Comparative Efficacy of Pharmacological Treatments for Acne Vulgaris: A Network Meta-Analysis of 221 Randomized Controlled Trials.

PURPOSE: Acne is an extremely common skin disease with an estimated global prevalence of 9.4%. We aim to provide comprehensive comparisons of the common pharmacological treatments for acne. METHODS: Randomized controlled trials comparing the efficacy of pharmacological therapies for acne vulgaris in patients of any age and sex and with a treatment duration of >2 weeks were included. PubMed and Embase databases were searched from inception until February 2022. Our prespecified primary end points were mean percentage reduction in total, inflammatory, and noninflammatory lesions. Treatment ranking was determined by P values. RESULTS: There were 210 articles describing 221 trials and 37 interventions included in the analysis. Our primary analysis of percentage reduction in total lesion count had 65,601 patients enrolled. Across all trials, the mean age was 20.4 years. The median duration of treatment was 12 weeks. The median total, inflammatory, and noninflammatory lesion counts were 72, 27, and 44, respectively. The most effective treatment was oral isotretinoin (mean difference [MD] = 48.41; P = 1.00), followed by triple therapy containing a topical antibiotic, a topical retinoid, and benzoyl peroxide (BPO) (MD = 38.15; P = .95) and by triple therapy containing an oral antibiotic, a topical retinoid, and BPO (MD = 34.83; P = .90). For monotherapies, oral or topical antibiotics or topical retinoids have comparable efficacy for inflammatory lesions, while oral or topical antibiotics have less effect on noninflammatory lesions. CONCLUSION: The most effective treatment for acne is oral isotretinoin, followed by triple therapies containing a topical retinoid, BPO, and an antibiotic. We present detailed comparisons of each intervention to serve as a practical database.

Association Between Aspirin Use and Sepsis Outcomes: A National Cohort Study.

BACKGROUND: Aspirin has anti-inflammatory and antiplatelet activities and directly inhibits bacterial growth. These effects of aspirin may improve survival in patients with sepsis. We retrospectively reviewed a large national health database to test the relationship between prehospital aspirin use and sepsis outcomes. METHODS: We conducted a retrospective population-based cohort study using the National Health Insurance Research Database of Taiwan from 2001 to 2011 to examine the relationship between aspirin use before hospital admission and sepsis outcomes. The association between aspirin use and 90-day mortality in sepsis patients was determined using logistic regression models and weighting patients by the inverse probability of treatment weighting (IPTW) with the propensity score. Kaplan-Meier survival curves for each IPTW cohort were plotted for 90-day mortality. For sensitivity analyses, restricted mean survival times (RMSTs) were calculated based on Kaplan-Meier curves with 3-way IPTW analysis comparing current use, past use, and nonuse. RESULTS: Of 52,982 patients with sepsis, 12,776 took aspirin before hospital admission (users), while 39,081 did not take any antiplatelet agents including aspirin before hospital admission (nonusers). After IPTW analysis, we found that when compared to nonusers, patients who were taking aspirin within 90 days before sepsis onset had a lower 90-day mortality rate (IPTW odds ratio [OR], 0.90; 95% confidence interval [CI], 0.88-0.93; P < .0001). Based on IPTW RMST analysis, nonusers had an average survival of 71.75 days, while current aspirin users had an average survival of 73.12 days. The difference in mean survival time was 1.37 days (95% CI, 0.50-2.24; P = .002). CONCLUSIONS: Aspirin therapy before hospital admission is associated with a reduced 90-day mortality in sepsis patients.

Temporal Trends in the Microbiological Characteristics of Sepsis in the United States: A Population Based Study.

BACKGROUND: Epidemiologic studies are needed for monitoring population-level trends in sepsis. This study examines sepsis-causing microorganisms from 2006 to 2014 in the United States using data from the Nationwide Inpatient Sample database. METHODS: 7 860 686 adults hospitalized with sepsis were identified using a validated ICD-9 coding approach. Associated microorganisms were identified by ICD-9 code and classified by major groups (Gram-positive, Gram-negative, fungi, anaerobes) and specific species for analysis of their incidence and mortality. RESULTS: The rate of sepsis incidence has increased for all four major categories of pathogens, while the mortality rate decreased. In 2014, Gram-negative pathogens had a higher incidence than Gram-positives. Anaerobes increased the fastest with an average annual increase of 20.17% (p < 0.001). Fungi had the highest mortality (19.28%) and the slowest annual decrease of mortality (-2.31%, p = 0.006) in 2013, while anaerobic sepsis had the highest hazard of mortality (adjusted HR 1.60, 95% CI 1.53-1.66). CONCLUSIONS: Gram-negative pathogens have replaced Gram-positives as the leading cause of sepsis in the United States in 2014 during the study period (2006-2014). The incidence of anaerobic sepsis has an annual increase of 20%, while the mortality of fungal sepsis has not decreased at the same rate as other microorganisms. These findings should inform the diagnosis and management of septic patients, as well as the implementation of public health programs.

