The International Family Study of Nonsyndromic Orofacial Clefts: Design and Methods.

BACKGROUND: The majority of research to understand the risk factors of nonsyndromic orofacial clefts (NSOFCs) has been conducted in high-income populations. Although patients with NSOFCs in low- and middle-income countries (LMICs) are at the highest risk of not receiving care, global health infrastructure allows innovative partnerships to explore the etiologic mechanisms of cleft and targets for prevention unique to these populations. METHODS: The International Family Study (IFS) is an ongoing case-control study with supplemental parental trio data designed to examine genetic, environmental, lifestyle, and sociodemographic risk factors for NSOFCs in 8 LMICs (through August 2020). Interview and biological samples are collected for each family. The interview includes demographics, family history of cleft, diet and water sources, maternal pregnancy history, and other lifestyle and environmental factors. RESULTS: Seven of 8 countries are currently summarized (2012-2017) for a total of 2955 case and 2774 control families with 11 946 unique biological samples from Vietnam, Philippines, Honduras, Madagascar, Morocco, Democratic Republic of the Congo, and Nicaragua. The phenotype distribution was 1641 (55.5%) cases with cleft lip and palate, 782 (26.5%) with cleft lip (CL), and 432 (14.6%) with cleft palate (CP). DISCUSSION: The International Family Study is the largest case set of NSOFCs with an associated biobank in LMICs currently assembled. The biobank, family, and case-control study now include samples from 8 LMICs where local health care infrastructure cannot address the surgical burden of cleft or investigate causal mechanisms. The International Family Study can be a source of information and may collaborate with local public health institutions regarding education and interventions to potentially prevent NSOFCs.

Journey mapping as a novel approach to healthcare: a qualitative mixed methods study in palliative care.

BACKGROUND: Journey mapping involves the creation of visual narrative timelines depicting the multidimensional relationship between a consumer and a service. The use of journey maps in medical research is a novel and innovative approach to understanding patient healthcare encounters. OBJECTIVES: To determine possible applications of journey mapping in medical research and the clinical setting. Specialist palliative care services were selected as the model to evaluate this paradigm, as there are numerous evidence gaps and inconsistencies in the delivery of care that may be addressed using this tool. METHODS: A purposive convenience sample of specialist palliative care providers from the Supportive and Palliative Care unit of a major Australian tertiary health service were invited to evaluate journey maps illustrating the final year of life of inpatient palliative care patients. Sixteen maps were purposively selected from a sample of 104 consecutive patients. This study utilised a qualitative mixed-methods approach, incorporating a modified Delphi technique and thematic analysis in an online questionnaire. RESULTS: Our thematic and Delphi analyses were congruent, with consensus findings consistent with emerging themes. Journey maps provided a holistic patient-centred perspective of care that characterised healthcare interactions within a longitudinal trajectory. Through these journey maps, participants were able to identify barriers to effective palliative care and opportunities to improve care delivery by observing patterns of patient function and healthcare encounters over multiple settings. CONCLUSIONS: This unique qualitative study noted many promising applications of the journey mapping suitable for extrapolation outside of the palliative care setting as a review and audit tool, or a mechanism for providing proactive patient-centred care. This is particularly significant as machine learning and big data is increasingly applied to healthcare.

Progression to Severe Hypernatremia in Hospitalized General Medicine Inpatients: An Observational Study of Hospital-Acquired Hypernatremia.

Background and objectives: Hypernatremia can be community or hospital-acquired, and there may be specific factors unique to the hospital environment, such as intravenous fluid treatment, which contribute to hypernatremia. The aim of this study was to determine the factors associated with the progression from moderate to severe hospital-acquired hypernatremia among patients admitted under general medicine. Materials and Methods: In this retrospective, single-center cohort study (2012 to 2017), we used ICD-10 coding and medical records to identify adult patients who developed moderate hypernatremia and followed them for progression to severe hypernatremia. We profiled the serum biochemistry and the volume and composition of prescribed intravenous fluids. We applied logistic regression to determine the factors associated with the progression to severe hypernatremia, using the patients with moderate hypernatremia as reference. Results: Of the 180 medical inpatients (median age of 81 years) with moderate hospital-acquired hypernatremia, 9.4% progressed to severe hypernatremia. Normal saline comprised 76% of intravenous fluid volume administered prior to onset of moderate hypernatremia. After the onset, 38% of fluid volume prescribed remained normal saline. The factors independently associated with progression to severe hypernatremia included chronic kidney disease stage (odds ratio 2.38, 95% CI: 1.26-4.50, P = 0.008) and serum creatinine increase (per 10 µmol/L, OR 1.29, 95% CI: 1.07-1.57, P = 0.009). Conclusions: Patients with chronic kidney disease and acute kidney injury may have an increased risk of severe hospital-acquired hypernatremia.

Prevalence and severity of menopause symptoms among perimenopausal and postmenopausal women aged 30-49 years in Gulele sub-city of Addis Ababa, Ethiopia.

