Acceptability of Healthcare Professionals to Get Vaccinated against COVID-19 Two Weeks before Initiation of National Vaccination.

Background and Objectives The greatest challenge vaccines face is that of acceptance from the general population. Healthcare professionals' (HCPs) recommendations have significant influence on general public vaccination behavior. The aim of this study was to assess the willingness of HCPs to get vaccinated against COVID-19, two weeks before initiation of vaccinations. Materials and Methods: We conducted an anonymous online survey from 11-15 December 2020 among HCPs by emails delivered from the local medical and nursing stuff associations. Results: The 71.1% of 656 HCPs intended to accept vaccination, 5.9% did not and 23% were still undecided. The acceptance rate was higher in physicians (76.5%) and significantly lower in nurses (48.3%). Most of the responders who intended to accept vaccination were males (p = 0.01), physicians (p = 0.001), older (p = 0.02), married (p = 0.054) with children (p = 0.001), and had treated patients with COVID-19 (p < 0.001). In the multivariate logistic regression, the predictors of HCPs willingness to get vaccinated were parenthood (OR = 4.19, p = 0.003), being a physician (OR = 2.79, p = 0.04), and treating confirmed/suspected COVID-19 patients (OR = 2.87, p = 0.036). Conclusions: Low vaccination acceptance rate was found especially in nurses, and as this may have a negative impact in the vaccination compliance of the general public, interventional educational programs to enhance vaccination are crucial.

Acute effects of e-cigarette vaping on pulmonary function and airway inflammation in healthy individuals and in patients with asthma.

BACKGROUND AND OBJECTIVE: The acute effects of e-cigarettes have not been scientifically demonstrated yet. The aim of this study was to assess the acute changes in pulmonary function and airway inflammation in patients with asthma after vaping one e-cigarette. METHODS: Twenty-five smokers suffering from stable moderate asthma according to GINA guidelines with no other comorbidities and 25 healthy smokers matched with the baseline characteristics of the asthmatic patients were recruited. PFT, IOS, FeNO and EBC were performed before and after vaping one e-cigarette with nicotine. pH and concentrations of IL-1ß, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17A, TNF-α, ISO8 and LTB4 were measured in EBC. RESULTS: FFEV1/FVC ratio and PEF were reduced in asthmatic patients after e-cigarette. Z5Hz and R5Hz, R10Hz and R20Hz increased in both groups. FeNO and EBC pH increased by 3.60 ppb (P = 0.001) and 0.15 (P = 0.014) in asthmatic patients after e-cigarette, whereas they decreased in control group by 3.28 ppb (P < 0.001) and 0.12 (P = 0.064), respectively. The concentrations of IL-10, TNF-α and ISO8 in EBC increased in asthmatic patients after e-cigarette and the changes in concentrations of IL-1ß and IL-4 differed significantly between the two groups. CONCLUSION: E-cigarette vaping resulted in acute alteration of both pulmonary function and airway inflammation in stable moderate asthmatic patients.

Acute Effects of a Heat-Not-Burn Tobacco Product on Pulmonary Function.

