Reg Anesth Pain Med. 2021 Aug 20:rapm-2021-102973. doi: 10.1136/rapm-2021-102973. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Transversus abdominis plane (TAP) blocks are associated with an improvement in postoperative analgesia following kidney transplant surgery. However, these blocks carry inherent risk and require a degree of expertise to perform successfully. Continuous intravenous lidocaine may be an effective alternative. In this randomized, non-inferiority study, we hypothesized that a continuous lidocaine infusion provides similar postoperative analgesia to a TAP block.

METHODS: Subjects presenting for kidney transplant surgery were randomized in a 1:1 ratio to either an ultrasound-guided unilateral, single-injection TAP block (TAP group) or a continuous infusion of lidocaine (Lido group). The primary outcome of this non-inferiority study was opioid consumption within the first 24 hours following surgery. Secondary outcomes included pain scores, patient satisfaction, opioid-related adverse events, time to regular diet, and persistent opioid use.

RESULTS: One hundred and twenty subjects, 59 from the TAP group and 61 from the Lido group, completed the study per protocol. Analysis of the primary outcome showed a cumulative geometric mean intravenous morphine equivalent difference between the TAP (14.6±3.2 mg) and Lido (15.9±2.4 mg) groups of 1.27 mg (95% CI -4.25 to 6.79; p<0.001), demonstrating non-inferiority of the continuous lidocaine infusion. No secondary outcomes showed clinically meaningful differences between groups.

CONCLUSIONS: This study demonstrates that a continuous infusion of lidocaine offers non-inferior postoperative analgesia compared with an ultrasound-guided unilateral, single-injection TAP block in the first 24 hours following kidney transplant surgery.

TRIAL REGISTRATION NUMBER: NCT03843879.

PMID:34417343 | DOI:10.1136/rapm-2021-102973

CNS Neurol Disord Drug Targets. 2021 Aug 19. doi: 10.2174/1871527320666210820091655. Online ahead of print.

ABSTRACT

AIMS: To investigate the efficacy and safety of Cerebrolysin and Cerebrolysin plus nootropics in the routine treatment of patients with acute ischemic stroke (AIS).

BACKGROUND: Acute ischemic stroke (AIS) is a leading cause of disability with unmet treatment needs lacking effective drug therapy. Multimodal drugs modulating stroke pathophysiology as Cerebrolysin constitute a good therapeutic option.

OBJECTIVE: In this study, we assessed the effects of Cerebrolysin and Cerebrolysin plus nootropics, in comparison with other nootropic drugs alone, on functional, neurological and cognitive recovery of patients with AIS in Vietnam.

METHODS: This non-interventional, controlled, open-label, prospective and multicenter study included 398 AIS patients (234 males) treated with Cerebrolysin (n=190; 20 i.v. infusions of 10 ml), other nootropics (comparator group; n=86), or a combination of both (n=122). The study primary endpoint was a modified Ranking Scale (mRS) score on day 90. Secondary endpoints included study-period change in NIHSS score; percentage of well-recovered (mRS 0-2) patients, the proportion of good NIHSS response (≥6 points) cases, and MoCA scores at day 90; and safety indicators.

RESULTS: Compared with other nootropics, both Cerebrolysin and combined therapy induced significant improvements (p<0.001) in: Functional recovery (mRS scores); percentage of well-recovered patients (Cerebrolysin: 81.6%; combination: 93.4%; comparator: 43.0%); neurological recovery (study-period NIHSS change); proportion of good NIHSS responders (Cerebrolysin: 77.5%; combination: 92.5%; comparator: 47.6%); and MoCA scores (Cerebrolysin: 23.3±4.8; combination: 23.7±4.1; comparator: 15.9±7.7). Compared to Cerebrolysin, combined therapy improved (p<0.01) mRS outcomes and NIHSS change, but not MoCA scores, in moderate-severe stroke (NIHSS>11) cases only. No drug-related adverse events were reported.

