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Journal of the American College of... Mar 2021In cholesterol guidelines, low-density lipoprotein (LDL) cholesterol remains the primary target while apolipoprotein B (apoB) and non-high-density lipoprotein (non-HDL)...
BACKGROUND
In cholesterol guidelines, low-density lipoprotein (LDL) cholesterol remains the primary target while apolipoprotein B (apoB) and non-high-density lipoprotein (non-HDL) cholesterol are secondary targets.
OBJECTIVES
This study sought to determine if elevated apoB and/or non-HDL cholesterol are superior to elevated LDL cholesterol in identifying statin-treated patients at residual risk of all-cause mortality and myocardial infarction.
METHODS
In total, 13,015 statin-treated patients from the Copenhagen General Population Study were included with 8 years median follow-up. Cox regressions among apoB, non-HDL cholesterol, and LDL cholesterol, respectively, and all-cause mortality or myocardial infarction were examined on continuous scales by restricted cubic splines and by categories of concordant and discordant values defined by medians.
RESULTS
High apoB and non-HDL cholesterol were associated with increased risk of all-cause mortality and myocardial infarction, whereas no such associations were found for high LDL cholesterol. Compared with concordant values below medians, discordant apoB above the median with LDL cholesterol below yielded hazard ratios of 1.21 (95% confidence interval [CI]: 1.07 to 1.36) for all-cause mortality and 1.49 (95% CI: 1.15 to 1.92) for myocardial infarction. Corresponding values for high non-HDL cholesterol with low LDL cholesterol were 1.18 (95% CI: 1.02 to 1.36) and 1.78 (95% CI: 1.35 to 2.34). In contrast, discordant high LDL cholesterol with low apoB or non-HDL cholesterol was not associated with increased risk of all-cause mortality or myocardial infarction. Also, discordant high apoB with low non-HDL cholesterol yielded hazard ratios of 1.21 (95% CI: 1.03 to 1.41) for all-cause mortality and of 0.93 (95% CI: 0.62 to 1.40) for myocardial infarction. Furthermore, dual discordant apoB and non-HDL cholesterol above the medians with LDL cholesterol below presented hazard ratios of 1.23 (95% CI: 1.07 to 1.43) for all-cause mortality and 1.82 (95% CI: 1.37 to 2.42) for myocardial infarction.
CONCLUSIONS
In statin-treated patients, elevated apoB and non-HDL cholesterol, but not LDL cholesterol, are associated with residual risk of all-cause mortality and myocardial infarction. Discordance analysis demonstrates that apoB is a more accurate marker of all-cause mortality risk in statin-treated patients than LDL cholesterol or non-HDL cholesterol, and apoB in addition is a more accurate marker of risk of myocardial infarction than LDL cholesterol.
Topics: Aged; Apolipoproteins B; Biomarkers; Causality; Cholesterol, LDL; Denmark; Female; Heart Disease Risk Factors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Mortality; Myocardial Infarction; Registries; Risk Assessment
PubMed: 33736827
DOI: 10.1016/j.jacc.2021.01.027 -
Annals of Oncology : Official Journal... Jun 2020In the PACIFIC trial, durvalumab significantly improved progression-free and overall survival (PFS/OS) versus placebo, with manageable safety, in unresectable, stage III...
BACKGROUND
In the PACIFIC trial, durvalumab significantly improved progression-free and overall survival (PFS/OS) versus placebo, with manageable safety, in unresectable, stage III non-small-cell lung cancer (NSCLC) patients without progression after chemoradiotherapy (CRT). We report exploratory analyses of outcomes by tumour cell (TC) programmed death-ligand 1 (PD-L1) expression.
PATIENTS AND METHODS
Patients were randomly assigned (2:1) to intravenous durvalumab 10 mg/kg every 2 weeks or placebo ≤12 months, stratified by age, sex, and smoking history, but not PD-L1 status. Where available, pre-CRT samples were tested for PD-L1 expression (immunohistochemistry) and scored at pre-specified (25%) and post hoc (1%) TC cut-offs. Treatment-effect hazard ratios (HRs) were estimated from unstratified Cox proportional hazards models (Kaplan-Meier-estimated medians).
