To perform an in‐depth analysis of opioid‐related ADRs reported by consumers, manufacturers and healthcare professionals. Delving into the depth and breadth of reported opioid‐related adverse drug ...reactions (ADRs) provides an opportunity to strategize better clinical management and alleviate safety concerns. Retrospective pharmacovigilance disproportionality analysis for opioid‐related ADRs in the FDA Adverse Event Reporting System (FAERS) database was performed. Detailed analysis of patient (sex, age) and report (year of report; reporter: healthcare worker vs consumer) characteristics were conducted using reports from 2004 quarter 1 to 2018 quarter 4. Reporting odds ratios and confidence intervals (RORs,CI) were calculated. Of the 1 916 674 ADR reports, 300 985 indicated opioids as the primary medication. There was a surge in opioid‐related ADRs reported in 2018 with six times more reports compared to 2004 and twice the number of reports compared to 2017. The largest ROR among the 20 common ADRs was depression and suicide‐self‐injury (ROR 3.12, 95% CI 3.01‐3.22) for reports in age group ≥65 compared to age group 18 to 64, and lack of efficacy (ROR 6.80, 95% CI 6.61‐7.00) for males compared to females. ADRs with the largest RORs for consumers included lack of efficacy/effect (ROR 3.37, 95% CI 3.28‐3.46), administration site reactions (ROR 3.21, 95% CI 3.11‐3.32), depression and suicide self‐injury (ROR 2.26, 95% CI 2.14‐2.38) compared to healthcare professionals. Important aspects of opioid ADR voluntary reporting included suicidal ideation in elderly patients and lack of efficacy, especially in male patients. This examination provides insight to better manage safety concerns of opioids.
The current narrative review discusses practical applications of stress and damage biomarkers for the management of acute kidney injury (AKI) based on clinical trials and real-world evaluations.
In ...2013 with the discovery and validation study of biomarkers for AKI (Sapphire) advancement in care was provided allowing for the early identification of patients at high risk for developing AKI. It was the combination of new biomarkers and the Kidney Disease Improving Global Outcomes (KDIGO) guidelines for managing patients with AKI that provided an opportunity to improve patient care. In 2017, the PrevAKI study implemented KDIGO guideline management in high-risk patients identified by biomarkers followed in 2018 with the BigPAK study that used a similar approach, both of which demonstrated positive outcomes in patient care. Next, real-world evaluations followed supporting biomarker guided management of AKI in clinical practice. Also, proposals for better nephrotoxin management, a major modifiable exposure to prevent AKI, were provided with the foresight in identifying high-risk patients.
Stress and damage biomarker-based approaches to patient care seem to be promising for identifying patients at high risk for developing AKI and thus offers an opportunity for early management to prevent and ameliorate AKI and drug-associated AKI.
The contribution of nephrotoxic medications to the development of acute kidney injury (AKI) is becoming better understood concomitant with the increased incidence of AKI in children. Treatment of AKI ...is not yet available, so prevention continues to be the most effective approach. There is an opportunity to mitigate severity and prevent the occurrence of AKI if children at increased risk are identified early and nephrotoxins are used judiciously. Early detection of AKI is limited by the dependence of nephrologists on serum creatinine as an indicator. Promising new biomarkers may offer early detection of AKI prior to the rise in serum creatinine. Early detection of evolving AKI is improving and offers opportunities for better management of nephrotoxins. However, the identification of patients at increased risk will remain an important first step, with a focus on the use of biomarker testing and interpretation of the results.
Regardless of practice setting, it is imperative that pharmacists be able to either participate in generating new knowledge or use the ever‐expanding body of literature to guide patient care. ...However, competing priorities in Pharm.D. curricula and residency training programs have resulted in limited emphasis on acquiring research and scholarly skills. Factors likely contributing to this reduced focus include the lack of curricular and postgraduate training standards emphasizing the development of research skills, time to commit to scholarly activity, and accessibility to experienced mentors. Strategies for increasing scholarly activity for pharmacy students and residents should therefore continue to be a focus of professional degree and residency training programs. Several resources are available for academic planners, program directors, and institutions to augment scholarly experience for pharmacy trainees and clinicians. This commentary highlights the importance of providing research opportunities for students and residents, describes the potential barriers to these activities, and provides recommendations on how to increase the instruction and mentoring of trainees to generate and use research.
