[Rare diseases and undiagnosed diseases: advances in neurodevelopment]. / Enfermedades sin diagnóstico y enfermedades raras: avances en neurodesarrollo.

Rare diseases and undiagnosed diseases have recently positioned themselves as clinical entities that provide important opportunities to advance our understanding of gene functions and the impact of them in the individual development. In this review, we present how efforts made over years to understand common diseases, rare diseases and even undiagnosed diseases come together today to cooperatively advances scientific knowledge. These advance in science and new acquired knowledge, make possible to apply the advances obtained in a group of clinical conditions to others with similar phenotypic characteristics or vice versa. The cooperative work of multidisciplinary teams and the communication between clinicians and researchers have and will provide opportunities for better treatments for patients and families across multiple common and rare diseases.

Las enfermedades raras y enfermedades sin diagnóstico se han posicionado en los últimos años como condiciones clínicas que han permitido avanzar el entendimiento de las funciones de los genes y el impacto en el desarrollo del individuo. En esta revisión, presentamos como los esfuerzos individuales hechos por muchos años para entender la fisiopatología de enfermedades comunes, enfermedades raras y otras aún más raras, como las enfermedades sin diagnóstico, que se unen hoy para, de manera cooperativa, avanzar en el conocimiento científico. Estos avances en el conocimiento permiten aplicar los avances obtenidos en un grupo de condiciones clínicas a otras con características fenotípicas similares o viceversa. El trabajo conjunto de equipos multidisciplinarios y la comunicación entre clínicos e investigadores proporcionarán oportunidades para proveer mejores oportunidades de tratamiento para pacientes y familias a lo largo de múltiples diagnósticos comunes o raros.

Prevalence and characterization of undiagnosed arterial hypertension in the eastern zone of Mexico.

Arterial hypertension is considered a public health problem with severe consequences at an individual and public health levels. However, there is a lack of information regarding its characterization in Mexico. The objective of this study is to estimate the proportion of undiagnosed arterial hypertension (UAH) and the overall prevalence and clinical management of arterial hypertension within the Eastern Zone of Mexico. Additionally, we explore associated factors related with both UAH and uncontrolled arterial hypertension. We obtained information from the May Measure Month (MMM) 2019 study. People were asked for cardiovascular risk factors and blood pressure was measured according to the protocols of the European Society of Hypertension (ESH). Data from 5901 subjects were extracted: 76.04% from the Eastern Zone of the State of Mexico. The overall prevalence of hypertension was 32.4% (95% CI 31.2-33.6). From all subjects living with hypertension, 28.3% had UAH, 22.1% had previous diagnosis but were untreated; 29.3% were treated but had uncontrolled hypertension. Younger men adults living in the State of Michoacán had increased proportion of UAH and untreated hypertension. We observed that male sex, age, obesity, living at Michoacán were risk factors for UAH. Finally, male sex, diabetes, and living at Michoacán were related risk conditions for having uncontrolled arterial hypertension. In summary, there is a high proportion of UAH in Easter Zone of Mexico. Younger adults had higher proportion of UAH and untreated hypertension profiles. Efficient actions are required to make a timely diagnosis in the young adult population to prevent long-term complications.

Prevalencia e incidencia de hipertensión arterial en Perú: revisión sistemática y metaanálisis / Prevalence and incidence of arterial hypertension in Peru: a systematic review and meta-analysis