CONCLUSION: Cerebrolysin alone or combined with other nootropics was effective and safe in routine AIS treatment, during both acute and recovery phases, which supports its use in daily clinical practice. Other. According to the results of this multicenter study, the importance of reducing differences in the treatment regimens of AIS in Vietnam should be further emphasized.

PMID:34414874 | DOI:10.2174/1871527320666210820091655

J Nucl Med. 2021 Aug 19:jnumed.121.262485. doi: 10.2967/jnumed.121.262485. Online ahead of print.

ABSTRACT

There is a need for in vivo diagnostic imaging probes that can noninvasively measure tumor infiltrating CD8+ leukocytes. Such imaging probes could be used to predict early response to cancer immunotherapy, help select effective single or combination immunotherapies, and facilitate the development of new immunotherapies or immunotherapy combinations. This study was designed to optimize conditions for performing CD8 PET imaging with 89Zr-Df-IAB22M2C and determine if CD8 PET imaging could provide a safe and effective non-invasive method of visualizing the whole body biodistribution of CD8+ leukocytes. Methods: We conducted a phase 1 first-in-human PET imaging study using an anti-CD8 radiolabeled minibody, 89Zr-Df-IAB22M2C, to detect whole body and tumor CD8+ leukocyte distribution in patients with metastatic solid tumors. Patients received 111 MBq of 89Zr-Df-IAB22M2C followed by serial PET scans over a 5-7-day period. A two-stage design included a dose-escalation phase and a dose-expansion phase. Biodistribution, radiation dosimetry, and semi-quantitative evaluation of 89Zr-Df-IAB22M2C uptake were performed in all patients. Results: 15 subjects with metastatic melanoma, non-small cell lung cancer, and hepatocellular carcinoma were enrolled. No drug-related adverse events or abnormal laboratory results were noted except for a transient increase in anti-drug antibodies in 1 subject. 89Zr-Df-IAB22M2C accumulated in tumors and CD8-rich tissues (e.g. spleen, bone marrow, nodes) with maximum uptake at 24-48 hours post injection and low background activity in CD8-poor tissues (e.g. muscle and lung). Radiotracer uptake in tumors was noted in 10/15 subjects, including 7/8 subjects on immunotherapy, 1/2 subjects on targeted therapy, and 2/5 treatment naïve subjects. In three patients with advanced melanoma or hepatocellular carcinoma on immunotherapy, post-treatment CD8 PET/CT scans demonstrated increased 89Zr-Df-IAB22M2C uptake in tumor lesions, which correlated with response. Conclusion: CD8 PET imaging with 89Zr-Df-IAB22M2C is safe and has the potential to visualize the whole-body biodistribution of CD8+ leukocytes in tumors and reference tissues, and may predict early response to immunotherapy.

PMID:34413145 | DOI:10.2967/jnumed.121.262485

J Chemother. 2021 Aug 19:1-10. doi: 10.1080/1120009X.2021.1963617. Online ahead of print.

ABSTRACT

Individualization of fosfomycin dosing based on therapeutic drug monitoring (TDM) of plasma concentrations could reduce drug-related adverse events and improve clinical outcome in complex clinical conditions. Quantification of fosfomycin in plasma samples was performed by a rapid ultraperformance liquid chromatography mass spectrometry method. Sample preparation involved protein precipitation with [13C3]-fosfomycin benzylamine salt as internal standard. The calibration curve ranged from 2 to 800 mg/L. Within- and between-day precision and accuracy, sensitivity, selectivity, dilution integrity, recovery were investigated and the results met the acceptance criteria. In patients, multiple drug dosing (every 6 or 8 hours) or in continuous administration were adopted, resulting in a large interpatient variability in drug concentrations (from 7.4 mg/L and 644.6 mg/L; CV: 91.1%). In critical care patient setting TDM can represent an important tool to identify the best fosfomycin dosing in single patients, taking into consideration clinical characteristics, infection sites and susceptibility of the treated pathogens.

