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Item A prospective observational description of frequency and timing of antenatal care attendance and coverage of selected interventions from sites in Argentina, Guatemala, India, Kenya, Pakistan and Zambia(Springer Nature, 2015) Bucher, Sherri; Marete, Irene; Tenge, Constance; Liechty, Edward A.; Esamai, Fabian; Patel, Archana; Goudar, Shivaprasad S.; Kodkany, Bhalchandra; Garces, Ana; Chomba, Elwyn; Althabe, Fernando; Barreuta, Mabel; Pasha, Omrana; Hibberd, Patricia; Derman, Richard J.; Otieno, Kevin; Hambidge, K. Michael; Krebs, Nancy F.; Carlo, Waldemar A.; Chemweno, Carolyne; Goldenberg, Robert L.; McClure, Elizabeth M.; Moore, Janet L.; Wallace, Dennis D.; Saleem, Sarah; Koso-Thomas, Marion; Pediatrics, School of MedicineBackground: The Global Network for Women’s and Children’s Health Research is one of the largest international networks for testing and generating evidence-based recommendations for improvement of maternal-child health in resource-limited settings. Since 2009, Global Network sites in six low and middle-income countries have collected information on antenatal care practices, which are important as indicators of care and have implications for programs to improve maternal and child health. We sought to: (1) describe the quantity of antenatal care attendance over a four-year period; and (2) explore the quality of coverage for selected preventative, screening, and birth preparedness components. Methods: The Maternal Newborn Health Registry (MNHR) is a prospective, population-based birth and pregnancy outcomes registry in Global Network sites, including: Argentina, Guatemala, India (Belgaum and Nagpur), Kenya, Pakistan, and Zambia. MNHR data from these sites were prospectively collected from January 1, 2010 – December 31, 2013 and analyzed for indicators related to quantity and patterns of ANC and coverage of key elements of recommended focused antenatal care. Descriptive statistics were generated overall by global region (Africa, Asia, and Latin America), and for each individual site. Results: Overall, 96% of women reported at least one antenatal care visit. Indian sites demonstrated the highest percentage of women who initiated antenatal care during the first trimester. Women from the Latin American and Indian sites reported the highest number of at least 4 visits. Overall, 88% of women received tetanus toxoid. Only about half of all women reported having been screened for syphilis (49%) or anemia (50%). Rates of HIV testing were above 95% in the Argentina, African, and Indian sites. The Pakistan site demonstrated relatively high rates for birth preparation, but for most other preventative and screening interventions, posted lower coverage rates as compared to other Global Network sites. Conclusions: Results from our large, prospective, population-based observational study contribute important insight into regional and site-specific patterns for antenatal care access and coverage. Our findings indicate a quality and coverage gap in antenatal care services, particularly in regards to syphilis and hemoglobin screening. We have identified site-specific gaps in access to, and delivery of, antenatal care services that can be targeted for improvement in future research and implementation efforts.Item Association of hemoglobin levels in the first trimester and at 26 to 30 weeks with fetal and neonatal outcomes: A secondary analyses of the Global Network for Women’s and Children’s Health’s ASPIRIN Trial(Wiley, 2021) Jessani, Saleem; Saleem, Sarah; Hoffman, Matthew K.; Goudar, Shivaprasad S.; Derman, Richard J.; Moore, Janet L.; Garces, Ana; Figueroa, Lester; Krebs, Nancy F.; Okitawutshu, Jean; Tshefu, Antoinette; Bose, Carl L.; Mwenechanya, Musaku; Chomba, Elwyn; Carlo, Waldemar A.; Das, Prabir Kumar; Patel, Archana; Hibberd, Patricia L.; Esamai, Fabian; Liechty, Edward A.; Bucher, Sherri; Nolen, Tracy