RESUMEN Objetivo. Determinar la prevalencia e incidencia de hipertensión arterial, y la prevalencia de diagnóstico previo de hipertensión arterial (autorreportado) en población general adulta del Perú. Materiales y métodos. Revisión sistemática y metaanálisis de estudios epidemiológicos disponibles en LILACS, EMBASE, MEDLINE y Global Health. Se incluyeron estudios que siguieron un muestreo aleatorio de la población general adulta. El tamizaje y estudio de los manuscritos fue realizado por dos investigadores de forma independientemente. Se hizo metaanálisis de efectos aleatorios para cuantificar la prevalencia e incidencia global. Los manuscritos fueron evaluados con la escala Newcastle-Ottawa para evaluar el riesgo de sesgo. Resultados. Se tamizaron 903 artículos, y se incluyeron 15 manuscritos para prevalencia, 8 para prevalencia de diagnóstico previo, y 4 para incidencia de hipertensión. El metaanálisis mostró una prevalencia agregada de hipertensión de 22,0% (IC 95%: 20,0% - 25,0%; I 2=99,2%). Esta prevalencia fue menor en estudios nacionales [20,0% (IC 95%: 17,0% - 22,0%; I 2 =99,4%] que en subnacionales [24,0% (IC 95%: 17,0% - 30,0%; I 2 =99,2%]. La prevalencia global de diagnóstico previo de hipertensión fue 51,0% (IC 95%: 43,0% - 59,0%; I 2=99,9%). La incidencia global fue de 4,2 (IC 95%: 2,0 - 6,4; I 2=98,6%) por cada 100 personas-año. Los manuscritos estudiados no presentaron alto riesgo de sesgo. Conclusiones. Nuestros hallazgos muestran que uno de cada cinco peruanos tiene hipertensión, y que aparecen cuatro nuevos casos por 100 personas en un año, además solo la mitad de los pacientes hipertensos tienen el diagnóstico previo de su condición.

ABSTRACT Objective . To determine the prevalence and incidence of arterial hypertension, as well as the prevalence of previous diagnosis of arterial hypertension (self-reported) among the adult population of Peru. Materials and methods. Systematic review and meta-analysis of epidemiological studies available in LILACS, EMBASE, MEDLINE and Global Health. Studies were included if they followed a random sampling approach in adult population. Screening and assessment of manuscripts was carried out independently by two researchers. A random-effects meta-analysis was conducted to quantify the overall prevalence and incidence of hypertension. The Newcastle-Ottawa scale was used to assess the risk of bias in the manuscripts. Results. A total of 903 papers were screened, and only 15 were included in the estimation of hypertension prevalence, 8 in the assessment of previous hypertension diagnosis, and 4 for incidence estimations. The pooled prevalence of hypertension was 22.0% (95% CI: 20.0% - 25.0%; I2=99.2%). This estimate was lower in national studies [20.0% (95% CI: 17.0% - 22.0%; I2=99.4%] than in sub-national studies [24.0% (95% CI: 17.0% - 30.0%; I2=99.2%]. The pooled prevalence of previous hypertension diagnosis was 51.0% (95% CI: 43.0% - 59.0%; I2=99.9%). The pooled incidence of hypertension was 4.2 (95% CI: 2.0 - 6.4; I2=98.6%) per 100 person-years. The included studies did not present high risk of bias. Conclusions. Our findings show that one in five Peruvians has hypertension, and that four new cases appear per 100 persons per year; in addition, only half of the subjects with hypertension are previously diagnosed.

A comparison of the effectiveness of respondent-driven and venue-based sampling for identifying undiagnosed HIV infection among cisgender men who have sex with men and transgender women in Tijuana, Mexico.

BACKGROUND: Efforts to increase HIV testing, diagnosis and care are critical to curbing HIV epidemics among cisgender men who have sex with men (MSM) and transgender women (TW) in low- and middle-income countries (LMIC). We compared the effectiveness of respondent-driven sampling (RDS) and venue-based sampling (VBS) for identifying previously undiagnosed HIV infection among MSM and TW in Tijuana, Mexico. METHODS: Between March 2015 and December 2018, we conducted RDS within the social networks of MSM and TW and VBS at venues frequented by MSM and TW to socialize and meet sexual partners. Those reached by RDS/VBS who reported at least 18 years of age, anal sex with MSM or TW, and no previous HIV diagnosis were eligible for HIV testing. RESULTS: Of those screened following recruitment via RDS (N = 1232; 98.6% MSM; 1.3% TW), 60.8% (749/1232) were eligible for HIV testing and 97.5% (730/749) were tested for HIV infection, which led to the identification of 36 newly diagnosed HIV infections (4.9%). Of those screened following recruitment via VBS (N = 2560; 95.2% MSM; 4.6% TW), 56.5% (1446/2560) were eligible for HIV testing and 92.8% (1342/1446) were tested for HIV infection, which led to the identification of 82 newly diagnosed HIV infections (6.1%). The proportion of new HIV diagnoses did not differ by recruitment method (ratio = 0.81, 95% confidence interval: 0.55 to 1.18). Compared to those recruited via RDS, those tested following recruitment via VBS were younger, more likely to identify as gay, and more likely to identify as TW. Compared to those recruited via VBS, those newly diagnosed with HIV infection following recruitment via RDS reported higher levels of internalized stigma and were more likely to report injection drug use and a history of deportation from the United States. CONCLUSIONS: Despite RDS and VBS being equally effective for identifying undiagnosed HIV infection, each recruitment method reached different subgroups of MSM and TW in Tijuana. Our findings suggest that there may be benefits to using both RDS and VBS to increase the identification of previously undiagnosed HIV infection and ultimately support HIV care engagement among MSM and TW in Mexico and other similar LMIC.