PMID:34410896 | DOI:10.1080/1120009X.2021.1963617

Front Immunol. 2021 Aug 2;12:707468. doi: 10.3389/fimmu.2021.707468. eCollection 2021.

ABSTRACT

Ovarian cancer is a leading cause of death among gynecological malignancies, and novel therapies are urgently needed. Here we report preliminary findings on the potential safety and efficacy of 6B11-OCIK, an adoptive cell therapy of autologous T cells induced by the humanized anti-idiotypic antibody 6B11 minibody plus dendritic cells and cytokines, against platinum-resistant recurrent or refractory ovarian cancer in three patients. We found that 6B11-OCIK treatment was safe and well tolerated after five cycles of intravenous infusion with an initial dose of 1-2×109 cells and a dose-climbing strategy. Hemoglobin, platelets, white cell count, creatinine or liver enzyme values, coagulation function, kidney and heart function were not significantly affected over the duration of therapy. Two of the three enrolled patients showed potentially drug-related grade 1 and 2 weakness, and no other adverse events were observed. Of the three enrolled patients, one had stable disease and two showed disease progression. The patient with favorable clinical efficacy had better immune response as measured by 6B11-OCIK proliferation capacity, activation ability of CD3+CD8+ tumor-specific cytotoxic T lymphocytes and CD3+CD56+ cytokine-induced killer cells, and tumor cell killing efficiency. Changes in circulating tumor cells after treatment were consistent with serum level CA125 in the patient with stable disease (both decreased), while differences were observed in the two patients with disease progression (increased CA125 in both and decreased CTC in the patient with better immune response), suggesting that variation of circulating tumor cells was more consistent with immune response and reflected efficacy directly. This preliminary study suggested that autologous 6B11-OCIK treatment was safe and had potential clinical efficacy against ovarian cancer. Patients with better immune response had more favorable efficacy. In addition to imaging, CA125 and immunophenotypes, CTC monitoring may represent a potential indicator of immunotherapy response.

PMID:34408750 | PMC:PMC8366315 | DOI:10.3389/fimmu.2021.707468

BJGP Open. 2021 Aug 18:BJGPO.2021.0083. doi: 10.3399/BJGPO.2021.0083. Online ahead of print.

ABSTRACT

BACKGROUND: Long-term nitrofurantoin (NF) treatment can result in pulmonary and hepatic injury. Current guidelines do not outline the type or frequency of monitoring required for detection of these injuries.

AIMS: To assess (1) awareness of NF complications among prescribers, (2) monitoring practice and (3) to describe the pulmonary sequelae of NF-related complications.

METHODS: (1) Electronic questionnaire to prescribers, interrogating prescribing/monitoring practices and awareness of complications; (2) Case-note review (June-July 2020) of NF monitoring among general practitioners (GPs) in our local clinical commissioning group; (3) Case review of patients diagnosed with nitrofurantoin-induced interstitial lung disease (NFILD) at our interstitial lung disease (ILD) centre (2014-2020).

RESULTS: 125 prescribers of long-term NF responded to the questionnaire (82% GPs; 12% urologists). Many were unaware of the potential for liver (42%) and lung (28%) complications. 41% and 53% never monitored for these, respectively. Only 53% of urologists believed themselves responsible for arranging monitoring, whilst nearly all GPs believed this to be the prescriber's responsibility (94%). One third of all respondents considered current British National Formulary (BNF) guidelines "not at all sufficient/clear", with mean clarity scoring of 2.2/5. Amongst NFILD patients (n=46), NF had been prescribed most often (70%) for treatment of recurrent UTI and 59% (n=27) were prescribed for >6 months. Upon withdrawal of the medication 61% displayed resolution (completely/minimal fibrosis), whilst 16% of patients had progressive lung fibrosis.

CONCLUSION: NF can cause marked or irreversible lung complications and there is currently a shortfall in awareness and monitoring. Existing monitoring guidelines should be augmented.

