Gan To Kagaku Ryoho. 2021 Jun;48(6):849-852.

ABSTRACT

We encountered 3 cases suggesting that coadministration of herbal medicines may reduce the side effects of anticancer drugs and reinforce cancer growth control. In 2 cases, on observing anticancer drug resistance, it was possible to regain control of cancer growth by coadministering herbal medicines. In the remaining 1 case, thrombocytopenia was observed during chemotherapy, which could be avoided by coadministering a herbal medicine. If the expected effect is not obtained even after herbal medicine administration, it is important to consider additional herbal medications.

PMID:34139738

Pharmacotherapy. 2021 Jun 15. doi: 10.1002/phar.2603. Online ahead of print.

ABSTRACT

Etoposide is an antineoplastic agent widely used for treatment of many pediatric cancers. Etoposide has been associated with infusion-related reactions. In this brief report we compare etoposide infusion-related reactions that occurred over a 10-year period at two freestanding pediatric hospitals. Infusion reactions occurred in 1% of patients at two hospitals across the study period. Rates of 4.8%, 3.4%, and 7.9% were observed at Children's Mercy Hospital during 2018, 2019, and 2020, respectively, after the implementation of in-line filters during etoposide infusions in late 2017. Of the 32 patients who experienced adverse reactions, 41% were rechallenged after the reaction and all were able to tolerate at least one future dose with either pre-treatment or extending infusion duration. This work highlights the importance of a multicenter approach to investigating adverse drug reactions (ADRs) as variation in practice can provide key information about ADRs and potential risk factors.

PMID:34129705 | DOI:10.1002/phar.2603

CNS Spectr. 2021 Apr;26(2):164-165. doi: 10.1017/S1092852920002655.

ABSTRACT

BACKGROUND: Chorea is a prominent motor dysfunction in Huntington's disease (HD). Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is FDA-approved for the treatment of chorea in HD. In the pivotal, 12-week First-HD trial, deutetrabenazine treatment reduced the Unified Huntington's Disease Rating Scale (UHDRS) total maximal chorea (TMC) score versus placebo. ARC-HD, an open-label extension study, evaluated long-term safety and efficacy of deutetrabenazine dosed in a response-driven manner for treatment of HD chorea.

METHODS: Patients who completed First-HD (Rollover) and patients who converted overnight from a stable dose of tetrabenazine (Switch) were included. Safety was assessed over the entire treatment period; exposure-adjusted incidence rates (EAIRs; adverse events [AEs] per person-year) were calculated. A stable, post-titration time point of 8 weeks was chosen for efficacy analyses.

RESULTS: Of 119 patients enrolled (Rollover, n=82; Switch, n=37), 100 (84%) completed ≥1 year of treatment (mean [SD] follow-up, 119 [48] weeks). End of study EAIRs for patients in the Rollover and Switch cohorts, respectively, were: any AE, 2.6 and 4.3; serious AEs, 0.13 and 0.14; AEs leading to dose suspension, 0.05 and 0.04. Overall, 68% and 73% of patients in Rollover and Switch, respectively, experienced a study drug-related AE. Most common AEs possibly related to study drug were somnolence (17% Rollover; 27% Switch), depression (23%; 19%), anxiety (9%; 11%), insomnia (10%; 8%), and akathisia (9%; 14%). Rates of AEs of interest include suicidality (9%; 3%) and parkinsonism (6%; 11%). In both cohorts, mean UHDRS TMC score and total motor score (TMS) decreased from baseline to Week 8; mean (SD) change in TMC score (units) was -4.4 (3.1) and -2.1 (3.3) and change in TMS was -7.1 (7.3) and -2.4 (8.7) in Rollover and Switch, respectively. While receiving stable dosing from Week 8 to 132 (or end of treatment), patients showed minimal change in TMC score (0.9 [5.0]), but TMS increased compared to Week 8 (9.0 [11.3]). Upon drug withdrawal, there were no remarkable AEs and TMC scores increased 4.4 (3.7) units compared to end of treatment.