Background and objectives: During the last decade, conventional tobacco smoking is experiencing a decline and new smoking products have been introduced. IQOS ("I-Quit-Ordinary-Smoking") is a type of "heat-not-burn" (HNB) tobacco product. The impact of IQOS on respiratory health is currently not defined. The objectives of this study were to evaluate the acute effects of IQOS on pulmonary function in non-smokers and current smokers. Materials and Methods: Fifty male healthy non-smokers and current smokers with no known co-morbidity underwent an exhaled CO measurement, oximetry (SaO2%), pulmonary function tests (flows, volumes and diffusion capacity), and a measurement of respiratory resistances with an impulse oscillometry system (IOS) before and immediately after IQOS use. Results: In the whole group of 50 participants, SaO2%, forced expiratory flow at 25% and 50% of vital capacity (FEF 25%, FEF 50%, respectively), peak expiratory flow (PEF), and diffusion lung capacity for carbon monoxide/VA (KCO) decreased significantly after IQOS use, whereas exhaled CO and airway resistance (R5 Hz, R10 Hz, r15 Hz, R20 Hz, R25 Hz, R35 Hz) increased. When the groups of smokers and non-smokers were compared, in both groups (all males, 25 smokers and 25 non-smokers), exhaled CO increased and SaO2% decreased after IQOS use (p < 0.001). In the group of non-smokers, PEF (pre 8.22 ± 2.06 vs. post 7.5 ± 2.16, p = 0.001) and FEF 25% (pre 7.6 ± 1.89 vs. 7.14 ± 2.06, p = 0.009) decreased significantly; respiratory resistances R20 Hz (pre 0.34 ± 0.1 vs. post 0.36 ± 0.09, p = 0.09) and R25 Hz (pre 0.36 ± 0.1 vs. post 0.38 ± 0.09, p = 0.08) increased almost significantly. In smokers, PEF (pre 7.69 ± 2.26 vs. post 7.12 ± 2.03, p = 0.007) and expiratory reserve volume (ERV) (pre 1.57 ± 0.76 vs. post1.23 ± 0.48, p = 0.03) decreased and R35 Hz (pre 0.36 ± 0.11 vs. post 0.39 ± 0.11, p = 0.047) increased. The differences in the changes after the use of IQOS did not differ between groups. Conclusions: IQOS had an impact on exhaled CO, SaO2%, and airways function immediately after use. Even though these changes were rather small to be considered of major clinical importance, they should raise concerns regarding the long-term safety of this product. Further research is needed for the short- and long-term effects of IQOS, especially in patients with respiratory disease.

Phenotyping Exercise Limitation in Systemic Sclerosis: The Use of Cardiopulmonary Exercise Testing.

BACKGROUND: Exercise impairment is a common symptom of systemic sclerosis (SSc), a disorder which is frequently complicated by cardiopulmonary involvement. OBJECTIVES: This study's aims were: (a) to define the prevalence and the potential causes of limited exercise capacity and (b) to study potential differences in clinical, radiological and functional characteristics and blood serology among SSc patients with exercise limitation of different etiology. METHODS: Prospectively collected data on SSc patients who had conducted full lung function testing, blood serology, thorax high-resolution computed tomography, Doppler echocardiogram and a maximal cardiopulmonary exercise testing (CPET) were retrospectively analyzed. Using a CPET algorithm, patients were characterized as having normal or subnormal exercise capacity (N), respiratory limitation (RL), left ventricular dysfunction (LVD) or pulmonary vasculopathy (PV). Group comparisons were conducted using either one-way ANOVA or the Kruskal-Wallis test. A p value <0.05 was considered significant. RESULTS: The study population consisted of 78 patients (53.7 ± 13.7 years old; 10.3% male). PV was present in 32.1%, LVD in 25.6% and RL in 10.2%, while 32.1% of the patients constituted the N group. The presence of antisclero-70 antibodies, low anaerobic threshold and low peak exercise capacity measures could discriminate LVD from the other groups. Low end-tidal carbon dioxide pressure and its change from rest to anaerobic threshold could discriminate between the PV, LVD and N groups, while respiratory restriction along with ventilatory inefficiency indices could differentiate the RL group from the rest. CONCLUSIONS: The combined evaluation of CPET gas exchange patterns with baseline measurements could discriminate the causes of exercise limitation among SSc patients.

Resting energy expenditure in OSAS: the impact of a single CPAP application.

PURPOSE: Data on the impact of obstructive sleep apnea syndrome (OSAS) and its treatment on resting energy expenditure (REE) are currently few and conflicting. The purpose of the present study was to investigate the impact of OSAS on REE, as measured before and after sleep, and the changes in REE after a single continuous positive airway pressure (CPAP) application, for the first time in literature. METHODS: This is a nested case-control study. From the initial study population, two groups were formed, based on the results of nocturnal polysomnography: a group of male OSAS patients and a group of male, age-matched non-OSAS controls. REE was measured in both groups before and after sleep by indirect calorimetry, while patients repeated REE measurements before and after a single nasal CPAP application. RESULTS: Ninety-two male OSAS patients (45.3 ± 12.8 years old) and 19 male non-OSAS controls (50.8 ± 11.7 years old) were studied. REE/lean body mass (LBM) was higher among patients compared to controls both pre- (29.6 ± 12 vs 22.9 ± 7.9 kcal/kg; p = 0.022, correspondingly) and post-sleep (26.4 ± 9.6 vs 21.6 ± 9 kcal/kg; p = 0.047 correspondingly). REE/LBM decreased significantly after sleep in OSAS patients (p = 0.002), but not in controls; this difference was most evident among patients with more severe disease and higher desaturation. A single nasal CPAP application diminished the pre-post REE/LBM difference (30.3 ± 8.2 vs 28.3 ± 10.3 kcal/kg; p = 0.265), but only among responders. CONCLUSIONS: In OSAS patients, REE values are high and vary significantly before and after sleep. A single nasal CPAP application diminishes this difference among responders, possibly through reversal of nocturnal desaturation.

