Diagnosis and management of postpartum hemorrhage and intrapartum asphyxia in a quality improvement initiative using nurse-mentoring and simulation in Bihar, India.

BACKGROUND: In the state of Bihar, India a multi-faceted quality improvement nurse-mentoring program was implemented to improve provider skills in normal and complicated deliveries. The objective of this analysis was to examine changes in diagnosis and management of postpartum hemorrhage (PPH) of the mother and intrapartum asphyxia of the infant in primary care facilities in Bihar, during the program. METHODS: During the program, mentor pairs visited each facility for one week, covering four facilities over a four-week period and returned for subsequent week-long visits once every month for seven to nine consecutive months. Between- and within-facility comparisons were made using a quasi-experimental and a longitudinal design over time, respectively, to measure change due to the intervention. The proportions of PPH and intrapartum asphyxia among all births as well as the proportions of PPH and intrapartum asphyxia cases that were effectively managed were examined. Zero-inflated negative binomial models and marginal structural methodology were used to assess change in diagnosis and management of complications after accounting for clustering of deliveries within facilities as well as time varying confounding. RESULTS: This analysis included 55,938 deliveries from 320 facilities. About 2% of all deliveries, were complicated with PPH and 3% with intrapartum asphyxia. Between-facility comparisons across phases demonstrated diagnosis was always higher in the final week of intervention (PPH: 2.5-5.4%, intrapartum asphyxia: 4.2-5.6%) relative to the first week (PPH: 1.2-2.1%, intrapartum asphyxia: 0.7-3.3%). Within-facility comparisons showed PPH diagnosis increased from week 1 through 5 (from 1.6% to 4.4%), after which it decreased through week 7 (3.1%). A similar trend was observed for intrapartum asphyxia. For both outcomes, the proportion of diagnosed cases where selected evidence-based practices were used for management either remained stable or increased over time. CONCLUSIONS: The nurse-mentoring program appears to have built providers' capacity to identify PPH and intrapartum asphyxia cases but diagnosis levels are still not on par with levels observed in Southeast Asia and globally.

Assessment of a storage system to deliver uninterrupted therapeutic oxygen during power outages in resource-limited settings.

Access to therapeutic oxygen remains a challenge in the effort to reduce pneumonia mortality among children in low- and middle-income countries. The use of oxygen concentrators is common, but their effectiveness in delivering uninterrupted oxygen is gated by reliability of the power grid. Often cylinders are employed to provide continuous coverage, but these can present other logistical challenges. In this study, we examined the use of a novel, low-pressure oxygen storage system to capture excess oxygen from a concentrator to be delivered to patients during an outage. A prototype was built and tested in a non-clinical trial in Jinja, Uganda. The trial was carried out at Jinja Regional Referral Hospital over a 75-day period. The flow rate of the unit was adjusted once per week between 0.5 and 5 liters per minute. Over the trial period, 1284 power failure episodes with a mean duration of 3.1 minutes (range 0.08 to 1720 minutes) were recorded. The low-pressure system was able to deliver oxygen over 56% of the 4,295 power outage minutes and cover over 99% of power outage events over the course of the study. These results demonstrate the technical feasibility of a method to extend oxygen availability and provide a basis for clinical trials.

Simulation-enhanced nurse mentoring to improve preeclampsia and eclampsia care: an education intervention study in Bihar, India.

