Early goal-directed therapy reduces mortality in adult patients with severe sepsis and septic shock: Systematic review and meta-analysis

Introduction:

Survival sepsis campaign guidelines have promoted early goal-directed therapy (EGDT) as a means for reduction of mortality. On the other hand, there were conflicting results coming out of recently published meta-analyses on mortality benefits of EGDT in patients with severe sepsis and septic shock. On top of that, the findings of three recently done randomized clinical trials (RCTs) showed no survival benefit by employing EGDT compared to usual care. Therefore, we aimed to do a meta-analysis to evaluate the effect of EGDT on mortality in severe sepsis and septic shock patients.

Methodology:

We included RCTs that compared EGDT with usual care in our meta-analysis. We searched in Hinari, PubMed, EMBASE, and Cochrane central register of controlled trials electronic databases and other articles manually from lists of references of extracted articles. Our primary end point was overall mortality.

Results:

A total of nine trails comprising 4783 patients included in our analysis. We found that EGDT significantly reduced mortality in a random-effect model (RR, 0.86; 95% confidence interval [CI], 0.72–0.94; P = 0.008;   I² =50%). We also did subgroup analysis stratifying the studies by the socioeconomic status of the country where studies were conducted, risk of bias, the number of sites where the trials were conducted, setting of trials, publication year, and sample size. Accordingly, trials carried out in low to middle economic income countries (RR, 0.078; 95% CI, 0.67–0.91; P = 0.002; I² = 34%) significantly reduced mortality compared to those in higher income countries (RR, 0.93; 95% CI, 0.33–1.06; P = 0.28; I² = 29%). On the other hand, patients receiving EGDT had longer length of hospital stay compared to the usual care (mean difference, 0.49; 95% CI, –0.04–1.02; P = 0.07; I² = 0%).

Conclusion:

The result of our study showed that EGDT significantly reduced mortality in patients with severe sepsis and septic shock. Paradoxically, EGDT increased the length of hospital stay compared to usual routine care.     

The immunological benefit of higher dose N-acetyl cysteine following mechanical ventilation in critically ill patients

Background

Sepsis complication is a major cause of death in multiple trauma critically ill patients. Defensin (cysteine rich anti-microbial peptides), as an important component of immune system, might play an important role in this process. There is also rising data on immunological effects of N-acetyl-cysteine (NAC), a commonly used anti-oxidant in oxidative stress conditions and glutathione (GSH) deficiencies. The aim of the present study was to evaluate the potential beneficial effects of NAC administration on multiple trauma patients with sepsis.

Methods

In a prospective, randomized controlled study, 44 multiple trauma critically ill patients who were mechanically ventilated and met the criteria of sepsis and admitted to the intensive care unit (ICU) were randomized into two groups . Control group received all standard ICU therapies and NAC group received intravenous NAC 3 gr every 6 hours for 72 hours in addition to standard therapies. Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, length of ICU stay, ICU mortality were recorded. Levels of serum Immunoglobulin M (IgM), Human β-Defensin 2 (HβD2) and GSH were assessed at baseline and 24, 72, 120 hours after intervention.

Results

During a period of 13-month screening, 44 patients underwent randomization but 5 patients had to be excluded. 21 patients in NAC group and 18 patients in control group completed the study. For both groups the length of ICU stay, SOFA score and systemic oxygenation were similar. Mortality rate (40% vs. 22% respectively, p = 0.209) and ventilator days (Mean ± SD 19.82 ± 19.55 days vs. 13.82 ± 11.89 days respectively, p = 0.266) were slightly higher for NAC group. IgM and GSH levels were similar between two groups (p = 0.325, 0.125 respectively), HβD2 levels were higher for NAC group (at day 3).

Conclusion

High dose of NAC administration not only did not improve patients’ outcome, but also raised the risk of inflammation and was associated with increased serum creatinine.     

Sub-optimal adherence to combination anti-retroviral therapy and its associated factors according to self-report,clinician-recorded and pharmacy-refill assessment methods among HIV-infected adults in Addis Ababa