L.; Koso-Thomas, Marion; Miodovnik, Menachem; McClure, Elizabeth M.; Goldenberg, Robert L.; Social and Behavioral Sciences, School of Public HealthObjective: Limited data are available from low- and middle-income countries (LMICs) on the relationship of haemoglobin levels to adverse outcomes at different times during pregnancy. We evaluated the association of haemoglobin levels in nulliparous women at two times in pregnancy with pregnancy outcomes. Design: ASPIRIN Trial data were used to study the association between haemoglobin levels measured at 6+0 -13+6 weeks and 26+0 -30+0 weeks of gestation with fetal and neonatal outcomes. Setting: Obstetric care facilities in Pakistan, India, Kenya, Zambia, The Democratic Republic of the Congo and Guatemala. Population: A total of 11 976 pregnant women. Methods: Generalised linear models were used to obtain adjusted relative risks and 95% CI for adverse outcomes. Main outcome measures: Preterm birth, stillbirth, neonatal death, small for gestational age (SGA) and birthweight <2500 g. Results: The mean haemoglobin levels at 6+0 -13+6 weeks and at 26-30 weeks of gestation were 116 g/l (SD 17) and 107 g/l (SD 15), respectively. In general, pregnancy outcomes were better with increasing haemoglobin. At 6+0 -13+6 weeks of gestation, stillbirth, SGA and birthweight <2500 g, were significantly associated with haemoglobin of 70-89 g/l compared with haemoglobin of 110-129 g/l The relationships of adverse pregnancy outcomes with various haemoglobin levels were more marked at 26-30 weeks of gestation. Conclusions: Both lower and some higher haemoglobin concentrations are associated with adverse fetal and neonatal outcomes at 6+0 -13+6 weeks and at 26-30 weeks of gestation, although the relationship with low haemoglobin levels appears more consistent and generally stronger.Item Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth(Massachusetts Medical Society, 2023) Tita, Alan T. N.; Carlo, Waldemar A.; McClure, Elizabeth M.; Mwenechanya, Musaku; Chomba, Elwyn; Hemingway-Foday, Jennifer J.; Kavi, Avinash; Metgud, Mrityunjay C.; Goudar, Shivaprasad S.; Derman, Richard; Lokangaka, Adrien; Tshefu, Antoinette; Bauserman, Melissa; Bose, Carl; Shivkumar, Poonam; Waikar, Manju; Patel, Archana; Hibberd, Patricia L.; Nyongesa, Paul; Esamai, Fabian; Ekhaguere, Osayame A.; Bucher, Sherri; Jessani, Saleem; Tikmani, Shiyam S.; Saleem, Sarah; Goldenberg, Robert L.; Billah, Sk M.; Lennox, Ruth; Haque, Rashidul; Petri, William; Figueroa, Lester; Mazariegos, Manolo; Krebs, Nancy F.; Moore, Janet L.; Nolen, Tracy L.; Koso-Thomas, Marion; A-PLUS Trial Group; Pediatrics, School of MedicineBackground: The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death. Methods: In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit. Results: A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P = 0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events. Conclusions: Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death.Item Can the date of last menstrual period be trusted in the first trimester? Comparisons of gestational age measures from a prospective cohort study in six low-income to middle-income countries(BMJ, 2023-09-20) Patel, Archana; Bann, Carla M.; Thorsten, Vanessa R.; Rao, Sowmya R.; Lokangaka, Adrien; Tshefu Kitoto, Antoinette; Bauserman, Melissa; Figueroa, Lester; Krebs, Nancy F.; Esamai, Fabian; Bucher, Sherri; Saleem, Sarah; Goldenberg, Robert L.; Chomba, Elwyn; Carlo, Waldemar A.; Goudar, Shivaprasad; Derman, Richard; Koso-Thomas, Marion; McClure, Elizabeth; Hibberd, Patricia L.; Pediatrics, School of MedicineObjectives: We examined gestational age (GA) estimates for live and still births, and prematurity rates based on last menstrual period (LMP) compared with ultrasonography (USG) among pregnant women at seven sites in six low-resource countries. Design: Prospective cohort study SETTING AND PARTICIPANTS: This study included data from the Global Network's population-based