BACKGROUND: Inadequately treated, preeclampsia and eclampsia (PE/E) may rapidly lead to severe complications in both mothers and neonates, and are estimated to cause 60,000 global maternal deaths annually. Simulation-based training on obstetric and neonatal emergency management has demonstrated promising results in low- and middle-income countries. However, the impact of simulation training on use of evidence-based practices for PE/E diagnosis and management in low-resource settings remains unknown. METHODS: This study was based on a statewide, high fidelity in-situ simulation training program developed by PRONTO International and implemented in collaboration with CARE India on PE/E management in Bihar, India. Using a mixed methods approach, we evaluated changes over time in nurse mentees' use of evidence-based practices during simulated births at primary health clinics. We compared the proportion and efficiency of evidence-based practices completed during nurse mentees' first and last participation in simulated PE/E cases. Twelve semi-structured interviews with nurse mentors explored barriers and enablers to high quality PE/E care in Bihar. RESULTS: A total of 39 matched first and last simulation videos, paired by facility, were analyzed. Videos occurred a median of 62 days apart and included 94 nurses from 33 primary health centers. Results showed significant increases in the median number of 'key history questions asked,' (1.0 to 2.0, p = 0.03) and 'key management steps completed,' (2.0 to 3.0, p = 0.03). The time from BP measured to magnesium sulfate given trended downwards by 3.2 min, though not significantly (p = 0.06). Key barriers to high quality PE/E care included knowledge gaps, resource shortages, staff hierarchy between physicians and nurses, and poor relationships with patients. Enablers included case-based and simulation learning, promotion of teamwork and communication, and effective leadership. CONCLUSION: Simulation training improved the use of evidence-based practices in PE/E simulated cases and has the potential to increase nurse competency in diagnosing and managing complex maternal complications such as PE/E. However, knowledge gaps, resource limitations, and interpersonal barriers must be addressed in order to improve care. Teamwork, communication, and leadership are key mechanisms to facilitate high quality PE/E care in Bihar.

Clinical cascades as a novel way to assess physical readiness of facilities for the care of small and sick neonates in Kenya and Uganda.

BACKGROUND: Globally, there were 2.7 million neonatal deaths in 2015. Significant mortality reduction could be achieved by improving care in low- and middle-income countries (LMIC), where the majority of deaths occur. Determining the physical readiness of facilities to identify and manage complications is an essential component of strategies to reduce neonatal mortality. METHODS: We developed clinical cascades for 6 common neonatal conditions then utilized these to assess 23 health facilities in Kenya and Uganda at 2 time-points in 2016 and 2017. We calculated changes in resource availability over time by facility using McNemar's test. We estimated mean readiness and loss of readiness for the 6 conditions and 3 stages of care (identification, treatment, monitoring-modifying treatment). We estimated overall mean readiness and readiness loss across all conditions and stages. Finally, we compared readiness of facilities with a newborn special care unit (NSCU) to those without using the two-sample test of proportions. RESULTS: The cascade model estimated mean readiness of 26.3-26.6% across the 3 stages for all conditions. Mean readiness ranged from 11.6% (respiratory distress-apnea) to 47.8% (essential newborn care) across both time-points. The model estimated overall mean readiness loss of 30.4-31.9%. There was mild to moderate variability in the timing of readiness loss, with the majority occurring in the identification stage. Overall mean readiness was higher among facilities with a NSCU (36.8%) compared to those without (20.0%). CONCLUSION: The cascade model provides a novel approach to quantitatively assess physical readiness for neonatal care. Among 23 facilities in Kenya and Uganda, we identified a consistent pattern of 30-32% readiness loss across cascades and stages. This aggregate measure could be used to monitor and compare readiness at the facility-, health system-, or national-level. Estimates of readiness and loss of readiness may help guide strategies to improve care, prioritize resources, and promote neonatal survival in LMICs.

Logistical, cultural, and structural barriers to immediate neonatal care and neonatal resuscitation in Bihar, India.

BACKGROUND: In India, the neonatal mortality rate is nearly double the Sustainable Development Goal target with more than half of neonatal deaths occurring in only four states, one of which is Bihar. Evaluations of immediate neonatal care and neonatal resuscitation skills in Bihar have demonstrated a need for significant improvement. However, barriers to evidence based practices in clinical care remain incompletely characterized. METHODS: To better understand such barriers, semi-structured interviews were conducted with 18 nurses who participated as mentors in the AMANAT maternal and child health quality improvement project, implemented by CARE India and the Government of Bihar. Nurse-mentors worked in primary health centers throughout Bihar facilitating PRONTO International emergency obstetric and neonatal simulations for nurse-mentees in addition to providing direct supervision of clinical care. Interviews focused on mentors' perceptions of barriers to evidence based practices in immediate neonatal care and neonatal resuscitation faced by mentees employed at Bihar's rural primary health centers. Data was analyzed using the thematic content approach. RESULTS: Mentors identified numerous interacting logistical, cultural, and structural barriers to care. Logistical barriers included poor facility layout, supply issues, human resource shortages, and problems with the local referral system. Cultural barriers included norms such as male infant preference, traditional clinical practices, hierarchy in the labor room, and interpersonal relations amongst staff as well as with patients' relatives. Poverty was described as an overarching structural barrier. CONCLUSION: Interacting logistical, cultural and structural barriers affect all aspects of immediate neonatal care and resuscitation in Bihar. These barriers must be addressed in any intervention focused on improving providers' clinical skills. Strategic local partnerships are vital to addressing such barriers and to contextualizing skills-based trainings developed in Western contexts to achieve the desired impact of reducing neonatal mortality.

