There is a shortage of radiation therapy service centers in low- to middle-income countries. TARGIT–intraoperative radiation therapy (IORT) may offer a viable alternative to improve radiation treatment efficiency and alleviate hospital patient loads. The Breast Care Unit in Johannesburg became the first facility in Africa to offer TARGIT-IORT, and the purpose of this study was to present a retrospective review of patients receiving IORT at this center between November 2017 and May 2020.Patient selection criteria were based mainly on the latest American Society of Radiation Oncology guidelines. Selection criteria included early-stage breast carcinoma  and luminal B with negative upfront sentinel lymph node biopsy that negated external-beam radiation therapy (EBRT). Patient characteristics, reasons for choosing IORT, histology, and use of oncoplastic surgery that resulted in complications were recorded.One hundred seven patients successfully received IORT/TARGIT-IORT. Mean age was 60.8 years . A total of 73.8% of patients presented with luminal A, 15.0% with luminal B, and 5.6% with triple-negative cancer. One patient who presented with locally advanced breast cancer (T4N2) opted for IORT as a boost in addition to planned EBRT. Eighty-seven patients underwent wide local excision (WLE) with mastopexy, and 12 underwent WLE with parenchymal. Primary reasons for selecting IORT/TARGIT-IORT were distance from the hospital (43.9%), choice (40.2%), and age (10.3%).This retrospective study of IORT/TARGIT-IORT performed in Africa confirms its viability, with low complication rates and no detrimental effects with breast conservation, resulting in positive acceptance and the potential to reduce Oncology Center patient loads. Limitations of the study include the fact that only short-term data on local recurrence were available. Health and socioeconomic value models must still be addressed in the African setting. Delivering a single fraction using TARGIT–intraoperative radiation therapy (IORT)  in theater after surgery reduces the need for postsurgical treatment, reduces the impact on the patient’s lifestyle, and reduces cost.3Breast cancer is one of the most common types of cancers affecting women, second to skin cancer, with a 100 times greater prevalence rate in women than in men.Key ObjectiveWhat are the results and nuances observed for patients treated at the first intraoperative radiation therapy (IORT) facility in Africa?Knowledge GeneratedThis retrospective study of IORT performed from November 2017 to May 2020 at the first IORT treating facility in Africa confirms its viability, with low complication rates , low recurrence rates , and no detrimental effects on breast conservation. No TARGIT–IORT recurrences were recorded in this study, but two IORT recurrences  were noted.RelevanceTARGIT-IORT can be a tantalizing option for patients meeting the criteria who are reluctant to travel long distances, would like to avoid numerous trips to medical facilities, and are averse to frequent cycles of external-beam radiation therapy.4 Traditional long-term studies deal primarily with recurrence rate, survival tests, and efficacy comparisons with EBRT.Although numerous studies detail the efficacy of IORT in early-stage breast carcinomas, limited information is available characterizing the post-treatment affects or detailing any nuances within the Southern Africa patient context.TARGIT-IORT has been largely adopted in developed countries, with protocols based on these countries; however, there is a paucity of data of value in middle- and lower-income countries such as South Africa. Exacerbating this problem was the complete absence of operational TARGIT-IORT equipment in Africa before November 2017.6 This has resulted in the implementation of extreme procedural measures to limit viral transmission in hospitals. However, improved cleaning procedures have led to reduced operating capacity in oncologic centers.8 Factors negatively affecting radiation treatment adherence include the requirement for COVID-19 tests before treatment, a lack of COVID-19 testing kits, the length of time it takes to receive COVID-19 test results, social distancing measures, and forced isolation.The emergence of a disease presenting with primary acute viral respiratory tract infection and other severe symptoms, which emanated from Wuhan, China, in late 2019, named COVID-19 and caused by SARS-CoV-2 infection, has resulted in a global epidemic spreading across all habitable regions.The purpose of this study was to characterize patient demographics; record multifactorial post-treatment effects such as complications, both local and those related to cardiac response; and identify early and late toxicities in adult females diagnosed with early-stage breast cancer receiving IORT/TARGIT-IORT in South Africa from November 2017 to May 2020. Subpopulation group benefits, quality of life, experiences with COVID-19 hospital protocols, and the value added by shorter treatment times compared with longer traditional EBRT procedures were also documented.9, with ethics reference number (Protocol number) 180520207.A retrospective analysis was performed on data collected from the Netcare Milpark Breast Care Unit from November 2017 to May 2020. The study investigated clinical outcomes and toxicity/adverse effects/complications associated with 107 consecutive patients (n = 107). Each patient signed an informed consent, and institutional ethics approval was obtained from Pharma-EthicsThe study population consisted of adult females displaying symptoms congruent with early-stage breast carcinoma who presented at the study site between November 2017 and May 2020. Patients presented primarily from the Southern African region.Before considering TARGIT-IORT for a patient presenting with early-stage breast cancer  detected by imaging or examination, a confirmation sentinel lymph node biopsy was performed to confirm negative lymph nodes together with other relevant factors. Patients were discussed in a multidisciplinary meeting before being assessed by specialist surgeons and radiation oncologists, who discussed applicable treatments, including advantages, disadvantages, and funding; if TARGIT-IORT was selected, informed consent was obtained. Patients choosing alternative therapies were referred to appropriate treatment facilities.10 Notably, patients who were included were those who were older than 50 years and who met the following criteria: invasive ductal carcinoma, tumor stage T1/T2, and tumor size < 3.5 cm; ductal carcinoma in situ (DCIS) was included if it was low to intermediate grade and < 2.5 cm, with resection margins > 1 cm.10 Exclusions included bilateral breast cancer at the time of diagnosis. However, any severe concomitant disease that may have limited life expectancy or a history of malignant disease did not preclude entry if the expectation of relapse-free survival at 10 years was 90% or greater.Inclusion criteria, which were more restrictive than those in the TARGIT-A trial, included patients presenting between November 2017 and May 2020 who had medical records available for review and those mainly meeting American Society of Radiation Oncology (ASTRO) guidelines.The majority of patients selected for TARGIT-IORT presented with early-stage disease and had a negative upfront sentinel lymph node biopsy, negating the need for EBRT. Patient characteristics, histology, the use of oncoplastic surgery, and any early complications were recorded.BCS with sentinel node harvesting was took place, after which TARGIT-IORT was performed using the Intrabeam system , as presented in Before each clinical case, the output of the Intrabeam mini-accelerator x-ray source (XRS) was measured using a PTW 23342 ionization chamber (IC) together with the probe adjuster/IC holder quality assurance device. The measured exposure was converted to absorbed dose to water using a factor of f = 0.881 cGy/Roentgen. Typically, a 20-Gy radiation dose at 0 mm depth is delivered to the tumor bed, with treatment times in the range of 16 to 50 min determined using the manufacturer’s calibration depth-dose curves. Iso-dose curves were verified using a special water phantom device provided by the manufacturer with a PTW-34013 soft chamber. This allowed the XRS to be mounted superiorly on the top of the phantom device with the probe intercepting the water bath; this probe could be adjusted incrementally in any three-dimensional  direction.One hundred seven patients were selected to undergo TARGIT-IORT during lumpectomy at the Breast Care Center between November 2017 and May 2020, with an average 2-year follow-up period per patient.The mean age was 60.8 years , and all patients were female. The patient and tumor characteristics are listed in Before administering the TARGIT-IORT treatment regimen, distance (43.9%) and choice (40.2%) were reported as the patients’ indication and primary reasons for opting to undergo TARGIT-IORT . PatientThe first confirmed case of COVID-19 in South Africa was reported on March 1, 2020, with a complete nationwide lockdown implemented on March 26, 2020. Five patients were treated between December 2019 and May 2020. No alterations to the TARGIT-IORT protocol were undertaken during this period. However, before surgery, patients suspected of contracting COVID-19 had to test negative to limit exposure to clinical staff.11 Conversely, a greater rise in the incidence of breast cancer was reported in developing countries  than in developed countries  in 2018.12In recent history, breast cancer mortality rates among developed countries have dropped, with the United States recording a 39% decreased mortality rate in breast cancer from 1989 to 2015.13 IORT has gained popularity in the past two decades, with multiple studies, including outcome-based studies, detailing its efficacy and noninferior results as compared with EBRT for early-stage breast cancer.21 IORT as a single fraction immediately after surgery  for early-stage small breast cancers, categorized as accelerated partial breast irradiation, has shown to produce positive cosmetic results with a single fraction of in situ RT delivered intraoperatively.22 More than 90% of recurrences of breast cancer occur at or near the tumor bed; hence, a targeted dose of radiation near the operation site should intuitively reduce the recurrence rate.24IORT is a combined modality therapy used to treat breast cancer by administering radiation directly to the tumor bed after surgery.21 The current study showed a 1.9% (two of 107) recurrence rate. In both of these cases, the patients had high grade (HG) and DCIS characteristics, suggesting that the cancer growth pattern type with HG paired