The financial crisis has an impact in sleep medicine: experience of a sleep clinic in Greece.

OBJECTIVE: Greece has entered a long period of economic crisis with adverse effects in daily life. The aim of our study was to evaluate the impact of the economic crisis on the population visiting a sleep clinic between years 2008 and 2011. METHODS: Comparison of the number of patients, anthropometric data, symptoms, and treatment between 2008 (beginning of crisis) to 2011(great impact of crisis) was conducted. RESULTS: The number of patients significantly reduced in 2011(n = 127) compared with that in 2008 (n = 463) and 2009 (n = 465). The mean age, body mass index, and Epworth Sleepiness Scale did not differ between the years (52.2 ± 13.7 years, 33 ± 7.4 kg/m(2), and 11.4 ± 5.4, respectively). The main symptom of the patients was daytime sleepiness, and the symptoms that worsened in 2011 compared with 2008 were headaches (32.4 vs. 49.6 %, p < 0.001) and nightmares (44 vs. 75.9 %, p < 0.001). In 2008, 69.1 % of patients required treatment for obstructive sleep apnea syndrome with continuous positive airway pressure (CPAP), and 81.6 % of them received CPAP. In 2011, 67.7 % required treatment, but only 52.3 % received CPAP. CONCLUSIONS: The economic crisis can be reflected in the number of patients, their symptoms and their treatment options.

Does Smoking Affect OSA? What about Smoking Cessation?

The connection between smoking and Obstructive sleep apnea (OSA) is not yet clear. There are studies that have confirmed the effect of smoking on sleep disordered breathing, whereas others did not. Nicotine affects sleep, as smokers have prolonged total sleep and REM latency, reduced sleep efficiency, total sleep time, and slow wave sleep. Smoking cessation has been related with impaired sleep. The health consequences of cigarette smoking are well documented, but the effect of smoking cessation on OSA has not been extensively studied. Smoking cessation should improve OSA as upper airway oedema may reduce, but there is limited data to support this hypothesis. The impact of smoking cessation pharmacotherapy on OSA has been studied, especially for nicotine replacement therapy (NRT). However, there are limited data on other smoking cessation medications as bupropion, varenicline, nortriptyline, clonidine, and cytisine. The aim of this review was to explore the current evidence on the association between smoking and OSA, to evaluate if smoking cessation affects OSA, and to investigate the possible effects of different pharmacologic strategies offered for smoking cessation on OSA.

Sleep Disorders and Mental Stress of Healthcare Workers during the Two First Waves of COVID-19 Pandemic: Separate Analysis for Primary Care.

Background: During the recent pandemic, Healthcare Professionals (HCPs) presented a significant prevalence of psychological health problems and sleep disturbances. The aim of this study was to assess the impact of COVID-19 on HCPs' sleep and mental stress with a separate analysis for primary care HCPs. Methods: A cross-sectional observational study with an online anonymized, self-reported questionnaire was conducted in May 2020 (1st wave) and repeated in December 2020 (2nd wave). Patient health questionnaire-4 (PHQ-4), dimensions of anger reactions-5 (DAR-5) scale, 3-item UCLA loneliness scale (LS) and sleep condition indicator (SCI) were used. Results: Overall, 574 participants were included from the 1st wave, 514 from the 2nd and 469 were followed during both. Anxiety and depression were significantly higher during the 2nd wave vs. the 1st (32.8% vs. 12.7%, p < 0.001 and 37.7% vs. 15.8%, p < 0.001). During the 2nd wave, HCPs scored significantly higher in DAR-5 (9.23 ± 3.82 vs. 7.3 ± 3.3, p < 0.001) and LS (5.88 ± 1.90 vs. 4.9 ± 1.9, p < 0.001) with worse sleep quality SCI (23.7 ± 6.6 vs. 25.4 ± 3.2, p < 0.001). This was more evident in primary care HCPs. Significant correlations were found between SCI and PHQ4, DAR5 and LS. Conclusion: There is a need to support HCPs' mental health and sleep, especially in those working in primary care.