Undiagnosed cardiovascular risk factors in overweight and obese individuals: a low income country experience.

BACKGROUND: Overweight and obesity are associated with diabetes, hypertension and chronic kidney disease (CKD). However, there is scarce information from lower income countries about undiagnosed obesity-associated conditions. This information is necessary for healthcare planning and for assessment of Global Burden of Disease. METHODS: We assessed the prevalence of obesity-associated conditions in 656 overweight (n = 360) and obese (n = 296) adults from inner-city Portoviejo (Ecuador), in descriptive field research, based on an opportunistic and selective sampling strategy. RESULTS: Of 316 men and 340 women, 73% met criteria for prehypertension (27%) or hypertension (46%), 50% met criteria for prediabetes (30%) or diabetes (20%), 11% had an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 consistent with chronic kidney disease (CKD) and 5.5% had pathological albuminuria for a total CKD prevalence of 16%. Age-related prevalence data were generated. In all participants, serum total cholesterol and triglycerides were >200 and >150 mg/dl, respectively. Hyperuricemia and microhematuria (<2%) were uncommon. Women were more likely to have low eGFR (18 vs 5%, p 0.000). Diabetes and pathological albuminuria prevalence were higher in obese than in overweight participants (15 vs 12%, p 0.018; and 8 vs 4%, p 0.0199, respectively). DISCUSSION: In conclusion, undiagnosed hypertension, diabetes and CKD were more common than expected in overweight and obese persons from Ecuador. Detection rates exceeded official estimates of prevalene of these conditions. Screening the overweight/obese for these conditions, especially at the age ranges at higher risk, may be cost-effective to identify a high number of persons who may benefit from early inexpensive intervention.

Comparative analysis of screening models for undiagnosed diabetes in Mexico.

BACKGROUND: It is estimated that 37% of Mexican adults have undiagnosed diabetes, and are therefore at high risk of developing the severe and devastating complications associated to it. In recent years, a variety of screening tools based on the characteristics of the adult Mexican population have been proposed in order to reduce the negative effects of the disease. OBJECTIVES: To assess the performance of screening models to diagnose diabetes in the Mexican adult population and to propose a screening model based on HbA1c measurements. MATERIALS AND METHODS: Data from the 2016 Halfway National Health and Nutrition Survey (NHNS) were used to assess the screening models and to develop and validate the proposed 2016 NHNS model, built using a multivariate logistic regression model. Explanatory variables included in the 2016 NHNS 2016 model were selected through a stepwise backward procedure, using sensitivity and specificity as performance indicators. RESULTS: Of the screening models assessed, only the model based on the 2006 NHNS survey showed a performance consistent with previous reports. The proposed 2016 NHNS model included age, waist circumference, and systolic blood pressure as explanatory variables and showed a sensitivity of 0.72 and a specificity of 0.80 in the validation data set. CONCLUSIONS: Age, waist circumference, and systolic blood pressure are variables of special importance for early detection of undiagnosed diabetes in Mexican adults. Based on the consistent performance of the 2006 NHNS model in different data sets, its use as a screening tool for adults with undiagnosed diabetes in Mexico is recommended.

Prevalence and correlates of diagnosed and undiagnosed hypertension in the indigenous Kuna population of Panamá.

