routine HIV testing and counselling for PrEP into FP clinics which was delivered by a PrEP dedicated-nurse. Results showed that PrEP uptake was 22% among HIV-negative women, overall, and 16% among AGYW (n=1271). Facilitators for an uptake of PrEP among study participants included unmarried women, women who had an HIV positive partner, and women >24 years old.et al’s study, a woman’s low perceived risk for HIV was an important reason for low PrEP uptake.In a qualitative study, Gombe et alet al’s findings revealed that PrEP discontinuation was high in women who accessed PrEP in FP clinics. After 1, 3, and 6 months post-initiation, only 41%, 24%, and 15% of all women, respectively, continued using PrEP. Most frequent reasons for discontinuation were a low perceived risk of acquiring HIV (25%), finding out that their male partner was HIV negative (24%), side effects (20%), and pill burden (17%); additionally, 7% of women reported discontinuing PrEP due to fear of intimate partner violence (IPV).In Zimbabwe, Gombe et alRoberts et alet al conducted a national survey which identified a lack of provider training as one of the main structural barriers to implementing PrEP, with <50% of FP providers answering questions on PrEP correctly.et al showed significant improvement of providers’ PrEP knowledge and confidence to identify eligible women after providing a 1.5 hour PrEP information training in public FP clinics in a high HIV prevalence area in the USA.Beima-Sofie This scoping review aimed to map and synthesise the existing literature on the integration of PrEP into FP services for women and adolescent girls; special emphasis was dedicated to barriers and facilitators when PrEP was accessed through FP services. Findings revealed multi-level barriers affecting the PrEP and SRH cascade  and its indicators at the client- as well as the provider-level. Identified barriers and enablers may affect the integration of PrEP into FP services and therefore have to be addressed by future implementation research studies and policies.In a Kenyan setting, awareness was significantly lower in younger women (<18 years), highlighting the need to find ways of specifically supporting this age group.et al’s findings revealing that a high risk perception was found to be a motivator for PrEP initiation and continuation.et alet al are currently investigating whether an interactive tablet-based education intervention can correct risk perception.Results identified a reduced risk perception to be a major barrier of PrEP interest,et al showed that being younger than 24 years of age decreased the likelihood of PrEP uptake and continuation.As a key barrier, this review revealed that particularly younger women were less likely to initiate or continue using PrEP. Mugwanya et al, establishing a daily pill routine, as well as accessible PrEP pill storage, were facilitating factors.Across settings, results identified pill burden and not being accustomed to taking pills as one of the major barriers for uptake or continuation of PrEP at the client-level.Follow-up visits, to test for HIV regularly and to provide support to continue PrEP, were also considered a barrier to PrEP uptake, which may also have an impact on the integration of PrEP in FP services.et al’s costing study was the only study that addressed this. It found that integrating PrEP into other medical or non-medical services may be an efficient strategy to reach priority populations and may have low incremental costs. However, the authors’ highlighted results were context-specific and not easily transferable to other settings.This review identified a lack of costing studies on the integration of PrEP into FP services. Roberts The facilitating role that trained providers play in improving the integration of PrEP into FP settings was emphasised by different studies across settingset al claiming that changes in policies on task sharing may be needed to enable the integration of PrEP into FP services.included task sharing or facility-specific client flow modifications . This is supported by Bhavaraju Inhibiting and enabling factors identified by this review impact on the integration of services and ultimately limit the impact oral PrEP may have when provided within FP settings. Exploiting potential synergies of both services may help to overcome barriers and enablers presented above.et alSynergy is defined as ‘the combined power of a group of things when they are working together that is greater than the total power achieved by each working separately’.This review found that research was primarily limited to Kenya and the USA, requiring more implementation of research from a variety of settings to ensure generalisability.Indicators alongside the PrEP and SRH cascade help to assess and monitor a programme’s effectiveness and to identify bottlenecks and opportunities for improvement.In the context of successful integration of services, the improvement of a programme’s cost-effectiveness through integration is often assumed.More information is needed to which extent potential facilitators may impact positively on the integration of PrEP into FP services. For example, HIVST is recommended in FP settings. In the context of PrEP delivery within these contexts, however, data especially on cost-effectiveness and client acceptability and feasibility are needed.The amount of novel data included into this review is limited since all types of articles  were included. Conference poster and abstracts were also included in this review, which made a systematic quality assessment of all studies unfeasible. Only material in English was reviewed. In LMIC, primary data mainly stemmed from three studies  which may have reduced the significance for this review’s results. Most studies were based in two countries, Kenya and the USA, which reduced generalisability of results and points to the need for research in other countries.et alMost of the included studies examined PrEP programmes delivered in the context of FP services by measuring PrEP indicators. This review found that figures on PrEP indicators  varied considerably across settings, and reasons for the variation remained unclear. For example, in LMIC, figures on uptake varied widely, ranging from 4%As a mapping and synthesis of currently available evidence in this field, this review identified barriers and facilitators for the integration of PrEP into FP services for women and adolescent girls. Multiple barriers along the PrEP and SRH cascade have an impact on clients  and providers (lack of training and knowledge) and indicate other areas needing further research. There is a need to enhance the integration of PrEP into FP services, including self-care interventions such as HIV self-testing or enhancing training of providers. Data on the integration of PrEP into FP services was limited, with most studies from Kenya and the USA. To prepare global scale-up of PrEP in FP services successfully, future studies have to be conducted in a variety of settings. As part of a comprehensive package, using a combination of PrEP and contraceptive delivery could reduce the number of new HIV infections and/or unintended pregnancies for at-risk women and girls.