Maternal and Newborn Health Registry which follows pregnant women in six low-income and middle-income countries (Democratic Republic of the Congo, Guatemala, India, Kenya, Pakistan and Zambia). Participants in this analysis were 42 803 women, including their 43 230 babies, who registered for the study in their first trimester based on GA estimated either by LMP or USG and had a live or stillbirth with an estimated GA of 20-42 weeks. Outcome measures: GA was estimated in weeks and days based on LMP and/or USG. Prematurity was defined as GA of 20 weeks+0 days through 36 weeks+6 days, calculated by both USG and LMP. Results: Overall, average GA varied ≤1 week between LMP and USG. Mean GA for live births by LMP was lower than by USG (adjusted mean difference (95% CI) = -0.23 (-0.29 to -0.17) weeks). Among stillbirths, a higher GA was estimated by LMP than USG (adjusted mean difference (95% CI)= 0.42 (0.11 to 0.72) weeks). Preterm birth rates for live births were significantly higher when dated by LMP (adjusted rate difference (95% CI)= 4.20 (3.56 to 4.85)). There was no significant difference in preterm birth rates for stillbirths. Conclusion: The small differences in GA for LMP versus USG in the Guatemalan and Indian sites suggest that LMP may be a useful alternative to USG for GA dating during the first trimester until availability of USG improves in those areas. Further research is needed to assess LMP for first-trimester GA dating in other regions with limited access to USG.Item Communities, birth attendants and health facilities: a continuum of emergency maternal and newborn care (the global network's EmONC trial)(BMC, 2010-12-14) Pasha, Omrana; Goldenberg, Robert L.; McClure, Elizabeth M.; Saleem, Sarah; Goudar, Shivaprasad S.; Althabe, Fernando; Patel, Archana; Esamai, Fabian; Garces, Ana; Chomba, Elwyn; Mazariegos, Manolo; Kodkany, Bhala; Belizan, Jose M.; Derman, Richard J.; Hibberd, Patricia L.; Carlo, Waldemar A.; Liechty, Edward A.; Hambidge, K. Michael Michael; Buekens, Pierre; Wallace, Dennis; Howard-Grabman, Lisa; Stalls, Suzanne; Koso-Thomas, Marion; Jobe, Alan H.; Wright, Linda L.; Pediatrics, School of MedicineBackground Maternal and newborn mortality rates remain unacceptably high, especially where the majority of births occur in home settings or in facilities with inadequate resources. The introduction of emergency obstetric and newborn care services has been proposed by several organizations in order to improve pregnancy outcomes. However, the effectiveness of emergency obstetric and neonatal care services has never been proven. Also unproven is the effectiveness of community mobilization and community birth attendant training to improve pregnancy outcomes. Methods/Design We have developed a cluster-randomized controlled trial to evaluate the impact of a comprehensive intervention of community mobilization, birth attendant training and improvement of quality of care in health facilities on perinatal mortality in low and middle-income countries where the majority of births take place in homes or first level care facilities. This trial will take place in 106 clusters (300-500 deliveries per year each) across 7 sites of the Global Network for Women's and Children's Health Research in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. The trial intervention has three key elements, community mobilization, home-based life saving skills for communities and birth attendants, and training of providers at obstetric facilities to improve quality of care. The primary outcome of the trial is perinatal mortality. Secondary outcomes include rates of stillbirth, 7-day neonatal mortality, maternal death or severe morbidity (including obstetric fistula, eclampsia and obstetrical sepsis) and 28-day neonatal mortality. Discussion In this trial, we are evaluating a combination of interventions including community mobilization and facility training in an attempt to improve pregnancy