Projections of mortality attributable to hot ambient temperatures in Cyprus under moderate and extreme climate change scenarios.

BACKGROUND: Heat-related mortality has become a growing public health concern in light of climate change. However, few studies have quantified the climate-attributable health burden in Cyprus, a recognized climate change hotspot. This study aims to estimate the heat-related mortality in Cyprus for all future decades in the 21st century under moderate (SSP2-4.5) and extreme (SSP5-8.5) climate scenarios. METHODS: We applied distributed lag non-linear models to estimate the baseline associations between temperature and mortality from 2004 to 2019 (data obtained from Department of Meteorology of the Ministry of Agriculture, Rural Development and Environment and the Health Monitoring Unit of the Cyprus Ministry of Health). The relationships were then extrapolated to future daily mean temperatures derived from downscaled global climate projections from General Circulation Models. Attributable number of deaths were calculated to determine the excess heat-related health burden compared to the baseline decade of 2000-2009 in the additive scale. The analysis process was repeated for all-cause, cardiovascular, and respiratory mortality and mortality among males, females, and adults younger or older than 65. We assumed a static population and demographic structure, no adaptation to hot temperatures over time, and did not evaluate potential interaction between temperature and humidity. RESULTS: Compared to 2000-2009, heat-related total mortality is projected to increase by 2.7% (95% empirical confidence interval: 0.6, 4.0) and 4.75% (2.2, 7.1) by the end of the century in the moderate and extreme climate scenarios, respectively. Cardiovascular disease is expected to be an important cause of heat-related death with projected increases of 3.4% (0.7, 5.1) and 6% (2.6, 9.0) by the end of the century. Reducing carbon emission to the moderate scenario can help avoid 75% of the predicted increase in all-cause heat-related mortality by the end of the century relative to the extreme scenario. CONCLUSIONS: Our findings suggest that climate change mitigation and sustainable adaptation strategies are crucial to reduce the anticipated heat-attributable health burden, particularly in Cyprus, where adaptation strategies such as air conditioning is nearing capacity.

Airborne particle radioactivity during desert dust days in Cyprus.

Mediterranean countries are often affected by desert dust storms, which have significant effects on the environment and public health. We compared airborne particle radioactivity levels during desert dust and non-dust days in Cyprus. Gross α- and ß-radioactivity from Total Suspended Particle (TSP) samples, collected at two urban routine monitoring stations in Limassol and Nicosia, were available for the period 2017-2020 and 2008-2020, respectively. Radionuclides 137Cs and 40K, from TSP samples, were also available from a semi-industrial monitoring station in Nicosia during 2008-2020. Information on desert dust presence, dust origin, particulate matter (PM) levels, and solar activity (KP index and solar sunspot numbers - SSN) were also obtained. We used linear regression models adjusting for seasonality and long-term trends, and solar activity to assess the effect of dust storms on TSP gross α- and ß-, and 137Cs and 40K radioactivity levels. Gross α- and ß-radioactivity, and 137Cs and 40K radioactivity levels were significantly higher on days with desert dust compared to days characterized with no influence of desert dust. Levels of gross α- and ß-radioactivity during dust days were higher when dust originated from the Middle East deserts than from the Sahara Desert. The same trend was observed for the ratios 137Cs to 40K and 137Cs to PM10. Conversely, ratios of TSP gross α- and ß-radioactivity to PM10 were significantly lower during desert dust days in comparison to days without dust influence. This study suggests that desert dust increase both TSP gross α- and ß-radioactivity, as well as 137Cs and 40K radioactivity levels. Further studies should clarify the contribution of anthropogenic and other natural sources to the emission or transportation of particles radioactivity, to better mitigate future exposures.

Temporal trends in temperature-related mortality and evidence for maladaptation to heat and cold in the Eastern Mediterranean region.