Adherence to combination antiretroviral therapy (cART) is generally high in most resource-limited settings. However, sub-optimal adherence occurs in a sizable proportion of patients, and is independently predictive of detectable viremia. We investigated sub-optimal adherence according to self-report, clinician-recorded, and pharmacy-refill assessment methods, and their associated factors among HIV-infected adults receiving cART in Addis Ababa, Ethiopia. Eight-hundred seventy patients who initiated cART between May 2009 and April 2012 were randomly selected, and 664 patients who were alive, had remained in clinical care and were receiving cART for at least six-months were included. Sub-optimal adherence was defined as patients’ response of less than “all-of the time” to the self-report adherence question, or any clinician-recorded poor adherence during the six most recent clinic visits, or a pharmacy-refill of <95% medication possession ratio (MPR). Logistic regression models were fitted to identify factors associated with sub-optimal adherence. The average adherence level to cART, expressed as MPR, was nearly 97%. However, sub-optimal adherence occurred in 12%, 4%, and 27% of patients according to self-report, clinician-recorded, and pharmacy-refill measures, respectively. More satisfaction with social support was significantly associated with less sub-optimal adherence according to self-report and clinician-record. Younger age, lower educational level, and lower CD4 cell count at cART initiation were significantly associated with sub-optimal refill-based adherence. Findings from our large multi-center study suggest that sub-optimal adherence was present in up to a quarter of the patients, despite a high degree of average adherence to cART. Interventions aimed at preventing sub-optimal adherence should focus on improving social support, on younger patients, on patients with lower educational level, and on those who started cART at a lower CD4 cell count.     

Health-related quality of life of HIV-infected adults receiving combination antiretroviral therapy in Addis Ababa

Health-related quality of life (HRQoL) is an important outcome measure among HIV-infected patients receiving combination antiretroviral therapy (cART), but has not been studied extensively in resource-limited settings. Insight in the predictors or correlates of poor HRQoL may be helpful to identify patients most in need of additional support and to design appropriate interventions. A cross-sectional study was conducted between September 2012 and April 2013 in 10 healthcare facilities in Addis Ababa, Ethiopia. Patients who were at least 6 months on cART were randomly selected and individual patient data were retrieved from medical records. HRQoL was measured by the WHOQoL-HIVBREF, depressive-symptoms by the Kessler-6 scale, and stigma by the Kalichman internalized AIDS-related stigma scale. Multivariate linear regression analysis was carried-out to examine associations between HRQoL and the other variables. A total of 664 patients (response-rate 95%) participated in the study. A higher level of depressive-symptoms was most strongly and consistently associated with a lower HRQoL, both in terms of the magnitude of the relationship and in the number of HRQoL domains associated with it. Also, a higher level of HIV-stigma was associated with a lower HRQoL except for the physical domain, while obtaining sufficient nutritious food and job opportunity were associated with a better HRQoL except for the spiritual and social domains, respectively. Demographics, clinical, and treatment characteristics yielded few significant associations with HRQoL. Our study findings suggest that interventions to improve HRQoL should focus on reducing depressive-symptoms and HIV-stigma, and on enhancing food security and job opportunity.     

Sleep correlates of substance use in community-dwelling Ethiopian adults

Sleep and Breathing - The relationship between sleep disturbances and substance use can have harmful effects. Evidence shows widespread use of substances, including khat, in the Ethiopian...     

COVID-19 vaccine acceptance among people living with HIV: A systematic review and meta-analysis

Objective

To assess coronavirus disease 2019 (COVID-19) vaccine acceptance among people living with HIV (PLHIV) worldwide.

Methods

We searched MEDLINE, PSYINFO, CINHAL, Scopus and EMBASE databases and other sources including free Google search and subject-specific journals from January 2020 to September 2021. The study population included adults (aged 18+ years) living with HIV and evaluated for COVID-19 vaccine acceptance. A random effect meta-analysis model was used to estimate the pooled COVID-19 vaccine acceptance rate. Subgroup analyses were performed, and factors associated with COVID-19 vaccine hesitancy underwent narrative analysis. Of 558 initial records, 14 studies were eligible for review.

Results

The overall pooled COVID-19 vaccine acceptance rate among adult PLHIV was 62% (95% confidence interval [CI], 56%–69%). In subgroup analysis, the estimated pooled COVID-19 vaccine acceptance rate was higher in high-income countries: 63% (95% CI, 55%–70%) versus 62% (95% CI, 54%–71%) in low- and middle-income countries, and in studies conducted in 2022 (66% [95% CI, 58%–75%]) than in studies conducted in 2021 (57% [95% CI, 47%–68%]). Reasons for lower COVID-19 vaccine acceptance included higher monthly income, being non-homosexual, history of chronic disease, COVID-19-related medical mistrust, not knowing anyone who died of COVID-19, believing oneself to be immune to COVID-19, general vaccine refusal, negative attitude to the vaccine, concerns about efficacy, safety and side effects, distrust in common sources of vaccine-related information and using social media as a source of information on COVID-19.

Conclusion

Among PLHIV, acceptance of COVID-19 vaccine is generally low. A greater emphasis on collaborative efforts between all concerned bodies is needed to boost vaccine acceptance in this population.