BACKGROUND: To determine the prevalence of hypertension and investigate sociodemographic correlates in an indigenous Kuna community living on the San Blas islands of Panama. METHODS: Data was collected from adults using a paper-based survey using a cross sectional study design. Blood pressure was measured, and hypertension defined at two cut-points: 130/80 mmHg and 140/90 mmHg. Individuals with undiagnosed hypertension had a blood pressure measurement that indicated hypertension, however, the individual had not been told by a doctor they had hypertension. Whereas individuals with diagnosed hypertension had been told by a healthcare provider that they had hypertension. Univariate tests compared diagnosed and undiagnosed hypertension by sociodemographic categories and logistic regression models tested individual correlates adjusting for all sociodemographic factors. RESULTS: Two hundred and eleven adult indigenous Kuna participated in the study. Overall prevalence of hypertension was 6.2% (95%CI:3.32-10.30) as defined by 140/90 mmHg, and 16.6% (95%CI:11.83-22.31) as defined by 130/80 mmHg. Hypertension was significantly higher in men (31.6, 95% CI:19.90-45.24, compared to 11.0, 95% CI:6.56-17.09). Individuals with low income were 3 times more likely to be hypertensive (OR = 3.13, 95% CI:1.02-9.60) and 3.5 times more likely to have undiagnosed hypertension (OR = 3.42, 95% CI:1.01-11.52); while those with moderate income were 6 times more likely to be hypertensive (OR = 7.37, 95% CI:1.76-30.90) compared to those who were poor. CONCLUSION: The prevalence of diagnosed and undiagnosed hypertension is higher in men and those with higher income. Investigating these factors remains vitally important in helping improve the health of the Kuna through targeted interventions to address chronic disease.

Burden of Illness, Primary Care Use, and Medication Utilization among US-México Border Children with Wheezing.

OBJECTIVE: Among high-risk, underserved populations, such as children living along the US-México border, suffering from asthma-like symptoms without an asthma diagnosis can result in a high burden of illness. We estimated the prevalence of physician-diagnosed and possible undiagnosed asthma among students with histories of wheezing in the US-México border community of El Paso, Texas, and evaluated their burden of illness, primary care use, and medication utilization. METHODS: We analyzed cross-sectional survey data collected in May 2012. The survey included validated International Study of Asthma and Allergies in Childhood (ISAAC) items. We performed bivariate and logistic regression analyses on data from 307 students who wheezed. RESULTS: Forty-two percent of students had possible undiagnosed asthma and 58% had physician-diagnosed asthma based on primary caretaker reports. Children of Mexican origin were more likely to report undiagnosed vs. diagnosed asthma (p < 0.05). Children with an asthma diagnosis were more likely to report any medication use for wheezing/asthma and to experience a higher burden of illness in the last year compared to students with possible undiagnosed asthma (p < 0.05). CONCLUSIONS: The burden of illness among these children was high; however, children with asthma-like symptoms were not faring worse than children with asthma symptoms and a diagnosis. Undiagnosed children were being evaluated and receiving treatment for their symptoms; however, by not receiving a diagnosis, they were eliciting an ameliorative rather than preventive treatment strategy.

Screening models for undiagnosed diabetes in Mexican adults using clinical and self-reported information.

BACKGROUND: Prevalence of diabetes in Mexico has constantly increased since 1993. Since type 2 diabetes may remain undiagnosed for many years, identification of subjects at high risk of diabetes is very important to reduce its impact and to prevent its associated complications. OBJECTIVE: To develop easily implementable screening models to identify subjects with undiagnosed diabetes based on the characteristics of Mexican adults. SUBJECTS AND METHODS: Screening models were developed using datasets from the 2006 and 2012 National Health and Nutrition Surveys (NHNS). Variables used to develop the multivariate logistic regression models were selected using a backward stepwise procedure. Final models were validated using data from the 2000 National Health Survey (NHS). RESULTS: The model based on the 2006 NHNS included age, waist circumference, and systolic blood pressure as explanatory variables, while the model based on the 2012 NHNS included age, waist circumference, height, and family history of diabetes. The sensitivity and specificity values obtained from the external validation procedure were 0.74 and 0.62 (2006 NHNS model) and 0.76 and 0.55 (2012 NHNS model) respectively. CONCLUSIONS: Both models were equally capable of identifying subjects with undiagnosed diabetes (∼75%), and performed satisfactorily when compared to other models developed for other regions or countries.

High Rate of Undiagnosed Obstructive Sleep Apnea in Patients Undergoing Total Joint Arthroplasty.

