Trends in Pregabalin Use and Prescribing Patterns in the Adult Population: A 10-Year Pharmacoepidemiologic Study.

BACKGROUND AND OBJECTIVE: Pregabalin is steadily gaining popularity worldwide, with epidemiological studies indicating an increase in labeled, off-labeled, and recreational uses. In Israel, pregabalin prescriptions are not regulated by the controlled substances legislations, prompting a need to examine its usage trends for potential policy adjustments. The objective of this study was to assess trends in pregabalin prescribing during a 10-year period, to characterize demographic and clinical characteristics of individuals prescribed pregabalin, and to identify risk factors associated with high-intensity pregabalin use. METHODS: This retrospective, longitudinal study examined trends in pregabalin prescribing from 2010 to 2019 based on data extracted from the Clalit Health Services (CHS) electronic database. Annual pregabalin prescribing rate was calculated individually for each reporting year. A univariable analysis was conducted to compare the demographic and clinical characteristics of pregabalin users in 2019 with those in 2010. Multivariable regression analysis was performed to assess dose-related patterns by specific demographic and clinical characteristics. RESULTS: Pregabalin prescription rate more than doubled over 10 years [odds ratio (OR) 2.3, p = 0.001], reaching 7.2 [95% confidence interval (CI) 7.18-7.28] prescriptions per 100 CHS members in 2019. The highest prescription rates were observed among the elderly population (13.2 and 24.1 prescriptions per 100 CHS members for those aged 55-74 and over 75 years old, respectively). Same-year administration of pregabalin with opioids, benzodiazepines, and Z-drugs was common; however, the percentage of patients using these drugs together declined in 2019 compared with 2010 (p < 0.001). Males, patients with low socioeconomic status, patients aged 35-54 years, and those who consumed opioids, benzodiazepines, and Z-drugs received higher pregabalin doses. CONCLUSION: Pregabalin use has increased significantly in the Israeli adult-based CHS population, consistent with worldwide data. A growing use over time may indicate overprescription. More studies are needed on misuse patterns to identify populations most susceptible to high-dose and high-intensity pregabalin use.

Efficacy and safety of antiviral treatments for symptomatic COVID-19 outpatients: Systematic review and network meta-analysis.

BACKGROUND: Remdesivir, molnupiravir, and nirmatrelvir/ritonavir are three antiviral agents approved by FDA emergency authorization for treating mild to moderate symptomatic COVID-19 adult outpatients at high risk for hospitalization and death. OBJECTIVES: To compare the efficacy and safety of these antivirals based on updated published RCT and real-world data. STUDY DESIGN: This systematic review followed the preferred reporting items for systematic reviews and meta-analysis framework guidelines. We searched all publications up to January 2023. RRs and 95% CIs for death, hospitalization, and adverse events were calculated. RESULTS: Six RCTs and seven cohort studies were included, with 1,456,523 participants, of whom 50,979 were treated with antivirals. Remdesivir was associated with the lowest probability of hospitalization and death compared to nirmatrelvir/ritonavir and molnupiravir (P-scores 0.99 and 0.90, respectively, for remdesivir, 0.64 and 0.55, respectively for nirmatrelvir/ritonavir, and 0.26 and 0.49, respectively for molnupiravir). Based on indirect comparisons, remdesivir was associated with a statistically significant decreased risk for hospitalization compared to molnupiravir (RR 0.09; 95% CI 0.02-0.40) and to nirmatrelvir/ritonavir (RR 0.11; 95% CI 0.03-0.73). No statistically significant difference was found between antivirals in the mortality risk reduction and the risk for side effects. CONCLUSIONS: This is the most comprehensive network meta-analysis integrating RCTs and real-world data. In our indirect comparison, remdesivir was associated with the highest efficacy in preventing hospitalization among high risk symptomatic COVID-19 outpatients, compared to nirmatrelvir/ritonavir and molnupiravir. This finding supports current guidelines, and may have importance when deciding which antiviral to use, together with other important factors.