Barriers and facilitators to the provision of optimal obstetric and neonatal emergency care and to the implementation of simulation-enhanced mentorship in primary care facilities in Bihar, India: a qualitative study.

BACKGROUND: Globally, an estimated 275,000 maternal deaths, 2.7 million neonatal deaths, and 2.6 million third trimester stillbirths occurred in 2015. Major improvements could be achieved by providing effective care in low- and middle-income countries, where the majority of these deaths occur. Mentoring programs have become a popular modality to improve knowledge and skills among providers in low-resource settings. Thus, a detailed understanding of interrelated factors affecting care provision and mentorship is necessary both to improve the quality of care and to maximize the impact of mentoring programs. METHODS: In partnership with the Government of Bihar, CARE India and PRONTO International implemented simulation-enhanced mentoring in 320 primary health clinics (PHC) across the state of Bihar, India from 2015 to 2017, within the context of the AMANAT mobile nurse mentoring program. Between June and August 2016, we conducted semi-structured interviews with 20 AMANAT nurse mentors to explore barriers and facilitators to optimal care provision and to implementation of simulation-enhanced mentorship in PHCs in Bihar. Data were analyzed using the thematic content approach. RESULTS: Mentors identified numerous factors affecting care provision and mentorship, many of which were interdependent. Such barriers included human resource shortages, nurse-nurse hierarchy, distance between labor and training rooms, cultural norms, and low skill level and resistance to change among mentees. In contrast, physical resource shortages, doctor-nurse hierarchy, corruption, and violence against providers posed barriers to care provision alone. Facilitators included improved skills and confidence among providers, inclusion of doctors in training, increased training frequency, establishment of strong mentor-mentee relationships, administrative support, and nursing supervision and feedback. CONCLUSIONS: This study has identified many interrelated factors affecting care provision and mentorship in Bihar. The mentoring program was not designed to address several barriers, including resource shortages, facility infrastructure, corruption, and cultural norms. These require government support, community awareness, and other systemic changes. Programs may be adapted to address some barriers beyond knowledge and skill deficiencies, notably hierarchy, violence against providers, and certain cultural taboos. An in-depth understanding of barriers and facilitators is essential to enable the design of targeted interventions to improve maternal and neonatal survival in Bihar and related contexts.

The power of practice: simulation training improving the quality of neonatal resuscitation skills in Bihar, India.

BACKGROUND: Globally, neonatal mortality accounts for nearly half of under-five mortality, and intrapartum related events are a leading cause. Despite the rise in neonatal resuscitation (NR) training programs in low- and middle-income countries, their impact on the quality of NR skills amongst providers with limited formal medical education, particularly those working in rural primary health centers (PHCs), remains incompletely understood. METHODS: This study evaluates the impact of PRONTO International simulation training on the quality of NR skills in simulated resuscitations and live deliveries in rural PHCs throughout Bihar, India. Further, it explores barriers to performance of key NR skills. PRONTO training was conducted within CARE India's AMANAT intervention, a maternal and child health quality improvement project. Performance in simulations was evaluated using video-recorded assessment simulations at weeks 4 and 8 of training. Performance in live deliveries was evaluated in real time using a mobile-phone application. Barriers were explored through semi-structured interviews with simulation facilitators. RESULTS: In total, 1342 nurses participated in PRONTO training and 226 NR assessment simulations were matched by PHC and evaluated. From week 4 to 8 of training, proper neck extension, positive pressure ventilation (PPV) with chest rise, and assessment of heart rate increased by 14%, 19%, and 12% respectively (all p ≤ 0.01). No difference was noted in stimulation, suction, proper PPV rate, or time to completion of key steps. In 252 live deliveries, identification of non-vigorous neonates, use of suction, and use of PPV increased by 21%, 25%, and 23% respectively (all p < 0.01) between weeks 1-3 and 4-8. Eighteen interviews revealed individual, logistical, and cultural barriers to key NR skills. CONCLUSION: PRONTO simulation training had a positive impact on the quality of key skills in simulated and live resuscitations throughout Bihar. Nevertheless, there is need for ongoing improvement that will likely require both further clinical training and addressing barriers that go beyond the scope of such training. In settings where clinical outcome data is unreliable, data triangulation, the process of synthesizing multiple data sources to generate a better-informed evaluation, offers a powerful tool for guiding this process.