with DCIS is not managed adequately with IORT and that EBRT should be offered instead. Additional studies with a longer follow-up should be undertaken to ascertain the causes and mechanisms associated with HG-DCIS recurrence rates. Although patients presenting with HG-DCIS were not included in the TARGIT-A trial, preliminary research provided evidence that TARGIT is a viable option for patients with DCIS because a low risk of additional therapy (7.3%) and a local recurrence rate of only 4.3% were reported.25Studies have revealed low local recurrence rates in standard-risk patients who received TARGIT-IORT rather than EBRT.14 Although this study provides compelling evidence, notable differences from contemporary IORT studies included the use of IOERT equipment and the visual assessment used for the evaluation of fibrosis.The Intraoperative Radiotherapy With Electrons (ELIOT) trials assessed the frequency and grade of RT–induced pulmonary fibrosis, comparing patients receiving intraoperative electron radiation therapy (IOERT) with those receiving EBRT; the results showed that 4% of the ELIOT arm versus 46% of the EBRT arm developed pulmonary fibrosis, with a higher risk-adjusted recurrence rate in the EBRT arm.14 Limitations of the study included the use of a cohort restricted to a single institution with a short follow-up time (4 years) as compared with the minimum 5 years recommended.A recent retrospective study of 127 female patients from 2009 to 2016 characterized patients treated exclusively or with TARGIT-IORT (Zeiss Intrabeam) and detailed demographics, treatment outcomes, complication rates and the feasibility of IORT as a substitute for salvage mastectomy.17 The study consisted of 3,451 patients , and it reported noninferior 5-year risk rates for local recurrence in conserved breast treatment of TARGIT-IORT verses EBRT and lower overall mortality for TARGIT-IORT (3.9% [95% CI. 2.7% to 5.8%]) compared with EBRT (5.3% [95% CI. 3.9% to 7.3%]).26 The study concluded that TARGIT-IORT was noninferior to EBRT and was a viable alternative for patients meeting the criteria, laying a scientific foundation for other efficacy trials comparing traditional cancer therapies.17 These findings were reaffirmed by the updated study and recommended TARGIT-IORT for breast carcinomas in patients ≥ 45 years of age with hormone-sensitive invasive ductal carcinoma up to 3.5 cm in size.27The TARGIT-A randomized trial, the largest noninferiority trial with 33 centers in 11 countries, tested the risk-adjusted RT of breast carcinomas between TARGIT-IORT and EBRT while reporting local occurrence rates and overall survival.28; however, it has been reported that the system requires improvement in the accuracy of the delivered dose.31 The calibration method, which was established before the start of the TARGIT-A trial (before the year 2000), has been maintained to ensure consistency of the delivered prescription dose, even though newer dosimetry protocols for photons in the kilovoltage energy range have been developed.33Treatment with the Intrabeam system has been shown to be safe and effectivePatients presenting at this study site displayed unique demographic characteristics and traveled long distances from African countries. Implementation rates of TARGIT-IORT therapies among clinicians in South Africa are low because of a lack of awareness, limited TARGIT-IORT expertise, and the complete absence of other facilities in Africa. These low adoption rates are mirrored by local medical aid funds, which results in most patients funding treatment modalities out of pocket. These factors, driven by the low socioeconomic status of the Southern African region, together with logistics, treatment funding, stigmatization of cancer, and other nonmedical-related taboos, adversely affect treatment adherence.Because of low medical aid acceptance rates, the majority of patients (> 90%) paid for their treatment, which consisted of surgical, hospital, oncology, technical, and professional fees, using their own resources, which resulted in TARGIT-IORT/IORT being available for the wealthy only. Post-treatment follow-up has yet to record a single case of post-decision dissonance related to IORT/TARGIT-IORT, and most patients recommended the procedure to peers.25 Four patients experienced hematomas, each requiring a single guided aspiration, and there was no subsequent accumulation of fluid. One patient experienced fat necrosis, but this softened up gradually over 1 year. One patient reported skin erythema, which was treated and resolved with steroid cream. One patient had both skin erythema and fat necrosis; the former was treated with steroid cream and the latter soften gradually over 1 year. The fourth patient reported cellulitis that could not be linked definitively to IORT exposure.A low complication rate of 2.8% (three of 107) was noted, and this compared well with that reported by the TARGIT-A trial of 3.3% when using a similar definition of complication rate.34 These challenges pose notable problems for patients requiring RT, such as the need to present numerous times at hospital treatment centers over a 6-week period. In particular, those meeting the TARGIT-IORT criteria are both elderly and immune compromised, which are key risk factors associated with the disease.5 Since December 2019, patients have become more amenable to IORT, because of single treatment therapy in surgery, minimized total hospital contact, and reduced risk of poor treatment adherence.The outbreak of COVID-19 adversely affected the South African health sector through the enforcement of extreme procedural changes specifically in oncologic centers, such as deep cleaning in between patient treatments, social distancing measures, 14-day quarantine rules for those testing positive for COVID-19, and timed slots that reduced the number of radiation treatments per day. Recent discussions within the radiation oncology community have highlighted the challenges affecting patient treatment, such as the patient’s frailty because of advanced disease, colocation with other patients in waiting areas, the specialized staff skill set being negatively affected, interruptions in treatments, and immune-compromised patients and palliative treatments being deprioritized.31To the best of our knowledge, before and during the study period, no other research center in Africa was able to administer TARGIT-IORT. This was determined by a comprehensive literature review, media search, verification with major manufacturers such as Carl Zeiss, international IORT conference review, and confirmation with the TARGIT-A trial team in the United Kingdom.Thirteen patients received EBRT after IORT treatment, either exclusively or in combination with endocrine therapy and/or chemotherapy. Three patients who received preoperative chemotherapy were meant to continue exclusively with EBRT but opted for IORT in combination with EBRT to reduce treatment times because they lived in rural Africa, travel was a problem, and extending treatment time was not an option. Ten patients had upstage of histology, including positive lymph nodes or human epidermal growth factor receptor 2–positive and higher oncotypes, which migrated them out of the TARGIT-A recommended guidelines hence, they required EBRT.As an estimate, more than 60% patients who presented at the study site with histologies similar to the prospective cohort before inception of TARGIT-IORT elected to have BCS. All treatment options, which included mastectomy and BCS, were presented to patients, but the majority elected breast conservation.27 Simultaneously, it is predicted that the number of new cancer cases will increase, with those in the United States projected to increase to 2.3 million (a 45% increase) by 2030.35 Factors negatively affecting newly diagnosed patients receiving adequate cancer care include a nonuniform oncology practice location, a shortage of oncologists, and lack of access to quality care.35 In this study, a critical indication for patients opting for IORT/TARGIT-IORT was distance (43.9%), although the actual travel distance from home to the radiation center was not recorded because multiple factors play a role in the concept of distance in the African environment. Patients from other sub-Saharan countries have limited access to radiation machines; they form a geographically diverse patient base with many from nonurban districts forced to travel long distances to attend radiation centers; and those in poorer socioeconomic areas lacking a regular domicile address have the added burden of transport logistics requiring various and multiple public transport services.134,36 Patients who chose TARGIT-IORT can expect to travel significantly fewer kilometers related to RT and contribute to lower carbon dioxide emissions which was reported for patients, treated in the UK, forming part of TARGIT-A trial measuring less distance traveled for treatment as compared with those undergoing EBRT.36 This retrospective cohort study took place within a 5-year period, which is insufficient time to draw meaningful conclusions related to local recurrence related and time to systemic progression; hence, additional follow-up is required. No TARGIT-IORT recurrences were recorded in this study; however, two IORT recurrences (DCIS group) were noted.TARGIT-IORT has been proven to be noninferior to traditional EBRT treatments, and subsequent research is underway to further hone its applicability, protocols, and benefits.TARGIT-IORT can be a tantalizing option for patients meeting the criteria who are reluctant to travel long distances, would like to avoid numerous trips to medical facilities, and are averse to the frequent cycles of EBRT. However, patients in the elderly subgroup (> 65 years) have reported difficulty in securing daily transport to and from oncology treatment centers because of reliance on family members, lack of adequate public transport, and lack of disposable income for private hire. Follow-on studies should investigate the long-term follow-up of the TARGIT-IORT patient group, potentially comparing this cohort with a cohort composed of EBRT patients, comparing factors such as complication rate, quality of life, and patient treatment preferences .This retrospective study of IORT performed in Africa confirms its viability, with low complication rates and no detrimental effects on breast conservation, resulting in positive acceptance and the potential to reduce Oncology Center patient loads caused by the COVID-19 pandemic. Limitations of the study include the use of only short-term data on local recurrence. Health and socioeconomic value models must still be investigated in the African setting.