BACKGROUND: Menopause is a natural phenomenon occurring as women approach middle-age. It is characterized by declining of ovarian function and onset of the last menstrual period and subsequent 12-month cessation of menstruation. Due to a growing aging population and longer life expectancies, sub-Saharan African women will spend a significant portion of their lives in postmenopause. Menopausal symptom research has been primarily conducted on Caucasian women from high-income countries. Understanding menopause symptom prevalence and perceptions among diverse women in Ethiopia will better inform reproductive health care. METHODS: We conducted a multi-stage, cross-sectional study on 226 perimenopausal and postmenopausal women aged 30-49 years in Gulele sub-city of Addis Ababa, Ethiopia. Data on socio-demographic characteristics, menopausal status and an 11-item Menopause Rating Scale (MRS) were collected using interviewer-administered questionnaire. Statistical analyses consisted of descriptive data and chi-squared analyses. RESULTS: Study participants were 40.4 ± 5.9 years, on average, with the majority married, educated at secondary school level, and comprised different ethnicities and wealth tertiles. The most prevalent types of menopausal symptoms reported from the MRS were from somatic subscale (65.9%) while psychological (46.0%) and urogenital subscale symptoms (30.5%) were also prevalent. The most commonly reported individual symptoms were: hot flushes (65.9% (95% CI: 59.4%-72.1%)), difficulty falling asleep (49.6% (95% CI: 42.9%-56.3%)), depressive mood (46.0% (95% CI: 39.4%-52.8%)), irritability (45.1% (95% CI: 38.5%-51.9%)), and anxiety (39.8% (95% CI: 33.4%-46.5%)). Each of the somatic, psychological, and urogenital MRS subscale scores were higher among postmenopausal women compared to perimenopausal women. Women self-reported differing severity levels of symptoms with high severity reported in 8.4% of total MRS, 1.3% of somatic, 10.6% of psychological, and 8.4% of urogenital scales. CONCLUSIONS: Our study provides the first presentation of menopausal symptoms among perimenopausal and postmenopausal women in the Gulele sub-city of Addis Ababa, Ethiopia. We capture the prevalence of menopausal symptoms experienced as well as self-rated severity through the MRS. Our findings reflect menopausal symptoms in our specific study population and have been found to be consistent with previous international research.

Paternal Risk Factors for Oral Clefts in Northern Africans, Southeast Asians, and Central Americans.

While several studies have investigated maternal exposures as risk factors for oral clefts, few have examined paternal factors. We conducted an international multi-centered case-control study to better understand paternal risk exposures for oral clefts (cases = 392 and controls = 234). Participants were recruited from local hospitals and oral cleft repair surgical missions in Vietnam, the Philippines, Honduras, and Morocco. Questionnaires were administered to fathers and mothers separately to elicit risk factor and family history data. Associations between paternal exposures and risk of clefts were assessed using logistic regression adjusting for potential confounders. A father's personal/family history of clefts was associated with significantly increased risk (adjusted OR: 4.77; 95% CI: 2.41-9.45). No other significant associations were identified for other suspected risk factors, including education (none/primary school v. university adjusted OR: 1.29; 95% CI: 0.74-2.24), advanced paternal age (5-year adjusted OR: 0.98; 95% CI: 0.84-1.16), or pre-pregnancy tobacco use (adjusted OR: 0.96; 95% CI: 0.67-1.37). Although sample size was limited, significantly decreased risks were observed for fathers with selected occupations. Further research is needed to investigate paternal environmental exposures as cleft risk factors.

The Tsao Fellowship in Global Health: A Model for International Fellowships in a Surgery Residency.

OBJECTIVE: To present a model for integrated global health fellowships in plastic surgical residency training. BACKGROUND: National surveys have found that North American surgical residents have significant interest in international training. While global health training opportunities exist, less than a third of these are housed within surgical residency programs; even fewer are designed specifically for plastic surgery residents. METHODS: The Tsao Fellowship was created through a partnership between Operation Smile, Children's Hospital Los Angeles, Shriners Hospital for Children, and the University of Southern California. Designed for Accreditation Council for Graduate Medical Education accredited plastic surgery residents between their third and fourth years of residency, the fellowship curriculum is completed over 24 months and divided into 3 areas: clinical research, international reconstructive surgery fieldwork, and the completion of a Master of Science in Clinical and Biomedical Investigations. RESULTS: The Tsao Fellowship has matriculated 4 fellows: 3 have graduated from the program and 1 is in the current cycle. Fellows completed 4 to 7 international missions each cycle and have performed an aggregate total of 684 surgical procedures. Each fellow also conducted 2 to 6 research projects and authored several publications. All fellows continue to assume leadership roles within the field of global reconstructive surgery. CONCLUSIONS: Comprehensive global health fellowships provide invaluable opportunities beyond surgical residency. The Tsao Fellowship is a model for integrating international surgical training with global health research in plastic surgical residency that can be applied to other residency programs and different surgical specialties.