This study described the incidence and severity of obstructive sleep apnea (OSA) and determined the sensitivity and specificity of the STOP-BANG Questionnaire in patients undergoing total joint arthroplasty (TJA) at a military academic medical center. All subjects completed the questionnaire and an unattended sleep study preoperatively. Incidence and severity of OSA (apnea-hypopnea index [AHI] ≥ 5) was calculated. Sensitivity and specificity for STOP-BANG cut scores greater than or equal to 3 and 5 for AHI of 5, 15, and 30 or more were determined. The rate of OSA was 51.2% (42/82), moderate to severe OSA was 29.3% (n = 29), and severe OSA was 7.3% (n = 6). Sensitivity and specificity for a STOP-BANG score of 3 or greater were 85.7% and 43.6% for OSA, 91.7% and 36.8% for moderate OSA, and 100% and 30.7% for severe OSA. A STOPBANG score of 5 or greater increased specificity for mild, moderate, and severe OSA to 84.6%, and 78.9%, and 72%. Patients undergoing TJA have a high rate of undiagnosed OSA. It is recommended to screen these patients using the STOP-BANG, implement OSA risk reduction strategies, and refer patients postoperatively for a sleep study if their STOP-BANG score is at least 3.

MSM in Bogotá are living with HIV for extended periods without diagnosis or treatment.

We examined recency of infection in serum samples obtained from 69 newly identified HIV-positive cases in a sample of 1000 men who have sex with men (MSM) in Bogotá. HIV antibody avidity assays were performed using the Architect HIV Ag/AB combo. Avidity indices ranged from 0.62 to 1.22, with a cut-off score below 0.80 indicative of recent infection. Two samples were classified as recent, six fell within the gray zone (0.75 to 0.85), and the remaining 61 were considered established infections. Results provided evidence of widespread, long-term, undiagnosed HIV infection, as well as an estimate of one-year incidence at .25 in the population of MSM in Bogotá. This incidence rate is approximately 8.5 times the rate estimated for the general adult population in Colombia. The large proportion of newly diagnosed cases found among individuals with established infections indicates that many MSM in Bogotá are living with HIV for extended periods without being diagnosed and treated. Greater efforts to detect and treat undiagnosed infections are crucial to decrease HIV incidence and increase maximum effectiveness of medical intervention. Given the over-representation of MSM and transgender women in the HIV epidemic in Colombia, such efforts should specifically target this population.

Prediabetes, undiagnosed diabetes, and diabetes among Mexican adults: findings from the Mexican Health and Aging Study.

PURPOSE: The purpose of the study was to examine the prevalence and determinants of prediabetes, undiagnosed diabetes, and diabetes among Mexican adults from a subsample of the Mexican Health and Aging Study. METHODS: We examined 2012 participants from a subsample of the Mexican Health and Aging Study. Measures included sociodemographic characteristics, body mass index, central obesity, medical conditions, cholesterol, high-density lipoprotein cholesterol, hemoglobin A1c, and vitamin D. Logistic regression was performed to identify factors associated with prediabetes, undiagnosed diabetes, and self-reported diabetes. RESULTS: Prevalence of prediabetes, undiagnosed, and self-reported diabetes in this cohort was 44.2%, 18.0%, and 21.4%, respectively. Participants with high waist-hip ratio (1.61, 95% confidence interval [CI] = 1.05-2.45) and high cholesterol (1.85, 95% CI = 1.36-2.51) had higher odds of prediabetes. Overweight (1.68, 95% CI = 1.07-2.64), obesity (2.38, 95% CI = 1.41-4.02), and high waist circumference (1.60, 95% CI = 1.06-2.40) were significantly associated with higher odds of having undiagnosed diabetes. Those residing in a Mexican state with high U.S. migration had lower odds of prediabetes (0.61, 95% CI = 0.45-0.82) and undiagnosed diabetes (0.53, 95% CI = 0.41-0.70). Those engaged in regular physical activity had lower odds of undiagnosed diabetes (0.74, 95% CI = 0.57-0.97). CONCLUSIONS: There is a high prevalence of prediabetes and undiagnosed diabetes among Mexican adults in this subsample. Findings suggest the need for resources to prevent, identify, and treat persons with prediabetes and undiagnosed diabetes.