Tenecteplase use in the management of acute ischemic stroke: Literature review and clinical considerations

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Several research articles have been published within the last decade comparing the use of tenecteplase to alteplase in ischemic stroke management. Prior reporting on the comparative therapeutic efficacy and safety profiles of tenecteplase and alteplase is reviewed. Summary Tenecteplase is a variant of native tissue-type plasminogen activator, which rapidly promotes thrombolysis by catalyzing formation of the serine protease plasmin. Tenecteplase has theoretical advantages over alteplase as it has greater fibrin specificity and has a longer half-life than alteplase. This allows the administration of a single bolus over 5 to 10 seconds, as opposed to a bolus followed by a 1-hour infusion with alteplase. While currently approved by the Food and Drug Administration for the treatment of ST-segment elevation myocardial infarction, tenecteplase has also been studied in the treatment of acute ischemic stroke and has extensive data for this off-label indication. The most comprehensive trials to date evaluating the use of tenecteplase in acute ischemic stroke include the TNK-S2B, Australian TNK, ATTEST, Nor-Test, and EXTEND-IA TNK trials. Findings from these randomized controlled studies suggest that tenecteplase is at least as efficacious as alteplase in terms of neurological outcomes. The majority of these studies also reported a trend toward improved safety profiles with the use of tenecteplase. Conclusion Current clinical evidence shows that tenecteplase is not inferior to alteplase for the treatment of ischemic stroke and suggests that tenecteplase may have a superior safety profile. Furthermore, tenecteplase also has practical advantages in terms of its administration. This can potentially lead to a decrease in medication errors and improvement in door to thrombolytic time.

Differentiated approach to the prescription of dexpanthenol drugs in the practice of a pediatrician

The article provides information about the features of the structure, development and differentiated approach to the appointment of dexapanthenol preparations used for the prevention and complex treatment of skin diseases in children of wounded age. Regular use of leave-on cosmetic products including body creams and lotions is very high among children aged 0–4 years. However, in most cases, recommendations for the use of topical baby skin care medicinal products and/or cosmetic products are based not on scientific evidence, but on common sense, expert opinions, advertising, personal preferences of parents, pharmacists, dermatologists and/or pediatricians. For example, adsorbing properties of baby powders are insufficient, and after absorbing moisture, they actually turn to “urine compresses” that aggravate the epidermis injury. After swelling, the starch-containing powders represent an excellent growth media for pathogenic and opportunistic microflora. It is noted that only proper skin care for young children allows you to preserve its integrity and functional state. Special attention is paid to the preparations of the Bepanten® series in the form of cream and ointment, which meet all the criteria for topical products, and can be used for the prevention and treatment of skin diseases in young children, effectively protecting the skin from irritants, promoting its healing and recovery, having an anti-inflammatory effect, increasing its elasticity, elasticity and are recommended for use as a means of basic care. Their effectiveness has been repeatedly confirmed in the numerous domestic and foreign randomized controlled studies in new-born populations at different gestational ages, which provided the scientific justification for their common use in the ‘real-life’ practice of pediatricians, dermatologists and allergists.

The extent to which non-conditional housing programs improve housing and well-being outcomes: a systematic review

Purpose To reduce rates of homelessness, recent efforts have been directed toward developing non-conditional supported housing programs that prioritize the delivery of housing support and individual services, without tenancy conditions (i.e. maintaining sobriety and adhering to mental health treatment). As promising as these programs are, findings generally show that while housing stability is improved, other individual outcomes remain largely unchanged. No review to date has synthesized the collective evidence base of non-conditional housing programs, rather the focus has been on specific programs of delivery (e.g. Housing First) or on specific population groups (e.g. those with mental illness). The purpose of this paper is to evaluate the extent to which non-conditional housing interventions improve housing and well-being outcomes for all persons. Design/methodology/approach A systematic search of the literature was conducted for randomized controlled studies that evaluated the effectiveness of a non-conditional housing intervention in improving housing and health outcomes among any participant group. Findings A total of 31 studies were included in this review. Non-conditional supported housing programs were found to be most effective in improving housing stability as compared to health and well-being outcomes. Policymakers should consider this when developing non-conditional supported housing programs and ensure that housing and other health-related outcomes are also mutually supported. Originality/value This is the first review, to the authors’ knowledge, to synthesize the collective impact of all non-conditional supported housing programs. The current findings may inform the (re)design and implementation of supported housing models to prioritize the health and well-being of residents.

