National Tunisian Study of Cardiac Implantable Electronic Devices: Design and Protocol for a Nationwide Multicenter Prospective Observational Study.

BACKGROUND: In Tunisia, the number of cardiac implantable electronic devices (CIEDs) is increasing, owing to the increase in patient life expectancy and expanding indications. Despite their life-saving potential and a significant reduction in population morbidity and mortality, their increased numbers have been associated with the development of multiple early and late complications related to vascular access, pockets, leads, or patient characteristics. OBJECTIVE: The study aims to identify the rate, type, and predictors of complications occurring within the first year after CIED implantation. It also aims to describe the demographic and epidemiological characteristics of a nationwide sample of patients with CIED in Tunisia. Additionally, the study will evaluate the extent to which Tunisian electrophysiologists follow international guidelines for cardiac pacing and sudden cardiac death prevention. METHODS: The Tunisian National Study of Cardiac Implantable Electronic Devices (NATURE-CIED) is a national, multicenter, prospectively monitored study that includes consecutive patients who underwent primary CIED implantation, generator replacement, and upgrade procedure. Patients were enrolled between January 18, 2021, and February 18, 2022, at all Tunisian public and private CIED implantation centers that agreed to participate in the study. All enrolled patients entered a 1-year follow-up period, with 4 consecutive visits at 1, 3, 6, and 12 months after CIED implantation. The collected data are recorded electronically on the clinical suite platform (DACIMA Clinical Suite). RESULTS: The study started on January 18, 2021, and concluded on February 18, 2023. In total, 27 cardiologists actively participated in data collection. Over this period, 1500 patients were enrolled in the study consecutively. The mean age of the patients was 70.1 (SD 15.2) years, with a sex ratio of 1:15. Nine hundred (60%) patients were from the public sector, while 600 (40%) patients were from the private sector. A total of 1298 (86.3%) patients received a conventional pacemaker and 75 (5%) patients received a biventricular pacemaker (CRT-P). Implantable cardioverter defibrillators were implanted in 127 (8.5%) patients. Of these patients, 45 (3%) underwent CRT-D implantation. CONCLUSIONS: This study will establish the most extensive contemporary longitudinal cohort of patients undergoing CIED implantation in Tunisia, presenting a significant opportunity for real-world clinical epidemiology. It will address a crucial gap in the management of patients during the perioperative phase and follow-up, enabling the identification of individuals at particularly high risk of complications for optimal care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05361759; https://classic.clinicaltrials.gov/ct2/show/NCT05361759. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/47525.

sCXCL16 as a prognostic biomarker for COVID-19 outcome.

As elevated levels of the soluble CXCL16 (sCXCL16) chemokine have been reported in severe coronavirus disease 2019 (COVID-19) patients, this study examined whether sCXCL16 concentration on the first day of hospitalization predicted death in COVID-19 patients. A total of 76 patients with COVID-19 were admitted to the Military Hospital of Tunis, Tunisia, between October 2020 and April 2021, and later classified as survivors or nonsurvivors based on their outcomes. At admission, the groups were matched by age, gender, comorbidities, and the percentage of patients with moderate conditions. On the first day of admission, serum's sCXCL16 concentrations were measured using a magnetic-bead assay. There was an eightfold increase in serum sCXCL16 levels in the nonsurvivors' group (3661.51 ± 2464.87 pg/mL vs. 454.3 ± 338.07 pg/mL, p < 0.0001). For the optimal cutoff value of sCXCL16 at 2095 pg/mL, we found a 94.6% sensitivity and a 97.4% specificity, with an area under curve of 0.981 (p = 5.03E-08; 95% confidence interval [95% CI]: 0.951-1.0114). Considering the risk of death at a concentration above the threshold, the unadjusted odds ratio was 36 (p < 0.0001). The adjusted odd ratio was estimated at 1.003 (p < 0.0001; 95% CI: 1.002-1.004). Finally, there was a significant difference between survival and nonsurvival groups in leukocyte numbers (p = 0.006), lymphocytes (p = 0.001), polymorphonuclear neutrophils (p = 0.001), and C-reactive protein levels (p = 0.007), except for monocytes (p = 0.881). Based on these results, sCXCL16 level could be used for detecting nonsurvival COVID-19 patients. Therefore, we recommend assessing this marker in hospitalized COVID-19 patients.