Clinical research provides evidence to underpin and inform advancements in the quality of care, services and treatments. Primary care research enables the general patient population access and opportunities to engage in research studies. Nurses play an integral role in supporting the delivery of primary care research, but there is limited understanding of nurses’ experiences of this role and how they can be supported to facilitate the delivery of research.To explore the experiences of nurses delivering research studies in primary care settings.We identified studies published between 2002 and June 2021 from key electronic databases. A two-level inclusion/exclusion and arbitration process was conducted based on study selection criteria. Data extraction and quality appraisal were performed simultaneously. Data were analysed in the form of a narrative synthesis.The key themes identified included: (1) what nurses value about primary care research and their motivations for study engagement, (2) the role of nurses in research, (3) working with research teams, (4) study training, (5) eligibility screening, data collection and study documentation, (6) nurse/participant dynamic, (7) gatekeeping, (8) relationships with colleagues and impact on recruitment, (9) time constraints and workload demands, and (10) health and safety.Nurses are integral to the delivery of research studies in primary care settings. The review highlights the importance of good communication by study teams, timely and study-specific training, and support from colleagues to enable nurses to effectively deliver research in primary care. Primary care research increases opportunities for the general patient population to access studies and plays an important role in providing evidence to support improvements in patient care  Primary Care Strategy outlines a vision to embed a coherent research theme within primary care through collaboration with the NIHR and wider strategic stakeholders, to encourage and support the delivery of high-quality research in a setting accessible to almost all the population NIHR, . Howeveret al., In the United Kingdom, the day-to-day delivery of research in primary care is often nurse-led, with clinical oversight from a lead GP. Practice nurses may be an underutilised resource in the ambition to expand primary care research delivery ; grey literature ; and from reference lists of retrieved articles.The search strategy used free text and medical subject headings; see Table Inclusion criteria:Qualitative and mixed-method studiesFocus groups, interviews and surveysConducted in primary care and community settingsNurses involved in the delivery of research studiesPublished in EnglishExclusion criteria:Quantitative studiesConference abstractsResearch conducted in underdeveloped countries.Box 1.Key recommendationsNurses should be asked rather than nominated to take part in research studies.Minimise the burden of work involved in delivering research studies.Study teams should provide regular communication and a recognised point of contact.Timely and study-specific training.Good communication, and support and understanding by colleagues.Protected/funded time for research activities when possible.Awareness of inadvertently acting as a gatekeeper to patients taking part in studies.Search outputs were uploaded to Endnote 20, and duplicates were removed. References were imported to Rayyan software for a two-level inclusion/exclusion and arbitration process. Titles were screened, and full copies of relevant papers were sought. The main reviewer (AB) screened records for inclusion and the second reviewer (RP) checked decisions to see if they concurred. Any disagreements were resolved by discussion. See Figure A customised data extraction spreadsheet was developed from an adapted version of the Joanna Briggs Institute (JBI) Data Extraction Tool for Qualitative Research , individual interviews (five), surveys (two), mixed methods (three) and a systematic review (one).Most studies (eight) included nurses as their sole participants: practice nurses (two), community nurses (two), nurses employed specifically to support the delivery of studies (one), health visitors and community midwives (one), nurses conducting their own research (one) and student nurses (one); herewith referred to collectively as nurses. The remaining six studies included nurses plus other health professionals, herewith referred to as ‘nurses and other staff’.Nurses were either employed solely to work on research studies (five), or the nurses incorporated research delivery alongside their routine clinical work (eight); in the remaining study, this was unclear.What nurses value about primary care research and their motivations for engaging in research?We identified 10 key themes relating to the experience of nurses supporting research in primary care:et al., et al., Nurses appreciated the importance of primary care research and wanted to increase their knowledge and involvement in research processes , encountering conflict between their roles, being a health professional with loyalty to patients and seeking to meet the demands of the practice, plus being part of the research team and striving to meet the obligations of a study , which improved nurses’ ability to recruit and retain participants  could be influential  and limits generalisability of research findings , stipulates that nurses should practice in accordance with best available evidence and collect, treat and store all research findings befittingly NMC, . Nurse-lA possible limitation of this review is that it only includes studies written in English, potentially omitting relevant studies and contributions to the subject area.Our inclusion criteria included publications from the last 20 years, a period of significant changes to nursing roles and the healthcare system. The earlier publications could, therefore, seem less relevant. However, some of the issues identified in the earlier publications remain pertinent today and help to reinforce the relevance of the review. Evidence from the earlier publications exploring the historic experiences of nurses supporting and delivering research studies in primary care should help inform contemporary work moving forward.Nurses are integral to the delivery of primary care research studies. This review explored the experiences of nurses delivering research studies in primary care and identified potential challenges and facilitators to effective study delivery. The review highlighted the importance of good communication by study teams, timely and study-specific training, and support and understanding from colleagues. Nurses value their relationships with patients and the benefits that research participation can achieve, but some nurses may inadvertently introduce bias when considering patient suitability for trial involvement. Offering nurses protected time to conduct research tasks improves trial recruitment and reduces conflict with competing demands.