Feasıbılıty of Transcutaneous Method for Carbon Dıoxıde Monıtorıng in an Intensive Care Unıt

Background: Transcutaneous partial pressure of carbon dioxide (PtCO2) monitorization provides a continuous and non-invasive measurement of partial pressure of carbon dioxide (pCO2). In addition, peripheral oxygen saturation (SpO2) can also be measured and followed by this method. However, data regarding the correlation between PtCO2 and arterial pCO2 (PaCO2) measurements acquired from peripheric arterial blood gas is controversial. Objective: We aimed to determine the reliability of PtCO2 with PaCO2 based on its advantages, like non-invasiveness and continuous applicability. Methods: Thirty-five adult patients with hypercapnic respiratory failure admitted to our tertiary medical intensive care unit (ICU) were included. Then we compared PtCO2 and PaCO2 and both SpO2 measurements simultaneously. Thirty measurements from the deltoid zone and 26 measurements from the cheek zone were applied. Results: PtCO2 could not be measured from the deltoid region in 5 (14%) patients. SpO2 and pulse rate could not be detected at 8 (26.7%) of the deltoid zone measurements. Correlation coefficients between PtCO2 and PaCO2 from deltoid and the cheek region were r: 0,915 and r: 0,946 (p = 0,0001). In comparison with the Bland-Altman test, difference in deltoid measurements was -1,38 ± 1,18 mmHg (p = 0.252) and in cheek measurements it was -5,12 ± 0,92 mmHg (p = 0,0001). There was no statistically significant difference between SpO2 measurements in each region. Conclusion: Our results suggest that PtCO2 and SpO2 measurements from the deltoid region are reliable compared to the arterial blood gas analysis in hypercapnic ICU patients. More randomized controlled studies investigating the effects of different measurement areas, hemodynamic parameters, and hemoglobin levels are needed.

Efficacy and safety of esketamine nasal spray by sex in patients with treatment-resistant depression: findings from short-term randomized, controlled trials

The objective of this analysis was to determine if there are sex differences with esketamine for treatment-resistant depression (TRD). Post hoc analyses of three randomized, controlled studies of esketamine in patients with TRD (TRANSFORM-1, TRANSFORM-2 [18–64 years], TRANSFORM-3 [≥ 65 years]) were performed. In each 4-week study, adults with TRD were randomized to esketamine or placebo nasal spray, each with a newly initiated oral antidepressant. Change from baseline to day 28 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score was assessed by sex in pooled data from TRANSFORM-1/TRANSFORM-2 and separately in data from TRANSFORM-3 using a mixed-effects model for repeated measures. Use of hormonal therapy was assessed in all women, and menopausal status was assessed in women in TRANSFORM-1/TRANSFORM-2. Altogether, 702 adults (464 women) received ≥ 1 dose of intranasal study drug and antidepressant. Mean MADRS total score (SD) decreased from baseline to day 28, more so among patients treated with esketamine/antidepressant vs. antidepressant/placebo in both women and men: TRANSFORM-1/TRANSFORM-2 women—esketamine/antidepressant -20.3 (13.19) vs. antidepressant/placebo -15.8 (14.67), men—esketamine/antidepressant -18.3 (14.08) vs. antidepressant/placebo -16.0 (14.30); TRANSFORM-3 women—esketamine/antidepressant -9.9 (13.34) vs. antidepressant/placebo -6.9 (9.65), men—esketamine/antidepressant -10.3 (11.96) vs. antidepressant/placebo -5.5 (7.64). There was no significant sex effect or treatment-by-sex interaction (p > 0.35). The most common adverse events in esketamine-treated patients were nausea, dissociation, dizziness, and vertigo, each reported at a rate higher in women than men. The analyses support antidepressant efficacy and overall safety of esketamine nasal spray are similar between women and men with TRD. The TRANSFORM studies are registered at clinicaltrials.gov (identifiers: NCT02417064 (first posted 15 April 2015; last updated 4 May 2020), NCT02418585 (first posted 16 April 2015; last updated 2 June 2020), and NCT02422186 (first posted 21 April 2015; last updated 29 September 2021)).