CONCLUSIONS: The type and severity of AEs observed in long-term deutetrabenazine exposure are consistent with the previous study. Efficacy in reducing chorea persisted over time. There was no unexpected worsening of HD or chorea associated with HD upon deutetrabenazine withdrawal.

FUNDING: Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel.

PMID:34127148 | DOI:10.1017/S1092852920002655

CNS Spectr. 2021 Apr;26(2):152. doi: 10.1017/S1092852920002412.

ABSTRACT

OBJECTIVE: Drug-induced movement disorders (DIMDs) may occur in patients treated with antipsychotics. The CommonGround Program supports the recovery and healing of psychiatric outpatients through tools which facilitate better patient-doctor communication regarding psychiatric symptoms, DIMDs, and the effectiveness of treatment.

METHODS: Patients responses to CommonGround's web-based waiting-room questionnaire were analyzed in patients who responded yes to having concerns about developing DIMDs (MD-YES) and those who responded no to this question (MD-NO). These groups were compared descriptively to assess the potential effects of DIMD concerns on self-reported functioning and beliefs about prescribed psychiatric medications.

RESULTS: Of 7874 responding patients, 312 (4.0%) and 7562 (96.0%) were in the MD-YES and MD-NO subgroups, respectively. A higher percentage of MD-YES patients reported poor / not so good ability to keep up with daily responsibilities (21.2% vs 15.2% vs MD-NO), along with low energy levels (37.1% vs 26.3% for MD-NO), bothersome thoughts/beliefs/fears (30.5% vs 16.0%), and nervousness/anxiety (35.3% vs 27.5%) all / most of the time. MD-YES patients were also more likely to wonder about stopping their medications (9.3% vs 0.6% for MD-NO) and were concerned about side effects such as sleepiness (31.4% vs 3.9%) and weight gain (37.2% vs 5.7%).

CONCLUSION: Patients from community mental health centers who were concerned about developing DIMDs tended to express problems with daily functioning and concerns about their psychiatric medications. For these patients, recognizing their fears and concerns may help clinicians discuss treatment options for DIMDs, which could increase patient confidence, encourage adherence to current psychiatric medications, and potentially improve outcomes.

PMID:34127113 | DOI:10.1017/S1092852920002412

Anesth Analg. 2021 Jun 11. doi: 10.1213/ANE.0000000000005634. Online ahead of print.

ABSTRACT

BACKGROUND: Opioids are the most commonly prescribed analgesics in the United States. Current guidelines have proposed education initiatives to reduce the risk of chronic opioid consumption, yet there is lack of efficacy data on such interventions. Our study evaluates the impact of perioperative opioid education on postoperative opioid consumption patterns including opioid cessation, number of pills consumed, and opioid prescription refills.

METHODS: The MEDLINE/PubMed, Embase, Cochrane Library, Scopus, and Google Scholar databases were systematically searched for randomized controlled trials (RCTs) assessing the impact of perioperative educational interventions (using either paper- or video-based instruments regarding pain management and drug-induced side effects) on postoperative opioid patterns compared to standard preoperative care among patients undergoing elective surgery. Our end points were opioid consumption (number of pills used), appropriate disposal of unused opioids, opioid cessation (defined as no use of opioids), and opioid refills within 15 days, 6 weeks, and 3 months.