To investigate whether risks of stillbirth and neonatal death differ after fresh and frozen embryo transfer (fresh and frozen-ET) compared to singletons conceived without medical assistance.Population-based cohort.Data linkage between the nationwide Medical Birth Registries in Denmark (1994-2014), Norway and Sweden (1988-2015), and national quality registries and databases on assisted reproductive technology.4,590,853 singletons, including 78,642 conceived by fresh transfer and 18,084 by frozen-ET.NoneStillbirth  and neonatal death (live born with death 0-27 days postpartum).Overall, 17,123 (0.37%) singletons were stillborn and 7,685 (0.17%) died neonatally. Compared to singletons conceived without medical assistance, the odds of stillbirth were similar after fresh and frozen-ET, while odds of neonatal death were higher after fresh  and frozen-ET .Preterm birth  was more common after fresh (8.0%) and frozen-ET (6.6%) compared to singletons conceived without medical assistance (5.0%), and strongly associated with neonatal mortality across all conception methods. Within gestational age categories, risk of stillbirth and neonatal death was similar for all conception methods, except that singletons from fresh-ET had a higher risk of stillbirth during gestational week 22-27 .Overall risk of stillbirth was similar after fresh and frozen-ET compared to singletons conceived without medical assistance, whereas neonatal mortality was higher, possibly mediated by the higher risk of preterm birth when compared to singletons conceived without medical assistance. Our results gave no clear support for choosing one treatment over the other. From its experimental beginning, assisted reproductive technology (ART) has grown into a successful treatment with >9 million children born worldwide., 2 WhilePerinatal loss, whether stillbirth or neonatal death, is a traumatic outcome for expecting couples and often associated with preterm birth, congenital malformations, and placental complications.–11StudieFurther, the increasing use of frozen-ET highlights the need to differentiate between different types of ART when assessing risk of stillbirth and neonatal death, which could not be done in most previous studies., 19, 20 Singletons conceived after both fresh-ET and frozen-ET are at increased risk of adverse perinatal outcomes, including preterm birth,, 17, 18 In this study we compared the risk of stillbirth and neonatal death in singletons born after fresh-ET and frozen-ET to singletons born without medical assistance, in a large Nordic population of births during 1988-2015. We also estimated risk according to gestational age.This study is based on the Committee of Nordic ART and Safety (CoNARTaS) cohort which includes data on all births registered in the nationwide Medical Birth Registries in Denmark 1994-2014), Norway (1984-2015) and Sweden (1985-2015).-2014, No From 198Exposures were fresh or frozen embryo transfer. Pregnancies with no ART registration was considered as conceptions without medical assistance. Our main outcomes were stillbirth and neonatal death, as defined by the Medical Birth Registry in each country. Until April 2004 in Denmark and July 2008 in Sweden, stillbirths were defined as deliveries at ≥28+0 weeks’ gestation with fetal death before or during delivery, thereafter the definition was expanded to include deliveries ≥22+0 weeks. Norway registered stillbirths delivered at ≥22+0 weeks throughout the study period. Live births were registered at any gestational age throughout the study period in all countries. Neonatal death was defined as a liveborn who died 0-27 days after birth.In pregnancies conceived without medical assistanece, gestational age was estimated from first (Denmark) or second (Norway and Sweden) trimester ultrasound examination when available, otherwise last menstrual period was used. For ART pregnancies, gestational age was estimated from embryo transfer date in Sweden. In Denmark and Norway, gestational age was estimated from ultrasound examination, or transfer date if ultrasound data were missing. We categorized gestational age as 22-27 (extremely preterm), 28-31 (very preterm), 32-36 (moderate to late preterm), 37-41 (term), and 42-44 (post-term). was calculated as weight in kilograms divided by height in meters squared. Maternal smoking habits were registered from 1999 in Norway and during the entire study period in Denmark and Sweden and was categorized as any versus no smoking during pregnancy. The number of embryos transferred in ART-conceived pregnancies were recorded in all countries during the entire study period. Culture duration in days was recorded from 1994 in Denmark, 2011 in Norway and 1985 in Sweden, and categorized as day 2-3 (cleavage stage embryo) and 5-6 (blastocyst). Placental complications included placental abruption, placenta previa and hypertensive disorders in pregnancy as described previously.Causes of death were available from the Cause of Death Registry in each country for the liveborn population. Causes of neonatal death were categorized as recommended by the World Health Organization.The first delivery after frozen-ET was registered in 1988. Eligibility was defined as all singleton deliveries in 1988 or later, with known conception method and parity, by women who gave their first birth during the study period . AdditioFor analyses of stillbirth, we included stillborn and live born singletons ≥22 weeks from Norway throughout the study period, while from Denmark and Sweden we included stillborn and live born ≥28 weeks until April 2004 and July 2008 respectively, thereafter all stillborn and live born ≥22 weeks . In totaTo analyze neonatal death, we included only live born singletons with gestational age 22-44 weeks and excluded singletons with extreme  or missing birthweights  with 95% confidence intervals (CIs). To increase interpretability, we used post estimation commands to obtain risk differences. Potential confounders were factors previously shown to influence both stillbirth or neonatal death and the need for ART. Based on available information, we made the following adjustments: year of birth (continuous), country, maternal age (continuous), and parity.We examined the consistency of results by repeating analyses in samples with 1) recorded maternal weight, height, and smoking status, where we adjusted for BMI, height, and smoking status, 2) primiparous women only, 3) ART-conceptions restricted to single embryo transfer, and 4) ART-conceptions restricted to blastocyst transfer and pregnancies conceived without medical assistance restricted to birth years when blastocyst culture was recorded. For stillbirths, we repeated the analyses in a sample restricted to deliveries ≥28 weeks to examine the potential impact of different definitions of stillbirth. To facilitate comparison with other studies, we also analyzed early neonatal deaths, defined as live born children who died 0-6 days after birth, 32, 33.To investigate whether conception method modified the impact of gestational age on risk of stillbirth and neonatal death, we repeated analyses within categories of gestational age. For stillbirth, we used ‘fetuses at risk’ as the denominator , with logistic models for categorical estimates and survival analysis for continuous gestational age. For neonIn Denmark, ethical approval is not required for anonymised registry-based research. In Norway, ethical approval was given by the Regional Committee for Medical and Health Research Ethics . In Sweden, approval was obtained from the Ethical committee in Gothenburg .Compared to pregnancies conceived without medical assistance, pregnancies after fresh and frozen-ET were at higher risk of preterm birth . In all conception groups, preterm birth was substantially more common in cases of stillbirth and neonatal death. Malformations were also common among infants who died neonatally, with higher prevalence among singletons born without medical assistance, than after fresh-ET and frozen-ET. For stillbirths, the reported prevalence of malformations was low across all conception methods, possibly due to autopsy reports being completed after birth reports are sent to the Medical Birth Registries. Placental complications were more common after fresh and frozen-ET compared to pregnancies conceived without medical assistance. This pattern was similar but with higher incidence in pregnancies ending with stillbirth or neonatal death. The main causes of neonatal death reported to the Cause of Death Registry were malformations, maternal conditions and preterm birth, where the latter two were more common after ART conception .We found no clear association between conception method and risk of stillbirth, while neonatal mortality was higher after both fresh and frozen-ET compared to singletons born without medical assistance . AdjustmIn analyses according to gestational age, the absolute risk of stillbirth was highest in term (37-41 weeks) gestations, when most deliveries occurred . For sinCompared to singletons born without medical assistance, singletons conceived after fresh and frozen-ET had an overall similar risk of stillbirth, but a higher risk of neonatal death. Apart from a higher risk of stillbirth in pregnancies after fresh-ET in weeks 22-27, we found no clear differences in associations for fresh and frozen-ET. The higher risk of neonatal death after both fresh and frozen-ET might be attributed to a higher risk of preterm birth in ART pregnancies.The lack of association between conception method and risk of stillbirth in our study is in contrast to results from a population-based study from the Netherlands, where a nearly doubled risk of stillbirth was found for any ART  compared to pregnancies conceived without medical assistance. A meta-aOur results are consistent with the limited number of previous studies on conception method and neonatal mortality, showing higher neonatal mortality after any ART,, 19, 23 We are not aware of previous studies assessing whether pregnancies after fresh and frozen-ET are more vulnerable to stillbirth or neonatal death at specific gestational ages. An Australian study compared pregnancies after any ART  to pregnancies conceived without medical assistance and found lower perinatal mortality <32 weeks. However,In the early years of our study period, slow freeze was the standard method of cryopreservation but was gradually replaced by vitrification from around 2008. In parallel culture duration shifted from cleavage stage to blastocyst before embryo freezing. A comparison of singletons from slow-frozen cleavage stage embryos vs vitrified blastocysts in Denmark and Sweden showed no difference in perinatal or neonatal death, but with very limited precision. Our senWe had no data on endometrial preparation in frozen-ET. Previous studies indicate lower risk of hypertensive disorders in pregnancies with no endometrial preparation , but simiDespite the higher risk of adverse perinatal outcomes in ART pregnancies, including preterm birth, low birthweight, and placental complications as shown previously in this study population,, 29, 41 In the country specific estimations  we foundEarly in our study period, women with ART conceptions had more antenatal visits than women conceiving without medical assistance., 44 HoweFuture studies should investigate whether indicators of infertility may improve risk stratification of pregnancies beyond current guidelines.For infertile couples and clinicians, the similar associations for fresh-ET and frozen-ET do not give reason to prefer one method over the other to prevent stillbirth or neonatal death.To our knowledge this is the largest study so far of stillbirth and neonatal mortality after fresh and frozen-ET compared to singletons conceived without medical assistance, including an additional 51,000 ART singletons born 2008-2014/2015 compared to previous Nordic registry studies., 23 The The national identity number ensured reliable data linkage and reporting to the registries is mandatory in all participating countries. Data onBecause gestational age is an intermediate factor between ART-conception and neonatal death, interpretation of our analyses of neonatal death according to gestational age requires careful consideration. In termDespite including data from three countries, statistical power was limited. Estimates according to gestational age had low precision due to the stratification itself, but also because stillbirths often had missing data on other factors, including gestational age.It should be noted that neonatal death and stillbirth rates are low in all Nordic countries, even when compared to other high-income countries, 55, 56.Our results suggest that singletons conceived by fresh and frozen embryo transfer are not at higher overall risk of stillbirth compared with pregnancies conceived without medical conceptions, though singletons after fresh-ET may be at higher risk in gestational week 22-27. Both types of ART-conception carry a higher risk of neonatal death, possibly mediated by preterm birth. The similarity of results between fresh and frozen-ET treatment, indicate that for couples in need of ART, reassurance can be provided that a frozen embryo is unlikely to increase risk of stillbirth and neonatal mortality compared with fresh transfer (and vice versa).Supplementary materialSupplementary Figures