Catheter-directed thrombolysis compared with systemic thrombolysis and anticoagulation in patients with intermediate- or high-risk pulmonary embolism: systematic review and network meta-analysis.

BACKGROUND: Therapeutic options for intermediate- or high-risk pulmonary embolism (PE) include anticoagulation, systemic thrombolysis and catheter-directed thrombolysis (CDT); however, the role of CDT remains controversial. We sought to compare the efficacy and safety of CDT with other therapeutic options using network meta-analysis. METHODS: We searched PubMed (MEDLINE), Embase, ClinicalTrials.gov and Cochrane Library from inception to Oct. 18, 2022. We included randomized controlled trials and observational studies that compared therapeutic options for PE, including anticoagulation, systemic thrombolysis and CDT among patients with intermediate- or high-risk PE. The efficacy outcome was in-hospital death. Safety outcomes included major bleeding, intracerebral hemorrhage and minor bleeding. RESULTS: We included data from 44 studies, representing 20 006 patients. Compared with systemic thrombolysis, CDT was associated with a decreased risk of death (odd ratio [OR] 0.43, 95% confidence interval [CI] 0.32-0.57), intracerebral hemorrhage (OR 0.44, 95% CI 0.29-0.64), major bleeding (OR 0.61, 95% CI 0.53-0.70) and blood transfusion (OR 0.46, 95% CI 0.28-0.77). However, no difference in minor bleeding was observed between the 2 therapeutic options (OR 1.11, 95% CI 0.66-1.87). Compared with anticoagulation, CDT was also associated with decreased risk of death (OR 0.36, 95% CI 0.25-0.52), with no increased risk of intracerebral hemorrhage (OR 1.33, 95% CI 0.63-2.79) or major bleeding (OR 1.24, 95% CI 0.88-1.75). INTERPRETATION: With moderate certainty of evidence, the risk of death and major bleeding complications was lower with CDT than with systemic thrombolysis. Compared with anticoagulation, CDT was associated with a probable lower risk of death and a similar risk of intracerebral hemorrhage, with moderate certainty of evidence. Although these findings are largely based on observational data, CDT may be considered as a first-line therapy in patients with intermediate- or high-risk PE. PROTOCOL REGISTRATION: PROSPERO - CRD42020182163.

The Risk for Prostate Cancer With Calcium Channel Blockers: A Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: For decades, conflicting results were published regarding the increased risk of Prostate cancer (PCa) among calcium channel blocker (CCB) users. OBJECTIVE: We aimed to evaluate the association between PCa and CCB exposure and assess moderating factors. METHODS: We performed a systematic literature search in PubMed, Embase, and Cochrane databases for observational and randomized studies published until November 2020 with no language limitations, including data on the risk for PCa in CCB users compared with non-CCB users. We applied a random-effects model meta-analysis to pool results. In addition, we investigated potential moderating factors, such as CCB type, study type, participants' age, and duration of exposure, using meta-regression methods. RESULTS: In our primary analysis, we included 18 studies. A statistically significant 5% increase in the risk for PCa was observed among CCB users (risk ratio [RR] = 1.05; 95% confidence interval [CI]: 1.01-1.10), with no significant association between the duration of exposure to CCBs and the risk for PCa (RR = 1.08; 95% CI: 0.98-1.19 for exposure for < 5years and RR = 1.01; 95% CI: 0.9-1.14 for exposure ≥ 5 years). The association remained statistically significant for the subgroup of dihydropyridines (RR = 1.13; 95% CI: 1.05-1.22). In addition, the association was not influenced by participants' age. CONCLUSION AND RELEVANCE: CCBs are an important modality in treating hypertension. The 5% increased risk observed in the current meta-analysis could be influenced by residual confounding factors and should not affect hypertension treatment guidelines until more studies provide additional clinical information.

Calcium Channel Blocker Use and the Risk for Breast Cancer: A Population-Based Nested Case-Control Study.