RESULTS: In total, 11 RCTs fulfilled the inclusion criteria, totaling 1604 patients (804 received opioid education, while 800 received standard care). Six trials followed patients for 15 days after surgery, and 5 trials followed patients up to 3 months. After 15 days, the opioid education group consumed a lower number of opioid pills than those in the control group (weighted mean difference [WMD], -3.39 pills; 95% confidence interval [CI], -6.40 to -0.37; P =.03; I2 = 69%) with no significant difference in overall opioid cessation (odds ratio [OR], 0.25; 95% CI, 0.04-1.56; P = .14; I2 = 83%). Likewise, perioperative opioid education did not have significant effects on opioid cessation at 6 weeks (OR, 0.69; 95% CI, 0.45-1.05; P = .10; I2 = 0%) and 3 months (OR, 0.59; 95% CI,0.17-2.01; P = .10; I2 = 0%) after surgery, neither reduced the need for opioid refills at 15 days (OR, 0.57; 95% CI, 0.28-1.15; P = .12; I2 = 20%) and 6 weeks (OR, 1.08; 95% CI, 0.59-1.98; P = .80; I2 = 37%). There was no statistically significant difference in the rate of appropriate disposal of unused opioids between both groups (OR, 1.99; 95% CI, 0.66-6.00; P = .22; I2 = 71%). Subgroup analysis by type of educational intervention showed a statistical reduction of opioid consumption at 15 days when implementing multimedia/audiovisual strategies (4 trials: WMD, -4.05 pills; 95% CI, -6.59 to -1.50; P = .002; I2 = 45%), but there was no apparent decrease when using only paper-based strategies (2 trials: WMD, -2.31 pills; 95% CI, -12.21 to 7.59; P = .65; I2 = 80%).

CONCLUSIONS: Perioperative educational interventions reduced the number of opioid pills consumed at 15 days but did not demonstrate a significant effect on opioid cessation or opioid refills at 15 days, 6 weeks, and 3 months. Further randomized trials should focus on evidence-based educational interventions with strict homogeneity of material to draw a more definitive recommendation.

PMID:34125081 | DOI:10.1213/ANE.0000000000005634

Pan Afr Med J. 2021 Mar 18;38:283. doi: 10.11604/pamj.2021.38.283.28478. eCollection 2021.

ABSTRACT

We here report the case of a 41-year-old female patient with maculopapular rash occurring a week after receiving hydroxychloroquine 400 mg for primary Gougerot-Sjögren syndrome with articular involvement. The patient had more than 1-year history of idiopathic minimal glomerular lesion, effectively treated with corticosteroid therapy. Maculopapular rashes resolved after hydroxychloroquine treatment was stopped and the patient was given hydrocortisone and desloratadine. Our case highlights the importance of prescribing low dose hydroxychloroquine in subjects with a history of kidney disease as well as of raising awareness and educating patients about side effects of hydroxychloroquine.

PMID:34122710 | PMC:PMC8180004 | DOI:10.11604/pamj.2021.38.283.28478

Reg Anesth Pain Med. 2021 Jun 11:rapm-2021-102517. doi: 10.1136/rapm-2021-102517. Online ahead of print.

NO ABSTRACT

PMID:34117104 | DOI:10.1136/rapm-2021-102517

Eur J Hosp Pharm. 2021 Jun 11:ejhpharm-2021-002730. doi: 10.1136/ejhpharm-2021-002730. Online ahead of print.

ABSTRACT

Cyclosporine is a widely used immunosuppressive agent to prevent rejection of solid organ transplant. Here, we describe the case of a 71-year-old man who received the prescribed dose of cyclosporine 10 times 6 days after a kidney transplantation because of a concentration miscalculation involving two galenic forms. The patient presented gastrointestinal and neurological disorders. Therapeutic drug monitoring revealed high cyclosporine blood concentrations (693 ng/mL, therapeutic range 100-300 ng/mL). Symptomatic management of digestive disorders was performed, and haemodialysis was started the day after the cyclosporine overdose in the face of acute renal failure. The patient's disorders were quickly resolved. The dosing regimen was adapted in order to administer the most appropriate galenic form and to avoid another administration error. Long-term follow-up showed no failure of renal transplantation. The purpose of this case report is to warn physicians and clinical pharmacists about the vigilance required on cyclosporine prescription, especially when two galenic forms are administered to obtain the prescribed dose.

PMID:34117088 | DOI:10.1136/ejhpharm-2021-002730

Medicine (Baltimore). 2021 Jun 11;100(23):e26300. doi: 10.1097/MD.0000000000026300.