Clinical and Radiological Factors Affecting Thoracolumbar Fractures Outcome: WFNS Spine Committee Recommendations

To obtain a list of recommendations about clinical and radiological factors affecting outcome in thoraco-lumbar fractures with the aim of helping spine surgeons in daily practice. A systematic literature search in PubMed and Google Scholar database was done from 2010 to 2020 on the topic “thoracolumbar fracture AND radiology AND surgical outcomes” and “thoracolumbar fracture AND radiology AND surgical outcomes.” A total of 58 papers were analyzed and WFNS (World Federation of Neurosurgical Societies) Spine Committee organized 2 consensus meetings to formulate the specific recommendations the first in Peshawar in December 2019 and in a subsequent virtual meeting in June 2020 to reach an agreement. Both meetings utilized the Delphi method to analyze preliminary literature review statements based on the current evidence levels to generate recommendations through a comprehensive voting session. Eight statements were presented and reached the consensus about this topic. A variety of clinical factors is known to influence outcome of patients with thoracolumbar fractures. Some of these are well-known established factors such as blood pressure augmentation and patient age, while some are not well studied. Overall, the quality of evidence is low and we need more randomized controlled studies to validate our results. Similarly, radiological factors that can predict outcome are well stated and there is a high accordance worldwide. In reverse, still under debate is the application to choose which surgical treatment is advisable based on them.

Intraoperative Use of Topical Retropharyngeal Steroids for Dysphagia after Anterior Cervical Fusion: A Systematic Review and Meta-Analysis

Purpose. The anterior cervical approach is commonly used clinically for cervical spondylosis, but it also results in frequent postoperative dysphagia, which can increase the risk of complications and poor treatment satisfaction in severe cases. Intraoperative local application of retropharyngeal steroids has an impact on reducing the occurrence and severity of dysphagia; however, the results of current studies vary. The meta-analysis of this randomized trial was to evaluate the effectiveness and safety of intraoperative topical retropharyngeal steroids for the control of dysphagia after anterior cervical spine surgery. Methods. Two authors searched electronic databases such as PubMed, MEDLINE, EMBASE, Cochrane Library, and Google Scholar, respectively. The search terms were “Dysphagia,” “Steroids,” “Anterior Cervical Discectomy and Fusion,” etc. A random effects model was used to conduct a meta-analysis based on deviance information criteria. Results. A total of 8 studies were included in this meta-analysis after screening of 792 studies. Bazaz scores were not significantly different in the steroid group at one day postoperatively ( P = 0.38 ), and dysphagia was significantly improved at 14 days postoperatively (95% CI: 0.15 to 0.64; P = 0.002 ). PSTSI was significantly improved one day ( P = 0.03 ) and 14 days after surgery ( P < 0.0001 ). VAS scores were all lower versus controls ( P < 0.001 ). Conclusion. Perioperative local retropharyngeal steroid administration as an adjunct to anterior cervical spine surgery reduces the incidence and severity of dysphagia compared with placebo control. However, future high-quality randomized controlled studies could incorporate nonsubjective dysphagia measures and long-term follow-up on the occurrence of associated complications or other side effects.