The loss of a close family member is usually assumed to be one of the most stressful experiences. In their classical work, indeed, Holmes and Rahe  classifiIn Italy, recent estimates reported more than 180.000 deaths for cancer (Italian Association of Medical Oncology, A lot of attention has been directed toward understanding psychological factors underneath grief reactions. However, bereavement theories identifying hypothetical stages of mourning have left unanswered many important questions. A major limitation of this kind of theory is the idea that grief resolution progressed in a linear fashion (Rothaupt and Becker, All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Autologous transplants were more frequently performed for Hodgkin's lymphoma as compared to non-Hodgkin's lymphoma and multiple myeloma. The use of peripheral and bone marrow stem cells was comparable. A myeloablative conditioning regimen was routinely used in patients with acute leukemia. This report provides an insight of HSCT trends in Pakistan which are different from those of Western centers contributing to transplant data from South Asia.Pakistan is the fifth most populous country with a population of 225 million and has health expenditure accounting for only 2.8 percent of gross domestic product (GDP). Accordingly, there are a limited number of haematology-oncology and transplant centers in the country. The Pakistan Blood and Marrow Transplant (PBMT) group was established in 2020, and this report is the first activity survey from January 2021 to December 2022 focusing on the trends of matched-related donor, haploidentical, and autologous transplants in a developing country. A total of 12 transplant centers contributed data on the modified PBMT survey form retrospectively and 806 haematopoietic stem cell transplants (HSCTs) were carried out during the study duration. Allogeneic HSCT constituted 595 (73.8%) of all the transplants; this is in stark contrast to Western data, where autologous HSCT accounts for the majority of transplants.  Haematopoietic stem cell transplant (HSCT) has been actively performed for the treatment of various haematological disorders since its discovery in 1957 , and in The Pakistan Blood and Marrow Transplant (PBMT) group was established in February 2020 to allow healthcare professionals and scientists in Pakistan involved in blood and marrow transplantation and related cellular therapies to collaborate and participate in promoting high-quality transplant services in the country. It has representation from all stem cell transplant centers and aims to promote and share current knowledge of all aspects of HSCT to establish, maintain, and promote the highest standards of care. The group commenced its first survey of HSCT activities in 2021 and was continued in 2022.This yearly activity will become an instrument used to observe the trends in transplant indications and transplant type, to update conditioning protocols, graft versus host disease (GvHD) prophylaxis, and infection prevention according to local and international guidelines. The survey will also compare transplant activities in Pakistan from Western countries and discuss reasons for disparity.This was a retrospective observational survey based on the data of HSCTs performed in 2021 and 2022, collected from 12 transplant centers in the country. The survey tool collected data on the main indication and stage of the disease for which a transplant was performed . Based on the type of transplant , information on the type of conditioning regimen used was also incorporated. Other variables were stem cell source and donor type. The number of HSCTs was counted as 2 in patients who had received transplants twice. Similarly, if a patient received HSCT using more than one donor source, the case was counted as a mixture that contained bone marrow (BM) and peripheral blood (PB) stem cells. We also collected data on haploidentical donor defined as a first-degree relative  with 2 or more loci mismatched at human leucocyte antigen (HLA) A, B, C, DRB1, and DQB1 in the graft versus host and/or host versus graft direction.The 12 teams and data managers who have contributed to the survey are located mainly in two provinces of the country. These include Armed Forces Bone Marrow Transplant Center (AFBMTC), Shaukat Khanum Memorial Cancer Hospital (SKMCH), Shifa International Hospital (SIH), Quaid-e-Azam International Hospital (QIH), Pakistan Institute of Medical Sciences (PIMS), Akbar Niazi Teaching Hospital (ANTH), the Children's Hospital Lahore (CHL), from the province of Punjab and Aga Khan University (AKU), National Institute of Blood Diseases (NIBD), Gambat Institute of Medical Sciences (GIMS), Dow University of Health Sciences (DUHS), and Children's Hospital Karachi (CHK) from the province of Sindh.Since no individual patient data were used, ethics committee approval was not mandated. Each center signed a data sharing agreement prior to the collection of information. All descriptive variables were analyzed using Excel and Statistical Package for the Social Sciences (SPSS) version 22.The number of allogeneic and autologous transplants performed from 2021 to 2022 across Pakistan was 595 and 211, respectively. The total match-related donor transplants were 521, while haploidentical procedures were 74 . For multiple myeloma, 40 procedures were performed while, for non-Hodgkin's (NHL) and Hodgkin's lymphoma (HL), 25 and 52 patients underwent autologous transplants, respectively, in 2021. The rest of the transplant indications are given in In 2021, transplants for acute myeloid leukemia (AML) in first complete remission (CR) were performed in 34 patients and in relapsed AML, 12 patients. Similarly, for acute lymphoid leukemia (ALL), the transplant procedure for patients in first complete remission was carried out in 30 patients and for subsequent remission in 10 patients. In 2021, approximately 70 transplants were performed for aplastic anemia, while 118 procedures were carried out for βTM in 2022. Twelve procedures were also carried out for Fanconi's anemia, while 10 patients underwent the procedure for myelodysplastic syndrome (MDS). For NHL and HL, 23 and 55 autologous transplants were carried out, respectively, and