Twice-Daily Oral Zinc in the Treatment of Patients With Coronavirus Disease 2019: A Randomized Double-Blind Controlled Trial.

BACKGROUND: Zinc supplementation has been considered a potential therapy for coronavirus disease 2019 (COVID-19). We aimed to examine zinc efficacy in adult patients with COVID-19 infection. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled multicenter trial. Patients who were tested positive for COVID-19 without end-organ failure were randomized to oral zinc (n = 231) or matching placebo (n = 239) for 15 days. The primary combined outcome was death due to COVID-19 or intensive care unit (ICU) admission ≤30 days after randomization. Secondary outcomes included length of hospital stay for inpatients and duration of COVID-19 symptoms with COVID-19-related hospitalization for outpatients. RESULTS: 190 patients (40.4%) were ambulatory and 280 patients (59.6%) were hospitalized. Mortality at 30 days was 6.5% in the zinc group and 9.2% in the placebo group (OR: .68; 95% CI .34-1.35); ICU admission rates were, respectively, 5.2% and 11.3% (OR: .43; 95% CI .21-.87). Combined outcome was lower in the zinc group versus the placebo group (OR: .58; 95% CI .33-.99). Consistent results were observed in prespecified subgroups of patients aged <65 years, those with comorbidity, and those who needed oxygen therapy at baseline. Length of hospital stay was shorter in the zinc group versus the placebo group (difference: 3.5 days; 95% CI 2.76-4.23) in the inpatient group; duration of COVID-19 symptoms decreased with zinc treatment versus placebo in outpatients (difference: 1.9 days; 95% CI .62-2.6). No severe adverse events were observed during the study. CONCLUSIONS: Our results showed that, in COVID-19 patients, oral zinc can decrease 30-day death, ICU admission rate and can shorten symptom duration. Clinical Trials Registration. ClinicalTrials.gov, NCT05212480.

Appropriateness of antibiotic treatment of acute respiratory tract infections in Tunisian primary care and emergency departments: a multicenter cross-sectional study.

BACKGROUND: Little is known about the pattern and appropriateness of antibiotic prescriptions in patients with acute respiratory tract infections (ARTIs). OBJECTIVE: Describe the antibiotics used to treat ARTIs in Tunisian primary care offices and emergency departments (EDs), and assess the appropriateness of their use. METHODS: It was a prospective multicenter cross-sectional observational clinical study conducted at 63 primary care offices and 6 EDS during a period of 8 months. Appropriateness of antibiotic prescription was evaluated by trained physicians using the medication appropriateness index (MAI). The MAI ratings generated a weighted score of 0 to 18 with higher scores indicating low appropriateness. The study was conducted in accordance with the Declaration of Helsinki and national and institutional standards. The study was approved by the Ethics committee of Monastir Medical Faculty. RESULTS: From the 12,880 patients screened we included 9886 patients. The mean age was 47.4, and 55.4% were men. The most frequent diagnosis of ARTI was were acute bronchitis (45.3%), COPD exacerbation (16.3%), tonsillitis (14.6%), rhinopharyngitis (12.2%) and sinusitis (11.5%). The most prescribed classes of antibiotics were penicillins (58.3%), fluoroquinolones (17.6%), and macrolides (16.9%). Antibiotic therapy was inappropriate in 75.5% of patients of whom 65.2% had bronchitis. 65% of patients had one or more antibiotic prescribing inappropriateness criteria as assessed by the MAI. The most frequently rated criteria were with expensiveness (75.8%) and indication (40%). Amoxicillin-clavulanic acid and levofloxacin were the most inappropriately prescribed antibiotics. History of cardiac ischemia ([OR] 3.66; 95% [CI] 2.17-10.26; p < 0.001), asthma ([OR] 3.29, 95% [CI] 1.77-6.13; p < 0.001), diabetes ([OR] 2.09, 95% [CI] 1.54-2.97; p = 0.003), history of COPD ([OR] 1.75, 95% [CI] 1.43-2.15; p < 0.001) and age > 65 years (Odds Ratio [OR] 1.35, 95% confidence interval [CI] 1.16-1.58; p < 0.001) were associated with a higher likelihood of inappropriate prescribing. CONCLUSION: Our findings indicate a high inappropriate use of antibiotics in ARTIs treated in in primary care and EDs. This was mostly related to antibiotic prescription in acute bronchitis and overuse of expensive broad spectrum antibiotics. Future interventions to improve antibiotic prescribing in primary care and EDs is needed. TRIAL REGISTRATION: the trial is registered at Clinicaltrials.gov registry (NCT04482231).