PMID:34407964 | DOI:10.3399/BJGPO.2021.0083

BMJ Case Rep. 2021 Aug 17;14(8):e243278. doi: 10.1136/bcr-2021-243278.

ABSTRACT

Hydralazine is a commonly prescribed antihypertensive agent. Some of its labelled adverse reactions include lupus-like syndrome, tachycardia, headache and fever. Despite its well-known side effects, little is known about hydralazine's hepatotoxic effects. We report the case of a 54-year-old female patient who was started on hydralazine for hypertension management but later presented with hydralazine-induced liver injury. Her initial presentation consisted of non-specific symptoms and a hepatocellular injury pattern. Liver biopsy revealed hepatic steatosis. Three weeks after discontinuation of hydralazine, the patient's liver enzymes normalised, and her symptoms resolved. Few studies have examined the incidence and mechanism by which hydralazine induces a liver injury pattern. With this case, we review the literature, the pathogenesis involved and the eventual management of hydralazine-induced liver injury. We propose close monitoring of liver enzymes for patients on hydralazine throughout their treatment course.

PMID:34404652 | DOI:10.1136/bcr-2021-243278

Dentomaxillofac Radiol. 2021 Aug 18:20210036. doi: 10.1259/dmfr.20210036. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate whether dynamic contrast-enhanced (DCE)-MR bone perfusion could serve as surrogate for morphologic ultra-short echo time (UTE) bone images and to correlate perfusion with morphologic hallmarks in histologically proven foci of medication-related osteonecrosis of the jaw (MRONJ).

METHODS: Retrospective study including 20 patients with established diagnosis of MRONJ. Qualitative consensus assessment of predefined jaw regions by two radiologists was used as reference standard using Likert scale (0-3) for standard imaging hallmarks in MRONJ (osteolysis, sclerosis, periosteal thickening). DCE-MRI measurements performed in corresponding regions of the mandible were then correlated with qualitative scores. Regions were grouped into "non-affected" and "pathologic" based on binarized Likert scores of different imaging hallmarks (0-1 vs 2-3). DCE-MRI measurements among hallmarks were compared using Mann-Whitney-U-testing. ROC (receiver-operating-characteristic) analysis was performed for each of the perfusion parameters to assess diagnostic performance for identification of MRONJ using morphologic ratings as reference standard.

RESULTS: Median perfusion measurements of "pathologic" regions in wash-in, peak enhancement intensity and integrated area under the curve are significantly higher than those of "non-affected" regions, irrespective of reference imaging hallmark (p < 0.05). No significant perfusion differences were found between "pathologic" regions with and without osteolysis (p = 0.180). ROC analysis showed fair diagnostic performance of DCE-MRI parameters for identification of MRONJ (AUC 0.626-0.727).

CONCLUSIONS: DCE bone perfusion parameters are significantly increased in MRONJ compared to non-affected regions, irrespective of osteolysis. Due to certain overlap DCE-MRI bone perfusion cannot serve as full surrogate for UTE bone imaging but may enhance reader confidence.

PMID:34406841 | DOI:10.1259/dmfr.20210036

Clin Transl Sci. 2021 Aug 18. doi: 10.1111/cts.13089. Online ahead of print.