The South African Triage Scale (SATS) is a validated in-hospital triage tool that has been innovatively adopted for use in the prehospital setting by Western Cape Government (WCG) Emergency Medical Services (EMS) in South Africa. The performance of SATS by EMS providers has not been formally assessed. The study sought to assess the validity and reliability of SATS when used by WCG EMS prehospital providers for single-patient triage.This is a prospective, assessment-based validation study among WCG EMS providers from March to September 2017 in Cape Town, South Africa. Participants completed an assessment containing 50 clinical vignettes by calculating the three components — triage early warning score (TEWS), discriminators , and a final SATS triage color. Responses were scored against gold standard answers. Validity was assessed by calculating over- and under-triage rates compared to gold standard. Inter-rater reliability was assessed by calculating agreement among EMS providers’ responses.A total of 102 EMS providers completed the assessment. The final SATS triage color was accurately determined in 56.5%, under-triaged in 29.5%, and over-triaged in 13.1% of vignette responses. TEWS was calculated correctly in 42.6% of vignettes, under-calculated in 45.0% and over-calculated in 10.9%. Discriminators were correctly identified in only 58.8% of vignettes. There was substantial inter-rater and gold standard agreement for both the TEWS component and final SATS color, but there was lower inter-rater agreement for clinical discriminators.This is the first assessment of SATS as used by EMS providers for prehospital triage. We found that SATS generally under-performed as a triage tool, mainly due to the clinical discriminators. We found good inter-rater reliability, but poor validity. The under-triage rate of 30% was higher than previous reports from the in-hospital setting. The over-triage rate of 13% was acceptable. Further clinically-based and qualitative studies are needed.Not applicable.The online version contains supplementary material available at 10.1186/s12873-021-00406-6. Medical triage is the process of systematically sorting patients based on acuity and anticipated resource need , 2. TriaSeveral in-hospital triage tools exist that are commonly used to triage undifferentiated patients on arrival to emergency departments, many with demonstrated clinical and operational benefits. In the prehospital setting, a singular, internationally-accepted tool or system for the initial triage of undifferentiated emergent patients in the field by EMS providers does not exist –3.A 2018 systematic review of in-hospital adult emergency care triage tools used in low-and-middle income countries concluded that the South African Triage Scale (SATS) had the highest quality of evidence with sensitivity and specificity of 70–75% and 91–97%, respectively . AdditioIn 2012, SATS was incorporated into routine prehospital emergency care use by the Western Cape Government (WCG) EMS system. The WCG EMS system is a public EMS system that provides 24/7 ambulance services to a catchment population of over 6 million in the Western Cape Province of South Africa . In 2017Although all cadres of EMS providers have the skills and tools to derive the SATS triage score in an ambulance, SATS was not intended for, nor formally adapted to, prehospital emergency care . To dateThe objective of this study is to assess the inter-rater reliability  and validity  of the SATS when used by WCG EMS prehospital providers for single-patient triage.The study was designed as a prospective, assessment-based validation study among WCG EMS providers from March to September, 2017 in Cape Town, South Africa.At the time of this study, foundational education for WCG EMS providers from across the Western Cape Province included a 6-week certificate courses for BLS (recently discontinued), a 12-week course for ILS (soon to be replaced with a 1-year certificate), and a 2-year (diploma) and 4-year (degree-earning) training for ALS providers . WCG EMSInitial training on the use of SATS occurred “on the job” by educators within the EMS system – however, all cadres of providers received the same SATS training. WCG EMS providers intermittently may participate in various refresher trainings, short courses, and advancement courses which are offered at the Western Cape Province College of Emergency Care several times per year. Topics at the College cover a variety of clinical and non-clinical content . All providers enrolled in courses at the College during the study period were eligible to participate in this study. One BLS, one ILS, and one ALS cohort each at the College was chosen from which study participants would be enrolled.From March to September 2017, study investigators recruited a convenience sample of 102 participants from the College. Sample size calculations were based on an intraclass correlation coefficient  of 0.2, power of 0.9, and alpha set of 0.05. None of the participants were actively enrolled in courses at the College that pertained to triage nor use of SATS . ParticiParticipants were briefed on the assessment procedures by a study investigator . Participants were individually administered the written SATS assessment under supervision of one study investigator. Participants were each given an examination booklet and a standard SATS adult color reference table  . For each clinical vignette, participants provided a TEWS value (between 0 and 17), a clinical discriminator (if applicable), and the final SATS color. Responses were manually entered into a password-protected Microsoft Excel spreadsheet Version 15.0  by a study staff member. A second research team member manually verified accurate data entry from a random selection of 10% of assessments.Reliability was assessed by inter-rater reliability, defined as level of agreement in vignette item  responses among EMS providers. Validity  was assessed using mistriage rates, defined as rates of over- or under-triage when comparing EMS raters to gold standard vignette responses.Cleaned data were exported from the Microsoft Excel spreadsheet into a statistical software program R, version 3.4.0 . Demographic data were descriptively analyzed. Vignette responses were scored in comparison to the gold standard answers to calculate the proportions of TEWS or SATS that were under, over or accurately determined , and the proportion of discriminators that were missing, correct or incorrect.A novel statistical measure of agreement, Sklar’s Omega, was used. Sklar’s Omega is a Gaussian copula-based framework that permits estimation of the degree of agreement between the EMS providers’ scores and the gold standard physicians’ scores . ConfideThe assessment was completed by 102 WCG EMS providers with mean age of 35-years (SD 7.7) and mean field experience of 6.3-years (SD 5.5)  vignette responses. The under-triage rate was 29.5%, and the over-triage rate was 13.1% (Table n = 5100) , under-calculated in 2296 (45.0%), and over-calculated in 555 (10.9%) of all vignette responses  and over-calculated in cases with gold standard SATS of orange , yellow , and green , but least-often over-calculated in cases with gold standard SATS of red .Out of 50 vignettes, 42 (84%) had at least one discriminator which was correctly identified (yes/no) in 3570 (70.0%) of all 5100 vignette responses  of cases and there was a high (30%) rate of under-triage. However, the over-triage rate was 13% which we considered acceptable, but not excellent. We based this conclusion from a report by Twomey et al. who reported that an under-triage rate of 10% and an over-triage rate of 15% were adequate when SATS was tested among South Africa in-hospital emergency physicians and nurses . In theiTEWS was often under-calculated. TEWS is an accurate predictor of need for emergency treatment, prognosis of emergency patients and identifying patients at risk for adverse outcomes. Calculation of TEWS requires two steps: first, assigning points to five physiologic parameters , mobility status, and trauma status; and second, adding all points to yield the total TEWS . TEWS waThe clinical discriminators were frequently incorrectly selected, or very often missing when one was indicated, which occurred uniformly across medical and trauma case types, and more frequently incorrect in red cases. This contributed to the overall high under-triage rate. The clinical discriminators were originally developed by the Cape Triage Group in 2006 to help identify high-risk emergency conditions that present to in-hospital front-line clinicians (emergency doctors and nurses) in South Africa , 19. ManIt was interesting to find that SATS was used reliably. Specifically, we found substantial inter-rater agreement in determination of the final SATS triage color (k = 0.71), which indicates consistency in application among EMS providers. A prior reliability study of South African in-hospital providers found comparable overall SATS kappa scores indicating substantial agreement among nurses (k = 0.66) and among physicians (k = 0.76) . Of noteBased on our findings, there are several key recommendations. First, there exists an opportunity for focused re-training of prehospital providers on clinical discriminators, with emphasis on trauma and neurologic complaints and several other frequently misused discriminators. Second, EMS providers may also benefit from re-training and reminders to help them consider the patient’s trauma and ambulatory status during calculation of the TEWS; however, this may be qualification dependent. Third, EMS providers may need computational assistance with calculation of the TEWS, and/or a re-formulation of the TEWS table to minimize the likelihood of a computational error, especially in critical (‘red’) cases. Last, the clinical discriminators may need re-formulation to be more compatible with prehospital providers’ clinical knowledge, ‘diagnostic’ capabilities and clinical context.This study utilized a written assessment rather than simulated cases or chart analysis and therefore may not reflect the true performance of SATS in the ‘live’ clinical environment. However, the artificiality of the testing environment should not affect inter-rater reliability, as the effect of the testing setting will be distributed between the group of subjects and within individual subjects. Additionally, the vignettes tested some, but not all, of the clinical discriminators or combinations of TEWS values, so findings are limited to only those tested. Analysis of results according to level of training ALS, ILS or BLS was not done due to the relatively small sample size.This study was the first assessment of validity and inter-rater reliability of prehospital SATS triage among a cohort of South African EMS providers. Overall, SATS under-performed as a prehospital triage tool. The study found good reliability, but poor validity, among EMS providers using SATS for prehospital triage in clinical vignettes. The final SATS triage color was correctly determined in only about one-half of cases. The under-triage rate of 30% was higher than previous reports from the in-hospital setting. The over-triage rate of 13% was acceptable. The high under-triage rate of SATS is attributable to under-calculation of TEWS and incorrect use of clinical discriminators. Discriminators could be better tailored to prehospital medicine. Additional clinical and qualitative studies of EMS providers are needed to fully understand the performance and use of SATS.Additional file 1.Additional file 2.