in 29 patients, transplants were completed for the diagnosis of multiple myeloma. The rest of the transplant indications are given in We performed 19 transplants for AML in the first CR and 10 for the subsequent CR in 2022. For ALL, 21 and 10 transplants were performed for patients in the first and subsequent CR. Sixty-six procedures were carried out for aplastic anemia and 88 for βTM) and haploidentical transplants.Bone marrow stem cells (BMSCs) as graft source were used in 380 patients, and in 407 patients, peripheral blood stem cells (PBSCs) were used. A bone marrow (BM) and peripheral blood (PB) stem cell mixture was used in 19 patients mainly in benign disorders  accounts for 10% of all haematological malignancies . Major dCurrently, the trend in all transplant centers has shown an increased tendency towards PBSCs as graft sources owing to faster engraftment and ease of collection despite a higher rate GvHD and decreased survival rates in patients with nonmalignant disorders . On the Myeloablative conditioning (MAC) regimens allow rapid engraftment of donor cells which may be followed in a proportion of patients by GvHD. The risk of transplant-related mortality (TRM) with MAC has decreased overtime due to improved HLA matching technology and supportive care . PatientThis report has several limitations, mainly reflecting that the data are from a retrospective, observational registry. PBMT has collected data of only those patients who underwent stem cell transplant; therefore, patients who were transplant eligible but could not undergo the procedure cannot be addressed. Secondly, we have not collected information on outcomes with respect to GvHD, transplant-related infections, progression-free survival, and overall survival. Still, this report provides directions towards further data collection processes which can be enhanced, and more parameters will be included for future analysis.β-thalassemia major and aplastic anemia were the common indications for allogeneic transplants while autologous transplant was more frequently performed for Hodgkin's lymphoma. PBSCs and BMSCs were comparable while myeloablative conditioning regimen was routinely used in transplants for acute leukemia. This report provides an insight of HSCT trends in Pakistan which are different from those of Western centers contributing to transplant data from South Asia.In summary, 806 transplant procedures were performed during the study period.


Data generated illustrative examples from these five domains.HETF members at each ISCCenters reported a range of approaches focusing on health equity in implementation research and capacity-building efforts, including (1) engaging diverse community partners/settings in making decisions about research priorities and projects; (2) applying health equity within a single TMF applied across projects or various TMFs used in specific projects; (3) evaluating health equity in operationalizing and measuring health and implementation outcomes; (4) building capacity for health equity-focused implementation science among trainees, early career scholars, and partnering organizations; and (5) leveraging varying levels of institutional resources and efforts to engage, include, and support underrepresented scholars.3 network can inform other investigators and centers’ efforts to build capacity and infrastructure to support growth and expansion of health equity-focused implementation science.Examples of approaches to integrating health equity across the ISC Over the past twenty years, the field of implementation science has contributed to identifying and understanding barriers and facilitators to implementing evidence-based practices (EBPs) in healthcare and public health service and practice and has generated evidence for effective strategies to improve adoption, implementation, sustainment, and scale-up of EBPs ,2. DespiHealth equity is the absence of avoidable, unfair, or remediable differences in health ,6. It isImplementation scientists are increasingly prioritizing an explicit focus on health equity in implementation research ,12,13. T3) in fiscal years 2019-2020  to engage clinical and community partners in research and capacity-building efforts …The HCCN Network is focused on quality improvement (QI) for federally qualified health centers (FQHCs) and look-alikes to aid in health equity. These connections provide the BRIDGE-C2 Center with strategic alignment around knowledge of QI initiatives  and electronic health record enhancements . These connections also allow the Center to leverage resources across teams for evaluation of specific interventions, survey activities and to access a cohort of clinics for deeper investigation , and understand community needs around health equity. For example, in May 2020, HCCN and BRIDGE-C2 co-designed an evaluation tool and conducted interviews with OCHIN staff about their technical assistance and QI efforts and the impacts that COVID-19 had on their direct work with community health centers. The I-Lab connects with HCCN and clinical team members through monthly meetings. This bidirectional support and community building at the leadership level offers multi-level engagement with downstream impacts particularly around health equity.”BRIDGE-C2: “Centers actively sought partner input using a wide range of methods and approaches to facilitate engagement, including pre-implementation needs assessments, key informant interviews, focus groups, user-centered design processes, feedback, and input on proposed pilot studies, as well as informal conversations. Some centers also reported that partner input and voice shaped the content and design of interventions and implementation strategies to advance health equity by integrating or adapting to their interests, priorities, and preferences on the intervention components. This included key aspects such as the length, language, terminology, and platforms used to deliver interventions and implement more equitably.Example 1.2In the first round of ISCCCE’s cancer prevention and control pilots, the I-Lab played a significant role in engaging Community Health Center (CHC) stakeholders by providing support and technical assistance as they implemented a paired cancer screening