RESULTS
In total, 713 patients were randomly assigned, 709 of whom received at least 1 dose of study treatment durvalumab (n = 473) or placebo (n = 236). Some 451 (63%) were PD-L1-assessable: 35%, 65%, 67%, 33%, and 32% had TC ≥25%, <25%, ≥1%, <1%, and 1%-24%, respectively. As of 31 January 2019, median follow-up was 33.3 months. Durvalumab improved PFS versus placebo (primary-analysis data cut-off, 13 February 2017) across all subgroups [HR, 95% confidence interval (CI); medians]: TC ≥25% (0.41, 0.26-0.65; 17.8 versus 3.7 months), <25% (0.59, 0.43-0.82; 16.9 versus 6.9 months), ≥1% (0.46, 0.33-0.64; 17.8 versus 5.6 months), <1% (0.73, 0.48-1.11; 10.7 versus 5.6 months), 1%-24% [0.49, 0.30-0.80; not reached (NR) versus 9.0 months], and unknown (0.59, 0.42-0.83; 14.0 versus 6.4 months). Durvalumab improved OS across most subgroups (31 January 2019 data cut-off; HR, 95% CI; medians): TC ≥ 25% (0.50, 0.30-0.83; NR versus 21.1 months), <25% (0.89, 0.63-1.25; 39.7 versus 37.4 months), ≥1% (0.59, 0.41-0.83; NR versus 29.6 months), 1%-24% (0.67, 0.41-1.10; 43.3 versus 30.5 months), and unknown (0.60, 0.43-0.84; 44.2 versus 23.5 months), but not <1% (1.14, 0.71-1.84; 33.1 versus 45.6 months). Safety was similar across subgroups.
CONCLUSIONS
PFS benefit with durvalumab was observed across all subgroups, and OS benefit across all but TC <1%, for which limitations and wide HR CI preclude robust conclusions.
Topics: Antibodies, Monoclonal; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms
PubMed: 32209338
DOI: 10.1016/j.annonc.2020.03.287 -
Epidemiologic Reviews Jan 2019We searched the PubMed database for clinical trials and observational human studies about postexposure vaccination effects, targeting infections with approved vaccines... (Review)
Review
We searched the PubMed database for clinical trials and observational human studies about postexposure vaccination effects, targeting infections with approved vaccines and vaccines licensed outside the United States against dengue, hepatitis E, malaria, and tick-borne encephalitis. Studies of animal models, serologic testing, and pipeline vaccines were excluded. Eligible studies were evaluated by definition of exposure; attempts to distinguish pre- and postexposure effects were rated on a scale of 1 to 4. We screened 4,518 articles and ultimately identified for this review 14 clinical trials and 31 observational studies spanning 7 of the 28 vaccine-preventable diseases. For secondary attack rate, the following medians were found for postexposure vaccination effectiveness: hepatitis A, 85% (interquartile range (IQR), 28; n = 5 sources); hepatitis B, 85% (IQR, 22; n = 5 sources); measles, 83% (IQR, 21; n = 8 sources); varicella, 67% (IQR: 48; n = 9 sources); smallpox, 45% (IQR, 39; n = 4 sources); and mumps, 38% (IQR, 7; n = 2 sources). For case fatality proportions resulting from rabies and smallpox, the median vaccine postexposure efficacies were 100% (IQR, 0; n = 6 sources) and 63% (IQR, 50; n = 8 sources), respectively. Many available vaccines can modify or preclude disease if administered after exposure. This postexposure effectiveness could be important to consider during vaccine trials and while developing new vaccines.
Topics: Adolescent; Adult; Child; Child, Preschool; Communicable Diseases; Humans; Infant; Post-Exposure Prophylaxis; Treatment Outcome; Vaccination; Young Adult
PubMed: 31680134
DOI: 10.1093/epirev/mxz014 -
Seizure Jan 2016We conducted a comprehensive review of the epidemiology of epilepsy in the Arab world. (Review)
Review
PURPOSE
We conducted a comprehensive review of the epidemiology of epilepsy in the Arab world.
METHODS
Epidemiological literature about epilepsy from 22 countries of the Arab League was searched in French and English using several keywords (specific and wider) and combinations, individually for each country. The search was conducted on Google first and then on PubMed. The results are presented as counts, proportions, and medians along with 95% confidence intervals (CI). Unpaired t-test with unequal variance and regressions were performed, altogether and individually, for lifetime and active epilepsy prevalence as well as incidence.