The eastern Mediterranean region is characterized by rising temperature trends exceeding the corresponding global averages and is considered a climate change hot-spot. Although previous studies have thoroughly investigated the impact of extreme heat and cold on human mortality and morbidity, both for the current and future climate change scenarios, the temporal trends in temperature-related mortality or the potential historical adaptation to heat and cold extremes has never been studied in this region. This study focuses on cardiovascular mortality and assesses the temporal evolution of the Minimum Mortality Temperature (MMT), as well as the disease-specific cold- and heat-attributable fraction of mortality in three typical eastern Mediterranean environments (Athens, Thessaloniki and Cyprus). Data on daily cardiovascular mortality (ICD-10 code: I00-I99) and meteorological parameters were available between 1999 and 2019 for Athens, 1999 to 2018 for Thessaloniki and 2004 to 2019 for Cyprus. Estimation of cardiovascular MMT and mortality fractions relied on time-series Poisson regressions with distributed lag nonlinear models (DLNM) controlling for seasonal and long-term trends, performed over a series of rolling sub-periods at each site. The results indicated that in Athens, the MMT decreased from 23 °C (67.5th percentile) in 1999-2007 to 21.8 °C (62nd percentile) in 2011-2019, while in Cyprus the MMT decreased from 26.3 °C (79th percentile) in 2004-2012 to 23.9 °C (66.5th percentile) in 2011-2019. In Thessaloniki, the decrease in MMT was rather negligible. In all regions under study, the fractions of mortality attributed to both cold and heat followed an upward trend throughout the years. In conclusion, the demonstrated increase in cold attributable fraction and the decreasing temporal trend of MMT across the examined sites are suggestive of maladaptation to extreme temperatures in regions with warm climate and highlight the need for relevant public health policies and interventions.

Improved childhood asthma control after exposure reduction interventions for desert dust and anthropogenic air pollution: the MEDEA randomised controlled trial.

INTRODUCTION: Elevated particulate matter (PM) concentrations of anthropogenic and/or desert dust origin are associated with increased morbidity among children with asthma. OBJECTIVE: The Mitigating the Health Effects of Desert Dust Storms Using Exposure-Reduction Approaches randomised controlled trial assessed the impact of exposure reduction recommendations, including indoor air filtration, on childhood asthma control during high desert dust storms (DDS) season in Cyprus and Greece. DESIGN, PARTICIPANTS, INTERVENTIONS AND SETTING: Primary school children with asthma were randomised into three parallel groups: (a) no intervention (controls); (b) outdoor intervention (early alerts notifications, recommendations to stay indoors and limit outdoor physical activity during DDS) and (c) combined intervention (same as (b) combined with indoor air purification with high efficiency particulate air filters in children's homes and school classrooms. Asthma symptom control was assessed using the childhood Asthma Control Test (c-ACT), spirometry (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC)) and fractional exhaled nitric oxide (FeNO). RESULTS: In total, 182 children with asthma (age; mean=9.5, SD=1.63) were evaluated during 2019 and 2021. After three follow-up months, the combined intervention group demonstrated a significant improvement in c-ACT in comparison to controls (ß=2.63, 95% CI 0.72 to 4.54, p=0.007), which was more profound among atopic children (ß=3.56, 95% CI 0.04 to 7.07, p=0.047). Similarly, FEV1% predicted (ß=4.26, 95% CI 0.54 to 7.99, p=0.025), the need for any asthma medication and unscheduled clinician visits, but not FVC% and FeNO, were significantly improved in the combined intervention compared with controls. CONCLUSION: Recommendations to reduce exposure and use of indoor air filtration in areas with high PM pollution may improve symptom control and lung function in children with asthma. TRIAL REGISTRATION NUMBER: NCT03503812.

Epidemiology, risk factors, clinical presentation and complications of late-onset neonatal sepsis among preterm neonates in Cyprus: a prospective case-control study.

BACKGROUND: Late-onset neonatal sepsis (LOS) is common in preterm neonates, with increasing incidence in recent years. In the present study, we examined the epidemiology, clinical presentation, and complications of LOS in Cyprus and quantified possible risk factors for the development of this condition. METHODS: The study subjects were preterm neonates admitted in the Neonatal Intensive Care Unit (NICU) of Archbishop Makarios III Hospital, the only neonatal tertiary centre in Cyprus. A prospective, case-control study was designed, and carried out between April 2017-October 2018. Depending on blood culture results, preterm neonates were classified as "Confirmed LOS": positive blood culture - microorganism isolated and LOS symptoms, "Unconfirmed LOS": negative blood culture and LOS symptoms, and "Controls" group: negative blood culture and absence of LOS symptoms. Comparisons between the 3 groups were performed and the associations between demographic, clinical and treatment characteristics with the likelihood of LOS were assessed using univariate and multivariate logistic regression. RESULTS: A total of 350 preterm neonates were included in the study and the incidence of LOS was 41.1%. 79 (22.6%) and 65 (18.6%) neonates were classified as "Confirmed LOS", and "unconfirmed LOS" cases respectively while 206 (58.9%) served as controls. The rate of confirmed LOS ranged from 12.2% in moderate to late preterm neonates to 78.6% in extremely preterm neonates. In the multivariate model, we demonstrated an independent association between LOS and duration of hospitalization (OR: 1.06, 95%CI: 1.01-1.10), duration of ventilation (OR: 1.23, 95%CI: 1.07-1.43) and necrotising enterocolitis (OR: 3.41, 95%CI: 1.13-10.25). CONCLUSIONS: The present study highlights the epidemiology of LOS in preterm neonates in Cyprus and its association with the duration of ventilation and hospitalization as well as with necrotizing enterocolitis. Establishment of protocols for the prevention of nosocomial infections during hospitalization in the NICUs and mechanical ventilation of preterm neonates is recommended.