and social determinants of health pilot. This work has included building capacity and engagement with community members and/or community-based organizations (CBOs). As an example, I-Lab staff worked directly with CHC stakeholders throughout the implementation process, starting with a needs assessment with CHC teams to learn about their response to COVID, how they were addressing social determinants of health and learning about their current FIT [colorectal cancer screening] test workflows. In the guided adaptation phase of the methods pilot, the I-Lab provided implementation facilitation to CHCs to conduct data comparisons of outreach and use of the intervention. This included individuals reached for colorectal cancer screening and those who completed screening through the pilot implementation phase with the goal of identifying population groups not being reached or screened with current workflows  in order to modify strategies to reach those groups.”Harvard ISCCCE: “We asked Centers to identify how they were applying and operationalizing theories, models, or frameworks (TMFs) addressing health equity in the research projects at their Centers, including modifying existing implementation science TMFs to bring a health equity focus, or identifying TMFs from outside the field to bring an explicit health equity focus. We found that Centers were taking variable approaches to applying TMFs with a focus on equity, with some integrating a single TMF across the projects and others applying to specific aspects of pilots. A wide range of TMFs were being applied to center equity in the context of research projects, including the Health Equity Implementation Framework  and an a3 activity expanded the widely used web tool https://dissemination-implementation.org/ to help research and evaluation teams select, adapt, combine, use, and assess TMFs. The expansion led by the Colorado and Washington University ISC3s includes a new section on health equity that provides concrete examples of applying different TMFs to address equity. The webtool also integrates equity centrally into the resource by 1) coding the existing TMFs on a health construct and 2) adding key health equity TMFs to the webtool and coding them on dissemination and implementation constructs.Centers reported applying TMFs to guide assessment of implementation outcomes with a focus on equity including tracking equitable/inequitable adoption, reach, and implementation with the Reach, Effectiveness, Adoption, Implementation, Maintenance Framework (RE-AIM)[31]. Finally, in response to a noted gap in implementation science TMFs that integrate health equity, a cross-ISCExample 2.1“In a recently-funded project, a researcher from the Center will use the Health Equity Implementation Framework  to guideWU-ISCCC: Example 2.2Our approach towards operationalizing health equity-related measures into the Penn ISC3 corpus of work is broadly informed by several implementation science frameworks. The Consolidated Framework for Implementation Research (CFIR)  determin).”Penn ISC3: “Centers reported operationalizing a wide range of health and implementation outcomes and evaluating research projects with an explicit focus on health equity. This focus often related to identifying when/where there were gaps in implementation occurring across the settings and populations in which centers were engaged in research . Additionally, several Centers reported tracking gaps in both reach and representation at individual and setting level along the implementation continuum and across a range of social and setting dimensions .Example 3.1One of our investigators is developing a ‘Usable Measure for Digital Divide in the Clinical Setting’ as a methods pilot study. Digital tools can improve effectiveness and reduce healthcare barriers. However, to fully realize their potential , implementation strategies must address the digital divide challenge. The digital divide for health-related technology may be a result of various factors. At the person level, it can include motivation, personality traits , and digital skills. Social determinants of health also impact the digital divide. At the population level, this understanding will allow implementers to develop the appropriate strategies to ameliorate or eliminate disparities. Understanding these factors and their interactions is helpful for clinical implementers to address the digital divide. Our first goal is to identify electronic health record ‘markers’ for measures for the digital divide. These markers can be augmented with questions (as deemed appropriate) to allow clinical implementations to better measure and address the value of digital tools during clinical implementation.”iDAPT “Example 3.2“The aim of the pilot is to conduct a feasibility trial of the implementation of a patient-centered shared decision-making and lung cancer screening (LCS) strategy in rural primary care clinics in Colorado. This intervention package includes a formal shared decision-making process and smoking cessation support for rural primary care clinics that is aligned with Center for Medicare and Medicaid Services criteria for LCS. We are using the PRISM  and RE-AColorado ISC3: Building capacity for applying and prioritizing a focus on health equity in implementation science was discussed in relation to (1) research training and mentoring for trainees, early career and established investigators, and members of partnering organizations; and (2) developing and disseminating tools and resources to advance application of health equity in implementation science. Specific strategies to build capacity ranged from research tools to changing organizational policies. These included (1) providing access to funding and consultation for pilot grants focusing on health equity in implementation science; (2) positioning community partners as co-investigators on pilot grants related to health equity; (3) creating tools that can be widely used to support a focus on health equity in implementation science ; (4) developing organizational policies that reinforce and encourage invitation of community partners to serve as manuscript co-authors; and (5) increasing research center and institutional knowledge, attitudes and awareness by