We investigated whether long-term exposure to calcium channel blockers (CCBs) is associated with an increased risk of breast cancer (BCa). We designed a nested case-control study based on data from the Clalit electronic database, the largest Israeli Health Services organization. All newly diagnosed breast cancer (BCa) cases were selected from a cohort of patients with hypertension. Ten controls were matched for each BCa case. The odds ratios (ORs) of BCa among CCBs users were calculated using multivariate conditional logistic regression analyses. A total of 4875 patients with newly diagnosed BCa were identified from the cohort with a median follow-up of 5.15 years. The exposure to CCBs was not associated with an increased risk of BCa (OR = 0.98; 95% CI, 0.92-1.04). Additionally, there was no association between long-term exposure to CCBs (above eight years) and increased BCa risk (OR = 0.91; 95% CI, 0.67-1.21). Higher cumulative doses of CCBs were not associated with an elevated risk of BCa (OR = 0.997; 95% CI, 0.962-1.034, calculated per 1000 DDD). Based on this large population-based study, long-term exposure to CCBs was not associated with an increased risk of BCa. Considering that CCBs are widely used medications, our results provide important safety information on a population level, especially for patients with an increased risk of BCa.

Efficacy and safety outcomes of long-term anti-thrombotic treatment of chronic coronary artery disease: A systematic review and network meta-analysis.

Background: Clopidogrel, prasugrel, ticagrelor, and low-dose rivaroxaban are all optional strategies in conjunction with aspirin for long-term treatment of chronic coronary artery disease. The aim of this research was to assess the efficacy and safety of long-term anti-thrombotic treatment of chronic coronary heart disease. Methods: PubMed (MEDLINE), Embase, Clinical Trials Registry ClinicalTrials.gov, and The Cochrane Library were searched through November 2021, to identify randomized controlled trials that compared long term anti-thrombotic therapy for coronary heart disease. Data were extracted to assess eligibility by two independent reviewers. Random-effects meta-analysis was used to pool results. Results: Eleven randomized controlled trials were included (88,462 patients). In a network meta-analysis, the rivaroxaban compared to the clopidogrel regimen showed lower relative risks (RRs) for death of any cause (0.71; 95% confidence interval [CI], 0.52-0.96), major adverse cardiac events (MACE) (0.73; 95% CI, 0.57-0.93), and cerebrovascular events (0.48; 95% CI, 0.30-0.78). The RR of cerebrovascular events was also lower for the rivaroxaban compared to the ticagrelor 60 mg regimen (0.72; 95% CI, 0.52-0.99). For the prasugrel regimen, the RRs were lower of myocardial infarction incidence versus all extended strategies: clopidogrel plus aspirin (0.76; 95% CI, 0.58-0.99), rivaroxaban (0.60; 95% CI, 0.38-0.93), ticagrelor 60 mg (0.61; 95% CI, 0.42-0.89), and ticagrelor 90 mg (0.63; 95% CI, 0.41-0.97). None of the dual strategies were associated with differences in major bleeding compared to the prasugrel regimen. Conclusions and relevance: The rivaroxaban regimen appeared to be the preferred long-term anti-thrombotic regimen in preventing all-cause mortality. Our available results tend to support the efficacy of extended anti-thrombotic therapy consisting of prasugrel in lowering MI incidence compared to the other strategies, without increased risk of bleeding. However, additional large-scale direct clinical trials are needed to further determine the adequate long-term anti-thrombotic regimens for treating chronic coronary syndrome. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020186583, identifier CRD42020186583.

Comparing the clinical efficacy of COVID-19 vaccines: a systematic review and network meta-analysis.