The impact of COVID-19 lockdown measures on symptoms control in children with asthma: A systematic review and meta-analysis of observational cohort studies.

OBJECTIVES: Reported reductions in emergency department visits and hospitalizations for asthma in previous studies have suggested a beneficial effect of the coronavirus disease of 2019 (COVID-19) lockdown measures on asthma morbidity. Nevertheless, studies relying on administrative data may overestimate the true impact of lockdowns due to changes in health-seeking behavior and reduced availability of pediatric asthma services during the pandemic. In this study, we systematically reviewed the literature and identified observational cohort studies that focused on nonadministrative data to assess the true impact of COVID-19 lockdowns on symptom control in children with asthma. METHODS: A systematic literature search was conducted between January 2020 and August 2022 (International Prospective Register of Systematic Reviews ID: CRD42022354369). The impact of COVID-19 lockdowns across studies was expressed as a standardized mean difference (SMD) for continuous outcomes and as a summary relative risk (RR) for binary outcomes. RESULTS: During the lockdown periods, the pooled asthma symptoms control test score (SMD: 1.99, 95% confidence interval [CI]: 0.75, 3.24, I2 : 98.4%) and the proportion of children with well-controlled asthma (RR: 1.35, 95% CI: 1.06, 1.71, I2 : 77.6%) were significantly increased. On the other hand, the pooled proportion of children with poorly controlled asthma (RR: 0.47, 95% CI: 0.38, 0.57, I2 : 0.0%) was significantly decreased. CONCLUSIONS: During COVID-19 lockdowns, asthma symptoms and breakthrough disease exacerbations were significantly reduced in children with asthma. Further research is warranted on potential interventions aiming to enhance asthma control after the pandemic while taking into consideration their acceptability and potential tradeoffs.

MEDEA randomised intervention study protocol in Cyprus, Greece and Israel for mitigation of desert dust health effects in adults with atrial fibrillation.

INTRODUCTION: Mediterranean countries experience frequent desert dust storm (DDS) events originating from neighbouring Sahara and Arabian deserts, which are associated with significant increase in mortality and hospital admissions, mostly from cardiovascular and respiratory diseases. Short-term exposure to ambient air pollution is considered as a trigger for symptomatic exacerbations of pre-existing paroxysmal atrial fibrillation (AF) and other types of heart arrhythmia. The Mitigating the Health Effects of Desert Dust Storms Using Exposure-Reduction Approaches clinical randomised intervention study in adults with AF is funded by EU LIFE+programme to evaluate the efficacy of recommendations aiming to reduce exposure to desert dust and related heart arrhythmia effects. METHODS AND ANALYSIS: The study is performed in three heavily exposed to desert dust regions of the Eastern Mediterranean: Cyprus, Israel and Crete-Greece. Adults with paroxysmal AF and implanted pacemaker are recruited and randomised to three parallel groups: (a) no intervention, (b) interventions to reduce outdoor exposure to desert dust, (c) interventions to reduce both outdoor and indoor exposure to particulate matter during desert dust episodes. Eligible participants are enrolled on a web-based platform which communicates, alerts and makes exposure reduction recommendations during DDS events. Exposure changes are assessed by novel tools (smartwatches with Global Positioning System and physical activity sensors, air pollution samplers assessing air quality inside and outside participant's homes, etc). Clinical outcomes include the AF burden expressed as the percentage of time with paroxysmal AF over the total study period, the incidence of ventricular arrhythmia episodes as recorded by the participants' pacemakers or cardioverters/defibrillators and the disease-specific Atrial Fibrillation Effect on QualiTy-of-Life questionnaire. ETHICS AND DISSEMINATION: Local bioethics' authorities approved the study at all sites, according to national legislations (Cyprus: National Bioethics Committee, Data Protection Commissioner and Ministry of Health; Greece, Scientific Committee and Governing Board of the University General Hospital of Heraklion; Israel: Institutional Review Board ('Helsinki committee') of the Soroka University Medical Center). The findings will be publicised in peer-reviewed scientific journals, in international conferences and in professional websites and newsletters. A summary of the results and participants' interviews will be included in a documentary in English, Greek and Hebrew. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier; NCT03503812.