conducting seminars and meetings to develop and disseminate health equity-focused implementation research and products. Many capacity-building initiatives and strategies leveraged existing resources and training programs at the university or across the implementation science community .Example 4.1In our Center, the main ways that we build capacity for researchers to apply health equity are through mentoring relationships. This is an area where our Center works in partnership with other initiatives at Wash U to support the training and mentorship of early career researchers and those who are mid-career and shifting to a focus on implementation science. For example, the Center has a T32 and an R25 focused on training and mentorship to build pathways and opportunities for diverse scholars in implementation science. These grants allow Center members to receive training and mentoring specifically focused on implementation science and health equity. The opportunities for learning about health equity through training and webinars are typically offered through other areas of Washington University  or the broader implementation science field although our Center supports those initiatives.”WU-ISCCC: “3 program and the broader field.Several Centers also described the development and dissemination of tools and resources with the explicit goal of advancing health equity in implementation science for the ISCExample 4.2One of UW OPTICC’s signature methods is a graphical tool called causal pathway diagrams (CPDs). Each of our pilot projects uses CPDs to depict how implementation strategies work in the context in which they will be implemented. Our Center helped a trainee develop CPDs for four known barriers, which helped operationalize study content, framing, graphics that the trainee vetted with end users in rapid prototyping focus group sessions to ensure the materials were patient-centered. We oversampled minoritized populations in our end user prototyping sessions to surface different barriers that might be experienced by different groups and tailor our materials accordingly.”UW OPTICC: “3 awards to provide support for scholars and faculty who are underrepresented groups (as defined by NIH):Example 5.1“Career training pathways in the iDAPT Center can begin at varying stages: doctoral, post-doctoral, early career. At Wake Forest School of Medicine, we collaborate with the T32 NCI-funded cancer training program to identify post-doctoral fellows who are interested in participating in the iDAPT Center activities. We also offer a ’scholar in residence’ program, which includes an invitation to diverse scholars to engage with the Department and Center activities. At UMass Chan, we collaborate with the T32 NCI-funded PRACCTIS training program, the NIH K12 Cardiopulmonary Implementation Science Scholars Program, and the UMass Chan Cancer Center’s Program in Cancer Population Health Sciences to identify post-doctoral fellows and early-stage investigators interested in participating in iDAPT Center activities. Our faculty hold joint appointments at the Medical School and the Graduate School of Biomedical Sciences, allowing us to formally provide mentorship for pre-doctoral candidates, an important stage of our ‘pipeline’.”iDAPT: Centers had variable levels of institutional and research resources and efforts dedicated to engaging, training, including, supporting, and retaining scholars in implementation science from underrepresented populations . Many CCenters noted the challenges and lessons learned from their efforts thus far, including short-term and circumscribed funding opportunities, the isolated nature of remote work and challenges building a sense of academic community amidst COVID-19, and broadening the typical channels used to advertise post-doctoral training opportunities.Example 5.2Our center prioritizes supporting diverse scholars through funding and training opportunities. We sought and obtained an NCI Diversity Supplement for our Center team. While it is a strategy for providing deep support with funding to students and junior investigators, it will have limited reach at each Center as there are limitations in the number of supplement grants for diverse trainees. However, Diversity Supplements are underutilized and can really help support racially/ethnically diverse and other underrepresented scholars ranging from students to investigators.”UW OPTICC: “This report provides applied examples, shares challenges, and highlights opportunities to integrate a focus on health equity in implementation science from a national network of implementation science centers. Centers reported a wide range of approaches in applying and operationalizing health equity in research and capacity-building efforts in the early stages of center development (years 1–3 of a five-year initiative). Potential opportunities to explicitly focus on health equity in implementation science in research networks identified from the survey results included: (a) assess and/or measure the impact on health equity-related outcomes in the context of implementation science; (b) promote the use of TMFs, measures, and evaluation metrics that include a focus on health equity to allow for comparisons across contexts and populations; (c) prioritize capacity-building efforts in implementation science that engage, include and support investigators across a range of career levels and diverse backgrounds to reflect the diversity of communities impacted by cancer; and (d) share and disseminate both successes as well as challenges and lessons learned from focusing on health equity in implementation science. In the following sections, we provide recommendations for other investigators’ and centers’ efforts to build capacity and infrastructure in this area.The Conceptual Model to Advance Health Equity through Transformed Systems, led by the National Academies of Medicine Organizing Committee for Assessing Meaningful Community Engagement in Health & Health Care Programs & Policies, is a resource for community-engaged, effective, and evidence-based tools to those who want to measure engagement to ensure that it is meaningful and impactful, emphasizing equity as a critical input, process, and outcome [Engaging community