Personalised health education against health damage of COVID-19 epidemic in the elderly Hungarian population (PROACTIVE-19): protocol of an adaptive randomised controlled clinical trial.

BACKGROUND: Early reports indicate that COVID-19 may require intensive care unit (ICU) admission in 5-26% and overall mortality can rise to 11% of the recognised cases, particularly affecting the elderly. There is a lack of evidence-based targeted pharmacological therapy for its prevention and treatment. We aim to compare the effects of a World Health Organization recommendation-based education and a personalised complex preventive lifestyle intervention package (based on the same WHO recommendation) on the outcomes of the COVID-19. METHODS: PROACTIVE-19 is a pragmatic, randomised controlled clinical trial with adaptive "sample size re-estimation" design. Hungarian population over the age of 60 years without confirmed COVID-19 will be approached to participate in a telephone health assessment and lifestyle counselling voluntarily. Volunteers will be randomised into two groups: (A) general health education and (B) personalised health education. Participants will go through questioning and recommendation in 5 fields: (1) mental health, (2) smoking habits, (3) physical activity, (4) dietary habits, and (5) alcohol consumption. Both groups A and B will receive the same line of questioning to assess habits concerning these topics. Assessment will be done weekly during the first month, every second week in the second month, then monthly. The composite primary endpoint will include the rate of ICU admission, hospital admission (longer than 48 h), and mortality in COVID-19-positive cases. The estimated sample size is 3788 subjects per study arm. The planned duration of the follow-up is a minimum of 1 year. DISCUSSION: These interventions may boost the body's cardiovascular and pulmonary reserve capacities, leading to improved resistance against the damage caused by COVID-19. Consequently, lifestyle changes can reduce the incidence of life-threatening conditions and attenuate the detrimental effects of the pandemic seriously affecting the older population. TRIAL REGISTRATION: The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (IV/2428- 2 /2020/EKU) and has been registered at clinicaltrials.gov ( NCT04321928 ) on 25 March 2020.

Oral clefts with associated anomalies: methodological issues.

OBJECTIVE: To discuss methodological factors that account for the wide variation in the reported prevalence rates of anomalies associated with oral clefts. CONCLUSIONS: The published prevalences of associated anomalies vary considerably because of the following: (1) differences in case definition and inclusion/exclusion criteria; (2) length of time after birth that cases are examined; (3) variability of clinical expression of associated anomalies; (4) knowledge and technology available to produce syndrome delineation; (5) selection of patients, sources of ascertainment, and sample size; and (6) true population differences and changes in frequency over time.

Oral clefts with associated anomalies: findings in the Hungarian Congenital Abnormality Registry.

BACKGROUND: Over the years, great efforts have been made to record the frequency of orofacial clefts in different populations. However, very few studies were able to account for the etiological and phenotypic heterogeneity of these conditions. Thus, data of cases with syndromic orofacial clefts from large population-based studies are infrequent. METHODS: Clinically recognized and notified syndromes and associations including cleft lip with or without cleft palate and other congenital anomalies were selected from the Hungarian Congenital Abnormality Registry (HCAR) between 1973 and 1982 and prevalence rates were calculated. RESULTS: Of 3,110 cases reported as having orofacial clefts, 653 had multiple congenital abnormalities. Of these, 60 (9.2%) had a known etiology (monogenic: 25 or 3.8%, chromosomal: 31 or 4.7%, teratogenic: 4 or 0.6%). Seventy-three subjects (11.2%) had schisis in addition to the oral cleft. Skeletal anomalies were the most common malformations among cases with cleft lip with/without cleft palate (CL/P) and cleft palate (CP). Disorders of the central nervous system and cardiovascular malformations were also frequently associated. CONCLUSION: Surveillance systems, such as the HCAR, provide useful information about prevalence rates of congenital anomalies in a population. However, in a field where new syndromes are being discovered and classifications regularly updated, these rates should only be accepted as provisional.

Protective effect of hyperemesis gravidarum for nonsyndromic oral clefts.

OBJECTIVE: To evaluate whether hyperemesis gravidarum is associated with a decreased risk for nonsyndromic oral clefts and to examine the relationship between hyperemesis gravidarum, birth weight, and gestational age. METHODS: This was a population-based, matched case-control study of 1950 subjects with oral clefts (1368 with cleft lip with or without cleft palate; 582 with cleft palate) collected from the Hungarian Congenital Abnormality Registry and 1955 controls identified from the National Birth Registry. RESULTS: Fewer mothers of newborns with oral clefts had early-onset hyperemesis gravidarum than did mothers of controls (cleft lip with or without cleft palate: 83 cases and 121 controls, odds ratio [OR] = 0.67, 95% confidence interval [CI] 0.50, 0.89; cleft palate: 42 cases and 64 controls, OR = 0.63, 95% CI 0.42, 0.94). The use of dimenhydrinate was more common among mothers of subjects with cleft palate (OR = 2.47, 95% CI 1.11, 5.49), whereas iron seemed to have a protective effect against this condition (OR = 0.26, 95% CI 0.09, 0.80). Gestational age and birth weight were not significantly associated with hyperemesis gravidarum. CONCLUSION: This study suggests that hyperemesis gravidarum provides a protective effect against risk to oral clefts in newborns.

Birth weight and gestational age of newborns with cleft lip with or without cleft palate and with isolated cleft palate.

The birth weight and gestational age of 1368 newborns with isolated cleft lip with or without cleft palate and 582 with isolated cleft palate were compared to those of matched healthy controls. The results indicate that fetuses with oral clefts are at elevated risk of having low and very low birth weight, but not of having a premature birth. Speculations on a relationship between these findings and the presence of oral clefts are presented.