New Coronavirus Disease 2019 (COVID-19) vaccines are available to prevent the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. We compared the efficacy of new COVID-19 vaccines to prevent symptomatic and severe disease in the adult population and to prevent symptomatic COVID-19 among the elderly. Leading medical databases were searched until August 30, 2021. Published phase 3 randomized controlled trials (RCTs) evaluated efficacy of the vaccine to prevent symptomatic and sever COVID-19 in adults were included. Two reviewers independently evaluated the literature search results and independently extracted summary data. The risk of bias was evaluated using the Cochrane Risk of Bias Assessment Tool. We performed a network meta-analysis (NMA) according to PRISMA-NMA 2015 to pool indirect comparisons between different vaccines regarding their relative efficacy. The primary outcomes were the efficacy of the vaccine against symptomatic COVID-19 in adults (PROSPERO registration number: CRD42021235364). Above 200,000 adult participants from eight phase 3 RCTs were included in NMA, of whom 52% received the intervention (active COVID-19 vaccine). While each of nine vaccines was tested in the unique clinical trial as compared to control, based on indirect comparison, BNT162b2 and mRNA-1273 vaccines were ranked with the highest probability of efficacy against symptomatic COVID-19 (P-scores 0.952 and 0.843, respectively), followed by Gam-COVID-Vac (P-score 0.782), NVX-CoV23730 (P-score 0.700), CoronaVac (P-score 0.570), BN02 (P-score 0.428), WIV04 (P-score 0.327), and Ad26.COV2.S (P-score 0.198). No statistically significant difference was seen in the ability of the vaccines to prevent symptomatic disease in the elderly population. No vaccine was statistically significantly associated with a decreased risk for severe COVID-19 than other vaccines, although mRNA-1273 and Gam-COVID-Vac have the highest P-scores (0.899 and 0.816, respectively), indicating greater protection against severe disease than other vaccines. In our indirect comparison, the BNT162b2 and mRNA-1273 vaccines, which use mRNA technology, were associated with the highest efficacy to prevent symptomatic COVID-19 compared to other vaccines. This finding may have importance when deciding which vaccine to use, together with other important factors as availability of the vaccines, costs, logistics, side effects, and patient acceptability.

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the risk for neurocognitive adverse events: A systematic review, meta-analysis and meta-regression.

BACKGROUND: It has been suggested that lipid lowering therapy causes impaired cognitive changes. The association between the use of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the risk of neurocognitive adverse events remains unclear. This meta-analysis aims to assess neurocognitive safety of PCSK9 inhibitors in randomized controlled trials (RCTs). METHODS AND RESULTS: The research was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed (MEDLINE), Embase and Cochrane library were searched through September 2019. Selection criteria included RCTs that addressed to neurocognitive adverse events of participants using Alirocumab, Evolocumab or Bococizumab, with a follow up duration of at least 6 months. The search results were screened by two independent reviewers. Safety data from included papers were extracted. Random effects meta-analysis was used to pool results, and meta-regression was utilized when applicable. Twenty-one studies were included. Among 59,733 patients, 31,611 were treated with PCSK9 inhibitors. The follow-up period ranged from 24 weeks to 48 months. No significant difference in the incidence of neurocognitive adverse effects between the groups was identified (RR = 1.01, 95% CI: 0.86-1.19, I2 = 3%). Similar results were seen in subgroup analysis for each of the medications (alirocumab- RR = 0.88, 95% CI: 0.72-1.08, I2 = 0%, evolocumab- RR = 1.42, 95% CI: 0.74-2.73, I2 = 55%). A meta-regression analysis for evolocumab revealed that prolonged study duration was associated with decreased risk for neurocognitive adverse events (ßweek = -0.0037, p-value = 0.03). CONCLUSIONS: Pooled results of our meta-analysis and meta-regression show that exposure to PCSK9 inhibitors is not associated with an increased risk of neurocognitive adverse effects.

Calcium Channel Blocker Use and the Risk for Prostate Cancer: A Population-Based Nested Case-Control Study.