partners in the earliest stages of implementation efforts and on an ongoing basis throughout implementation is a best practice for centering the voices of those most impacted and elevating a more grounded understanding of equity ,17. Howe outcome . In addiRelevant community engagement constructs and processes previously identified in implementation science, including communication, partnership exchange, community capacity-building, leadership, and collaboration , may be Another opportunity to advance a focus on health equity in implementation science is to promote the use of implementation TMFs, measures, and evaluation metrics focused on health equity ,6,13. AlWhich health equity domains do clinical, community, and public health partners prioritize across a diverse range of settings?Which TMFs developed to address health equity from outside implementation science are being leveraged with successful outcomes?What are ways to determine when implementation efforts and/or strategies have equitable impact?For research center networks, we recommend providing education, training, and mentored research opportunities for investigators interested in focusing on health equity in implementation science within the institution and across the network. To date, implementation scientists have found innovative ways to deliver and scale educational materials, training, and resources to meet a wide range of learning needs, including online modules with readings, mentored experiential learning, and video libraries . SimilarAnother significant opportunity to advance health equity in implementation science is to engage, include, and support the professional and research career growth of scholars underrepresented in the scientific workforce. Such efforts will help to increase the breadth and depth of research to reflect broader social contemporary issues and injustices . PromotiFinally, sharing challenges and lessons learned in developing research and capacity building that focuses on health equity will help identify where change and resources are needed ,47. Cent3 network has a cross-center evaluation work group that conducts annual evaluations of each center and a bi-annual social network analysis [Additional challenges of doing this work include the unintended exacerbations of inequities of implementation research. Investigator willingness to disclose and share these experiences with others can help mitigate such consequences in the future. Incorporating theories that explicitly focus on power, social inequities, and structural racism affecting communities and individuals ,48 can banalysis . These e3) to work together to accelerate the growth of health equity-focused implementation science. The Clinical and Translational Science Awards (CTSA) Program supports a national network of medical research institutions  that work together to accelerate the translational research process. One goal of the CTSA program is to disseminate innovative research programs and partnerships across institutions and communities to address health inequities and increase the reach of translational science. In addition, the Prevention Research Centers of the Centers for Disease Control and Prevention are a national network of research centers that study how communities can reduce the risk for chronic disease, with a focus on solutions that can be applied widely in marginalized populations. Together, networks with similar emphasis on implementation science and advancement of health equity may consider partnering to facilitate the large-scale dissemination of lessons learned, engage in collaborative research and training opportunities, and share effective engagement approaches. Initial ideas for innovations include hosting virtual and in-person meetings and events highlighting health equity-focused implementation methods and projects that provide explicit opportunities for community member engagement and input; such events could provide innovative research training programs that bring together mentorship, educational, and research opportunities across networks of Centers and Hubs . To take action on these ideas, partners may consider incentives and greater value and culture for collaborative achievements and co-learning, open access, and shared resources, across funded networks of health equity-focused Centers and Hubs.There is enormous potential for large research centers, research networks, and hubs across the U.S. (beyond the ISC3 program engaged in early work to develop research and build capacity for integrating health equity in implementation science. Respondents were instructed to provide illustrative case examples related to domains that were most relevant to their respective centers. The case examples presented in this report are not necessarily a comprehensive overview of health equity-focused activities across the centers, nor do they highlight all of the challenges of doing this work well. Also, while we acknowledge that majority of HETF members and co-authors on this manuscript are white female academics, there is representation in ISC3 from other groups underrepresented in science. Similar to capacity-building efforts reported by the ISC3 Centers, the ISC3 HETF actively seeks to increase engagement and inclusion of individuals underrepresented in the implementation science workforce to increase diversity of members’ perspectives.The results of this survey are from a network of seven Centers in the NCI-funded ISC3 centers reported a wide range of approaches in applying health equity in research and capacity-building efforts. Recommendations for advancing opportunities to focus on health equity in implementation science include identifying effective approaches for engaging community partners in health equity-focused implementation science; harmonizing implementation theories, models, and frameworks, measures, and metrics that include a focus on health equity; education, training, and mentored research focused on health equity in implementation science; increasing diversity and inclusion of scholars who are underrepresented in the implementation science workforce; and disseminating challenges, potential solutions, and lessons learned conducting health equity-focused implementation science. Dedicated leadership supported by strategic resources can help investigators pursue these research and capacity-building opportunities to advance health equity in implementation science.ISCAschbrenner et al. supplementary material