ABSTRACT

CD70 is expressed in up to 80% of nasopharyngeal carcinoma (NPC) cases. Cusatuzumab is a humanized anti-CD70 monoclonal antibody, with dual action mechanisms: induction of cytotoxicity against CD70+ tumor cells and reduction in CD70-CD27 signaling mediated immune evasion. The aim of this study was to assess the safety, pharmacokinetic profile, immunogenicity, pharmacodynamic profile, and preliminary activity of cusatuzumab in advanced NPC. Eleven patients were enrolled: one patient was assigned to arm A (adjuvant cusatuzumab monotherapy after curative chemoradiation), nine patients to arm B (cusatuzumab monotherapy; non-curative setting), and one patient to arm C (cusatuzumab + chemotherapy; non-curative setting); irrespective of tumoral CD70 expression. Both patients in arms A and C completed the study. All patients in arm B discontinued at an early stage. Five patients experienced grade ≥3 non-drug related treatment-emergent adverse events, most commonly fatigue and pneumonia (18%). An infusion-related reaction was observed in two out of 11 patients. Laboratory results showed no trend over time. Seven patients were eligible for response evaluation. No objective response to cusatuzumab was observed with stable disease being the best response. The current study indicates that the safety profile of cusatuzumab (with or without concurrent chemotherapy) is manageable in patients with advanced NPC which is consistent with known safety profile. Limited activity of cusatuzumab in advanced NPC was observed. Combination therapies of cusatuzumab and other types of therapy should be explored for the improvement of activity in NPC and other CD70-expressing malignancies.

PMID:34405542 | DOI:10.1111/cts.13089

Cephalalgia. 2021 Aug 18:3331024211038656. doi: 10.1177/03331024211038656. Online ahead of print.

ABSTRACT

BACKGROUND: In 2013, one of the authors described a 36-year-old female with orthostatic headache without documented intracranial hypotension or evidence of cerebrospinal fluid leak, despite extensive workup. Headache was unresponsive to conservative treatment since 2010, showed only transient benefit after repeated epidural blood patches while vitamin A supplementation resulted in progressive improvement.

CASE: Since 2013, the patient followed a relapsing and remitting course yet relapse control became difficult after a drug induced liver injury required vitamin A discontinuation in 2017, when her headache became chronic. Greater occipital nerve blocks provided pain relief as alternative but were stopped due to the pandemic and her latest severe relapse, in late 2020, required not only restarting anaesthetic blocks and aggressive medication management, but also reassessing and treating comorbidities (obstructive sleep apnoea and major depressive disorder) with modest benefit.

CONCLUSION: Orthostatic headache without intracranial hypotension is rare, with only 28 cases reported so far, all treated empirically and all treatment options revealing to be mostly ineffective. Vitamin A anecdotally appeared to be useful in our case but had to be stopped for severe side effects, so unfavourable long-term prognosis, in ours and 2/3 of the reported cases, seems to be the rule in this intriguing entity.

PMID:34404249 | DOI:10.1177/03331024211038656

Int J Qual Health Care. 2021 Aug 28;33(3):mzab118. doi: 10.1093/intqhc/mzab118.

ABSTRACT

BACKGROUND: A computerized drug utilization review (DUR) program has provided physicians and pharmacists with alerts on drug-drug interactions (DDIs), drug-age precautions and therapeutic duplication in Korea since 2010.

OBJECTIVE: The purpose of this study was to evaluate the impact of the DUR program on health outcomes associated with DDIs.

METHODS: An uncontrolled before-after study was performed to investigate the impact of the nationwide DUR program on DDIs and related health outcomes. The study population consisted of people who used two types of DDI pairs before DUR implementation (from January 2009 to December 2010) and post-DUR implementation (from January 2012 to December 2013); (i) benzodiazepines with concurrent use of metabolic enzyme inhibitors and (ii) QTc (heart-rate corrected QT interval) prolongation agents. The main outcome measures were all-cause and cause-specific hospitalization admissions or emergency department (ED) visits.

RESULTS: This study included 107 874 people who used benzodiazepines with enzyme inhibitors and 8489 who received co-medication of QTc prolongation agents. For patients receiving a combination of benzodiazepines and enzyme inhibitors, both all-cause hospitalization and cause-specific hospitalization decreased after DUR implementation, from 43.2% to 41.7% and from 4.6% to 4.5% (adjusted odds ratio [OR] = 0.96; 95% confidence interval (CI), 0.93-0.98; OR = 0.89, 95% CI = 0.84-0.99, respectively). For patients receiving co-medication of QTc prolongation agents, all-cause hospitalization (54.2%) was lower than before (54.9%) (OR = 0.87, 95% CI = 0.79-0.96), but no significant change was found for cause-specific hospitalization and ED visits.