Observation study showed that the continuity of skin-to-skin contact with low-birthweight infants in Uganda was suboptimal.

AIM: Kangaroo mother care (KMC) is a safe and effective method of reducing neonatal mortality in resource-limited settings, but there has been a lack of data on the duration of skin-to-skin contact (SSC) in busy, low-resource newborn units. Previous studies of intermittent KMC suggest the duration of SSC ranged from 10 minutes to 17 hours per day. METHODS: This was an observational study of newborn infants born weighing less than 2000 g, which collected quantitative data on SSC over the first week after birth. The study took place in July 2016 in the newborn unit of a low-resource facility in Uganda. RESULTS: The mean daily duration of SSC over the first week after birth was three hours. This differed significantly from the World Health Organization recommendation of at least 20 hours of SSC per day. SSC was provided by mothers most of the time (73.5%), but other family members also took part, especially on the day of birth. CONCLUSION: Our study found a disappointingly low daily duration of SSC in this Ugandan newborn unit. However, advocacy and community education of SSC may help to decrease the stigma of KMC, improve overall acceptance and reduce the age at SSC initiation.

Kangaroo mother care for clinically unstable neonates weighing ≤2000 g: Is it feasible at a hospital in Uganda?

BACKGROUND: Kangaroo mother care (KMC) for stable neonates ≤2000 g (g) is associated with decreased mortality, sepsis, hypothermia, and length of stay compared to conventional care. The World Health Organization states that KMC "should be initiated… as soon as newborns are clinically stable" [12]. However, the majority of deaths occur in unstable neonates. We aimed to determine the proportion of admitted neonates meeting proposed instability criteria, assess the feasibility of providing KMC to unstable neonates, and evaluate the acceptability of this intervention to parents and providers at Jinja Regional Referral Hospital in Uganda. METHODS: This was a mixed-methods study. We recorded data including birthweight, chronological age, and treatments administered from medical charts, and calculated the percentage of clinically unstable neonates, defined as the need for ≥2 medical therapies in the first 48 hours of admission. We enrolled a sample of neonates meeting pre-defined instability criteria. Mothers were counselled to provide KMC as close to continuously as possible. We calculated the median duration of KMC per episode and per day. To explore acceptability, we conducted semi-structured interviews with parents and newborn unit care providers, and analysed data using the thematic content approach. FINDINGS: We included 254 neonates in the audit, 10 neonates in the feasibility sub-study, and 20 participants in the acceptability sub-study. Instability criteria were easily implementable, identifying 89% of neonates as unstable in the audit. The median duration of individual KMC episodes ranged from 115 to 134 minutes. The median daily duration ranged from 4.5 to 9.7 hours. Seventy-five percent of interviewees felt KMC could be used in neonates concurrently receiving other medical therapies. Barriers included lack of resources (beds/space, monitoring devices), privacy issues, inadequate education, and difficulties motivating mothers to devote time to KMC. Recommendations included staff/peer counselling, resources, family support, and community outreach. CONCLUSIONS: There remains a need for an evidence-based approach to consistently define stability criteria for KMC to improve care. We found that KMC for unstable neonates weighing ≤2000g was feasible and acceptable at Jinja Hospital in Uganda. Randomised controlled trials are needed to demonstrate the effect of KMC on survival among unstable neonates in low-resource settings.

Pulse oximetry values of neonates admitted for care and receiving routine oxygen therapy at a resource-limited hospital in Kenya.