ESRD patients were selected as cases, while propensity scores for age, sex, comorbidities and year-of-surgery-matched patients without chronic kidney disease constituted the controls. Patients who had undergone eye surgery within 3 years before cataract surgery were excluded. The main outcome measures were target cataract surgery-related complications within 3 months after surgery. A total of 352 cases and 1,760 controls were analysed. Patients with ESRD had a 5.06-fold  risk of vitreous haemorrhage and a 2.74-fold  risk of re-operation for dropped nucleus or vitreous complications. Non-diabetic ESRD patients had a 3.49-fold  risk of corneal oedema. In conclusion, ESRD patients have a higher risk of vitreous haemorrhage, re-operation for dropped nucleus or vitreous complications and corneal oedema (non-diabetic patients) after cataract surgery. Pre-surgery corneal examination, surgery procedure and medication adjustment, closer and longer post-surgery follow-up may lower the risk and improve the visual outcome.This nationwide retrospective case-control study was aimed at elucidating the risk from cataract surgery in end-stage renal disease (ESRD) patients. Cataract surgery patients were identified using the diagnostic and procedural codes for International Classification of Diseases, 9 Although cataract surgery is a minor procedure, complications sometimes develop that influence the visual outcome. In particular, cataract surgery can lead to glaucoma, vitreous haemorrhage (VH), retinal detachment, intraocular dislocation, dropped nucleus, and wound dehiscence4. ESRD patients were noted to have a higher risk of cataract5. Only a few studies have reported cataract surgery-related risk in ESRD patients7, and these studies involved only a small number of patients and no control group.Patients with end-stage renal disease (ESRD) were reported to have an increased risk of complications such as bleeding, infection and perioperative mortality when they received major inpatient surgeriesThe purpose of the present study was to elucidate the risk of cataract surgery-related complications in patients receiving dialysis and to compare this risk to those in patients without chronic kidney disease (CKD) or ESRD. As such, the study may inform better patient care and improve surgical outcomes.http://nhird.nhri.org.tw/en/Data_Subsets.html). Taiwan’s National Health Insurance program currently covers more than 23 million people, representing more than 99% of the population of Taiwan. The LHID2000 was a longitudinal dataset randomly selected sample of one million health insurance beneficiaries (4.5% of Taiwan’s population) from the original NHIRD in 2000 to Dec-2013. The sample was not significantly different from the entire population in terms of age, sex, or average insured payroll-related amount. All diseases of both inpatients and outpatients were identified using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnostic and procedural codes. NHIRD is released to the public for research purposes; patient identification numbers and other sensitive personal data have been encrypted to protect individual privacy. The Institutional Review Board (IRB) of Chi Mei medical centre approved this study and waived the requirement for patients’ informed consent as part of the study approval (IRB number: 10709 –E02).This retrospective, case-control study used the Longitudinal Health Insurance Database 2000 (LHID2000), which is a subset database of the Taiwan National Health Insurance Research Database (NHIRD) provided by the Bureau of National Health Insurance of the Ministry of Health and Welfare  who had submitted medical expenditure applications for cataract removal surgery  between January 1, 2002, and December 31, 2013. To avoid potential biasing of the incidence of complications, patients who had undergone the following eye surgery procedures within 3 years before or at the same day of cataract surgery were excluded: removal of either implanted lens or pseudophakos (ICD-9-OP: 13.8), other lens operations (ICD-9-OP: 13.9), removal of foreign body from the posterior segment of the eye (ICD-9-OP: 14.0), repair of retinal detachment with scleral buckling and implant (ICD-9-OP: 14.4), other repair of retinal detachment, including that with drainage (ICD-9-OP: 14.5), removal of surgically implanted material from the posterior segment of eye (ICD-9-OP: 14.6), operations on the vitreous (ICD-9-OP: 14.7). Patients with a history of any CKD diagnosis  but not on regular dialysis and patients with history of glaucoma (ICD-9-CM: 365) were also excluded.The cases group was defined as those patients with ESRD (ICD-9 code: 585) who had been receiving either HD or PD for more than 3 months and had both catastrophic illness certification and records of medical expenditure applications. In Taiwan, patients with the certificated catastrophic illness, including ESRD, could get care for the illness or related conditions without co-payment for outpatient or inpatient care under Department of Health and Welfare guidelines via physician diagnosis. The records of medical expenditure applications were used to identify the HD  or PD .9. Figure For reducing the potential bias and understanding the individual effect of PD and HD on surgery outcome, patients who underwent both HD and PD treatments were not included. In addition, the following variables were considered as adjustment factors: hospital level, history of antiplatelet drug/anticoagulants or steroid use and B-scan ultrasonography (B-scan) examination Controls were defined as those patients undergoing cataract surgery who were not receiving dialysis therapy. One to five propensity score matching was used to reduce the potential selection bias. The propensity score was estimated from a multivariable logistic regression model with age, sex, year of surgery +/−1 year), and comorbidities within 1 year before cataract surgery, namely HTN , DM (ICD-9-CM: 250), and myopia (ICD-9-CM: 367), as covariates. This approach could consider the baseline differences between cases and controls year, an11.The outcomes of interest were complications that occurred within 3 months after the cataract surgery, identified by ICD-9 diagnosis codes that may require hospitalisation or surgical intervention, namely glaucoma (ICD-9-CM: 365), endophthalmitis , vitreous haemorrhage (VH) (ICD-9-CM: 379.23) and corneal oedema (372.10), and by ICD-9 procedure codes which were cataract reoperation-related complications: retinal detachment , intraocular lens dislocation , dropped nucleus or vitreous complications  and wound dehiscence .These complications definitions are adapted from previous studies with modification13. In addition, for matched controls, conditional logistic regression using Firth’s penalised likelihood approach was used to estimate the ORs and 95% CIs of all complications of interest between the case and control groups. To estimate the bias of rare outcome parameters, we used Firth’s penalised likelihood approach15. In addition, the stratified analysis was performed to evaluate the effect of DM and HTN. P-values < 0.05 were considered statistically significant. SAS 9.4 for Windows software  was used to carry out all the analyses.Categorical variables are presented as frequencies with percentages, and differences between the case and control groups were evaluated using the chi-square test. The logistic regression with Firth’s penalised likelihood approach was used to estimate the association risk of complications between the ESRD patients and controls for initial analysis. Considering the potential effects of multiple confounding factors to estimate the association, the disease risk scores (DRS) was used to make the compared group with similar underlying diseasesThe Research Ethics Committee of Chi Mei Medical Center approved this study and waived the requirement for patients’ informed consent as part of the study approval (IRB No.: 10709–E02).In total, 43,488 patients received cataract surgery during the 2000–2013 period; 18,961 patients were excluded according to the criteria. In the remaining 24,527 patients, 352 with ESRD were identified as the case group, and 1,760 patients with matching age, sex, and year of surgery were selected as the control group. Figure Under propensity score matching analysis, the most common cataract surgery-related complications of interest were VH (15 4.26%]) in the ESRD group and glaucoma (55 3.13%]) in the control group. The second most common complication was corneal oedema and glaucoma in the ESRD group (both being 12 [3.41%]) and corneal oedema in the control group (41 [2.33%]). Patients in ESRD group had a significant higher rate to have a VH (15 [4.26%] vs 15 [0.85%] with an odds ratio (OR) of 5.06, 95% Confidence Interval (CI): 2.36–10.87; p < 0.001) and a higher rate to have a re-operation for dropped nucleus or vitreous complications . The majority of re-operation was for vitreous complications with 10/10 in the ESRD group and 13/16 in the control group. Other complications rarely occurred with a rate less than one percent. (Table 6%) in th.13%) in Because DM and HTN are important risk factors for cataract surgery related complications, we performed the stratified analysis. Patients who have both DM and ESRD carried a significantly higher risk of VH than patients who have DM but no CKD/ESRD . Patients who were non-diabetic ESRD had a significantly higher risk of corneal oedema  and borderline increased risk of re-operation for dropped nucleus or vitreous complications  than patients without DM and CKD/ESRD.  that are more susceptible to damage.18. The Chronic Renal Insufficiency Cohort study reported that the severity of retinopathy was correlated with the level of CKD19. This correlation may have arisen because the same microvascular damage process causes both retinopathy and nephropathy. Besides, the higher rate of retinal vein occlusion and age-related macular degeneration in ESRD patients may also contribute to the increased risk of VH after cataract surgery21.VH is the extravasation of blood into space within or near the vitreous body. It can be caused by retinal trauma, abnormal retinal neovascularization, and bleeding from other eye structures due to age-related macular degeneration or choroidal melanoma. In particular, abnormal retinal neovascularisation can occur as a result of diabetic retinopathy, retinal vein occlusion and other rare diseases. Several studies have shown a close association between retinal disorders and CKD in hypertensive patients both with and without DMet al.22 and they suggested that these alterations may contribute to the retinal complications after cataract surgery. In ESRD patients, changes in intraocular pressure (IOP)25 and ocular structures27 during HD were reported in different studies. The ocular structure changes include decrease in choroidal thickness and retina thickness after HD. The changes of colloid osmotic pressure caused by uraemia toxin and fluid removal during HD was considered the explanation for intradialytic IOP and ocular structure changes, which may predispose ESRD patient to have VH after cataract surgery.Alterations to the composition of vitreous humour in pseudophakic eyes after cataract surgery was discovered by Neal 28 .It is most often caused by platelet dysfunction, but also by renal anaemia and antiplatelet drugs for medical comorbidities. Anticoagulant treatment during HD to prevent dialysis circuit clotting may further lead ESRD patients to bleed29.The bleeding tendency in patients with uraemia has been known for decades30, but less CD with no polymegethism and pleomorphism in HD patients was demonstrated in another study31. In both studies, patients with DM were excluded, the difference in patient age and race between the two studies might cause the conflicting results. Our finding of increased corneal oedema in non-diabetic ESRD patients after cataract surgery might be explained by the susceptibility to damage from the altered structure of corneal EC. On the other side, the underlying special diabetic ketrotopathy in DM patients may explain the insignificant difference between diabetic ESRD patients and DM matched controls32.Several studies had compared the corneal EC in HD patients with those in normal controls. Polymegethism and pleomorphism of corneal EC with normal cell density (CD) in HD patients was reported in one studyThe strengths of the present study included a matched control group; consideration of antiplatelet drugs/anticoagulants as a variable and more case numbers. Nonetheless, our study had several limitations. Firstly, we did not know the severity of cataracts, which is related to surgery difficulty and associated complications. However, we tried to evaluate it by checking the numbers of patients who received B-mode ocular ultrasound before surgery date because it is usually arranged when the cataract is too severe to check the fundus as a pre-operation evaluation. Secondly, we could not verify that the complication code was recorded in the eye that underwent surgery. To reduce the bias, we shortened the follow-up period to 3 months. Thirdly, our 3-month follow-up period did not include the information about late onset complications such as late onset IOL dislocation. Fourthly, we did not know whether the antiplatelet drugs/anticoagulants were adjusted after surgery.Although cataract surgery is a minor procedure, ESRD patients still carry a higher risk of VH and re-operation for vitreous complications. Upon our study results, we suggested ophthalmologists could communicate with nephrologists regarding possible anticoagulant-free HD for at least 2 months after cataract surgery; this may decrease the risk of VH and improve the visual outcome. Moreover, examination of cornea before cataract surgery in ESRD patients and adjustment of surgery procedure might avoid or attenuate the corneal oedema after surgery.