Kratom is a widely used Asian botanical that has gained popularity in the United States due to a perception that it can treat pain, anxiety, and opioid withdrawal symptoms. The American Kratom ...Association estimates 10–16 million people use kratom. Kratom‐associated adverse drug reactions (ADRs) continue to be reported and raise concerns about the safety profile of kratom. However, studies are lacking that describe the overall pattern of kratom‐associated adverse events and quantify the association between kratom and adverse events. ADRs reported to the US Food and Drug Administration Adverse Event Reporting System from January 2004 through September 2021 were used to address these knowledge gaps. Descriptive analysis was conducted to analyze kratom‐related adverse reactions. Conservative pharmacovigilance signals based on observed‐to‐expected ratios with shrinkage were estimated by comparing kratom to all other natural products and drugs. Based on 489 deduplicated kratom‐related ADR reports, users were young (mean age 35.5 years), and more often male (67.5%) than female patients (23.5%). Cases were predominantly reported since 2018 (94.2%). Fifty‐two disproportionate reporting signals in 17 system‐organ‐class categories were generated. The observed/reported number of kratom‐related accidental death reports was 63‐fold greater than expected. There were eight strong signals related to addiction or drug withdrawal. An excess proportion of ADR reports were about kratom‐related drug complaints, toxicity to various agents, and seizures. Although further research is needed to assess the safety of kratom, clinicians and consumers should be aware that real‐world evidence points to potential safety threats.
Drug associated kidney injury (D-AKI) occurs in 19-26% of hospitalized patients and ranks as the third to fifth leading cause of acute kidney injury (AKI) in the intensive care unit (ICU). Given the ...high use of antimicrobials in the ICU and the emergence of new resistant organisms, the implementation of preventive measures to reduce the incidence of D-AKI has become increasingly important.
Artificial intelligence is showcasing its capabilities in early recognition of at-risk patients for acquiring AKI. Furthermore, novel synthetic medications and formulations have demonstrated reduced nephrotoxicity compared to their traditional counterparts in animal models and/or limited clinical evaluations, offering promise in the prevention of D-AKI. Nephroprotective antioxidant agents have had limited translation from animal studies to clinical practice. The control of modifiable risk factors remains pivotal in avoiding D-AKI.
The use of both old and new antimicrobials is increasingly important in combating the rise of resistant organisms. Advances in technology, such as artificial intelligence, and alternative formulations of traditional antimicrobials offer promise in reducing the incidence of D-AKI, while antioxidant medications may aid in minimizing nephrotoxicity. However, maintaining haemodynamic stability using isotonic fluids, drug monitoring, and reducing nephrotoxic burden combined with vigilant antimicrobial stewardship remain the core preventive measures for mitigating D-AKI while optimizing effective antimicrobial therapy.
To summarize the effectiveness of implementation strategies for ICU execution of recommendations from the 2013 Pain, Agitation/Sedation, Delirium (PAD) or 2018 PAD, Immobility, Sleep Disruption ...(PADIS) guidelines.
PubMed, CINAHL, Scopus, and Web of Science were searched from January 2012 to August 2023. The protocol was registered with PROSPERO (CRD42020175268).
Articles were included if: 1) design was randomized or cohort, 2) adult population evaluated, 3) employed recommendations from greater than or equal to two PAD/PADIS domains, and 4) evaluated greater than or equal to 1 of the following outcome(s): short-term mortality, delirium occurrence, mechanical ventilation (MV) duration, or ICU length of stay (LOS).
Two authors independently reviewed articles for eligibility, number of PAD/PADIS domains, quality according to National Heart, Lung, and Blood Institute assessment tools, implementation strategy use (including Assess, prevent, and manage pain; Both SAT and SBT; Choice of analgesia and sedation; Delirium: assess, prevent, and manage; Early mobility and exercise; Family engagement and empowerment ABCDEF bundle) by Cochrane Effective Practice and Organization of Care (EPOC) category, and clinical outcomes. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation.
Among the 25 of 243 (10.3%) full-text articles included ( n = 23,215 patients), risk of bias was high in 13 (52%). Most studies were cohort ( n = 22, 88%). A median of 5 (interquartile range IQR 4-7) EPOC strategies were used to implement recommendations from two (IQR 2-3) PAD/PADIS domains. Cohort and randomized studies were pooled separately. In the cohort studies, use of EPOC strategies was not associated with a change in mortality (risk ratio RR 1.01; 95% CI, 0.9-1.12), or delirium (RR 0.92; 95% CI, 0.82-1.03), but was associated with a reduction in MV duration (weighted mean difference WMD -0.84 d; 95% CI, -1.25 to -0.43) and ICU LOS (WMD -0.77 d; 95% CI, -1.51 to 0.04). For randomized studies, EPOC strategy use was associated with reduced mortality and MV duration but not delirium or ICU LOS.