CONCLUSION: Implementation of a DUR program may reduce the adverse health outcomes posed by DDIs in patients on combination of benzodiazepines and enzyme inhibitors potentially QTc-prolongation agents.

PMID:34402911 | DOI:10.1093/intqhc/mzab118

JAMA Netw Open. 2021 Aug 2;4(8):e2121310. doi: 10.1001/jamanetworkopen.2021.21310.

NO ABSTRACT

PMID:34402893 | DOI:10.1001/jamanetworkopen.2021.21310

Biomark Med. 2021 Aug 17. doi: 10.2217/bmm-2021-0443. Online ahead of print.

NO ABSTRACT

PMID:34402659 | DOI:10.2217/bmm-2021-0443

J Korean Med Sci. 2021 Aug 9;36(31):e198. doi: 10.3346/jkms.2021.36.e198.

ABSTRACT

BACKGROUND: Vaccine safety surveillance is important because it is related to vaccine hesitancy, which affects vaccination rate. To increase confidence in vaccination, the active monitoring of vaccine adverse events is important. For effective active surveillance, we developed and verified a machine learning-based active surveillance system using national claim data.

METHODS: We used two databases, one from the Korea Disease Control and Prevention Agency, which contains flu vaccination records for the elderly, and another from the National Health Insurance Service, which contains the claim data of vaccinated people. We developed a case-crossover design based machine learning model to predict the health outcome of interest events (anaphylaxis and agranulocytosis) using a random forest. Feature importance values were evaluated to determine candidate associations with each outcome. We investigated the relationship of the features to each event via a literature review, comparison with the Side Effect Resource, and using the Local Interpretable Model-agnostic Explanation method.

RESULTS: The trained model predicted each health outcome of interest with a high accuracy (approximately 70%). We found literature supporting our results, and most of the important drug-related features were listed in the Side Effect Resource database as inducing the health outcome of interest. For anaphylaxis, flu vaccination ranked high in our feature importance analysis and had a positive association in Local Interpretable Model-Agnostic Explanation analysis. Although the feature importance of vaccination was lower for agranulocytosis, it also had a positive relationship in the Local Interpretable Model-Agnostic Explanation analysis.

CONCLUSION: We developed a machine learning-based active surveillance system for detecting possible factors that can induce adverse events using health claim and vaccination databases. The results of the study demonstrated a potentially useful application of two linked national health record databases. Our model can contribute to the establishment of a system for conducting active surveillance on vaccination.

PMID:34402232 | DOI:10.3346/jkms.2021.36.e198

Eur J Hosp Pharm. 2021 Aug 16:ejhpharm-2021-002776. doi: 10.1136/ejhpharm-2021-002776. Online ahead of print.

ABSTRACT

BACKGROUND: Nosocomial bloodstream infection (nBSI) is an important clinical concern among COVID-19 hospitalised patients. It can cause sepsis and septic shock leading to high morbidity, mortality, and the emergence of antibiotic resistance. The aim of this case-control study is to identify the risk factors associated with the nBSI development in COVID-19 hospitalised patients and its incidence.

METHODS AND ANALYSIS: A retrospective case-control study will be performed. Cases will include nBSI episodes of adult patients (≥18 years) admitted to Hospital Universitari Germans Trias i Pujol, Barcelona, Spain, from April to December 2020 with a diagnosis of SARS-CoV-2 pneumonia. Patients transferred from other hospitals will be excluded. Controls will include hospitalisation episodes of COVID-19 patients without nBSI. We will recruit a minimum of 74 nBSI episodes (cases) and 74 controls (according to sample size calculation). We will collect data on sociodemographics, clinical status at admission, hospital admission, in-hospital mortality, and exposure data (use of antivirals, glucocorticoids or immunomodulatory agents, length of hospitalisation, and use of medical devices such as intravenous catheters). A bivariate and a subsequent multivariate regression analysis will be performed to assess the independent effect of the associated risk factors after adjusting for confounders. The nBSI incidence rate will be estimated according to the number of nBSI episodes in admitted COVID-19 patients among the total person-month of follow-up.