Setup of Consumer Wearable Devices for Exposure and Health Monitoring in Population Studies.

Wearable sensors, which are often embedded in commercial smartwatches, allow for continuous and non-invasive health measurements and exposure assessments in clinical studies. Nevertheless, the real-life application of these technologies in studies involving a large number of participants for a significant observation period may be hindered by several practical challenges. In this study, we present a modified protocol from a previous intervention study for the mitigation of health effects from desert dust storms. The study involved two distinct population groups: asthmatic children aged 6-11 years and elderly patients with atrial fibrillation (AF). Both groups were equipped with a smartwatch for the assessment of physical activity (using a heart rate monitor, pedometer, and accelerometer) and location (using GPS signals to locate individuals in indoor "at home" or outdoor microenvironments). The participants were required to wear the smartwatch equipped with a data collection application on a daily basis, and data were transmitted via a wireless network to a centrally administered data collection platform for the near real-time assessment of compliance. Over a period of 26 months, more than 250 children and 50 patients with AF participated in the aforementioned study. The main technical challenges identified included restricting access to standard smartwatch features, such as gaming, internet browser, camera, and audio recording applications, technical issues, such as loss of GPS signal, especially in indoor environments, and the internal smartwatch settings interfering with the data collection application. The aim of this protocol is to demonstrate how the use of publicly available application lockers and device automation applications made it possible to address most of these challenges in a simple and cost-effective way. In addition, the inclusion of a Wi-Fi received signal strength indicator significantly improved indoor localization and largely minimized GPS signal misclassification. The implementation of these protocols during the roll-out of this intervention study in the spring of 2020 led to significantly improved results in terms of data completeness and data quality.

Responses of schoolchildren with asthma to recommendations to reduce desert dust exposure: Results from the LIFE-MEDEA intervention project using wearable technology.

Current public health recommendations for desert dust storms (DDS) events focus on vulnerable population groups, such as children with asthma, and include advice to stay indoors and limit outdoor physical activity. To date, no scientific evidence exists on the efficacy of these recommendations in reducing DDS exposure. We aimed to objectively assess the behavioral responses of children with asthma to recommendations for reduction of DDS exposure. In two heavily affected by DDS Mediterranean regions (Cyprus & Crete, Greece), schoolchildren with asthma (6-11 years) were recruited from primary schools and were randomized to control (business as usual scenario) and intervention groups. All children were equipped with pedometer and GPS sensors embedded in smartwatches for objective real-time data collection from inside and outside their classroom and household settings. Interventions included the timely communication of personal DDS alerts accompanied by exposure reduction recommendations to both the parents and school-teachers of children in the intervention group. A mixed effect model was used to assess changes in daily levels of time spent, and steps performed outside classrooms and households, between non-DDS and DDS days across the study groups. The change in the time spent outside classrooms and homes, between non-DDS and DDS days, was 37.2 min (pvalue = 0.098) in the control group and -62.4 min (pvalue < 0.001) in the intervention group. The difference in the effects between the two groups was statistically significant (interaction pvalue < 0.001). The change in daily steps performed outside classrooms and homes, was -495.1 steps (pvalue = 0.350) in the control group and -1039.5 (pvalue = 0.003) in the intervention group (interaction pvalue = 0.575). The effects on both the time and steps performed outside were more profound during after-school hours. To summarize, among children with asthma, we demonstrated that timely personal DDS alerts and detailed recommendations lead to significant behavioral changes in contrast to the usual public health recommendations.

Improved indoor air quality during desert dust storms: The impact of the MEDEA exposure-reduction strategies.