Serum Homocysteine, Folate, and Vitamin B12 Levels in Patients with Systemic Lupus Erythematosus: A Meta-Analysis and Meta-Regression.

BACKGROUND: Patients with systemic lupus erythematosus (SLE) have elevated cardiovascular risk. Hyperhomocysteinemia may be one of the contributing factors to this phenomenon. This study therefore aimed to compare the serum homocysteine levels and the levels of folate and vitamin B12, cofactors for homocysteine metabolism, between individuals with and without SLE. METHODS: A literature search was performed in PubMed, Embase, and the Cochrane library (from inception to March 31, 2019). Studies comparing serum homocysteine, folate or vitamin B12 levels between individuals with and without SLE were selected. Of the 1040 screened studies, 50 studies met the inclusion criteria. RESULTS: A total of 50 studies involving 4396 patients with SLE were included. Patients with SLE had a significantly higher serum level of homocysteine (standardized mean difference [SMD], 1.134; 95% CI, 0.795-1.474) and lower level of vitamin B12 (SMD, -0.359; 95% CI, -0.638 to -0.080) than controls. The folate level didn't differ markedly between SLE patients and the control group (SMD, -0.276; 95% CI, -0.674-0.123). Subgroup analysis showed consistent results in adult SLE patients. A random effects meta-regression analysis revealed a significantly inverse correlation between the SMD of homocysteine levels and C3 levels (coefficient, -0.0356, 95% CI, -0.054 to -0.0171; P < .001) and C4 levels (coefficient, -0.0876, 95% CI, -0.1407 to -0.0345; P = .0012). CONCLUSIONS: Serum homocysteine levels were higher and vitamin B12 levels were lower among individuals with SLE than those without SLE. Physicians are encouraged to monitor these parameters and offer timely interventions for patients with SLE.

Comparison of clinical manifestations and outcome of community-acquired bloodstream infections among the oldest old, elderly, and adult patients.

Valid studies comparing the clinical characteristics among adult, elderly, and the oldest old bacteremic patients are lacking. We conducted a prospective, observational study in the emergency department (ED) of a university medical center between June 2001 and June 2002. All patients >18 years of age who registered in the ED with a clinically significant, culture-positive, bloodstream infection (BSI) were enrolled. Patients were divided into 3 groups based on age: 1) oldest old (> or =85 yr), 2) elderly (65-84 yr), and 3) adult (18-64 yr). The clinical and laboratory manifestations and 30-day mortality were recorded. Group comparisons were performed using the chi-square test or analysis of variance (ANOVA) test, as indicated. Survival was analyzed using the Kaplan-Meier method and the Cox-regression model, adjusted for potential confounders.A total of 890 cases of community-acquired BSI were eligible for analysis. Compared to the adult group, both the elderly and the oldest old patients had more atypical clinical manifestations, a higher propensity to develop organ failure, and a worse prognosis. Elderly patients had significantly less tachycardia (p = 0.001), but more acute respiratory (p = 0.007) and renal failure (p = 0.037); the oldest old patients had more afebrile episodes (p = 0.006), leukocytosis (p = 0.012), and more patients developed respiratory failure (p = 0.009), acute renal failure (p = 0.011), septic shock (p = 0.022), and altered mental status (p = 0.013). Urinary tract infections were the main source of BSI for both the elderly and oldest old, while the oldest old patients had significantly more pneumonia than the elderly or adults. As a group, older patients had fewer signs and symptoms of BSI, but a higher risk of organ failure and a worse prognosis than younger patients.

Epidemiology and prognostic determinants of patients with bacteremic cholecystitis or cholangitis.