COVID-19 prophylaxis with doxycycline and zinc in health care workers: a prospective, randomized, double-blind clinical trial.

OBJECTIVES: This study aims to assess the efficacy of a combination treatment of doxycycline and zinc in the primary prevention of COVID-19 infection in Tunisian health care workers compared with two control groups. METHODS: We conducted a prospective, randomized, double-blind clinical trial over 5 months to determine the efficacy of a preventive combination treatment dose of doxycycline (100 mg/day) and zinc (15 mg/day), compared with a single-dose treatment with doxycycline versus placebo. The effectiveness of preventive treatment was measured by the significant decline in the number of cases of COVID-19 infection and/or a decrease in the viral load as determined by SARS-CoV-2 cycle threshold value using reverse transcription polymerase chain reaction tests. RESULTS: We detected a significant decrease of SARS-CoV-2 infection in the group that received both doxycycline and zinc compared with other participants. We also demonstrated that COVID-19 infection was neither associated with diabetes (P = 0.51) nor associated with hypertension (P = 0.99), asthma (P = 0.52), and chronic obstructive pulmonary disease (P = 0.27). CONCLUSION: Our findings indicated that preventive therapy reduced the risk of SARS-CoV-2. These results suggest that the combination of doxycycline and zinc has a protective effect in patients with SARS-CoV-2 infection.

Two-day versus seven-day course of levofloxacin in acute COPD exacerbation: a randomized controlled trial.

INTRODUCTION: Duration of antibiotic treatment in acute exacerbation of COPD (AECOPD) is most commonly based on expert opinion. Typical administration periods range from 5 to 7 days. A 2-day course with levofloxacin was not previously assessed. We performed a randomized clinical trial to evaluate the efficacy of 2-day versus 7-day treatment with levofloxacin in patients with AECOPD. METHODS AND ANALYSIS: Patients with AECOPD were randomized to receive levofloxacin for 2 days and 5 days placebo (n = 155) or levofloxacin for 7 days (n = 155). All patients received a common dose of intravenous prednisone daily for 5 days. The primary outcome measure was cure rate, and secondary outcomes included need for additional antibiotics, ICU admission rate, re-exacerbation rate, death rate, and exacerbation-free interval (EFI) within 1-year follow-up. The study protocol has been prepared in accordance with the revised Helsinki Declaration for Biomedical Research Involving Human Subjects and Guidelines for Good Clinical Practice. The study was approved by ethics committees of all participating centers prior to implementation (Monastir and Sousse Universities). RESULTS: 310 patients were randomized to receive 2-day course of levofloxacin (n = 155) or 7-day course (n = 155). Cure rate was 79.3% (n = 123) and 74.2% (n = 115), respectively, in 2-day and 7-day groups [OR 1.3; 95% CI 0.78-2.2 (p = 0.28)]. Need for additional antibiotics rate was 3.2% and 1.9% in the 2-day group and 7-day group, respectively; (p = 0.43). ICU admission rate was not significantly different between both groups. One-year re-exacerbation rate was 34.8% (n = 54) in 2-day group versus 29% (n = 45) in 7-day group (p = 0.19); the EFI was 121 days (interquartile range, 99-149) versus 110 days (interquartile range, 89-132) in 2-day and 7-day treatment groups, respectively; (p = 0.73). One-year death rate was not significantly different between the 2 groups, 5.2% versus 7.1% in the 2-day group and 7-day group, respectively; (p = 0.26). No difference in adverse effects was detected. CONCLUSION: Levofloxacin once daily for 2 days is not inferior to 7 days with respect to cure rate, need for additional antibiotics and hospital readmission in AECOPD. Our findings would improve patient compliance and reduce the incidence of bacterial resistance and adverse effects.