Desert dust storms (DDS) are natural events that impact not only populations close to the emission sources but also populations many kilometers away. Countries located across the main dust sources, including countries in the Eastern Mediterranean, are highly affected by DDS. In addition, climate change is expanding arid areas exacerbating DDS events. Currently, there are no intervention measures with proven, quantified exposure reduction to desert dust particles. As part of the wider "MEDEA" project, co-funded by LIFE 2016 Programme, we examined the effectiveness of an indoor exposure-reduction intervention (i.e., decrease home ventilation during DDS events and continuous use of air purifier during DDS and non-DDS days) across homes and/or classrooms of schoolchildren with asthma and adults with atrial fibrillation in Cyprus and Crete-Greece. Participants were randomized to a control or intervention groups, including an indoor intervention group with exposure reduction measures and the use of air purifiers. Particle sampling, PM10 and PM2.5, was conducted in participants' homes and/or classrooms, between 2019 and 2022, during DDS-free weeks and during DDS days for as long as the event lasted. In indoor and outdoor PM10 and PM2.5 samples, mass and content in main and trace elements was determined. Indoor PM2.5 and PM10 mass concentrations, adjusting for premise type and dust conditions, were significantly lower in the indoor intervention group compared to the control group (PM2.5-intervention/PM2.5-control = 0.57, 95% CI: 0.47, 0.70; PM10-intervention/PM10-control = 0.59, 95% CI: 0.49, 0.71). In addition, the PM2.5 and PM10 particles of outdoor origin were significantly lower in the intervention vs. the control group (PM2.5 infiltration intervention-to-control ratio: 0.49, 95% CI: 0.42, 0.58; PM10 infiltration intervention-to-control ratio: 0.68, 95% CI: 0.52, 0.89). Our findings suggest that the use of air purifiers alongside decreased ventilation measures is an effective protective measure that reduces significantly indoor exposure to particles during DDS and non-DDS in high-risk population groups.

Pediatric asthma symptom control during lockdown for the COVID-19 pandemic in Spring 2020: A prospective community-based study in Cyprus and Greece.

OBJECTIVES: To prospectively quantify at the community level changes in asthma symptom control and other morbidity indices, among asthmatic schoolchildren in response to coronavirus disease 2019 (COVID-19) lockdown measures. METHODS: In Spring 2019 and Spring 2020, we prospectively assessed monthly changes in pediatric asthma control test (c-ACT), asthma medication usage, infections and unscheduled visits for asthma among schoolchildren with active asthma in Cyprus and Greece. We compared asthma symptom control and other morbidity indices before and during lockdown measures, while participants' time spent at home was objectively assessed by wearable sensors. RESULTS: A total of 119 asthmatic children participated in the study during Spring 2020. Compared to a mean baseline (pre-COVID-19 lockdown) c-ACT score of 22.70, adjusted mean increases of 2.58 (95% confidence interval [CI]: 1.91, 3.26, p < 0.001) and 3.57 (95% CI: 2.88, 4.27, p < 0.001) in the 2nd and 3rd monthly assessments were observed after implementation of lockdown measures. A mean increase in c-ACT score of 0.32 (95% CI: 0.17, 0.47, p < 0.001) was noted per 10% increase in the time spent at home. Improvement was more profound in children with severe asthma, while significant reductions in infections, asthma medication usage and unscheduled visits for asthma were also observed. During Spring 2019, 39 children participated in the study in the absence of lockdown measures and no changes in c-ACT or other indices of disease severity were observed. CONCLUSIONS: Clinically meaningful improvements in asthma symptom control, among asthmatic schoolchildren were observed during the COVID-19 lockdown measures in Spring 2020. Improvements were independently associated with time spent at home and were more profound in the children with severe asthma.

Observational study of health utilities in adult primary ciliary dyskinesia patients: preliminary data on associations with molecular diagnosis, clinical phenotype and HRQOL measures.

Background: Primary ciliary dyskinesia (PCD) is a congenital disorder characterized by chronic respiratory morbidity. To date, there is no information on PCD-specific preference-based quality of life measures such as health utilities (HU). We cross-sectionally assessed HU in adult PCD patients and explored relationships with genotype, phenotype and quality of life (QOL)-PCD scales. Methods: Diagnostic testing was performed according to international guidelines, while participants completed the visual analog scale (VAS), time trade off (TTO), standard gamble (SG), and EuroQol 5 dimensions (EQ5D) HU instruments, as well as the QOL-PCD questionnaire. Hierarchical regression was used to identify the QOL-PCD scales that are most predictive of HU. Results: Among 31 patients, median HU are 0.75 (VAS), 0.86 (EQ5D), 0.91 (TTO) and 0.99 (SG). The underlying genotype is not associated with HU measures. VAS and EQ5D are associated with lung function, while TTO and SG values are not sensitive to any of the examined factors. Among the QOL-PCD scales, physical functioning and lower respiratory symptoms explained much of VAS (R2= 0.419) and EQ5D (R2= 0.538) variability. Conclusions: Our study demonstrates that HU elicitation in PCD is feasible using both direct and indirect methods. Overall, HU scores are relatively high among adult patients, with higher scores observed in SG and TTO, followed by EQ5D and VAS. VAS and EQ5D HU values are sensitive to lung function as well as to QOL-PCD physical functioning and lower respiratory symptom scores.