Young people are disproportionately impacted by HIV infection and exhibit poor HIV care continuum outcomes. Mobile health  interventions are promising approaches to meet the unique needs of young people living with HIV. Youth-focused interventions are needed to improve HIV care continuum outcomes.This study assessed the preliminary efficacy and impact of a digital HIV care navigation intervention among young people living with HIV in San Francisco. Health electronic navigation (eNavigation or eNav) is a 6-month, text message–based, digital HIV care navigation intervention, in which young people living with HIV are connected to their own HIV care navigator through text messaging to improve engagement in HIV primary care.This study had a single-arm, prospective, pre-post design. The analysis included 120 young men who have sex with men or transwomen living with HIV aged between 18 and 34 years. We analyzed self-reported sociobehavioral information pre- and postintervention at baseline and 6 months, which was collected using computer-assisted self-interviewing surveys. We characterized the sample and built generalized estimating equation (GEE) models to assess differences in HIV care continuum outcomes at baseline and 6 months.21=4.68, P=.03). More than half of the sample reported taking antiretroviral therapy  and having an undetectable viral load . The 6-month follow-up surveys were completed by 73.3% (88/120) of participants, and these participants were not characteristically different from the overall sample at baseline. GEE models indicated that participants had increased odds of viral suppression at 6 months as compared with baseline. No relevant additive or multiplicative interactions were noted on comparing outcome effects over time according to intervention completion.The characteristics according to the intervention completion status were not different from those of the overall sample. The mean age of the participants was 27.75 years (SD 4.07). Most participants  identified as men, and the sample was racially/ethnically diverse. At baseline, majority  of the participants had recently received primary HIV care, yet this was more likely in those who completed the intervention than in those who did not (54/60, 90% vs 45/60, 75%; χDigital HIV care navigation fills a critical gap in public health and HIV care systems, making these systems more responsive and accountable to the needs of the most vulnerable individuals. Our intervention bridges the time between primary care visits with interactive, tailored, personalized, and peer-delivered social support; information; and motivational interviewing to scaffold behavioral change. This study is part of the next wave of system-informed mHealth intervention research that will offer potentially disruptive solutions to traditional in-person delivered interventions and improve the health of the most vulnerable individuals.RR2-10.2196/16406 HIV remains a pressing public health issue, with over a million people in the United States living with HIV . AlthougMobile health  interventions have greatly increased over the last decade. A systematic review of systematic reviews identified 23 systematic reviews representing more than 10,000 scientific articles and involving close to 80,000 participants in 371 mHealth studies . Yet, evHealth electronic navigation (eNavigation or eNav) is a 6-month, text message–based, digital HIV care navigation intervention, in which young people living with HIV are connected to their own HIV care navigator through text messaging to improve engagement in HIV primary care. The intervention includes delivery of the following: (1) HIV care navigation, (2) health promotion and education, (3) motivational interviewing, and (4) social support. HIV care navigation guides participants in knowing where, when, and how to access all health and related services, and increases access to appropriate resources  . Health All procedures were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study protocol was approved by the Institutional Review Board of the University of California, San Francisco (IRB #16-19675).Data for the present analysis were collected from the Health eNav study at San Francisco Department of Public Health 2017-2018). Health eNav is a digital care navigation intervention designed to improve HIV care continuum outcomes among young men who have sex with men and transwomen living with HIV. A digital care navigator delivered the intervention via two-way SMS text messaging. This study had a single-arm, prospective, pre-post design. Study procedures are described in-depth in a prior manuscript [. Health Eligibility criteria for the study were as follows: identifying as a man who has sex with men or a transwoman; being between the ages of 18 and 34 years; and being newly diagnosed with HIV, not being engaged/retained in HIV care, or having a detectable viral load. Participants were recruited via convenience sampling from five clinics and community-based organizations in San Francisco serving young people living with HIV. If eligible, participants visited research staff at study offices within the San Francisco Department of Public Health, where informed consent was obtained. Of 170 individuals screened, 140 were eligible. However, 20 were subsequently lost to follow-up and were not enrolled. The final sample had 120 young men who have sex with men or transwomen living with HIV.Data for this analysis were collected using computer-assisted self-interviewing (CASI) surveys. Instruments collected self-reported sociobehavioral information pre- and postintervention at baseline and 6 months.We assessed age at interview (in years), gender identity (transwoman vs man), race/ethnicity , and education level . We also examined the current living situation, defined as stable (owning or renting a house or apartment) or unstable . Income was classified as earning US $0 to 250, US $251 to 600, US $601 to 1300, or US $1301 or more in the last month. Finally, we assessed history of incarceration.We defined intervention completion as retention in the 6-month intervention. Among the 120 participants enrolled in the intervention, 60 were lost to follow-up and did not complete the 6-month intervention. The most common reason for loss to follow-up during the intervention was unknown , followed by participant phone loss , moving out of jurisdiction , incarceration , withdrawal , and death from causes unrelated to intervention participation . For participants who lost their phones, a maximum of one phone replacement was provided during the intervention. Participants who again lost their phones were unable to complete the intervention. The intervention completion status was dichotomously coded as “yes (1)” if participants completed the 6-month intervention and “no (0)” if they did not complete the intervention.Self-reported HIV care outcome data were collected using CASI surveys. In accordance with HIV care goals designated in 90-90-90 objectives [t test). As every participant received the digital care navigation intervention, we analyzed HIV care continuum outcome effects for all participants over the 6-month follow-up period. We produced three models using generalized estimating equations (GEEs) to account for within-subject correlations and to calculate the odds of HIV care continuum outcomes for the 6-month follow-up compared with baseline.Initially, we characterized the sample by describing baseline sociodemographics and self-reported HIV care continuum outcomes using baseline CASI data. Differences in baseline sociodemographics and outcomes on comparing participants who completed the intervention and those who did not were analyzed with bivariate statistical tests  and computed stratum-specific results. Initially, outcome odds or prevalences from the GEE models with interaction terms were converted to probabilities. We then calculated probability ratios for multiplicative interactions , probability differences for additive interactions , and stratum-specific differences . We reported statistically significant stratum-specific results and statistically significant interactions between intervention completion and time. All statistical analyses were performed using Stata 14  ; compari21=4.36, P=.04).21=4.68, P=.03). More than half of the sample reported taking ART  and having an undetectable viral load   of the participants had recently received primary HIV care, yet this was more likely in those who completed the intervention than in those who did not complete the intervention  .The 6-month follow-up surveys were completed by 73.3% (88/120) of participants , and theOur findings suggest that digital HIV care navigation is effective at promoting viral suppression at post-test compared with pretest. While many mHealth interventions developed for youth and young adults living with HIV are increasingly utilizing methods that leverage automated functionalities , Health eNav demonstrates the importance of real-time bidirectional interaction with an interventionist using text messaging. In other research, we found that digital HIV care navigation is feasible and acceptable and, in particular, responsive to the diverse needs of young people living with HIV in a metropolitan city with complex structural barriers . DespiteThe findings should be interpreted with some limitations in mind. This study had a single-arm, prospective, pre-post design. Future studies using more robust study designs with randomization of participants to multiple study arms are needed to develop a cogent understanding of the short- and long-term efficacies of digital HIV care navigation. Additionally, future analyses that examine dose-response or employ just-in-time stepped wedge designs may offer more dynamic and responsive flexibility to the study population of young men who have sex with men and transwomen living with HIV. These individuals not only are the most vulnerable to HIV acquisition and the most likely to have poor HIV care continuum outcomes, but also face multiple structural barriers and complex stigma. While adolescence and young adulthood are already dynamic critical periods, for sexual and gender minorities living with HIV, the situation is exacerbated by intersectional stigma. More research on the understanding of how the critical axes of race, sexuality, gender identity, and HIV interact is needed. mHealth interventions addressing intersectional stigma must be developed.Despite the study limitations, digital HIV care navigation fills a critical gap in public health and HIV care systems, making these systems more responsive and accountable to the needs of the most vulnerable individuals. Our intervention bridges the time between primary care visits with interactive, tailored, personalized, peer-delivered social support; information; and motivational interviewing to scaffold behavioral changes, such as ART adherence. This study is part of the next wave of system-informed mHealth intervention research that will offer potentially disruptive solutions to traditional in-person delivered interventions and improve the health of the most vulnerable individuals. For ending the HIV epidemic in San Francisco, the United States, and globally, novel applications of low-tech hi-touch mHealth technologies, such as digital HIV care navigation, should be considered.