Spirometry values in a Greek population: is there an appropriate reference equation?

BACKGROUND AND OBJECTIVE: Most published reference values for lung function test (LFT) parameters introduce systematic bias. The aim of this study was to compare measured values of FEV(1) and FVC with the corresponding normal predicted values in a Greek population, and to produce reference equations for LFT parameters in this population. METHODS: In a cross-sectional study conducted in Macedonia, Greece, 1080 adult healthy, non-smokers (432 men, 648 women, aged 18-80 years), underwent spirometry. Measured values of FVC and FEV(1) were compared with predicted values determined using three existing sets of reference equations: one recently derived from a European population and two others widely used in Europe (European Coal and Steel Community; ECSC) and the USA (National Health and Nutrition Examination Survey; NHANES III). Height and age were entered into the multivariate regression analysis to produce reference equations for LFT parameters. RESULTS: All three published sets of equations underpredicted FEV(1) in men. FVC was accurately predicted by all equations except NHANES III. The discrepancy was even greater among women; the ECSC equation underpredicted both FEV(1) and FVC, the NHANES III equation overpredicted both FEV(1) and FVC, while the third set of equations accurately predicted FEV(1) but overpredicted FVC. The derived reference equation for FEV(1) in men was -0.28 × age + 0.057 × height - 4.91, and in women -0.021 × age + 0.039 × height - 2.58. The derived reference equation for FVC in men was -0.28 × age + 0.071 × height - 6.763, and in women -0.019 × age + 0.056 × height - 5.018. CONCLUSIONS: Measured FEV(1) and FVC values in a Greek population differed significantly from those predicted using previously published reference equations. The new locally derived spirometry reference equations may be more suitable for evaluation of lung function in everyday practice.

Exercise capacity in idiopathic pulmonary fibrosis: the effect of pulmonary hypertension.

BACKGROUND AND OBJECTIVE: Increased pulmonary arterial pressure (PAP) usually coexists with impaired lung function in IPF. Data on the effect of pulmonary hypertension (PH) on cardiopulmonary responses during exercise in IPF patients is very limited. We sought to investigate the impact of PH on exercise capacity and the correlation between systolic PAP (sPAP) and pulmonary function testing, as well as cardiopulmonary exercise parameters, in patients with IPF and PH. METHODS: Eighty-one consecutive patients with IPF, who were evaluated over a 6-year period, were retrospectively studied. Patients underwent pulmonary function testing, Doppler echocardiography and maximal cardiopulmonary exercise testing. PH was defined as sPAP > 35 mm Hg. RESULTS: PH was diagnosed in 57% of the patients. Categorization of patients according to severity of PH indicated a significant reduction in maximum work rate, peak O(2) uptake, anaerobic threshold and peak O(2) pulse in those with sPAP > 50 mm Hg. In IPF patients with PH, estimated sPAP correlated with peak O(2) uptake, anaerobic threshold, peak O(2) pulse and end-tidal CO(2) at anaerobic threshold, while the strongest correlation was between sPAP and ventilatory equivalent for CO(2) at anaerobic threshold (r = 0.611, P < 0.001). There were no differences in pulmonary function or exercise parameters indicative of lung volume reduction, across the patient categories, and none of these parameters correlated with sPAP. CONCLUSIONS: PH has a negative impact on exercise capacity in IPF patients. In IPF patients with PH, resting sPAP correlated with exercise parameters indicative of gas exchange and circulatory impairment, but not with defective lung mechanics.

Anemia of chronic disease in chronic obstructive pulmonary disease: a case-control study of cardiopulmonary exercise responses.