AIM: There are 2.7 million neonatal deaths annually, 75% of which occur in sub-Saharan Africa and South Asia. Effective treatment of hypoxaemia through tailored oxygen therapy could reduce neonatal mortality and prevent oxygen toxicity. METHODS: We undertook a two-part prospective study of neonates admitted to a neonatal unit in Nairobi, Kenya, between January and December 2015. We determined the prevalence of hypoxaemia and explored associations of clinical risk factors and signs of respiratory distress with hypoxaemia and mortality. After staff training on oxygen saturation (SpO2 ) target ranges, we enrolled a consecutive sample of neonates admitted for oxygen and measured SpO2 at 0, 6, 12, 18 and 24 h post-admission. We estimated the proportion of neonates outside the target range (≥34 weeks: ≥92%; <34 weeks: 89-93%) with 95% confidence intervals (CIs). RESULTS: A total of 477 neonates were enrolled. Prevalence of hypoxaemia was 29.2%. Retractions (odds ratio (OR) 2.83, 95% CI 1.47-5.47), nasal flaring (OR 2.68, 95% CI 1.51-4.75), and grunting (OR 2.47, 95% CI 1.27-4.80) were significantly associated with hypoxaemia. Nasal flaring (OR 2.85, 95% CI 1.25-6.54), and hypoxaemia (OR 3.06, 95% CI 1.54-6.07) were significantly associated with mortality; 64% of neonates receiving oxygen were out of range at ≥2 time points and 43% at ≥3 time points. CONCLUSION: There is a high prevalence of hypoxaemia at admission and a strong association between hypoxaemia and mortality in this Kenyan neonatal unit. Many neonates had out of range SpO2 values while receiving oxygen. Further research is needed to test strategies aimed at improving the accuracy of oxygen provision in low-resource settings.

Care of the mother-infant dyad: a novel approach to conducting and evaluating neonatal resuscitation simulation training in Bihar, India.

BACKGROUND: As the global under-five mortality rate declines, an increasing percentage is attributable to early neonatal mortality. A quarter of early neonatal deaths are due to perinatal asphyxia. However, neonatal resuscitation (NR) simulation training in low-resource settings, where the majority of neonatal deaths occur, has achieved variable success. In Bihar, India, the poorest region in South Asia, there is tremendous need for a new approach to reducing neonatal morality. METHODS: This analysis aims to assess the impact of a novel in-situ simulation training program, developed by PRONTO International and implemented in collaboration with CARE India, on NR skills of nurses in Bihar. Skills were evaluated by clinical complexity of the simulated scenario, which ranged from level 1, requiring NR without a maternal complication, to level 3, requiring simultaneous management of neonatal and maternal complications. A total of 658 nurses at 80 facilities received training 1 week per month for 8 months. Simulations were video-recorded and coded for pre-defined clinical skills using Studiocode™. RESULTS: A total of 298 NR simulations were analyzed. As simulation complexity increased, the percentage of simulations in which nurses completed key steps of NR did not change, even with only 1-2 providers in the simulation. This suggests that with PRONTO training, nurses were able to maintain key skills despite higher clinical demands. As simulation complexity increased from level 1 to 3, time to completion of key NR steps decreased non-significantly. Median time to infant drying decreased by 7.5 s (p = 0.12), time to placing the infant on the warmer decreased by 21.7 s (p = 0.27), and time to the initiation of positive pressure ventilation decreased by 20.8 s (p = 0.12). Nevertheless, there remains a need for improvement in absolute time elapsed between delivery and completion of key NR tasks. CONCLUSIONS: PRONTO simulation training enabled nurses in Bihar to maintain core NR skills in simulation despite demands for higher-level triage and management. Although further evaluation of the PRONTO methodology is necessary to understand the full scope of its impact, this analysis highlights the importance of conducting and evaluating simulation training in low-resource settings based on simultaneous care of the mother-infant dyad.

Oxygen saturation ranges for healthy newborns within 24†hours at 1800†m.

There are minimal data to define normal oxygen saturation (SpO2) levels for infants within the first 24 hours of life and even fewer data generalisable to the 7% of the global population that resides at an altitude of >1500 m. The aim of this study was to establish the reference range for SpO2 in healthy term and preterm neonates within 24 hours in Nairobi, Kenya, located at 1800 m. A random sample of clinically well infants had SpO2 measured once in the first 24 hours. A total of 555 infants were enrolled. The 5th-95th percentile range for preductal and postductal SpO2 was 89%-97% for the term and normal birthweight groups, and 90%-98% for the preterm and low birthweight (LBW) groups. This may suggest that 89% and 97% are reasonable SpO2 bounds for well term, preterm and LBW infants within 24 hours at an altitude of 1800 m.

Implementation of a neonatal transcutaneous bilirubin screening programme in rural India.