OBJECTIVES: To compare mortalities in patients with sepsis due to biliary tract infections (BTIs) and due to infections from other sources, and to identify independent predictors of mortality in these patients. METHODS: This study was part of a community-acquired bloodstream infection (BSI) study that prospectively collected comprehensive clinical, laboratory, and outcome data from 937 consecutive patients with microbiologically documented BSI in the emergency department. BTI was the confirmed source of 145 of the 937 BSIs. We determined the independent prognostic factors by evaluating the correlation between 30-day mortality and various factors, for example, comorbidity, clinical severity, related hepatobiliary complication, and decompressive procedures. RESULTS: Patients with biliary sepsis had a high percentage of Gram-negative (88.3%), polymicrobial (26.9%), and anaerobic infections (6.9%). The 30-day overall mortality was 11.7%. Cox proportional hazard regression analysis disclosed five significant independent predictors: acute renal failure (hazard ratio, 95% confidence interval: 6.86, 6.02-25.5), septic shock (5.83, 4.36-15.64), malignant obstruction (4.35, 1.89-12.96), direct type hyperbilirubinemia (1.26, 1.1-1.42), and Charlson score > or =6 (1.57, 1.12-2.22). Compared with the remaining 792 patients in the source population, patients with bacteremic BTI had significantly better prognosis (log-rank test, P= 0.007). Adjusting for age, comorbidity, and clinical severity, BTI was still independently associated with better 30-day survival (0.25-0.76). CONCLUSIONS: Though the mortality rate in patients with bacteremic BTI is substantial, survival is better than in those with bacteremia from other sources. The main prognostic factors identified in this study may help clinicians recognize patients at high risk for early mortality so that they can give prompt, appropriate treatment.

Delayed fluid resuscitation in hemorrhagic shock induces proinflammatory cytokine response.

STUDY OBJECTIVE: This study is designed to determine the effects of delayed fluid resuscitation on the hemodynamic changes and cytokine responses in a rat model of hemorrhagic shock. METHODS: Wistar male rats (n=40; 8/group) were subjected to a volume-controlled hemorrhagic shock for 30 minutes and received lactated Ringer's solution resuscitation as follows: (1) immediate resuscitation, (2) delayed resuscitation begun 30 minutes after hemorrhage (delayed resuscitation 30), (3) delayed resuscitation begun 45 minutes after hemorrhage (delayed resuscitation 45), (4) delayed resuscitation begun 60 minutes after hemorrhage (delayed resuscitation 60), or (5) unresuscitated group, induction of hemorrhagic shock without resuscitation. Hemodynamic parameters were recorded and blood samples were collected at 0 minutes and at 30, 90, 150, 210, 270, and 330 minutes after hemorrhage for plasma levels of interleukin (IL) 6, IL-10 and tumor necrosis factor alpha (TNF-alpha). Repeated-measurement analysis of variance was used for within- and between-groups comparisons. RESULTS: Final mean blood pressure, serum levels of lactate, and hematocrit levels after immediate resuscitation were not different from those in the delayed resuscitation groups. Comparing with the unresuscitated group, TNF-alpha and IL-6 concentrations were significantly higher, whereas IL-10 concentrations were significantly lower in the 4 resuscitation groups. Circulating concentrations of IL-6 were significantly higher in the delayed resuscitation 45 (P<.001) and delayed resuscitation 60 (P<.001) groups. Circulating concentrations of TNF-alpha and IL-10 in the 4 resuscitation groups were comparable throughout the experimental period. CONCLUSION: Delayed fluid resuscitation in hemorrhagic shock induces increased production of proinflammatory cytokines, and the release of cytokine was correlated with the time delayed for resuscitation.

Effect of different resuscitation fluids on cytokine response in a rat model of hemorrhagic shock.

This study was designed to determine the effects of different resuscitation fluids on the production of proinflammatory and anti-inflammatory cytokines in an animal model of hemorrhagic shock. Wistar male rats (n = 24; 8/group) were subjected to a volume-controlled hemorrhagic shock for 30 minutes and resuscitated as follows: (1) sham group without resuscitation, (2) lactated Ringer solution (LR), 3:1; (3) 4% hydroxyethyl starch (HES) solution, 1:1; and (4) 4% modified fluid gelatin (GEL), 1:1. Hemodynamic parameters were recorded, and blood samples were collected at 0 min and 30, 90, 150, 210, 270, and 330 min after hemorrhage for plasma levels of IL-6, IL-10, and TNFalpha. The circulating concentrations of IL-6 at 90, 150, 210, 270, and 330 min and TNFalpha levels at 150, 210, and 270 min after hemorrhage were significantly elevated in animals resuscitated with GEL compared with HES or LR (P < 0.05). At 210, 270, and 330 min, IL-10 concentration was decreased significantly in GEL-resuscitated rats compared with rats resuscitated with LR or HES (P < 0.05). Mean blood pressure and serum levels of lactate after resuscitation were not different among three kinds of fluids. LR, HES, and GEL are comparable in volume efficacy for resuscitation of hemorrhagic shock but are associated with different postresuscitation immune responses. Resuscitation with GEL may be associated with cytokine production favoring a proinflammatory response. The marked elevation of IL-6 observed in the GEL-treated animals may play a role in the relatively high frequency of anaphylactoid reaction in clinical use of GEL.