Use of SMS for data collection is expanding, but coverage, bias, and logistical constraints are poorly described.The aim of this study is to assess the use of SMS to capture clinical outcomes that occur at home and identify potential biases in reporting compared to in-person ascertainment.In the PrEP Implementation in Young Women and Adolescents program, which integrated pre-exposure prophylaxis (PrEP) into antenatal care, postnatal care, and family planning facilities in Kisumu County, Kenya, HIV-negative women 14 years of age or older were offered oral HIV self-tests (HIVSTs) to take home to male partners. Women that brought a phone with a Safaricom SIM to the clinic were offered registration in an automated SMS system (mSurvey) to collect information on HIVST outcomes. Women were asked if they offered the test to their male partners, and asked about the test process and results. HIVST outcomes were collected via SMS (sent 2.5 weeks later), in-person (if women returned for a follow-up scheduled 1 month later), or using both methods . The SMS prompted women to reply at no charge. HIVST outcomes were compared between women with scheduled follow-up visits and those without (follow-up visits were only scheduled for women who initiated PrEP). HIVST outcomes were also compared between women reporting via SMS and in-person.P=.31), partners using the HIVST , women using HIVST with partners , and seeing partner’s HIVST results  were similar between women reporting in-person only versus by SMS only. However, frequency of reports of experiencing harm or negative reactions from partners was more commonly reported in the SMS group . Barriers to the SMS system registration included not having a Safaricom SIM or a functioning phone.Among 2123 women offered HIVSTs and mSurvey registration, 486 (23.89%) accepted HIVSTs, of whom 359 (73.87%) were eligible for mSurvey. Additionally, 76/170 (44.7%) women with scheduled follow-up visits and 146/189 (77.3%) without scheduled follow-up visits registered in mSurvey. Among the 76 women with scheduled follow-ups, 62 (82%) had HIVST outcomes collected: 19 (31%) in-person, 20 (32%) by SMS, and 23 (37%) using both methods. Among the 146 women without scheduled visits, 87 (59.6%) had HIVST outcomes collected: 3 (3%) in-person, 82 (94%) by SMS, and 2 (2%) using both methods. SMS increased the collection of HIVST outcomes substantially for women with scheduled follow-up visits (1.48-fold), and captured 82 additional reports from women without scheduled follow-up visits. Among 222 women with reported HIVST outcomes, frequencies of offering partners the HIVST (85/95, 89% in-person vs 96/102, 94% SMS; Our results suggest that the use of SMS substantially improves completeness of outcome data, does not bias reporting of nonsensitive information, and may increase reporting of sensitive information.   SMS has enormous potential for public health. This technology is inexpensive and has increasing reach with expanding global cellular network coverage and phone ownership. SMS has been used to provide reminders ,2, returStudies in low- and middle-income countries comparing SMS to other data collection approaches or offering choices in approaches are limited -10. SomeFrom November 20, 2017, to June 15, 2018, 3425 women seeking antenatal care (ANC), postpartum care (PNC), or family planning (FP) services at 8 facilities in Kisumu County, Kenya were asked to take an HIVST home to their male partners as part of a pre-exposure prophylaxis (PrEP) implementation program. Women were offered PrEP, and those that accepted had a PrEP follow-up visit scheduled 1 month later where HIVST outcomes were ascertained in-person. Women were classified as having scheduled follow-up visits if they initiated PrEP. Women who declined PrEP but still took an HIVST had outcomes ascertained in-person if they returned for maternal and child health or family planning services .A subset of women who agreed to take an HIVST were asked to register in an automated SMS communication system  to assess HIVST outcomes. Registration was offered in all program sites over time  for eligible women. Women were eligible to register if they had their phone at the clinic and a Safaricom SIM card, and provided oral consent. Registered women selected their preferred language  and were asked to save the mSurvey phone number as a contact in their phone to ensure the phone number would be recognized when the follow-up survey was sent (2.5 weeks later). Women were informed that responding to the mSurvey SMS was free, and they could opt-out at any time. HIVST outcomes were assessed through sequential SMS inquiries sent by mSurvey for women to respond to using numerical responses representing survey answers. Women who initiated registration or follow-up surveys were given 72 hours to complete surveys before they were timed-out of the system and unable to complete the survey.Mode of HIVST outcome ascertainment (SMS vs in-person) was compared between women with and without scheduled follow-up visits. HIVST outcomes were compared between SMS and in-person responders. The primary analysis was restricted to women offered HIVSTs at facilities when mSurvey registration was available. Women who reported having a partner with HIV at enrollment were excluded from the analysis. Continuous and categorical variables were compared using the Wilcoxon rank-sum and chi-square tests, respectively. Statistical analyses were performed using Stata v14 .This study was reviewed and approved by the University of Washington Institutional Review Board and the Kenyatta National Hospital Ethics & Research Committee.In total, 486 women accepted HIVSTs; 359 were eligible for registration in the mSurvey SMS system, and 222 successfully registered . Some woP=.01), or if they had a partner of unknown HIV status . Marital status (P=.84), history of IPV (P=.16), and risk factors for HIV  were similar between women with HIVST outcomes assessed in-person and via SMS.Overall, among 222 women enrolled in mSurvey: 116 (52.3%) were from ANC, 80 (36.0%) were from PNC, and 26 (11.7%) were from FP. The median age was 25 (IQR 22-28); 86.4% (191/222) were married and 17.1% (38/222) knew their male partners were HIV-negative. Intimate partner violence (IPV) was experienced by 4.5% (10/222) of the enrolled women within the last 6 months. HIVST outcomes were more likely to be reported through SMS only (vs in-person only), by women who were older  had HIVST outcome data available. SMS increased outcome ascertainment 1.48-fold ; an additional 32% of HIVST outcomes would have been missed without SMS. The majority of women enrolled in mSurvey but without scheduled follow-up visits  reported HIVST outcomes by SMS only. SMS responses captured 102/149 (68.5%) of all HIVST outcomes assessed by women in mSurvey.HIVST outcomes were also assessed for 73 women who were ineligible or not registered in mSurvey. The frequency of reporting on HIVST outcomes by women with scheduled follow-up visits who were ineligible  or who did not register in mSurvey  was similar to the frequency of women who registered in mSurvey. Most HIVST outcomes were reported near the time SMS surveys were sent to women using SMS , or near the scheduled follow-up date for women reporting in-person .P=.13). However, reports of experiencing harm or negative reactions from partners as a result of the HIVST were significantly more frequent in women with HIVST outcomes assessed via SMS than in-person.We found that nearly half of women seeking reproductive health services were willing and able to use SMS to respond to surveys on sensitive HIVST outcomes for their male partners. The SMS-based survey substantially increased the proportion of women that reported HIVST outcomes among women with scheduled follow-up visits (1.48-fold increase), and was a successful strategy to capture HIVST outcomes for those without scheduled follow-up visits. We did not detect differences in the proportions of women who reported that partners used HIVSTs or reported their partner’s HIV status; however, we did note a significant difference in the frequency of reported social harm related to HIVSTs. This suggests that the mode of outcome ascertainment did not bias responses for nonsensitive questions and may have improved the reporting of sensitive information, such as reports of social harm related to HIVSTs.Our analysis was subject to some limitations, but also provided insight on logistical barriers to SMS registration. Restricting registration to the primary mobile carrier and requiring phones to be present led to exclusions of 21.3% (104/486) of women accepting HIVSTs. We were unable to disaggregate lack of phone ownership from phones not being brought to the clinic. Women in our study may also have had intermittent access to a mobile phone due to shared phones with male partners or other community members, which have previously been reported as potential barriers to including women in SMS surveys . System SMS has successfully been used to remotely collect survey data -20. StudIn conclusion, SMS enhanced our ability to measure male partner HIVST outcomes. Our study demonstrates that SMS can be used to collect brief survey data on sensitive information, even in the absence of financial incentives. SMS should be considered to capture health outcomes, which may alleviate health system constraints and burdens associated with in-person visits.