INTRODUCTION: Calcium channels play a significant role in the regulation of cell proliferation and apoptosis. This study investigates associations between calcium channel blocker (CCB) use and the incidence of prostate cancer (PCa). METHODS: A nested case-control study was conducted using the Clalit Health Services database. We formed a population-based cohort of patients who were prescribed their first antihypertensive agent between 2000 and 2014. For each newly diagnosed PCa case in the cohort, 10 controls were matched by age, calendar year of cohort entry, and duration of follow-up. Multivariate conditional logistic regression analyses were used to evaluate the odds ratios (ORs) of PCa among CCB users compared with users of other antihypertensive drugs. RESULTS: We identified 4346 patients with newly diagnosed PCa during the median follow-up of 5.3 years. The exposure to CCBs was associated with a slight increase in risk for PCa (OR 1.10, 95% confidence interval [CI] 1.02-1.18) when compared with non-CCB antihypertensive drugs. In secondary analyses, evidence was found of a duration-response relationship, with the association for PCa increasing by 27% for every 10-year increment of CCB use (OR 1.27, 95% CI 1.04-1.56). CONCLUSIONS: The results of this large population-based study indicate a modest but significant increase in the risk of PCa among CCB users, and the risk increases with duration of use.

Calcium Channel Blockers and the Risk for Lung Cancer: A Population-Based Nested Case-Control Study.

BACKGROUND: It has been suggested that calcium channel blockers (CCBs) may increase the risk of lung cancer; however, current evidence is conflicting and limited. OBJECTIVE: Investigate the associations between CCB use and lung cancer. METHODS: We conducted a population-based nested case-control study. A cohort was formed of patients prescribed their first antihypertensive agent from 2000 to 2014. CCB exposure information was obtained by identification of all prescriptions dispensed during study follow-up. Cases were patients newly diagnosed with lung cancer during follow-up. Each case was matched with 10 controls by age, sex, calendar year of cohort entry, and duration of follow-up. Multivariate conditional logistic regression was used to estimate odds ratios (ORs) with 95% CIs of lung cancer associated with ever use of CCBs. RESULTS: During a median follow-up of 6.2 years, we identified 4174 cases of lung cancer. Ever use of CCBs was associated with an increased risk of lung cancer (adjusted OR = 1.13; 95% CI = 1.06-1.21), when compared with the use of other antihypertensive drugs. A duration-response relation was observed, with the ORs gradually increasing with longer cumulative duration of CCB use (<5 years: OR = 1.12, 95% CI = 1.04-1.20; 5-10 years: OR = 1.22, 95% CI = 1.07-1.40; >10 years: OR = 1.33, 95% CI = 0.90-1.96; P trend < 0.001). Conclusion and Relevance: The results of this large population-based study indicate that the use of CCBs is associated with a modest but significant increase in the risk of lung cancer. This association appeared to increase with longer duration of use.

Fluoroquinolones and Cardiovascular Risk: A Systematic Review, Meta-analysis and Network Meta-analysis.

INTRODUCTION: Several fluoroquinolone antibiotics have been associated with cardiac adverse effects, leading to the withdrawal of some of these agents from the market. Cardiac side effects such as QT prolongation and torsades de pointes (TdP) have also been observed with fluoroquinolones currently on the market. In order to evaluate the cardiac risk of fluoroquinolones as a class, and the comparative risk for each individual drug, we conducted a systematic review, meta-analysis, and network meta-analysis. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched, up to March 2018, for randomized controlled trials, cohort studies, and case-control studies that investigated the association between fluoroquinolone treatment and the risk of cardiovascular events and cardiovascular mortality. We followed the PRISMA 2009 guidelines for data selection and extraction. Outcomes were pooled using random effects models. Direct and indirect comparisons in network meta-analysis were performed using frequentist methods. RESULTS: Thirteen studies were included in our analyses. Fluoroquinolone use was associated with a statistically significant 85% increase in the risk for arrhythmia (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.22-2.81) and 71% increase in the risk for cardiovascular mortality (OR 1.71; 95% CI 1.39-2.09). Moxifloxacin ranked most likely to have the highest risk for arrhythmia (P-score 0.99) and for cardiovascular mortality (P-score 0.95) by network meta-analysis. CONCLUSIONS: Our findings show a significant association between fluoroquinolone use and an increased risk for arrhythmia and cardiovascular mortality. Moxifloxacin ranked with the highest probability for cardiovascular adverse events. Further study is required to determine how to reduce the risk for fluoroquinolone-associated cardiac toxicity.