ABSTRACT

In view of the renewed interest in psychedelics in psychiatry it is timely to analyze psychedelic treatment in historical cohorts. Recently the therapeutic efficacy of psychedelics has been linked to the so-called phenomenon of "connectedness." The aim of the present study was to explore whether long-lasting personality changes were observed in any of the 151 Danish psychiatric patients who were treated with Lysergic acid diethylamide (LSD) from 1960 to 1974.The exploration included a reanalysis of a subgroup as well from a 1964 Danish historical cohort. Medical records and other case materials of the above mentioned 151 patients are kept in the Danish State Archives. The present author was granted access to the LSD case materials in the Danish State Archives, and respected confidentiality per the Archives Law. According to the LSD Damages Law from 1986, they all received financial compensation for LSD-inflicted harm.Analysis did not reveal any personality changes such as "connectedness;" however, other lasting personality changes were observed in 2 to 4 patients and in quite a few patients unwanted effects persisted for weeks or months following acute treatment. In the present analysis of the 1964 cohort, the same percentage of patients improved with LSD treatment as in the historical analysis. In the latter, however, little attention was given to side effects, such as suicide attempts, suicides, and one homicide.Future psychedelic research with psychiatric patients should respect the potential toxicity of LSD and other psychedelics and meticulously monitor possible side effects.

PMID:34115036 | PMC:PMC8202585 | DOI:10.1097/MD.0000000000026300

Clin Immunol. 2021 Jun 8:108777. doi: 10.1016/j.clim.2021.108777. Online ahead of print.

ABSTRACT

Everyone carries a set of genetic variants that contribute to regulation of the levels of blood cells, with unknown clinical impact. One of them, rs445 within the cell-cycle checkpoint gene CDK6, reduces the levels of myeloid cell types including granulocytes. We treated CD3+ T cells and whole blood with palbociclib in 41 individuals, who were stratified by genotype for analyses. In T cells we assessed cell cycle and apoptosis, whereas in whole blood, apoptosis in activated (CD11b+), unactivated (CD11b-) granulocytes, cytotoxic (CD8 + CD4-), and helper (CD8-CD4+) T cells. We find that rs445 modulates the immune response of CD8+ T cells. It also increases the level of apoptotic CD11b + activated granulocytes after palbociclib treatment, which, in synergy with neutropenia, may affect drug related adverse events. These results suggest that the effect of palbociclib treatment may depend on underlying genetically encoded individual immune response as well as the direct response to the drug.

PMID:34116212 | DOI:10.1016/j.clim.2021.108777

Eur J Haematol. 2021 Jun 11. doi: 10.1111/ejh.13674. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the incidence and severity of adverse drug reactions of cyclosporine using AUC targeted Therapeutic Drug Monitoring (TDM) compared to trough levels (Ctrough ) targeted TDM in adult allogeneic stem cell recipients.

METHODS: Blind, monocentre, intervention study. Subjects were 1:1 randomized into either an AUC group or a Ctrough group. Adverse drug reactions were accessed two and four weeks after start of treatment.

RESULTS: 40 patients were included, resulting in 15 evaluable subjects (AUC group) and 13 evaluable subjects (Ctrough group). Grade two/three toxicity was observed in 46% (Ctrough group) versus 60% of subjects (AUC group) (p=0.463). There was no significant difference two and four weeks after start of cyclosporine for nausea (p=0.142 resp. p=0.122), renal dysfunction (p=0.464 resp. p=1.000) and hypomagnesemia (p=1.000 resp. p=0.411). Subjects in the AUC group reached the therapeutic goal earlier (72,7% versus 43,0% at third sampling point, p=0.332) and were within the target range more consistently.

CONCLUSION: This study showed no reduction in incidence and severity of cyclosporine induced toxicity with AUC versus trough levels targeted TDM. Although modelled dosing based on AUC led to faster optimal target attainment, this did not result in less toxicity in the early days after transplantation.

PMID:34114691 | DOI:10.1111/ejh.13674

Front Endocrinol (Lausanne). 2021 May 25;12:676083. doi: 10.3389/fendo.2021.676083. eCollection 2021.