RESULTS
Google provided 21 prevalence, four camp and nine incidence estimates while PubMed provided ten such estimates; none of them was identified by Google. No epidemiological data about epilepsy was found from 10/22 countries. Excluding pediatric studies, 13 prevalence estimates from six countries were identified. Including pediatric studies, 21 estimates from nine countries were found. Median lifetime and active epilepsy prevalence were 7.5/1000 (95% CI 2.6-12.3, range 1.9-12.9) and 4.4/1000 (95% CI 2.1-9.3, range 2.1-9.3), respectively, excluding pediatric studies (1984-2014, N=244081). Median incidence was 56.0/100,000 (n=9, N=122484, 95% CI 13.7-147.9, range 10.4-190).
CONCLUSION
The fact that no epidemiological data about epilepsy is available in the public domain for almost one half of all Arab countries offers opportunities for future research. This thorough review of existing literature demonstrates a prevalence of epilepsy three times higher than previously reported for this region. The median incidence is similar to other regions of the world, e.g. North America. Google yielded additional valuable sources not indexed in PubMed and provided pertinent references more quickly.
Topics: Epilepsy; Humans; Middle East; Prevalence
PubMed: 26724591
DOI: 10.1016/j.seizure.2015.12.002 -
Journal of the National Cancer Institute Sep 2021Chronic inflammation may promote initiation and progression of pancreatic cancer, but no studies have examined the association between inflammation in the period before...
BACKGROUND
Chronic inflammation may promote initiation and progression of pancreatic cancer, but no studies have examined the association between inflammation in the period before diagnosis and pancreatic cancer survival.
METHODS
We prospectively examined the association of prediagnostic plasma levels of C-reactive protein, interleukin-6, and tumor necrosis factor-α receptor 2 with survival among 492 participants from 5 large US prospective cohort studies who developed pancreatic cancer. Using an empirical dietary inflammatory pattern (EDIP) score, we evaluated whether long-term proinflammatory diets were associated with survival among 1153 patients from 2 of the 5 cohorts. Cox proportional hazards regression was used to estimate hazard ratios for death with adjustment for potential confounders. All statistical tests were 2-sided.
RESULTS
Higher prediagnostic levels of C-reactive protein, interleukin-6, and tumor necrosis factor-α receptor 2 were individually associated with reduced survival (Ptrend = .03, .01, and .04, respectively). Compared with patients with a combined inflammatory biomarker score of 0 (all 3 marker levels below medians), those with a score of 3 (all 3 marker levels above medians) had a hazard ratio for death of 1.57 (95% confidence interval = 1.16 to 2.12; Ptrend = .003), corresponding to median overall survival times of 8 vs 5 months. Patients consuming the most proinflammatory diets (EDIP quartile 4) in the prediagnostic period had a hazard ratio for death of 1.34 (95% confidence interval = 1.13 to 1.59; Ptrend = .01), compared with those consuming the least proinflammatory diets (EDIP quartile 1).
CONCLUSION
Prediagnostic levels of inflammatory biomarkers and long-term proinflammatory diets were inversely associated with pancreatic cancer survival.
Topics: Humans; Inflammation; Pancreatic Neoplasms; Proportional Hazards Models; Prospective Studies; Risk Factors
PubMed: 33739411
DOI: 10.1093/jnci/djab040 -
Toxins Mar 2022Animal feed (including forage and silage) can be contaminated with mycotoxins. Here, 200 maize silage samples from around China were collected in 2019 and analyzed for...
Animal feed (including forage and silage) can be contaminated with mycotoxins. Here, 200 maize silage samples from around China were collected in 2019 and analyzed for regulated mycotoxins, masked mycotoxins (deoxynivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, and deoxynivalenol-3-glucoside), and emerging mycotoxins (beauvericin, enniatins, moniliformin, and alternariol). Deoxynivalenol and zearalenone were detected in 99.5% and 79.5% of the samples, respectively. Other regulated mycotoxins were detected in fewer samples. The highest deoxynivalenol and zearalenone concentrations were 3600 and 830 μg/kg, respectively. The most commonly detected masked mycotoxin was 15-acetyldeoxynivalenol, which was detected in 68.5% of the samples and had median and maximum concentrations of 61.3 and 410 μg/kg, respectively. The emerging mycotoxins beauvericin, alternariol, enniatin A, enniatin B1, and moniliformin were detected in 99.5%, 85%, 80.5%, 72.5%, and 44.5%, respectively, of the samples but at low concentrations (medians <25 μg/kg). The samples tended to contain multiple mycotoxins, e.g., the correlation coefficients for the relationships between the concentrations of beauvericin and deoxynivalenol, deoxynivalenol and zearalenone, and zearalenone and beauvericin were 1.0, 0.995, and 0.995, respectively. The results indicated that there needs to be more awareness of the presence of one or more masked and emerging mycotoxins in maize silage in China.