Health effects of desert dust storm events in the south-eastern Mediterranean: perceptions and practices of local stakeholders.

BACKGROUND: The south-eastern Mediterranean experiences frequent desert dust storm events (DDS) that have been shown to be associated with adverse health effects. AIMS: This study assessed the perceptions and practices towards DDS of local authorities and stakeholders from 3 countries in the region, Cyprus, Greece and Israel. METHODS: Between October 2017 and April 2018, we administered a semi-structured questionnaire to regulatory authorities involved in public protection from DDS as well as social stakeholders in the 3 countries. The questionnaire addressed their knowledge regarding DDS, perceptions on the relationship between DDS and health effects and relevant actions taken towards public protection. RESULTS: Out of 58 stakeholders contacted, 49 participated in the study (84.5% response rate). Fourteen (28.6%) were regulatory authorities and 35 (71.4%) were social stakeholders. All responders were familiar with DDS but several underestimated the frequency of events while the majority (73%) instinctively reported that elders, children and respiratory patients are susceptible subpopulations. Nevertheless, 71% were unaware of a national policy on DDS, or considered that this was lacking in their country. Although several stakeholders reportedly receive questions from the public regarding DDS effects, only few reply according to a pre-determined action plan. CONCLUSIONS: Regulatory authorities and social stakeholders in Cyprus, Greece and Israel are characterized by good knowledge of DDS and associated health effects, although implementation of pre-determined action plans for public protection is limited. Future efforts should concentrate on increasing awareness among stakeholders and the public and developing national policies, including effective measures to minimize DDS exposure.

Demographic characteristics, clinical and laboratory features, and the distribution of pathogenic variants in the CFTR gene in the Cypriot cystic fibrosis (CF) population demonstrate the utility of a national CF patient registry.

BACKGROUND: Specialized clinical care for cystic fibrosis (CF) in Cyprus, a small island country, has been implemented since the 1990s. However, only recently, a national CF patient registry has been established for the systematic recording of patients' data. In this study, we aim to present data on the epidemiological, genotypic and phenotypic features of CF patients in the country from the most recent data collection in 2019, with particular emphasis on notable rare or unique cases. RESULTS: Overall, data from 52 patients are presented, 5 of whom have deceased and 13 have been lost to follow-up in previous years. The mean age at diagnosis was 7.2 ± 12.3 years, and the mean age of 34 alive patients by the end of 2019 was 22.6 ± 13.2 years. Patients most commonly presented at diagnosis with acute or persistent respiratory symptoms (46.2%), failure to thrive or malnutrition (40.4%), and dehydration or electrolyte imbalance (32.7%). Sweat chloride levels were diagnostic (above 60 mmol/L) in 81.8% of examined patients. The most common identified mutation was p.Phe508del (F508del) (45.2%), followed by p.Leu346Pro (L346P) (6.7%), a mutation detected solely in individuals of Cypriot descent. The mean BMI and FEV1 z-scores were 0.2 ± 1.3 and - 2.1 ± 1.7 across all age groups, respectively, whereas chronic Pseudomonas aeruginosa colonization was noted in 26.9% of patients. The majority of patients (74.5%) were eligible to receive at least one of the available CFTR modulator therapies. In 25% of patients we recovered rare or unique genotypic profiles, including the endemic p.Leu346Pro (L346P), the rare CFTR-dup2, the co-segregated c.4200_4201delTG/c.489 + 3A > G, and the polymorphism p.Ser877Ala. CONCLUSIONS: CF patient registries are particularly important in small or isolated populations, such as in Cyprus, with rare or unique disease cases. Their operation is necessary for the optimization of clinical care provided to CF patients, enabling their majority to benefit from evolving advances in precision medicine.

Maternal and neonatal risk factors for neonatal respiratory distress syndrome in term neonates in Cyprus: a prospective case-control study.