ABSTRACT

OBJECTIVE: The International Cooperative Growth Study, NutropinAq® European Registry (iNCGS) (NCT00455728) monitored long-term safety and effectiveness of recombinant human growth hormone (rhGH; NutropinAq® [somatropin]) in paediatric growth disorders.

METHODS: Open-label, non-interventional, post-marketing surveillance study recruiting children with growth disorders. Endpoints included gain in height standard deviation score (SDS), adult height, and occurrence of adverse events (AEs).

RESULTS: 2792 patients were enrolled. 2082 patients (74.6%) had growth hormone deficiency (GHD), which was isolated idiopathic in 1825 patients (87.7%). Non-GHD diagnoses included Turner syndrome (TS) (n=199), chronic renal insufficiency (CRI) (n=10), other non-GHD (n=498), and missing data for three participants. Improvements from baseline height SDS occurred at all time points to Month 132, and in all subgroups by disease aetiology. At Month 12, mean (95% CI) change in height SDS by aetiology was: idiopathic GHD 0.63 (0.61;0.66), organic GHD 0.71 (0.62;0.80), TS 0.59 (0.53; 0.65), CRI 0.54 (-0.49;1.56), and other non-GHD 0.64 (0.59;0.69). Mean height ( ± SD) at the last visit among the 235 patients with adult or near-adult height recorded was 154.0 cm ( ± 8.0) for girls and 166.7 cm ( ± 8.0) for boys. The most frequent biological and clinical non-serious drug-related AEs were increased insulin-like growth factor concentrations (314 events) and injection site haematoma (99 events). Serious AEs related to rhGH according to investigators were reported (n=30); the most frequent were scoliosis (4 events), epiphysiolysis (3 events), and strabismus (2 events).

CONCLUSIONS: There was an improvement in mean height SDS in all aetiology subgroups after rhGH treatment. No new safety concerns were identified.

PMID:34113318 | PMC:PMC8185283 | DOI:10.3389/fendo.2021.676083

Clin Drug Investig. 2021 Jun 10. doi: 10.1007/s40261-021-01042-5. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Immune checkpoint inhibitors (ICIs) such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors have greatly improved cancer treatment. However, they are associated with immune-related adverse events, including autoimmune diseases (ADs) owing to their immune enhancement effect. As there are few comprehensive studies of ADs by ICIs, it is necessary to analyze the period information of drug-induced ADs. We also assumed that the temporal information may be useful to estimate the similarity of the pathogenic mechanism between spontaneous and ICI-induced ADs.

METHODS: A period analysis including the Weibull analysis was performed on ICI-induced ADs using the Japanese Adverse Drug Event Report (JADER) database. For evaluating the similarity of spontaneous and ICI-induced ADs, a hierarchical cluster analysis was conducted to compare the different onset-time ranges.

RESULTS: Type 1 diabetes mellitus, autoimmune colitis, and pemphigoid occurred earlier with CTLA-4 inhibitors (median: 46, 29.5 and 28 days, respectively) than with PD-1 inhibitors (> 130 days). Myasthenia gravis had a median time to onset of approximately 1 month, and the risk of onset would increase over time in ipilimumab combination therapy. This result reveals ADs that require attention. Using cluster analysis, we estimated six clusters with different patterns of onset times. Based on these results and a detailed previous research survey, the possible pathogenesis of drug-induced ADs was also discussed.

CONCLUSIONS: This paper describes risk profiles with temporal information of ICI-induced ADs and proposes certain indicators for deciphering the mechanism of AD onset.

PMID:34110613 | DOI:10.1007/s40261-021-01042-5

Target Oncol. 2021 Jun 10. doi: 10.1007/s11523-021-00822-5. Online ahead of print.

ABSTRACT

BACKGROUND: For research with human participants to be ethical, risk must be in a favorable balance with potential benefits. Little is known about the risk/benefit ratio for pediatric cancer phase II trials testing targeted therapies.