Topics: Animal Feed; Animals; Food Contamination; Mycotoxins; Silage; Zea mays; Zearalenone
PubMed: 35448850
DOI: 10.3390/toxins14040241 -
American Journal of Preventive Medicine Sep 2017The health and economic burden of hypertension, a major risk factor for cardiovascular disease, is substantial. This systematic review evaluated the economic evidence of... (Review)
Review
CONTEXT
The health and economic burden of hypertension, a major risk factor for cardiovascular disease, is substantial. This systematic review evaluated the economic evidence of self-measured blood pressure (SMBP) monitoring interventions to control hypertension.
EVIDENCE ACQUISITION
The literature search from database inception to March 2015 identified 22 studies for inclusion with three types of interventions: SMBP used alone, SMBP with additional support, and SMBP within team-based care (TBC). Two formulae were used to convert reductions in systolic BP (SBP) to quality-adjusted life years (QALYs) to produce cost per QALY saved. All analyses were conducted in 2015, with estimates adjusted to 2014 U.S. dollars.
EVIDENCE SYNTHESIS
Median costs of intervention were $60 and $174 per person for SMBP alone and SMBP with additional support, respectively, and $732 per person per year for SMBP within TBC. SMBP alone and SMBP with additional support reduced healthcare cost per person per year from outpatient visits and medication (medians $148 and $3, respectively; median follow-up, 12-13 months). SMBP within TBC exhibited an increase in healthcare cost (median, $369 per person per year; median follow-up, 18 months). SMBP alone varied from cost saving to a maximum cost of $144,000 per QALY saved, with two studies reporting an increase in SBP. The two translated median costs per QALY saved were $2,800 and $4,000 for SMBP with additional support and $7,500 and $10,800 for SMBP within TBC.
CONCLUSIONS
SMBP monitoring interventions with additional support or within TBC are cost effective. Cost effectiveness of SMBP used alone could not be determined.
Topics: Blood Pressure Monitoring, Ambulatory; Cost of Illness; Cost-Benefit Analysis; Health Care Costs; Humans; Hypertension; Models, Economic; Patient Care Team; Quality-Adjusted Life Years; Stroke
PubMed: 28818277
DOI: 10.1016/j.amepre.2017.03.002 -
Pain Physician Nov 2022The diagnosis and treatment of neuropathic pain is often clinically challenging, with many patients requiring treatments beyond oral medications. To improve our...
BACKGROUND
The diagnosis and treatment of neuropathic pain is often clinically challenging, with many patients requiring treatments beyond oral medications. To improve our percutaneous treatments, we established a clinical pathway that utilized ultrasound (US) guidance for steroid injection and alcohol ablation for patients with painful neuropathy.
OBJECTIVES
To describe a collaborative neuropathy treatment pathway developed by a neurosurgeon, pain physicians, and a sonologist, describing early clinical experiences and patient-reported outcomes.
STUDY DESIGN
A retrospective case series was performed.
METHODS
Patients that received percutaneous alcohol ablation with US guidance for neuropathy were identified through a retrospective review of a single provider's case log. Demographics and treatment information were collected from the electronic medical record. Patients were surveyed about their symptoms and treatment efficacy. Descriptive statistics were expressed as medians and the interquartile range ([IQR]; 25th and 75th data percentiles). Differences in the median follow-up pain scores were assessed using a Wilcoxon signed-rank test.
RESULTS
Thirty-five patients underwent US-guided alcohol ablation, with the average patient receiving one treatment (range: 1 to 2), having a median duration of 4.8 months until reinjection (IQR: 2.9 to 13.1). The median number of steroid injections that individuals received before US-guided alcohol ablation was 2 (IQR: 1 to 3), and the median interval between steroid injections was 3.7 months (IQR: 2.0 to 9.6). Most (20/35 [57%]) patients responded to the survey, and the median pain scores decreased by 3 units (median: -3, IQR: -6 to 0; P < 0.001) one week following the alcohol ablation. This pain reduction remained significant at one month (P < 0.001) and one year (P = 0.002) following ablation. Most (12/20 [60%]) patients reported that alcohol ablation was more effective in improving their pain than oral pain medications.