Home Telemonitoring of Arterial Hypertension With Antihypertensive Treatment Titration: Protocol for a Randomized Controlled Prospective Trial (HOROSCOPE Study).

BACKGROUND: Despite the availability of effective treatment, the control of hypertension remains insufficient. Telemonitoring in the management of hypertension would be an effective way to improve blood pressure control. OBJECTIVE: The aim of our study will be to evaluate the effects of telemonitoring with antihypertensive treatment titration on blood pressure control in Tunisian patients with hypertension. METHODS: Our trial will be a prospective, rater-blinded randomized controlled trial carried out with primary care physicians in the Sahel region of Tunisia. Patients will be eligible for enrollment if they are aged over 35 years, are newly diagnosed with hypertension, or are known to be poorly controlled on antihypertensive therapy. Participants will be randomly assigned in a 1:1 ratio to the telemonitoring arm or usual care arm. The telemonitoring arm will involve a weekly telephone call for the collection of the home blood pressure measurements, therapeutic education, and treatment compliance assessment as well as a monthly call for treatment titration and a side effect check. Randomization will be done via the use of an interactive web responsive system, and patients will be stratified by investigation center. Neither participants nor investigators will be masked to the group assignments. The primary outcome will be the change in mean 24-hour systolic blood pressure from baseline to the 6-month follow-up in the 2 groups. All randomized patients who attend the follow-up visit at 6 months and have no missing data for the primary outcome will be included in the analysis. RESULTS: Recruitment to the trial started in July 2020. The study was initiated with 17 primary care physicians. We expect the inclusion period to last for approximately 6 months. We expect to complete data collection by the end of 2021 and plan to disseminate the results subsequently. CONCLUSIONS: The HOROSCOPE (Home Telemonitoring of Arterial Hypertension With Antihypertensive Treatment Titration: Randomized Controlled Prospective Trial) study will provide important new evidence that could shed some light on the feasibility and impact of telemonitoring and self-monitoring in a Tunisian population of patients with hypertension who consult primary care physicians. TRIAL REGISTRATION: ClinicalTrials.gov NCT04607239; https://clinicaltrials.gov/ct2/show/NCT04607239. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26184.

Effects of Ramadan fasting on aspirin resistance in type 2 diabetic patients.

AIMS: Ramadan fasting (RF) may affect aspirin resistance. We conducted this study in patients with cardiovascular risk (CVR) factors to assess the effect of RF on aspirin resistance and explore whether type 2 diabetes mellitus (DM) would influence this effect. METHODS: A total of 177 stable patients with ≥2 CVR factors were recruited. All patients observed RF and were taking aspirin. Physical exam and standard biological tests including glycaemia and serum lipids data were performed before Ramadan (Pre-R), at the last week of Ramadan (R) and four weeks after the end of Ramadan (Post-R). In the same visits caloric intake was calculated and platelet reactivity to aspirin was assessed using Verify Now point-of-care assay. RESULTS: In the overall population, there was no significant change in absolute aspirin reaction unit (ARU) values and in metabolic parameters. In DM patients (n = 127), ARU change from Pre-R values was+19.7 (p = 0.01) and +14.4 (p = 0.02) respectively at R and Post-R. During Ramadan, glycaemia, triglycerides, and cholesterol levels increased significantly and returned to Pre-R values thereafter. These changes were not observed in non-DM patients. CONCLUSIONS: During RF aspirin resistance increased only in DM patients. This effect persisted one month after Ramadan. Simultaneous alteration of glycemic control and increase of serum lipids levels could potentially be a favorable factor. STUDY REGISTRATION: The protocol was registered at clinicaltrials.gov under: NCT02720133.