BACKGROUND: Neonatal respiratory distress syndrome (NRDS) is strongly associated with premature birth, but it can also affect term neonates. Unlike the extent of research in preterm neonates, risk factors associated with incidence and severity of NRDS in term neonates are not well studied. In this study, we examined the association of maternal and neonatal risk factors with the incidence and severity of NRDS in term neonates admitted to Neonatal Intensive Care Unit (NICU) in Cyprus. METHODS: In a prospective, case-control design we recruited term neonates with NRDS and non-NRDS admitted to the NICU of Archbishop Makarios III hospital, the only neonatal tertiary centre in Cyprus, between April 2017-October 2018. Clinical data were obtained from patients' files. We used univariate and multivariate logistic and linear regression models to analyse binary and continuous outcomes respectively. RESULTS: During the 18-month study period, 134 term neonates admitted to NICU were recruited, 55 (41%) with NRDS diagnosis and 79 with non-NRDS as controls. In multivariate adjusted analysis, male gender (OR: 4.35, 95% CI: 1.03-18.39, p = 0.045) and elective caesarean section (OR: 11.92, 95% CI: 1.80-78.95, p = 0.01) were identified as independent predictors of NRDS. Among neonates with NRDS, early-onset infection tended to be associated with increased administration of surfactant (ß:0.75, 95% CI: - 0.02-1.52, p = 0.055). Incidence of pulmonary hypertension or systemic hypotension were associated with longer duration of parenteral nutrition (pulmonary hypertension: 11Vs 5 days, p < 0.001, systemic hypotension: 7 Vs 4 days, p = 0.01) and higher rate of blood transfusion (pulmonary hypertension: 100% Vs 67%, p = 0.045, systemic hypotension: 85% Vs 55%, p = 0.013). CONCLUSIONS: This study highlights the role of elective caesarean section and male gender as independent risk factors for NRDS in term neonates. Certain therapeutic interventions are associated with complications during the course of disease. These findings can inform the development of evidence-based recommendations for improved perinatal care.

Implementation of multigene panel NGS diagnosis in the national primary ciliary dyskinesia cohort of Cyprus: An island with a high disease prevalence.

We aimed to determine a genetic diagnosis in the national primary ciliary dyskinesia (PCD) cohort of Cyprus, an island with a high disease prevalence. We used targeted next-generation sequencing (NGS) of 39 PCD genes in 48 patients of Greek-Cypriot and other ancestries. We achieved a molecular diagnosis in 74% of the unrelated families tested. We identified 24 different mutations in 11 genes, 12 of which are novel. Homozygosity was more common in Greek-Cypriot than non-Greek-Cypriot patients (88% vs. 46.2%, p = .016). Four mutations (DNAH11:c.5095-2A>G, CFAP300:c.95_103delGCCGGCTCC, TTC25:c.716G>A, RSPH9:c.670+2T>C) were found in 74% of the diagnosed Greek-Cypriot families. Patients with RSPH9 mutations demonstrated higher nasal nitric oxide (57 vs. 15 nl/min, p <.001), higher forced expiratory volume in 1 s (-0.89 vs. -2.37, p = .018) and forced vital capacity (-1.00 vs. -2.16, p = .029) z scores than the rest of the cohort. Targeted multigene-panel NGS is an efficient tool for early diagnosis of PCD, providing insight into genetic disease epidemiology and improved patient stratification.

Use of wearable sensors to assess compliance of asthmatic children in response to lockdown measures for the COVID-19 epidemic.

Between March and April 2020, Cyprus and Greece health authorities enforced three escalated levels of public health interventions to control the COVID-19 pandemic. We quantified compliance of 108 asthmatic schoolchildren (53 from Cyprus, 55 from Greece, mean age 9.7 years) from both countries to intervention levels, using wearable sensors to continuously track personal location and physical activity. Changes in 'fraction time spent at home' and 'total steps/day' were assessed with a mixed-effects model adjusting for confounders. We observed significant mean increases in 'fraction time spent at home' in Cyprus and Greece, during each intervention level by 41.4% and 14.3% (level 1), 48.7% and 23.1% (level 2) and 45.2% and 32.0% (level 3), respectively. Physical activity in Cyprus and Greece demonstrated significant mean decreases by - 2,531 and - 1,191 (level 1), - 3,638 and - 2,337 (level 2) and - 3,644 and - 1,961 (level 3) total steps/day, respectively. Significant independent effects of weekends and age were found on 'fraction time spent at home'. Similarly, weekends, age, humidity and gender had an independent effect on physical activity. We suggest that wearable technology provides objective, continuous, real-time location and activity data making possible to inform in a timely manner public health officials on compliance to various tiers of public health interventions during a pandemic.

The MEDEA childhood asthma study design for mitigation of desert dust health effects: implementation of novel methods for assessment of air pollution exposure and lessons learned.