BACKGROUND: Universal pre-discharge assessment of risk for neonatal hyperbilirubinaemia is recommended by the American Academy of Pediatrics. A common algorithm is universal transcutaneous bilirubin (TcB) screening, followed by confirmatory total serum bilirubin (TSB) testing for results which cause concern. There is a paucity of data on the feasibility of TcB screening in low-income settings. OBJECTIVES: To evaluate the acceptability and feasibility of implementing universal TcB screening at a resource-limited hospital in rural India, and to determine if it was associated with increased recognition of high-risk hyperbilirubinaemia. METHODS: In December 2012 at Vivekananda Memorial Hospital, Karnataka, India, universal TcB screening at 24-48 hours of life was implemented, with TSB estimated if TcB was >75th percentile for age. The proportion of families that provided consent and the proportion of infants who underwent TcB and TSB testing were calculated. The rates of phototherapy pre- and post-implementation and the rate of high-risk hyperbilirubinaemia (TSB >95th percentile for age) post-implementation among infants ≥ 35 weeks gestation were determined. RESULTS: Parents of 568 of 660 (86%) eligible infants consented to participation. All of these infants were screened with TcB. The proportion who had TSB testing was similar in the pre- (6%) and post-implementation (7%) periods. The rate of phototherapy was not significantly different after implementation (2% vs 3%). Five cases of high-risk hyperbilirubinaemia were identified post-implementation. CONCLUSIONS: The study demonstrates the acceptability and feasibility of universal TcB screening at a resource-limited hospital in rural India. In settings in which early post-discharge follow-up cannot be assured, TcB can play a valuable role in identifying infants who need evaluation.

Factors affecting breastfeeding cessation after discontinuation of antiretroviral therapy to prevent mother-to-child transmission of HIV.

In the Kisumu Breastfeeding Study (KiBS), prevention of mother-to-child HIV transmission study, highly active antiretroviral therapy (HAART) is provided from 34 weeks gestation, through delivery to six months postpartum. The study recommends that women practice exclusive breastfeeding for six months, then wean abruptly. We sought to explore factors such as, education, family support, cultural norms, and sources of information about perinatal HIV transmission, which may influence a mother's decision to comply or not comply with the study's recommendation to stop breastfeeding when HAART is discontinued. We used semi-structured interviews of a purposive sample of 18 mothers participating in the KiBS. By interviewing 10 mothers who stopped breastfeeding and eight mothers who continued, it was possible to examine how different factors may have affected the groups of participants. All participants stated that it was not traditional to stop breastfeeding at six months. Participants who stopped breastfeeding reported more family support, were more educated, and were more likely to disclose their HIV status. Participants who continued breastfeeding more often expressed concern about stigma. Participants learned about mother-to-child transmission from clinics, churches, community groups, and other HIV-positive mothers. This substudy suggests that family support, education, and cultural norms are important factors that may influence a mother's decision regarding breastfeeding cessation. Thus, counseling and family support may play integral roles in the promotion of early breastfeeding cessation.

The effect of phototherapy on neutrophils.

BACKGROUND: The role of phototherapy on neutrophils has not been reviewed previously. This novel and non-invasive therapeutic approach is of particular interest for potential use in the treatment of pathologic processes in dermatology and infectious diseases in which neutrophils are the primary culprit. OBJECTIVES: The primary aim of this study was to systematically review the role of phototherapy on neutrophils. METHOD: Original publications were identified through searches in PubMed, Medline, Ovid, and the Cochrane Library. Search terms used included "phototherapy and neutrophils," "light therapy and neutrophils," and "laser and neutrophils." Studies were selected based on the level of evidence-based research. RESULTS: The literature search revealed a total of 22 controlled laboratory studies that evaluated the role of phototherapy on neutrophils. Among the effects of phototherapy noted were increases in: the respiratory burst of neutrophils, apoptosis of polymorphonuclear cells, and plasma NO and iNOS mRNA. Other notable findings include decreased: number of neutrophils in areas of inflammation, ROS production, neutrophil anti-apoptotic factors, and IL-1beta concentration. Studies on PDT demonstrated neutrophilia and resultant decreased tumor growth. CONCLUSION: Evidence indicates that phototherapy has a significant impact on neutrophils, the effect of which varies according to the specific type of phototherapy. These findings have a variety of potential clinical applications including the treatment of various autoimmune conditions, inflammatory diseases, and cancers.