outcomes. If successful, the results of this trial will provide important information for policy makers and clinicians as they attempt to improve delivery services for pregnant women and newborns in low-income countries.Item Corrigendum to The impact of risk factors on aspirin's efficacy for the prevention of preterm birth. American Journal of Obstetrics & Gynecology MFM. Volume 5, Issue 10, October 2023, 101095(Elsevier, 2024) Nuss, Emily E.; Hoffman, Matthew K.; Goudar, Shivaprasad S.; Kavi, Avinash; Metgud, Mrityunjay; Somannavar, Manjunath; Okitawutshu, Jean; Lokangaka, Adrien; Tshefu, Antoinette; Bauserman, Melissa; Tembo, Abigail Mwapule; Chomba, Elwyn; Carlo, Waldemar A.; Figueroa, Lester; Krebs, Nancy F.; Jessani, Saleem; Saleem, Sarah; Goldenberg, Robert L.; Kurhe, Kunal; Das, Prabir; Hibberd, Patricia L.; Achieng, Emmah; Nyongesa, Paul; Esamai, Fabian; Liechty, Edward A.; Bucher, Sherri; Goco, Norman; Hemingway-Foday, Jennifer; Moore, Janet; McClure, Elizabeth M.; Silver, Robert M.; Derman, Richard J.; Patel, Archana; Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas Study Group; Pediatrics, School of MedicineThe authors regret that the originally published manuscript erroneously excluded a contributing author Archana Patel MD, PhD. The authors would like to apologise for any inconvenience caused.Item Cost-effectiveness of low-dose aspirin for the prevention of preterm birth: a prospective study of the Global Network for Women's and Children's Health Research(Elsevier, 2023) Patterson, Jackie K.; Neuwahl, Simon; Goco, Norman; Moore, Janet; Goudar, Shivaprasad S.; Derman, Richard J.; Hoffman, Matthew; Metgud, Mrityunjay; Somannavar, Manjunath; Kavi, Avinash; Okitawutshu, Jean; Lokangaka, Adrien; Tshefu, Antoinette; Bose, Carl L.; Mwapule, Abigail; Mwenechanya, Musaku; Chomba, Elwyn; Carlo, Waldemar A.; Chicuy, Javier; Figueroa, Lester; Krebs, Nancy F.; Jessani, Saleem; Saleem, Sarah; Goldenberg, Robert L.; Kurhe, Kunal; Das, Prabir; Patel, Archana; Hibberd, Patricia L.; Achieng, Emmah; Nyongesa, Paul; Esamai, Fabian; Bucher, Sherri; Liechty, Edward A.; Bresnahan, Brian W.; Koso-Thomas, Marion; McClure, Elizabeth M.; Pediatrics, School of MedicineBackground: Premature birth is associated with an increased risk of mortality and morbidity, and strategies to prevent preterm birth are few in number and resource intensive. In 2020, the ASPIRIN trial showed the efficacy of low-dose aspirin (LDA) in nulliparous, singleton pregnancies for the prevention of preterm birth. We sought to investigate the cost-effectiveness of this therapy in low-income and middle-income countries. Methods: In this post-hoc, prospective, cost-effectiveness study, we constructed a probabilistic decision tree model to compare the benefits and costs of LDA treatment compared with standard care using primary data and published results from the ASPIRIN trial. In this analysis from a health-care sector perspective, we considered the costs and effects of LDA treatment, pregnancy outcomes, and neonatal health-care use. We did sensitivity analyses to understand the effect of the price of the LDA regimen, and the effectiveness of LDA in reducing both preterm birth and perinatal death. Findings: In model simulations, LDA was associated with 141 averted preterm births, 74 averted perinatal deaths, and 31 averted hospitalisations per 10 000 pregnancies. The reduction in hospitalisation resulted in a cost of US$248 per averted preterm birth, $471 per averted perinatal death, and $15·95 per disability-adjusted life year. Interpretation: LDA treatment in nulliparous, singleton pregnancies is a low-cost, effective treatment to reduce preterm birth and perinatal death. The low cost per disability-adjusted life year averted strengthens the evidence in support of prioritising the implementation of LDA in publicly funded health care in low-income and middle-income countries.Item Evaluating the effect of care around