OBJECTIVE: Our aim was to conduct a systematic review of preliminary efficacy and safety profiles of phase II targeted therapy clinical trials in pediatric oncology.

METHODS: Our protocol was prospectively registered in PROSPERO (CRD42020146491). We searched EMBASE and PubMed for phase II pediatric cancer trials testing targeted agents. We included solid and hematological malignancy studies published between 1 January, 2015 and 27 February, 2020. We measured risk using drug-related grade 3 or higher adverse events, and benefit by response rates. When possible, data were meta-analyzed. All statistical tests were two-sided.

RESULTS: We identified 34 clinical trials (1202 patients) that met our eligibility criteria. The pooled overall response rate was 24.4% (95% confidence interval [CI] 14.5-34.2) and was lower in solid tumors, 6.4% (95% CI 3.2-9.6), compared with hematological malignancies, 55.1% (95% CI 35.9-74.3); p < 0.001. The overall fatal drug-related (grade 5) adverse event rate was 1.6% (95% CI 0.6-2.5), and the average drug-related grade 3/4 adverse event rate per person was 0.66 (95% CI 0.55-0.78).

CONCLUSIONS: We provide an estimate for the risks and benefits of participation in pediatric phase II cancer trials. These data may be used as an empirical basis for informed communication about benefits and burdens in pediatric oncology research.

PMID:34110559 | DOI:10.1007/s11523-021-00822-5

JMIR Res Protoc. 2021 Jun 10;10(6):e28616. doi: 10.2196/28616.

ABSTRACT

BACKGROUND: Adverse drug event reporting is critical for ensuring patient safety; however, numbers of reports have been declining. There is a need for a more user-friendly reporting system and for a means of verifying reports that have been filed.

OBJECTIVE: This project has 2 main objectives: (1) to identify the perceived benefits and barriers in the current reporting of adverse events by patients and health care providers and (2) to develop a distributed ledger infrastructure and user interface to collect and collate adverse event reports to create a comprehensive and interoperable database.

METHODS: A review of the literature will be conducted to identify the strengths and limitations of the current UK adverse event reporting system (the Yellow Card System). If insufficient information is found in this review, a survey will be created to collect data from system users. The results of these investigations will be incorporated into the development of a mobile and web app for adverse event reporting. A digital infrastructure will be built using distributed ledger technology to provide a means of linking reports with existing pharmaceutical tracking systems.

RESULTS: The key outputs of this project will be the development of a digital infrastructure, including a backend distributed ledger system and an app-based user interface.

CONCLUSIONS: This infrastructure is expected to improve the accuracy and efficiency of adverse event reporting systems by enabling the monitoring of specific medicines or medical devices over their life course while protecting patients' personal health data.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/28616.

PMID:34110292 | DOI:10.2196/28616

EClinicalMedicine. 2021 Jun 4:100926. doi: 10.1016/j.eclinm.2021.100926. Online ahead of print.

ABSTRACT

BACKGROUND: Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG) is an unexplored therapy amidst the rapidly evolving spectrum of medical therapies for COVID-19 and is expected to counter the three most life-threatening consequences of COVID-19 including lung injury by the virus, cytokine storm and sepsis.

METHODS: A single center, phase I/II, randomized controlled, single-blinded trial was conducted at Dow University of Health Sciences, Karachi, Pakistan. Participants were COVID-19 infected individuals, classified as either severely or critically ill with Acute Respiratory Distress Syndrome (ARDS). Participants were randomized through parallel-group design with sequential assignment in a 4:1 allocation to either intervention group with four C-IVIG dosage arms (0.15, 0.20, 0.25, 0.30 g/kg), or control group receiving standard of care only (n = 10). Primary outcomes were 28-day mortality, patient's clinical status on ordinal scale and Horowitz index (HI), and were analysed in all randomized participants that completed the follow-up period (intention-to-treat population). The trial was registered at clinicaltrials.gov (NCT04521309).