ETHICS AND DISSEMINATION: The protocol of this study was approved by the Ethical Committee for Drug Investigation of the Hospital Universitari Germans Trias i Pujol. The results of this case-control study will be published in a peer reviewed journal.

PMID:34400550 | DOI:10.1136/ejhpharm-2021-002776

BMC Pediatr. 2021 Aug 16;21(1):345. doi: 10.1186/s12887-021-02820-y.

ABSTRACT

BACKGROUND: Drug-induced aseptic meningitis is a rare, but challenging diagnosis, most commonly reported with nonsteoroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Trimethoprim/sulfamethoxazole (TMP/SMX) is a sulfonamide that is widely used in clinical practice for the treatment and prophylaxis of various infections. The most common side effects associated with TMP/SMX are generally mild and self-limited, but serious side effects have been reported, including liver injury and aseptic meningitis.

CASE PRESENTATION: We report a 2,5 year old Dutch girl with both drug-induced aseptic meningitis and drug-induced liver injury while using TMP/SMX prophylaxis. Ursodeoxycholic acid was started because of cholestatic injury. After cessation of TMP/SMX, full convalescence was reached within weeks.

CONCLUSIONS: This is the first report of a young patient with both aseptic meningitis and drug-induced liver injury caused by TMP/SMX. Drug-induced aseptic meningitis and cholestatic hepatitis constitute a considerable diagnostic challenge to clinicians. In addition to a thorough evaluation for infectious causes, clinicians should be aware of drug-induced aseptic meningitis and cholestatic hepatitis.

PMID:34399711 | DOI:10.1186/s12887-021-02820-y

Medicine (Baltimore). 2021 Jul 23;100(29):e26673. doi: 10.1097/MD.0000000000026673.

ABSTRACT

BACKGROUND: Since the combination of chemotherapy and immunotherapy, such as new molecular targeted drugs or vaccines, is controversial in terms of survival advantages compared with chemotherapy therapy alone, we conducted a meta-analysis to compare the efficacy and safety of immunotherapy combined with chemotherapy and chemotherapy alone for advanced pancreatic cancer.

METHODS: We searched PubMed, Embase, and Cochrane Library from the establishment of the database to November 2020. We included some studies that reported pancreatic cancer patients receiving immunotherapy, and we excluded duplicate publications, research without full text, incomplete information or inability to conduct data extraction, animal experiments, reviews, and systematic reviews.

RESULTS: The risk ratio of the objective response rate and disease control rate was 1.10 (95% confidence interval [CI]: 0.88-1.38) and 1.17 (95% CI: 1.06-1.31), respectively, indicating that there was no significant difference between the objective response rate of combination therapy and chemotherapy alone, while the disease control rate of the combined treatment was higher than that of chemotherapy alone. The hazard ratio of overall survival and progression-free survival was 0.91 (95% CI: 0.82-1.01) and 0.87 (95% CI: 0.77-0.98), respectively, indicating that there was no significant difference between the overall survival of combination therapy and chemotherapy alone, while progression-free survival of the combined treatment was longer than that of chemotherapy alone. We also found that in addition to the combination treatment, the incidence of vomiting in pancreatic cancer was higher than that of chemotherapy alone, and the incidence of other complications was not significantly different from that of treatment alone.

CONCLUSION: Chemotherapy combined with immunotherapy for pancreatic cancer not only improves treatment efficiency but also does not cause serious adverse reactions. This treatment strategy should be widely used clinically.

PMID:34398033 | PMC:PMC8294910 | DOI:10.1097/MD.0000000000026673

J Clin Pharmacol. 2021 Aug;61 Suppl 2:S129-S141. doi: 10.1002/jcph.1860.