LIMITATIONS
Given the small sample size, treatment efficacy for alcohol neurolysis cannot be generalized to the broader population.
CONCLUSIONS
US-guided percutaneous treatments for neuropathic pain present a growing opportunity for interprofessional collaboration between neurosurgery, clinicians who treat chronic pain, and sonologists. US can provide valuable diagnostic information and guide accurate percutaneous treatments in skilled hands. Further studies are warranted to determine whether a US-guided treatment pathway can prevent unnecessary open surgical management.
Topics: Humans; Chronic Pain; Retrospective Studies; Pain Measurement; Ethanol; Neuralgia; Steroids
PubMed: 36375203
DOI: No ID Found -
BMC Infectious Diseases May 2022Monitoring of antimicrobial resistance (AMR) is of great importance due to the frequency of strains becoming increasingly resistant to antibiotics. This review, using a... (Review)
Review
BACKGROUND
Monitoring of antimicrobial resistance (AMR) is of great importance due to the frequency of strains becoming increasingly resistant to antibiotics. This review, using a public health focused approach, which aims to understand and describe the current status of AMR in Morocco in relation to WHO priority pathogens and treatment guidelines.
METHODS
PubMed, ScienceDirect and Google Scholar Databases and grey literature are searched published articles on antimicrobial drug resistance data for GLASS priority pathogens isolated from Morocco between January 2011 and December 2021. Articles are screened using strict inclusion/exclusion criteria. AMR data is extracted with medians and IQR of resistance rates.
RESULTS
Forty-nine articles are included in the final analysis. The most reported bacterium is Escherichia coli with median resistance rates of 90.9%, 64.0%, and 56.0%, for amoxicillin, amoxicillin-clavulanic acid, and co-trimoxazole, respectively. Colistin had the lowest median resistance with 0.1%. A median resistance of 63.0% is calculated for amoxicillin-clavulanic acid in Klebsiella pneumonia. Imipenem resistance with a median of 74.5% is reported for Acinetobacter baumannii. AMR data for Streptococcus pneumonie does not exceed 50.0% as a median.
CONCLUSIONS
Whilst resistance rates are high for most of GLASS pathogens, there are deficient data to draw vigorous conclusions about the current status AMR in Morocco. The recently join to the GLASS system surveillance will begin to address this data gap.
Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Humans; Morocco
PubMed: 35525923
DOI: 10.1186/s12879-022-07412-4 -
JACC. Clinical Electrophysiology Oct 2021This study aimed to review the utility of quinidine in patients presenting with recurrent sustained ventricular arrhythmia (VA) and limited antiarrhythmic drug (AAD)... (Review)
Review
OBJECTIVES
This study aimed to review the utility of quinidine in patients presenting with recurrent sustained ventricular arrhythmia (VA) and limited antiarrhythmic drug (AAD) options.
BACKGROUND
Therapeutic options are often limited in patients with structural heart disease and recurrent VAs. Quinidine has an established role in rare arrhythmic syndromes, but its potential use in other difficult VAs has not been assessed in the present era.
METHODS
We performed a retrospective analysis of 37 patients who had in-hospital quinidine initiation after multiple other therapies failed for VA suppression at our tertiary referral center. Clinical data and outcomes were obtained from the medical record.
RESULTS
Of 30 patients with in-hospital quantifiable VA episodes, quinidine reduced acute VA from a median of 3 episodes (interquartile range [IQR]: 2 to 7.5) to 0 (IQR: 0 to 0.5) during medians of 3 days before and 4 days after quinidine initiation (p < 0.001). VA events decreased from a median of 10.5 episodes per day (IQR: 5 to 15) to 0.5 episodes (IQR: 0 to 4) after quinidine initiation in the 12 patients presenting with electrical storm (p = 0.004). Among the 24 patients discharged on quinidine, 13 (54.2%) had VA recurrence during a median of 138 days. Adverse effects in 9 of the 37 patients (24.3%) led to drug discontinuation, most commonly gastrointestinal intolerance.
CONCLUSIONS
In patients with recurrent VAs and structural heart disease who have limited treatment options, quinidine can be useful, particularly as a short-term therapy.
Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Humans; Quinidine; Retrospective Studies; Ventricular Fibrillation
PubMed: 34217656
DOI: 10.1016/j.jacep.2021.03.024