FINDINGS: Fifty participants were enrolled in the study from June 19, 2020 to February 3, 2021 with a mean age of 56.54±13.2 years of which 22 patients (44%) had severe and 28 patients (56%) had critical COVID-19. Mortality occurred in ten of 40 participants (25%) in intervention group compared to six of ten (60%) in control group, with relative risk reduction in intervention arm I (RR, 0.333; 95% CI, 0.087-1.272), arm II (RR, 0.5; 95% CI, 0.171-1.463), arm III (RR, 0.167; 95% CI, 0.024-1.145), and arm IV (RR, 0.667; 95% CI, 0.268-1.660). In intervention group, median HI significantly improved to 359 mmHg [interquartile range (IQR) 127-400, P = 0.009)] by outcome day, while the clinical status of intervention group also improved as compared to control group, with around 15 patients (37.5%) being discharged by 7th day with complete recovery. Additionally, resolution of chest X-rays and restoration of biomarkers to normal levels were also seen in intervention groups. No drug-related adverse events were reported during the study.

INTERPRETATION: Administration of C-IVIG in severe and critical COVID-19 patients was safe, increased the chance of survival and reduced the risk of disease progression.

FUNDING: Higher Education Commission (HEC), Pakistan (Ref no. 20-RRG-134/RGM/R&D/HEC/2020).

PMID:34109306 | PMC:PMC8177439 | DOI:10.1016/j.eclinm.2021.100926

Salud Colect. 2021 Apr 26;17:e3155. doi: 10.18294/sc.2021.3155.

ABSTRACT

Medication errors represent one of the main causes of incidents and adverse events during the perioperative period. Therefore, this study analyzes errors before, during, and after the administration of general anesthesia for abdominal surgery at a high-complexity hospital in Bogota, Colombia. A descriptive cross-sectional study was conducted with 390 patients between January and September 2019. Of the 3,677 medication administrations, some type of error was made in 60% of cases, mostly in emergency surgeries. The pharmacological group with the most errors was general anesthetics, with 32%. All identified errors constituted situations with harm potential, indicating the need to promote the standardization of activities involving the use of medications and a culture of healthcare safety in order to avoid adverse events.

PMID:34105334 | DOI:10.18294/sc.2021.3155

Nat Commun. 2021 Jun 8;12(1):3427. doi: 10.1038/s41467-021-23748-y.

ABSTRACT

Partially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells, and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical peptide from alpha-lactalbumin is shown to gain lethality for tumor cells by forming oleic acid complexes (alpha1-oleate). Nuclear magnetic resonance measurements and computational simulations reveal a lipid core surrounded by conformationally fluid, alpha-helical peptide motifs. In a single center, placebo controlled, double blinded Phase I/II interventional clinical trial of non-muscle invasive bladder cancer, all primary end points of safety and efficacy of alpha1-oleate treatment are reached, as evaluated in an interim analysis. Intra-vesical instillations of alpha1-oleate triggers massive shedding of tumor cells and the tumor size is reduced but no drug-related side effects are detected (primary endpoints). Shed cells contain alpha1-oleate, treated tumors show evidence of apoptosis and the expression of cancer-related genes is inhibited (secondary endpoints). The results are especially encouraging for bladder cancer, where therapeutic failures and high recurrence rates create a great, unmet medical need.

PMID:34103518 | DOI:10.1038/s41467-021-23748-y

BMC Cancer. 2021 Jun 7;21(1):672. doi: 10.1186/s12885-021-08375-6.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that lack of effective therapeutic drugs. K-001 is an oral antitumor drug made from active ingredients of marine microorganisms. The current study aimed to evaluate safety and antitumor activity of K-001 in patients with advanced PDAC.

METHODS: In this phase I, open-label trial, patients with advanced PDAC were recruited to a dose-escalation study in a standard 3 + 3 design. K-001 was administered twice daily in four-week cycles, and dose escalation from 1350 mg to 2160 mg was evaluated twice daily. Physical examination and laboratory tests were done at screening and then weekly. The safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of K-001 were assessed while tumor response was estimated by Response Evaluation Criteria in Solid Tumor (RECIST).