Using multiple implementation strategies to adopt PAD/PADIS guideline recommendations may reduce mortality, duration of MV, and ICU LOS. Further prospective, controlled studies are needed to identify the most effective strategies to implement PAD/PADIS recommendations.
Objective:
To critically evaluate the use of analgosedation in the management of agitation in critically ill mechanically ventilated patients.
Data Sources:
Literature was accessed through MEDLINE ...(1948-November 2011) and Cochrane Library (2011, issue 1) using the terms analgosedation, analgosedation, or analgesia-based sedation alone or in combination with intensive care unit or critically ill. Reference lists of related publications were also reviewed.
Study Selection and Data Extraction:
All articles published in English were evaluated. Randomized controlled trials examining critically ill mechanically ventilated patients older than 18 years were included.
Data Synthesis:
Limitations of current sedation practices include serious adverse drug events, prolonged mechanical ventilation time, and intensive care unit (ICU) length of stay. Studies have demonstrated that analgosedation, a strategy that manages patient pain and discomfort first, before providing sedative therapy, results in improved patient outcomes compared to standard sedative-hypnotic regimens. Nine randomized controlled trials comparing remifentanil-based analgosedation to other commonly used agents (fentanyl, midazolam, morphine, and propofol) for ICU sedation and 1 trial comparing morphine to daily sedation interruption with propofol or midazolam were reviewed. Remifentanil is an ideal agent for analgosedation due to its easy titratability and organ-in dependent metabolism. When compared to sedative-hypnotic regimens, remifentanil-based regimens were associated with shorter duration of mechanical ventilation, more rapid weaning from the ventilator, and shorter ICU length of stay. Compared to fentanyl-based regimens, remifentanil had similar efficacy with the exception of increased pain requirements upon remifentanil discontinuation. Analgosedation was well tolerated, with no significant differences in hemodynamic stability compared to sedative-hypnotic regimens.
Conclusions:
Analgosedation is an efficacious and well-tolerated approach to management of ICU sedation with improved patient outcomes compared to sedative-hypnotic approaches. Additional well-designed trials are warranted to clarify the role of analgosedation in the management of ICU sedation, including trials with nonopioid analgesics.
Background: Guidelines recommend initiating metformin at the time of T2D diagnosis in the absence of contraindications for asymptomatic patients. However, the evidence is scarce regarding real-world ...patterns and factors associated with antidiabetic treatment initiation in patients with newly diagnosed T2D.
Methods: We used a 5% random sample of Medicare beneficiaries newly diagnosed with T2D in 2007-2017 and followed them for one year. The outcome was time to initiation of an antidiabetic agent within the first year of diagnosis. We examined trends in the proportion of outcome and the therapeutic class initiated by year. We constructed Cox Proportional Hazard models to identify factors associated with treatment initiation.
Results: Of 231,408 patients newly diagnosed with T2D, the mean age was 71.7, and 62.2% were female. Only 13.7% initiated an antidiabetic agent within the first year of diagnosis. Although the proportion of initiation within one year of T2D diagnosis was relatively constant over time (12.7% in 2007 to 15.4% in 2017), the mean time to initiation decreased from 74.1 days in 2007 to 21.7 days in 2017 (p<0.05). Of those who initiated treatment, 54.2% and 21.5% initiated metformin and sulfonylurea in 2007, while 84.4% and 6.0% initiated metformin and sulfonylurea in 2017, respectively. In the adjusted model, age (HR 0.92, 95%CI 0.91-0.93 for 10-year increase), female sex (HR 0.89, 95%CI 0.87-0.91), number of comorbidities (HR 0.86, 95%CI 0.86-0.87 for one additional) and residence in urban areas (HR 0.78, 95%CI 0.76-0.80) were associated with decreased hazards of antidiabetic initiation.
Conclusion: We found unexpectedly low rates of initiation of first-line treatment among Medicare beneficiaries with newly diagnosed T2D. The changes in the proportion of different drug classes reflect the change in guideline recommendations. Further investigation is needed to understand the causes underlying the low initiation.
Disclosure
Y. Li: None. I. Hernandez: Consultant; Self; Bristol-Myers Squibb Company, Pfizer Inc. N. Gabriel: None. S. L. Kane-gill: None. U. Essien: None. F. Toledo: Consultant; Self; AstraZeneca. J. Guo: None.
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