Systematic Review, Meta-analysis, and Network Meta-analysis of the Cardiovascular Safety of Macrolides.

Studies reporting an increased risk for cardiac toxicities with macrolide antibiotics have raised concern regarding their cardiovascular safety. We sought to assess the cardiac safety of macrolide antibiotics as a class and of the individual agents by conducting a systematic review and network meta-analysis. Medline, Embase, and the Cochrane Library were searched up to February 2018 for studies reporting on cardiovascular outcomes with macrolides. We followed the PRISMA 2009 guidelines for data selection and extraction. Outcomes were pooled using random-effects models and odds ratios (OR), and 95% confidence intervals (CI) were calculated for arrhythmia, cardiovascular death, and myocardial infarction (MI). A total of 33 studies and data on 22,601,032 subjects were retrieved and included in the current meta-analyses. Macrolide use was not associated with the risk of arrhythmia or cardiovascular mortality. In the primary analysis, macrolide use was associated with a small but statistically significant 15% increase in risk for MI (OR = 1.15 [95% CI, 1.01 to 1.30]). In indirect network meta-analysis, erythromycin and clarithromycin were ranked considerably more likely to be associated with a higher risk for MI and significantly associated with increased risk of MI compared to azithromycin (OR = 1.58 [95% CI, 1.18 to 2.11] and OR = 1.41 [95% CI, 1.11 to 1.81], respectively). Our findings indicate that macrolide antibiotics as a group are associated with a significant risk for MI but not for arrhythmia and cardiovascular mortality. Among the macrolides, erythromycin and clarithromycin were associated with a greater risk of MI. However, it is possible that the association between macrolide use and risk of MI is the result of residual confounding.

The Risk for Lung Cancer Incidence with Calcium Channel Blockers: A Systematic Review and Meta-Analysis of Observational Studies.

INTRODUCTION: There are conflicting findings regarding the association between the use of calcium channel blockers (CCBs) and the risk of lung cancer. Considering the public health importance of lung cancer prevention, and emerging evidence of a significant biologic role of calcium channel regulation in the development of lung cancer, we conducted a meta-analysis to assess the risk of lung cancer in CCB users compared with non-CCB users. MATERIALS AND METHODS: We conducted a comprehensive systematic search of leading medical databases for observational studies published up to December 2017 that examined CCB use and the risk of lung cancer. We used random-effects models to pool results. The impact of duration of CCB use on the estimated effect size was explored using random effects meta-regression. RESULTS: Ten studies (six cohort and four case-control studies) that evaluated the overall cancer risk among 38,758 CCB users were included in the analysis. Overall risk ratio (RR) for CCB use and lung cancer was 1.15 (95% confidence interval [CI] 1.01-1.32). Subgroup analysis by duration of CCB use suggested that the observed increase in lung cancer risk was driven by the results of five studies with prolonged (≥ 4 years) exposure (RR 1.18; 95% CI 1.08-1.30). CONCLUSIONS: Our analysis suggests exposure to CCBs is associated with an increased risk of lung cancer. Considering their widespread use, and the paucity of data on the long-term effects of chronic exposure to CCBs, these results are reason for concern and warrant further investigation. SYSTEMATIC REVIEW REGISTRATION: The protocol for this study was registered at the PROSPERO registry of systematic reviews (registry number: CRD42017056362).

[Assessing cardiovascular risk factors among patients living with HIV/AIDS - survey of patients treated at the Hadassah Aids Center, Hadassah Ein Kerem, Jerusalem].