labor and delivery practices on early neonatal mortality in the Global Network's Maternal and Newborn Health Registry(Springer Nature, 2020-11-30) Patel, Archana B.; Simmons, Elizabeth M.; Rao, Sowmya R.; Moore, Janet; Nolen, Tracy L.; Goldenberg, Robert L.; Goudar, Shivaprasad S.; Somannavar, Manjunath S.; Esamai, Fabian; Nyongesa, Paul; Garces, Ana L.; Chomba, Elwyn; Mwenechanya, Musaku; Saleem, Sarah; Naqvi, Farnaz; Bauserman, Melissa; Bucher, Sherri; Krebs, Nancy F.; Derman, Richard J.; Carlo, Waldemar A.; Koso‑ThomasMcClure, Marion Elizabeth M.; Hibberd, Patricia L.; Pediatrics, School of MedicineBackground: Neonatal deaths in first 28-days of life represent 47% of all deaths under the age of five years globally and are a focus of the United Nation's (UN's) Sustainable Development Goals. Pregnant women are delivering in facilities but that does not indicate quality of care during delivery and the postpartum period. The World Health Organization's Essential Newborn Care (ENC) package reduces neonatal mortality, but lacks a simple and valid composite index that measures its effectiveness. Methods: Data on 5 intra-partum and 3 post-partum practices (indicators) recommended as part of ENC, routinely collected in NICHD's Global Network's (GN) Maternal Newborn Health Registry (MNHR) between 2010 and 2013, were included. We evaluated if all 8 practices (Care around Delivery - CAD), combined as an index was associated with reduced early neonatal mortality rates (days 0-6 of life). Results: A total of 150,848 live births were included in the analysis. The individual indicators varied across sites. All components were present in 19.9% births (range 0.4 to 31% across sites). Present indicators (8 components) were associated with reduced early neonatal mortality [adjusted RR (95% CI):0.81 (0.77, 0.85); p < 0.0001]. Despite an overall association between CAD and early neonatal mortality (RR < 1.0 for all early mortality): delivery by skilled birth attendant; presence of fetal heart and delayed bathing were associated with increased early neonatal mortality. Conclusions: Present indicators (8 practices) of CAD were associated with a 19% reduction in the risk of neonatal death in the diverse health facilities where delivery occurred within the GN MNHR. These indicators could be monitored to identify facilities that need to improve compliance with ENC practices to reduce preventable neonatal deaths. Three of the 8 indicators were associated with increased neonatal mortality, due to baby being sick at birth. Although promising, this composite index needs refinement before use to monitor facility-based quality of care in association with early neonatal mortality.Item Impact of exposure to cooking fuels on stillbirths, perinatal, very early and late neonatal mortality - a multicenter prospective cohort study in rural communities in India, Pakistan, Kenya, Zambia and Guatemala(Springer (Biomed Central Ltd.), 2015) Patel, Archana B.; Meleth, Sreelatha; Pasha, Omrana; Goudar, Shivaprasad S.; Esamai, Fabian; Garces, Ana L.; Chomba, Elwyn; McClure, Elizabeth M.; Wright, Linda L.; Koso-Thomas, Marion; Moore, Janet L.; Saleem, Sarah; Liechty, Edward A.; Goldenberg, Robert L.; Derman, Richard J.; Hambidge, K. Michael; Carlo, Waldemar A.; Hibberd, Patricia L.; Department of Pediatrics, IU School of MedicineBACKGROUND: Consequences of exposure to household air pollution (HAP) from biomass fuels used for cooking on neonatal deaths and stillbirths is poorly understood. In a large multi-country observational study, we examined whether exposure to HAP was associated with perinatal mortality (stillbirths from gestation week 20 and deaths through day 7 of life) as well as when the deaths occurred (macerated, non-macerated stillbirths, very early neonatal mortality (day 0-2) and later neonatal mortality (day 3-28). Questions addressing household fuel use were asked at pregnancy, delivery, and neonatal follow-up visits