Visual Outcome after Vitrectomy with Subretinal tPA Injection to Treat Submacular Hemorrhage Secondary to Age-Related Macular Degeneration or Macroaneurysm

Purpose. To determine the efficacy and safety of 23G transconjunctival sutureless vitrectomy, subretinal injection of tissue plasminogen activator using the EVA Surgical System, and pneumatic displacement with air to treat submacular hemorrhages. Methods. Retrospective analysis of 93 eyes surgically treated for submacular hemorrhage caused by neovascular AMD or retinal macroaneurysms. Main Outcome Measures. Postoperative visual acuity and surgical complications. Results. After surgery, visual acuity improved after 6 weeks but decreased again at the final postoperative visit at 8 months due to progression of the underlying disease. Complications consisted of 2 cases of retinal pigment epithelial tear, 7 vitreous hemorrhages, 4 hyphema, 6 cases of retinal detachment, and 2 subchoroidal hemorrhages during the follow-up period. Conclusions. This study suggests that a surgical approach with 23G vitrectomy, subretinal tPA injection, and pneumatic displacement using air may be an effective procedure for submacular hemorrhage displacement in patients with AMD and retinal macroaneurysms. However, visual outcome is limited by the underlying macular pathology. Larger multicenter randomized controlled studies are warranted to determine the therapeutic effect of this surgical approach.

Clinical Utility of Intravascular Ultrasound (IVUS) in Carotid Artery Interventions: A Systematic Review and Meta-analysis

Background: Carotid plaque morphology plays an important role in determining outcome of carotid artery stenting (CAS). Intravascular ultrasound (IVUS) and its extension VH (Virtual Histology)-IVUS evaluate plaque characteristics in real time and guide decision making during stenting. To date, there is no consensus about indications of IVUS and its validated methods. This systematic review and meta-analysis aims to evaluate the clinical utility of IVUS in carotid artery interventions (CAS) and develop a future consensus for research and practice parameters. Methods: A systematic review and meta-analysis was performed of the English literature articles published till February 2021. Studies reporting on IVUS parameters and findings and also its performance compared with other imaging modalities were included in review. Pooled prevalence with 95% confidence intervals (CI) was calculated. The statistical analysis was conducted in R version 3.6.2. Results: A total of 2015 patients from 29 studies were included. Proportional meta-analysis was performed on 1566 patients from 11 studies. In 9 studies, stroke/transient ischemic attack (TIA) had a pooled prevalence of 4% (95% CI 3%–5%) while asymptomatic stroke had a pooled prevalence of 46% (95% CI 31%–62%) in 4 studies following IVUS. Two studies reported that IVUS detected more plaque protrusion compared with angiography (n=33/396 vs 11/396). IVUS led to stent type or size change in 8 of 48 cases which were missed on angiography in 3 other studies. Concordance between VH-IVUS and true histology was good at 80% to 85% reported in 2 studies. Conclusions: This systematic review and meta-analysis showed, though IVUS fared better to computed tomography (CT)/magnetic resonance (MR) angiography for better stent selection during CAS, with low to moderate risk of bias in the studies included. However, large scale, preferably randomized controlled studies are needed to predict its role in determining clinical outcome.

Baduanjin Exercise for Adults Aged 65 Years and Older: A Systematic Review and Meta-Analysis of Randomized Controlled Studies

This study performed a systematic review and meta-analysis to evaluate the health effects of Baduanjin exercise on adults aged 65 years and older. Chinese and English databases were electronically searched using search terms related to the PICO model from inception through June 2021. The study quality assessment and meta-analysis were conducted using the PEDro scale and RevMan 5.4 software. Eleven included Chinese studies, published between 2015 and 2021, recruited participants from the mainland of China. The aggregated results showed significant benefits of Baduanjin on physical function, walking ability, balance, and anxiety. A long-term Baduanjin intervention could also improve quality of life and reduce falls and pain. Baduanjin appears to have the potential to improve the health of older adults, but conclusions are limited due to the lack of rigorous and robust studies within and outside of mainland China. Larger, well-designed RCTs are needed to confirm these findings.