The aim of this study was to determine the proportion of ophthalmic self-medication and associated factors among adult ophthalmic patients attending Borumeda Hospital, Northeast Ethiopia, 2019. P values of less than 0.05 were considered statistically significant.  An institution-based cross-sectional study design was conducted on 402 participants at Borumeda Hospital from April 29 to May 24, 2019. Systematic random sampling technique was used to get study participants. Data were collected with a face-to-face interview by using a semistructured questionnaire. Data were entered into Epi Info 7 and analyzed by SPSS 20. Descriptive statistics and binary logistic regression analysis were employed. Conclusion and Recommendations. The proportion of ophthalmic self-medication was high, which needs stakeholders' attention. The policymakers and regulatory body better to scale-up health insurance coverage, nearby accessible eye care services, improve knowledge of patients regarding the effect of ophthalmic self-medication, and proper disposal of leftover eye medication from the house. It is better to take regulatory actions on those who dispense ophthalmic medications without prescription. The proportion of ophthalmic self-medication was 28.6% . Age-group 29–42 years , absence of health insurance , more than 10 kilometer traveling distance to get eye services , previous experience of ocular illness , family or friend experience of ocular illness , availability of ophthalmic medicine bottle/tube at home , and poor knowledge about hazards of self-medication  were significantly associated with ophthalmic self-medication.  Self-medication is defined as selection and use of medicines by individuals to treat self-recognized illnesses or symptoms . OphthalPeople practice ophthalmic self-medication for a variety of reasons. Ocular symptoms like redness, watering of the eye, foreign body sensation, and itching of the eye are common symptoms that initiate to use ophthalmic self-medication. In addition to this, previous ocular illness, living far from the hospital, unaware and poor knowledge about hazards of self-medication, and simplifying their illness are among the factors for ophthalmic self-medication –6.Globally, the prevalence of ophthalmic self-medication ranges from 25.6% to 73.6% . The preSelf-medication practice is highly prone to irrational use of medications. The study showed that almost 90% of the ophthalmic self-medication was used inappropriately . PossiblEven though various studies were conducted on self-medication practices in different parts of Ethiopia, there was limited published evidence specifically on ophthalmic self-medication practice and factors that influence it among ophthalmic patients.Therefore, this study aimed to determine the proportion of ophthalmic self-medication practice and associated factors among adult ophthalmic patients attending Borumeda Hospital, Northeast Ethiopia. The result of this study will be important as a baseline for the researcher and a source of information for policymakers as well as eye health care provider for appropriate interventions to prevent the risks associated with self-medication practice.An institution-based cross-sectional study was conducted to assess the proportion and associated factors of ophthalmic self-medication practice among adult ophthalmic patients attending Borumeda Hospital, Northeast Ethiopia, 2019.The study was conducted at Borumeda Hospital from April 29 to May 24, 2019. Borumeda Hospital is found in Dessie town. Dessie town is located in 401 km far from Northeast of Addis Ababa, the capital city of Ethiopia. It has two public hospitals, four private hospitals, one private eye clinic, three government health centers, and thirty-six private clinics, and 56 drug retail outlets , 19.Borumeda Hospital was established in 1955 G. C by Missionary to give ophthalmology and dermatology services. It has a catchment of approximately 2.5 million people according to the data obtained from the hospital office.The secondary eye care unit has two ophthalmologists, five optometrists, one cataract surgeon, and two ophthalmic nurses. It provides comprehensive eye care services including major and minor ocular surgery, refraction service, and outpatient and inpatient service.rd individual).A total of 407 sample size was determined by a single proportional formula by considering 10% nonresponse rate. Then, a systematic random sampling method was used to select participants with a sampling fraction of three . The participant who answered correctly was given a score of one, and those did not answer correctly or did not know was given a score of zero. The total score was out of ten. A participant said to be having good knowledge if he/she answers ≥50% (≥5/10) of the question. Otherwise, it was considered as poor knowledge .A female who has husband, not employed by governmental and nongovernmental employers, who spent their time at home to keep house clean, cook foods, and take care of the child was considered as a housewife.The pretested and structured questionnaire of local language “Amharic” was used to carry out an interview with adults older than 18 years (S1 questioner). Regular check-up for completeness and consistency of the data was made on a daily basis. On the fieldwork, data quality was ensured through 5% on spot cross-checking of the sample at hospital by principal investigators. The collected data have been checked for accuracy and completeness by the principal investigators. The questioner included questions to assess sociodemographic factors, socioeconomic factors, healthcare-related factors, knowledge, and practice of ophthalmic self-medication.P < 0.2 at bivariable logistic regression were entered to multivariable analysis. Variables were fitted into the model by using the enter method. The Hosmer and Lemeshow model fitness was used to check the model fitness of data. Multicollinearity between the independent variables was checked by the variance inflation factor. Adjusted odds ratio with a 95% confidence interval was used to show the strength of association. Those variables with a P value less than 0.05 were considered as statistically significant.After coding, the data were entered into Epi Info version 7, exported, and analyzed by using SPSS version 20. Both descriptive and analytical methods were employed for analysis. Summary statistics, frequencies, and cross-tabulations were performed for the descriptive analysis of the data. Bivariable and multivariable logistic regression was used to determine the associated factors. The variables that were found with A total of 402 adults participated with a response rate of 98.7%. The median age was 42 years with an interquartile range of 32 years. The majority  of the respondents were males. One hundred eight (26.9%) of the respondents were in the age-group 18–28 years. One hundred thirty-four (33.3%) of the population were unable to read and write .One hundred ninety-six (48.8%) of the study participants had health insurance. Majority 300 (74.6%) of the participants were traveled greater than ten km distance to get eye care services. One hundred sixty-five (41.0%) of the participants had the previous history of eye illness and about 79 (19.7%) of the participants had a positive history of family or friends ocular illness. Sixty-three (15.7%) of participants had an eye medication bottle/tube at their own home. All participants heard about the hazards of self-medication and 321 (79.9%) of participants had good knowledge about the hazards of self-medication.The proportion of ophthalmic self-medication practice was 115 (28.6%) (95% CI: 24.6–33.3). Among them, 100 (87.0%) did not know the name of the medication they had used and 95 (82.6%) did not check the expiry date of the drug before they use it. Regarding the effects of the medication, the majority  of self-utilized participants did not improve from their illness, 20 (17.4%) of participants improved from their illness, and 14 (12.2%) of participants were worse their problem after self-medication.The common symptoms/illnesses that initiated for self-medication were redness, blurring of vision, and itching .The major sources of ophthalmic medicine for self-medication were pharmacy house (83 (72.2%)), followed by leftover medication (20 (17.4%)). The other source of medicine for ophthalmic self-medication was borrowing from friends or family 12 (10.4%).The major reason for ophthalmic self-medication was the far distance to get eye health care service (18.8%), followed by no time to visit at the eye health care center (17.6%) .Binary logistic regression analysis showing age-group 29–42 years, absence of health insurance, previous history of ocular illness, family or friends experience of ocular illness, availability of eye medication bottle/tube at home, far traveling distance to get eye care services, and poor knowledge about self-medication were significant factors associated with ophthalmic self-medication practice.Respondents of age-group 29–42 years were 2.19 times  more likely to practice ophthalmic self-medication than those of age-group 18–28 years.Ophthalmic patients who did not have health insurance were more than four times  more likely to practice self-medication than those who had health insurance. Ophthalmic patients who traveled more than ten km to get eye health services were nearly three  times more likely to practice self-medication than those who traveled less than or equal to ten km.Ophthalmic patients with previous experience of ocular illness were more than two times  more likely to practice ophthalmic self-medication than those without previous experience of ocular illness. Adult ophthalmic patients with family or friend experience of ocular illness were nearly three  times more likely to practice self-medication than those without family or friend experience of ocular illness. Ophthalmic patients who had ophthalmic medication (bottle/tube) at home were more than four times  more likely to practice self-medication than those who had not available ophthalmic medicines at home.Adult ophthalmic patients who had poor knowledge about the hazards of self-medication were more than six  times more likely to practice self-medication than those who had good knowledge .In this study, the proportion of ophthalmic self-medication practice was 28.6% . This finding is in line with a study from Argentina (25.6%)  and ColoThis finding is lower than the report from Tanzania 59.8%) [9.8% [5],Regarding associated factors, respondents of age-group 29–42 years were more likely to practice self-medication than those of age-group 18–28 years. This might be due to eye diseases being more common in older people, and this could lead to ophthalmic medicines without consultation of eye-care providers .Noninsured ophthalmic patients were more likely to practice self-medication than insured ophthalmic patients. This finding agrees with studies done in Ghana . This miOphthalmic patients who traveled a far distance to get eye health services were more likely to practice self-medication than those who traveled near distance. This might be due to inaccessibility of eye-care center around. In addition to this, it might be due to the financial constraint that participants might not afford transportation cost to come to the eye health center and may prefer to buy ophthalmic medicine from a nearby pharmacy.Adult ophthalmic patients with a history of previous ocular illness were more likely to practice self-medication than patients without a previous history of ocular illness. This was supported by different studies , 6. ThisOphthalmic patients who had ophthalmic medication bottle/tube at home were more likely to practice self-medication than those who had not available ophthalmic medicines at home. This might be due to the similarity of symptoms of eye diseases patients believing that ocular medications taken previously can cure their current eye disease.Those study participants with positive family/friend history of ocular illness were more likely to practice ophthalmic self-medication than those who had no family/friend history ocular illness. This might be due to the similarity of symptoms or illness leading to the use of similar ophthalmic medicine.Adult ophthalmic patients who had poor knowledge about the hazards of self-medication were more likely to practice self-medication than those who had good knowledge. This finding was agreed with different studies , 22. ThiSince optometrists participated for data collection, this study has social desirability bias.The study also has a limitation of recall bias because ophthalmic self-medication is assessed based on the self-report of the participants for their last two years of experiences. Income was not assessed by wealth index.The proportion of ophthalmic self-medication was high, which needs stakeholders' attention. Absence of health insurance, history of previous ocular illness, family or friends experience of ocular illness, availability of eye medication bottle/tube at home, far-traveling distance to get eye care services, and poor knowledge about hazards of self-medication were significantly associated factors. The policymakers and regulatory body better to scale-up health insurance coverage, nearby accessible eye care services, improve knowledge of patients regarding the effect of ophthalmic self-medication, and proper disposal of leftover eye medication from the house. It is better to take regulatory actions on those who dispense ophthalmic medications without prescription.