BACKGROUND: Anemia may be present in patients with chronic obstructive pulmonary disease (COPD) and further impair their functional capacity. OBJECTIVES: This study investigated the prevalence of anemia of chronic disease (ACD) in COPD patients and its impact on dyspnea and exercise capacity, utilizing cardiopulmonary exercise testing (CPET). METHODS: ACD prevalence was assessed in 283 consecutive patients with stable COPD (263 males, 60 females; age 60.31 ± 5.34 years; percent forced expiratory volume in 1 s 46.94 ± 6.12). ACD diagnosis was based on a combination of clinical and laboratory parameters [hemoglobin (Hb) <13 g/dl for males, <12 g/dl for females; ferritin >30 ng/ml; total iron-binding capacity <250 µg/dl, and transferrin saturation rate between 15 and 50%]. Twenty-seven patients who were identified with ACD (cases) and 27 matched nonanemic patients (controls) completed maximal CPET, and data were compared between the groups. RESULTS: ACD was diagnosed in 29 patients, which represents a prevalence of 10.24%; the severity of anemia was generally mild (mean Hb: 12.19 ± 0.66 g/dl). Patients with ACD had a higher Medical Research Council dyspnea score compared to controls (2.78 ± 0.44 vs. 2.07 ± 0.55; p <0.001) and lower peak O(2) uptake (VO(2)) (59.54 ± 17.17 vs. 71.26 ± 11.85% predicted; p <0.05), peak work rate (54.94 ± 21.42 vs. 68.72 ± 20.81% predicted; p <0.05) and peak VO(2)/heart rate (69.07 ± 17.26 vs. 82.04 ± 18.22% predicted; p <0.05). There was also a trend for a lower anaerobic threshold (48.48 ± 15.16 vs. 55.42 ± 9.99% predicted; p = 0.062). No exercise parameter indicative of respiratory limitation differed between the groups. CONCLUSIONS: ACD occurs in approximately 10% of stable COPD patients and has a negative impact on dyspnea and circulatory efficiency during exercise.

The use of open source and Web2.0 in developing an integrated EHR and e-learning system for the Greek Smoking Cessation Network.

Technologies of information and communication are incrementally integrated with all facets of healthcare practice and education. Although Electronic Health Records (EHRs) have long been used in healthcare the introduction of open source tools has empowered their further expansion of use. Simultaneously the use of Web 2.0 tools has opened up new ways of enhancing both healthcare practice and education. In this paper, we describe our approach towards the development of an integrated system supporting the smoking cessation network initiatives in the Greek public hospitals. The system combines the availability of an open source, web based EHR subsystem, with a Web 2.0 facilitated e-learning component for supporting continuing medical education and promoting public awareness.

Sleep questionnaires for the screening of obstructive sleep apnea in patients with type 2 diabetes mellitus compared with non-diabetic patients.

BACKGROUND: Several tools have been used to screen for obstructive sleep apnea (OSA). Evaluation of the predictive performance of different questionnaires is essential in patients with type 2 diabetes mellitus (T2DM) because the prevalence of OSA in this population is high. The aim of this study was to evaluate different sleep questionnaires to identify T2DM patients with OSA, and to compare the predictive values of these questionnaires with a matched sample of non-diabetic patients. METHODS: The study was a retrospective study of two patients groups (n = 350 with T2DM, n = 350 without T2DM) visiting a sleep clinic and matched by age, gender, body mass index, and the apnea-hypopnea index (AHI). Symptoms of OSA and Epworth Sleepiness Scale (ESS), STOP-Bang, Berlin questionnaire, and Athens insomnia scale (AIS) scores were compared, and sleep studies were performed. RESULTS: Diabetic patients with OSA complained more frequently of nocturia (P = 0.025), morning headaches (P = 0.04), restless sleep (P = 0.002), and leg movements (P = 0.01) than non-diabetic patients with OSA. Most predictive values of the sleep questionnaires did not differ significantly between the two groups; however, the AIS was higher only in T2DM women (P = 0.01). In both groups, the Berlin and STOP-Bang questionnaires had the highest sensitivity. The ESS had the highest specificity in T2DM patients and the STOP and S-B questionnaires had the highest specificity in non-diabetics. CONCLUSIONS: The predictive performance of the questionnaires was similar in both groups, especially in the case of moderate and severe OSA.

Central Venous Oxygen Saturation as a Predictor of a Successful Spontaneous Breathing Trial from Mechanical Ventilation: A Prospective, Nested Case-Control Study.