BACKGROUND: It has recently become evident that people living with HIV/AIDS have an increased cardiovascular risk. The reasons leading to this risk are multifactorial. In this study, we aimed to evaluate the cardiovascular risk (CVR) among patients treated at the Hadassah AIDS Center. MATERIALS AND METHODS: We conducted a cross-sectional study. CVR was calculated using the Framingham risk score (FRS). LDL-cholesterol optimal levels were defined using National Cholesterol Education Program (NCEP) criteria. RESULTS: We analyzed data from 150 patients during 2010. Their median age was 41 years and 60% were male. Nearly 52% of our patients were immigrants from Ethiopia. Most patients (90%) were on antiretroviral therapy (ART). The median time for ART exposure was 6.5 years. Rates of hypertension (HTN) (18.5%), diabetes (5.7%) and smoking (25%) were similar to the rates found in the general Israeli population (15%, 5.7% and 24%, respectively). Smoking was significantly less frequent among patients originating from Ethiopia (8%). Increased CVR (FRS >10%) was observed in 21% of the patients. Significantly lower rates were observed among Ethiopian patients (11%), compared with non-Ethiopians (39%). Increased CVR was correlated with increased age (p<0.05), male gender (p=0.034) and HTN (p=0.002), but not with smoking (p=0.53), change in CD4 (p=0.7) or viral suppression (p=0.64). CONCLUSION: Rates of hypertension, diabetes and smoking among patients living with HIV/AIDS were comparable to those found in the general Israeli population. Significantly lower rates of increased Framingham risk score (>or=10%) were observed among Ethiopian HIV/AIDS patients, than among non-Ethiopians. .

Empiric treatment with once-daily cefonicid and gentamicin for febrile non-neutropenic pediatric cancer patients with indwelling central venous catheters.

SUMMARY: The approach to treating febrile non-neutropenic hematooncologic patients with central venous catheters varies. We recently introduced once-daily administration of cefonicid and gentamicin for such children who were in good clinical condition and without focal signs of infection. Our 2-year experience of 125 episodes in 54 children is hereby reported. Absolute neutrophil counts were 550 to 16,700/mm. Bacteremia occurred in 6.4% episodes: only in patients with Hickman/Broviac catheters and not in those with port-a-caths [8/37 (21.6%) vs. 0/17 patients, P=0.046; 8/86 (9.3%) vs. 0/39 episodes, P=0.056]. The pathogens were coagulase-negative staphylococci (3), Streptococcus pneumoniae (2), Pseudomonas aeruginosa and Klebsiella pneumoniae (1), methicillin-sensitive Staphylococcus aureus (1), and Streptococcus milleri (1). All patients remained in stable clinical condition and all, except for 2 who became neutropenic and 1 with S. aureus bacteremia who developed cellulitis, defervesced while on the empiric therapy. Three episodes could not be managed as outpatients. No adverse effects were observed. We conclude that our approach is efficacious and safe and, furthermore, that empiric antibiotic therapy may not be indicated for selected patients with port-a-caths. Future study of children with Hickman/Broviac catheters will evaluate the use of cefonicid alone.

Investigation of the enhancing mechanism of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate effect on the intestinal permeability of polar molecules utilizing a voltage clamp method.

Oral administration of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) has been reported to increase the bioavailability of various macromolecules. The present study was aimed to study the effect of SNAC on the intestinal tissue permeability of polar charged molecules, using 6-carboxy-fluorescein (6-CF) as a model. The effects of SNAC on rat intestinal permeability was investigated ex vivo by utilizing voltage clamp experiments in a side-by-side diffusion chamber model in comparison with the effect of EDTA (10mM). The intestinal permeability of 6-CF was increased two-fold in the presence of 33-66 mM SNAC, and by 6.5-fold in the presence of 10mM EDTA. The voltage clamp experiments show that the effect of SNAC was particularly on the transcellular 7-folds increase (that was five times larger than the paracellular transport of the model agent). While EDTA affected predominantly paracellular pathway transport, SNAC 33-66 mM had no effect on [(3)H]-mannitol transport or any toxic effect on tissue integrity measured by TEER values. In conclusion, this study demonstrates that SNAC can facilitate passive transport of polar charged molecules through the membrane of epithelial enterocytes. This is noteworthy in view of the very low tendency of a charged molecule to permeate across the lipophilic inter-phase of the enterocytes membrane.