The Global Surgery Partnership: An Innovative Partnership for Education, Research, and Service.

PROBLEM: An estimated two billion people worldwide lack access to adequate surgical care. Addressing surgical disparities requires both immediate relief efforts and long-term investments to improve access to care and surgical outcomes, train the next generation of surgical professionals, and expand the breadth of formative research in the field. While models exist for establishing short-term surgical missions in low- and middle-income countries, far less focus has been placed on models for multi-institutional partnerships that support the development of sustainable solutions. APPROACH: In 2011, the Global Surgery Partnership (GSP) was founded by an established children's hospital (Children's Hospital Los Angeles), an academic medical center (University of Southern California), and a nonprofit organization (Operation Smile) to build oral cleft surgical capacity in resource-poor settings through education, research, and service. OUTCOMES: Leveraging the strengths of each partner, the GSP supports three global health education programs for public health graduate students and surgical residents, including the Tsao Fellowship in Global Health; has initiated two international research projects on cleft lip and palate epidemiology; and has built upon Operation Smile's service provision. As of January 2015, Tsao fellows had operated on over 600 patients during 13 missions in countries including China, Vietnam, Mexico, and India. NEXT STEPS: The GSP plans to conduct a formal evaluation and then to expand its programs. The GSP encourages other global health organizations and academic and medical institutions to engage with each other. The partnership described here provides a basic model for structuring collaborations in the global health arena.

Parental risk factors for oral clefts among Central Africans, Southeast Asians, and Central Americans.

BACKGROUND: Several lifestyle and environmental exposures have been suspected as risk factors for oral clefts, although few have been convincingly demonstrated. Studies across global diverse populations could offer additional insight given varying types and levels of exposures. METHODS: We performed an international case-control study in the Democratic Republic of the Congo (133 cases, 301 controls), Vietnam (75 cases, 158 controls), the Philippines (102 cases, 152 controls), and Honduras (120 cases, 143 controls). Mothers were recruited from hospitals and their exposures were collected from interviewer-administered questionnaires. We used logistic regression modeling to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Family history of clefts was strongly associated with increased risk (maternal: OR = 4.7; 95% CI, 3.0-7.2; paternal: OR = 10.5; 95% CI, 5.9-18.8; siblings: OR = 5.3; 95% CI, 1.4-19.9). Advanced maternal age (5 year OR = 1.2; 95% CI, 1.0-1.3), pregestational hypertension (OR = 2.6; 95% CI, 1.3-5.1), and gestational seizures (OR = 2.9; 95% CI, 1.1-7.4) were statistically significant risk factors. Lower maternal (secondary school OR = 1.6; 95% CI, 1.2-2.2; primary school OR = 2.4, 95% CI, 1.6-2.8) and paternal education (OR = 1.9; 95% CI, 1.4-2.5; and OR = 1.8; 95% CI, 1.1-2.9, respectively) and paternal tobacco smoking (OR = 1.5, 95% CI, 1.1-1.9) were associated with an increased risk. No other significant associations between maternal and paternal factors were found; some environmental factors including rural residency, indoor cooking with wood, chemicals and water source appeared to be associated with an increased risk in adjusted models. CONCLUSION: Our study represents one of the first international studies investigating risk factors for clefts among multiethnic underserved populations. Our findings suggest a multifactorial etiology including both maternal and paternal factors.

Genetic risk factors for orofacial clefts in Central Africans and Southeast Asians.

Genome-wide association studies (GWAS) for orofacial clefts have identified several susceptibility regions, but have largely focused on non-Hispanic White populations in developed countries. We performed a targeted genome-wide study of single nucleotide polymorphisms (SNPs) in exons using the Illumina HumanExome+ array with custom fine mapping of 16 cleft susceptibility regions in three underserved populations: Congolese (87 case-mother, 210 control-mother pairs), Vietnamese (131 case-parent trios), and Filipinos (42 case-mother, 99 control-mother pairs). All cases were children with cleft lip with or without cleft palate. Families were recruited from local hospitals and parental exposures were collected using interviewer-administered questionnaires. We used logistic regression models for case-control analyses, family-based association tests for trios, and fixed-effect meta-analyses to determine individual SNP effects corrected for multiple testing. Of the 16 known susceptibility regions tested, SNPs in four regions reached statistical significance in one or more of these populations: 1q32.2 (IRF6), 10q25.3 (VAX1), and 17q22 (NOG). Due to different linkage disequilibrium patterns, significant SNPs in these regions differed between the Vietnamese and Filipino populations from the index SNP selected from previous GWAS studies. Among Africans, there were no significant associations identified for any of the susceptibility regions. rs10787738 near VAX1 (P = 4.98E-3) and rs7987165 (P = 6.1E-6) were significant in the meta-analysis of all three populations combined. These results confirm several known susceptibility regions and identify novel risk alleles in understudied populations.