BACKGROUND: Desert dust events in Mediterranean countries, originating mostly from the Sahara and Arabian deserts, have been linked to climate change and are associated with significant increase in mortality and hospital admissions from respiratory causes. The MEDEA clinical intervention study in children with asthma is funded by EU LIFE+ program to evaluate the efficacy of recommendations aiming to reduce exposure to desert dust and related health effects. METHODS: This paper describes the design, methods, and challenges of the MEDEA childhood asthma study, which is performed in two highly exposed regions of the Eastern Mediterranean: Cyprus and Greece-Crete. Eligible children are recruited using screening surveys performed at primary schools and are randomized to three parallel intervention groups: a) no intervention for desert dust events, b) interventions for outdoor exposure reduction, and c) interventions for both outdoor and indoor exposure reduction. At baseline visits, participants are enrolled on MEDena® Health-Hub, which communicates, alerts and provides exposure reduction recommendations in anticipation of desert dust events. MEDEA employs novel environmental epidemiology and telemedicine methods including wearable GPS, actigraphy, health parameters sensors as well as indoor and outdoor air pollution samplers to assess study participants' compliance to recommendations, air pollutant exposures in homes and schools, and disease related clinical outcomes. DISCUSSION: The MEDEA study evaluates, for the first time, interventions aiming to reduce desert dust exposure and implement novel telemedicine methods in assessing clinical outcomes and personal compliance to recommendations. In Cyprus and Crete, during the first study period (February-May 2019), a total of 91 children participated in the trial while for the second study period (February-May 2020), another 120 children completed data collection. Recruitment for the third study period (February-May 2021) is underway. In this paper, we also present the unique challenges faced during the implementation of novel methodologies to reduce air pollution exposure in children. Engagement of families of asthmatic children, schools and local communities, is critical. Successful study completion will provide the knowledge for informed decision-making both at national and international level for mitigating the health effects of desert dust events in South-Eastern Europe. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03503812 , April 20, 2018.

Registries and collaborative studies for primary ciliary dyskinesia in Europe.

Primary ciliary dyskinesia (PCD) is a rare inherited disease characterised by malfunctioning cilia leading to a heterogeneous clinical phenotype with many organ systems affected. There is a lack of data on clinical presentation, prognosis and effectiveness of treatments, making it mandatory to improve the scientific evidence base. This article reviews the data resources that are available in Europe for clinical and epidemiological research in PCD, namely established national PCD registries and national cohort studies, plus two large collaborative efforts (the international PCD (iPCD) Cohort and the International PCD Registry), and discusses their strengths, limitations and perspectives. Denmark, Cyprus, Norway and Switzerland have national population-based registries, while England and France conduct multicentre cohort studies. Based on the data contained in these registries, the prevalence of diagnosed PCD is 3-7 per 100 000 in children and 0.2-6 per 100 000 in adults. All registries, together with other studies from Europe and beyond, contribute to the iPCD Cohort, a collaborative study including data from over 4000 PCD patients, and to the International PCD Registry, which is part of the ERN (European Reference Network)-LUNG network. This rich resource of readily available, standardised and contemporaneous data will allow obtaining fast answers to emerging clinical and research questions in PCD.

Health related quality of life in adult primary Ciliary dyskinesia patients in Cyprus: development and validation of the Greek version of the QOL-PCD questionnaire.

BACKGROUND: The QOL-PCD questionnaire is a recently developed Health Related Quality of Life (HRQoL) instrument for Primary Ciliary Dyskinesia. The aim of this study was to translate the adult QOL-PCD questionnaire into Greek language and to conduct psychometric validation to assess its performance. METHODS: Forward translations to Greek and backward translation to English were performed, followed by cognitive interviews in 12 adult PCD patients. The finalized translated version was administered to a consecutive sample of 31 adult, Greek speaking PCD patients in Cyprus for psychometric validation, which included assessment of internal consistency, test-retest reliability, construct and convergent validity. Internal consistency was assessed by Cronbach's alpha test in terms of the overall and sub-scales. Test-retest reliability was assessed by repeat administration of the questionnaire within 2 weeks and calculation of the intra-class correlation (ICC). Construct validity was assessed by comparing different groups of patients based on a-priori hypotheses and convergent validity was evaluated by examining associations between the QOL-PCD and SF-36 questionnaires. RESULTS: Moderate to good internal consistency was observed (Cronbach's α: 0.46-0.88 across sub-scales) and test-retest reliability assessment demonstrated good repeatability for most scales (ICC: 0.67-0.91 across subscales). Patients of female gender, older age and lower lung function exhibited lower QOL-PCD scores in general, while high correlations for most QOL-PCD scales with corresponding SF-36 scales were observed, in particular for physical functioning (r = 0.78, p < 0.05). CONCLUSION: The adult version of QoL-PCD questionnaire has been translated according to international guidelines resulting to a cross-culturally validated Greek version which exhibited moderate to good metric properties in terms of internal consistency, stability, known-group and convergent validity.