The relationship between climate change and adverse health impacts is driven principally the combustion of fossil fuels. Yet the health sector’s engagement with fossil fuel policy has largely been restricted to health facility decarbonisation. Health sector action can focus on three pillars;Framing fossil fuel fiscal policy as a dominant commercial determinant of health;Advocating for and co-creating systemic legislative reform; andDirect support to fossil fuel subsidy reform (FFSR).While increasing engagement in reform, the health sector must ensure that health inequities are not increased through the appropriate design of social protection mechanisms and protection guarantees for the health sector itself, especially in its service delivery capacity to most vulnerable populations.2, black carbon, methane and nitrous oxides) principally from the combustion of fossil fuels.5The WHO declared in 2018 that ‘climate change is the greatest challenge of the 21st century, threatening human health and development’.The inter-relationship between ill-health, health inequities and fossil fuels is arguably today’s single most important social determinant of health. Continued unabated fossil fuel consumption and accompanying fiscal policies should be of singular concern, especially to the health sector. Yet the health sector’s engagement with fossil fuel policy and action has, however, been largely limited to health sector decarbonisation. While this is itself an important contribution to climate change mitigation, the health sector is the source of roughly 5.2% of greenhouse gas (GHG) emissions The fossil fuel industry benefits from subsidies of US$11 million every minute, or US$5.9 trillion (6.8% of GDP) in 2020.13cobenefits of moving from fossil fuel subsidy to fossil fuel taxation.While at the COP26 in Glasgow, governments committed to phase down the use of ‘unabated’ coal power and to phase out ‘inefficient” fossil fuel subsidies, the health-specific commitments madeFossil fuels are a litmus test for whole-of-society approaches that are compelled to assess how to reduce, mitigate and manage health-harming processes and activities inherent within society, tackle adverse externalities and not view them as inevitable by-products of development. Our crossing of planetary boundaries and witnessing of the rise of non-communicable diseases and climate change-induced health impacts mean that pollution, carbon emissions and health harming products and processes are not being adequately managed at societal scale. Bearing their mounting costs is a deliberate choice. They are not technical failures but rather governance ones, including the avoidance of confronting the adverse commercial determinants of health.commercial determinant of present and future health. The BMJ and fossil fuel divestment initiative is a valuable move in this regard.Increased advocacy and action of the health sector can be built on a pre-existing platform of trust that public health professionals and institutions enjoyA second route of engagement is in the legal domain, following the July 2022 United Nations General Assembly recognition that a clean, healthy and sustainable environment is a human right. While the right to a healthy environment remains undefined in legislative terms,the right is generally understood to include substantive and procedural elements. The substantive elements include clean air; a safe and stable climate; access to safe water and adequate sanitation; healthy and sustainably produced food; non-toxic environments in which to live, work, study and play; and healthy biodiversity and ecosystems.22The development of framework legislation instruments, most critically at the national level, should be driven by coherent advocacy by the health sector, while it also advances its own environmental protection agenda. In a structured transition, forms of subsidisation should ultimately be reduced and eliminated and become replaced with taxation.Third, direct support to the fossil fuel subsidy reform (FFSR) agenda at multiple levels is required. This would highlight, above all, the health equity dimensions, which supplement and reiterate a climate justice frame. But further action is needed, as the world needs to move beyond addressing fossil fuel subsidies towards imposing fossil fuel taxes, as part of a larger carbon pricing policy arena, towards the overall aim of the correct pricing of carbon.do levy taxes on fossil fuel consumption. These, however, are wholly insufficient. For example, the Organisation for Economic Cooperation and Development (OECD) found that 97% of energy-related CO2 emissions in 2019 (outside of road transport) are taxed far below levels that would reflect their true cost, even if only considering the cost of environmental impacts.23Additional taxes on the point of sale of fossil fuels are also needed. These would internalise the external costs of their consumption. While the vast majority of countries that are fossil-fuel producers have subsidies on their sale, importantly most Subsidy reduction, elimination and implementation of taxation should initially target the most environmentally harmful pollutants and the fuels on which the poorest households are the least dependent.25While engaging in complex reform, it is imperative to recognise that although the world’s poorest communities and households are disproportionately affected by the impacts of climate change, these groups are also potentially most impacted by poorly designed reforms in the absence of social protection remediation measures. Rising costs of fuel would increase energy poverty levels in the socioeconomic groups most sensitive to price changes, potentially increasing health inequities, without offsets driven by social assistance that specifically targets affected groups. Understanding the degree of sensitivity and associated health equity implications of reform is essential, as research shows that it is inconsistent and unevenly applied.As the March 2023 IPC report