in a prospective cohort study of pregnant women in rural communities in five low and lower middle income countries participating in the Global Network for Women and Children's Health's Maternal and Newborn Health Registry. The study was conducted between May 2011 and October 2012. Polluting fuels included kerosene, charcoal, coal, wood, straw, crop waste and dung. Clean fuels included electricity, liquefied petroleum gas (LPG), natural gas and biogas. RESULTS: We studied the outcomes of 65,912 singleton pregnancies, 18 % from households using clean fuels (59 % LPG) and 82 % from households using polluting fuels (86 % wood). Compared to households cooking with clean fuels, there was an increased risk of perinatal mortality among households using polluting fuels (adjusted relative risk (aRR) 1.44, 95 % confidence interval (CI) 1.30-1.61). Exposure to HAP increased the risk of having a macerated stillbirth (adjusted odds ratio (aOR) 1.66, 95%CI 1.23-2.25), non-macerated stillbirth (aOR 1.43, 95 % CI 1.15-1.85) and very early neonatal mortality (aOR 1.82, 95 % CI 1.47-2.22). CONCLUSIONS: Perinatal mortality was associated with exposure to HAP from week 20 of pregnancy through at least day 2 of life. Since pregnancy losses before labor and delivery are difficult to track, the effect of exposure to polluting fuels on global perinatal mortality may have previously been underestimated. TRIAL REGISTRATION: ClinicalTrials.gov NCT01073475.Item Including ultrasound scans in antenatal care in low-resource settings: Considering the complementarity of obstetric ultrasound screening and maternity waiting homes in strengthening referral systems in low-resource, rural settings(Elsevier, 2019) Swanson, David L.; Franklin, Holly L.; Swanson, Jonathan O.; Goldenberg, Robert L.; McClure, Elizabeth M.; Mirza, Waseem; Muyodi, David; Figueroa, Lester; Goldsmith, Nicole; Kanaiza, Nancy; Naqvi, Farnaz; Pineda, Irma Sayury; López-Gomez, Walter; Hamsumonde, Dorothy; Bolamba, Victor Lokomba; Newman, Jamie E.; Fogleman, Elizabeth V.; Saleem, Sarah; Esamai, Fabian; Bucher, Sherri; Liechty, Edward A.; Garces, Ana L.; Krebs, Nancy F.; Hambidge, K. Michael; Chomba, Elwyn; Bauserman, Melissa; Mwenechanya, Musaku; Carlo, Waldemar A.; Tshefu, Antoinette; Lokangaka, Adrien; Bose, Carl L.; Nathan, Robert O.; Pediatrics, School of MedicineRecent World Health Organization (WHO) antenatal care recommendations include an ultrasound scan as a part of routine antenatal care. The First Look Study, referenced in the WHO recommendation, subsequently shows that the routine use of ultrasound during antenatal care in rural, low-income settings did not improve maternal, fetal or neonatal mortality, nor did it increase women's use of antenatal care or the rate of hospital births. This article reviews the First Look Study, reconsidering the assumptions upon which it was built in light of these results, a supplemental descriptive study of interviews with patients and sonographers that participated in the First Look study intervention, and a review of the literature. Two themes surface from this review. The first is that focused emphasis on building the pregnancy risk screening skills of rural primary health care personnel may not lead to adaptations in referral hospital processes that could benefit the patient accordingly. The second is that agency to improve the quality of patient reception at referral hospitals may need to be manufactured for obstetric ultrasound screening, or remote pregnancy risk screening more generally, to have the desired impact. Stemming from the literature, this article goes on to examine the potential for complementarity between obstetric ultrasound screening and another approach encouraged by the WHO, the maternity waiting home. Each approach may address existing shortcomings in how the other is currently understood. This paper concludes by proposing a path toward developing and testing such a hybrid approach.