RESULTS: Eighteen patients with advanced PDAC were screened, and twelve eligible patients were analyzed in the study. No DLT was observed. Totally, 47 adverse events (AEs) presented, and 14 drug-related AEs were reported in 7 patients, including 8 grade 1 events (57.1%) and 6 grade 2 events (42.9%). There was no grade 3 or 4 drug-related AE. In these 14 drug-related AEs, the most frequent ones were dyspepsia (21.4%), followed by flatulence, constipation, and hemorrhoid bleeding (above 10% of each). Among all 12 patients, 10 patients (83.3%) maintained stable disease (SD), and 2 patients (16.7%) had progressive disease (PD). The objective response rate (ORR) was 0% and the disease control rate (DCR) was 83.3%.

CONCLUSIONS: K-001 manifests satisfactory safety and tolerability, as well as meaningful antitumor activity in advanced PDAC patients. Further evaluation of K-001 in phase II/III appears warranted.

TRIAL REGISTRATION: NCT02720666 . Registered 28 Match 2016 - Retrospectively registered.

PMID:34098895 | DOI:10.1186/s12885-021-08375-6

Am J Nephrol. 2021 Jun 7:1-11. doi: 10.1159/000516156. Online ahead of print.

ABSTRACT

INTRODUCTION: Phosphate binders are used to treat hyperphosphatemia. Some patients have inappropriately controlled serum phosphorus levels, which may occur for many reasons, including a high pill burden and adverse events (AEs). Tenapanor selectively inhibits the passive paracellular transfer of phosphate in the gastrointestinal tract, thereby reducing serum phosphorus levels. This novel mechanism of action may contribute to improved phosphate management. The efficacy and safety of tenapanor have not been evaluated in Japanese patients with high serum phosphorus levels despite treatment with phosphate binders. This study aimed to assess the efficacy and safety of add-on tenapanor therapy for reducing serum phosphorus levels in this population.

METHODS: This multicenter, double-blind, randomized, placebo-controlled trial enrolled patients with refractory hyperphosphatemia undergoing hemodialysis. Patients were randomly assigned in a 1:1 ratio to receive tenapanor or placebo as an add-on to their phosphate binder regimen for 6 weeks. Change in serum phosphorus levels at week 6 (day 43) compared with the baseline value (day 1, week 0) (primary endpoint), achievement of target serum phosphorus levels (serum phosphorus level ≤6.0 or ≤5.5 mg/dL), and safety, based on all AEs and drug-related AEs, were among the outcomes evaluated.

RESULTS: In total, 24 patients were randomly assigned to the placebo group and 23 to the tenapanor group. The mean serum phosphorus level decreased from 7.01 mg/dL on day 1 to 6.69 mg/dL on day 43 in the placebo group and from 6.77 mg/dL on day 1 to 4.67 mg/dL on day 43 in the tenapanor group. In the placebo and tenapanor groups (modified intent-to-treat population), the mean (standard deviation) change in the serum phosphorus level at day 43 (last observation carried forward [LOCF]) was 0.08 (1.52) mg/dL and -1.99 (1.24) mg/dL, respectively, with a between-group difference of -2.07 (95% confidence interval: -2.89, -1.26; p < 0.001). The target achievement rate (serum phosphorus level ≤6.0 mg/dL at week 6 [LOCF]) was 37.5 and 87.0% in the placebo and tenapanor groups, respectively. Diarrhea was the most common drug-related AE, and it occurred in 8.3 and 65.2% of patients in the placebo and tenapanor groups, respectively. No specific AEs were observed with add-on tenapanor or with phosphate binders.

DISCUSSION/CONCLUSION: Therapy with existing phosphate binders and add-on tenapanor resulted in a significant decrease in serum phosphorus level compared with the placebo group in patients with refractory hyperphosphatemia despite treatment with phosphate binders. No new safety signals were raised, and add-on tenapanor was generally well tolerated.

PMID:34098559 | DOI:10.1159/000516156