ABSTRACT

Use of US Food and Drug Administration-approved substances of abuse has innate risks due to pharmacologic and pharmacokinetic properties of the medications, but the risk when using nonapproved drug products is much greater. Unbeknownst to the user, the dose of active ingredients in substances of abuse can vary substantially between different products because of manufacturing practices or improper storage. Even naturally occurring substances of abuse can have extensive dosage variability because of effects of the growing season and conditions, or differences in harvesting, storage, or manufacture of the finished products. Many illicit substances are adulterated, to make up for intentional underdosing or to enhance the effect of the intended active ingredient. These adulterants can be dangerous and produce direct cardiovascular, neurologic, hematologic, or dermatologic reactions or obscure adverse effects. Finally, an illicit substance can be contaminated or substituted for another one during its manufacture, leading to differences in adverse events, adverse event severity, or the drug interaction profile. Substances can be contaminated with microbes that induce infections or heavy metals that can damage organs or cause cancer. This milieu of undisclosed substances can also induce drug interactions. For reasons that are discussed, individuals who use substances of abuse are at increased risk of morbidity or mortality if they develop coronavirus disease 2019. Health professionals who treat patients with acute, urgent events associated with substances of abuse, or those treating the chronic manifestations of addiction, need to appreciate the complex and variable composition of substances of abuse and their potential health effects.

PMID:34396559 | DOI:10.1002/jcph.1860

Rev Med Suisse. 2021 Aug 4;17(746):1374-1376.

ABSTRACT

Tizanidine is an alpha2 agonist with central action whose myorelaxant effects are often used off-label against primary backpain in clinical practice. It is mainly metabolized by the liver. The concomitant use of CYP1A2 inhibitor drugs increases the plasmatic concentration and thus can cause serious adverse effects. Severe hypotension is the most memorable example. Its narrow therapeutic range and the interindividual different sensitivity to the molecule justify using it wisely. A clinical case is reported as illustration.

PMID:34397185

J Acquir Immune Defic Syndr. 2021 Sep 1;88(1):86-95. doi: 10.1097/QAI.0000000000002731.

ABSTRACT

BACKGROUND: With the highest rates of HIV/AIDS in the United States, Black Americans are still underrepresented in HIV medical research.

SETTING: BRAAVE (NCT03631732) is a randomized, phase 3b, multicenter, open-label US study.

METHODS: Adults identifying as Black or African American and virologically suppressed on 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus third agent were randomized (2:1) to switch to open-label bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) once daily or stay on baseline regimen (SBR) for 24 weeks, after which SBR had delayed switch to B/F/TAF. Resistance to non-NRTIs, protease inhibitors, and/or NRTIs was permitted; integrase strand transfer inhibitor resistance was exclusionary. Primary endpoint was proportion of participants with HIV-1 RNA ≥50 copies/mL at week 24 (snapshot algorithm; noninferiority margin of 6%).

RESULTS: Of 558 screened, 495 were randomized/treated (B/F/TAF n = 330; SBR n = 165). Overall, 32% were ciswomen, 2% transwomen, and 10% had an M184V/I mutation. At week 24, 0.6% on B/F/TAF vs 1.8% on SBR had HIV-1 RNA ≥50 copies/mL (difference -1.2%; 95% confidence interval -4.8% to 0.9%), demonstrating noninferiority of B/F/TAF vs SBR. Proportions with HIV-1 RNA <50 copies/mL at week 24 were 96% B/F/TAF and 95% SBR and remained high at week 48. No participant had treatment-emergent resistance to study drug. Treatments were well tolerated. Study drug-related adverse events, mostly grade 1, occurred in 10% of participants on B/F/TAF through week 48 and led to discontinuation in 9 participants through week 48.

CONCLUSIONS: For Black Americans with HIV, switching to B/F/TAF was noninferior to continuing a variety of regimens, including those with pre-existing NRTI mutations.

PMID:34397746 | DOI:10.1097/QAI.0000000000002731