BACKGROUND: Weaning from mechanical ventilation is a key element in the care of critically ill patients, and Spontaneous Breathing Trial (SBT) is a crucial step in this procedure. This nested case-control study aimed to evaluate whether central oxygen saturation (ScvO2) values and their changes could independently predict the SBT outcome among mechanically ventilated patients. METHODS: A prospective cohort of patients who were mechanically ventilated for at least 48hours and fulfilled the criteria of readiness to wean constituted the study population. All patients attempted a SBT and were then categorized in SBT success group and SBT failure group, based on a combination of criteria which indicated whether SBT was successful or not. Multivariate binary logistic regression analysis was utilized to indicate the independent predictors of SBT success, while the Receiver Operating Characteristic (ROC) curves were used to demonstrate the diagnostic accuracy of these independent predictors. RESULTS: Seventy-seven patients 69(18-86) years old; 62.3% male) constituted the study population. SBT was successful among 63.6% of them. A decrease in ScvO2 values (ΔScvO2) < 4% between the beginning and the end of the trial independently predicted the successful outcome (OR=18.278; 95% CI=4.017-83.163), along with age, Hemoglobin concentration (Hb) and arterial oxygen saturation (SaO2). Diagnostic accuracy for ΔScvO2 alone (ROC area=0.715) was slightly superior to that of either SaO2 (0.625) or Hb (0.685) to predict SBT success. CONCLUSION: ScvO2 is an independent predictor of the weaning outcome and its evaluation may further facilitate the accurate categorization among those patients who pass or fail the SBT.

Sleep apnea syndrome, inflammation and oxidative stress in hemodialysis patients.

INTRODUCTION: Sleep apnea syndrome (SAS) is an established cardiovascular risk factor in the general population related to inflammation and oxidative stress and is very common among hemodialysis patients. Cardiovascular disease and its complications is the main cause of death among hemodialysis patients. The aim of the present study was to investigate the role of SAS in the promotion of inflammation and oxidative stress and thus in the augmentation of cardiovascular risk in hemodialysis patients. METHODS: Thirty-seven hemodialysis patients underwent an overnight full polysomnography study. The following morning blood samples were obtained and TNF-α (tumor necrosis factor-α), IL-6 (interleukin-6), MPO (myeloperoxidase), and oxLDL (oxidized low density lipoprotein) were measured. FINDINGS: We investigated the correlation of patients' markers of inflammation and oxidative stress with their sleep parameters (total sleep time, AHI, apnea/hypopnea index; RDI, respiratory disturbance index; DI, desaturation index, mean and minimum SpO2 and percentage of sleep time with SpO2 < 90%). TNF-α correlated positively with BMI (r = 0.510, P < 0.0001) and total sleep time (r = 0.370, P = 0.027). IL-6 correlated positively with age (r = 0.363, P = 0.027), AHI (r = 0.385, P = 0.018), DI (r = 0.336, P = 0.042) and percentage of sleep time with SpO2 < 90% (r = 0.415, P = 0.012) and negatively with mean SpO2 (r = -0.364, P = 0.027). Myeloperoxidase correlated positively with AHI (r = 0.385, P = 0.018), DI (r = 0.380, P = 0.02) and percentage of sleep time with SpO2 < 90% (r = 0.388, P = 0.019). Finally, oxLDL correlated positively with BMI (r = 0.443, P = 0.007), AHI (r = 0.395, P = 0.015), RDI (r = 0.328, P = 0.048) and total sleep time with SpO2 <90% (r = 0.389, P = 0.019). CONCLUSIONS: These results indicate that, in hemodialysis patients, the severity of SAS and nocturnal hypoxia correlated positively with markers of inflammation and oxidative stress.

Acute paraplegia after the initiation of anti-tumour necrosis factor-alpha therapy for Crohn's disease.

Therapies aimed at inhibiting tumour necrosis factor are currently successfully administered to an increasing number of patients with autoimmune diseases. Infliximab has been approved to induce and maintain remission in Crohn's disease and fistulizing Crohn's disease. We report a case of acute-onset flaccid paraplegia after the initiation of anti-tumour necrosis factor therapy (infliximab) for Crohn's disease. Neuroimaging findings revealed an extensive longitudinal myelopathy. Two months later, no abnormal signal intensity was observed in the spinal cord and after 4 months, the patient presented improvement of motor function. A possible correlation between anti-tumour necrosis factor therapy and acute myelitis is discussed. This case highlights that patients developing new neurological symptoms while on anti-tumour necrosis factor medication should be monitored closely.