Retrieval of Additional Doses of Epinephrine From the New Teva Epinephrine Autoinjector Pen.

Epinephrine autoinjectors are commonly used in urban environments for anaphylaxis. In remote environments, the effects of a single dose of epinephrine may diminish before one can access higher medical care. By retrieving additional epinephrine from common autoinjectors, a medical provider may be able to treat or delay decompensation of anaphylaxis in the field during evacuation. The new Teva epinephrine autoinjectors were obtained. The design of the mechanism was researched by studying patents and disassembling trainers and medication-containing autoinjectors. Multiple methods of access were tried to find the quickest, most reliable method that required minimal tools or equipment. A quick, reliable method of removing the injection syringe from the autoinjector using a knife was determined, as outlined in this article. The syringe plunger had a security design to prevent dispensing further doses from the syringe, so a long narrow object is also required to dispense additional doses. There are 4 additional doses of approximately 0.3-mg epinephrine in these Teva autoinjectors. Prior knowledge of epinephrine equipment and the devices that may be encountered in the field is important for providing life-saving medical care. The ability to retrieve additional doses of epinephrine from a used autoinjector can provide additional life-saving medication while evacuating to a higher level of medical care. This method does carry risks to rescuers and patients; however, it can potentially be life saving.

Prefilled pen versus prefilled syringe: a pilot study evaluating two different methods of methotrexate subcutaneous injection in patients with JIA.

BACKGROUND: Methotrexate is the most commonly used disease-modifying antirheumatic drug recommended in the treatment of juvenile idiopathic arthritis. It can be administered orally or subcutaneously, the latter method is associated with fewer side effects and higher drug bioavailability. Nevertheless, the pain associated with injection is a considerable drawback of this treatment option in the pediatric population. Currently, there are two single-use subcutaneous injection devices available: the prefilled syringe and the prefilled pen. This prospective, two-sequence crossover study aimed to compare ease of use, frequency of therapy side effects, injection-site pain and parent/patient preference of those methotrexate parenteral delivery systems. METHODS: Twenty-three patients with juvenile idiopathic arthritis, already treated with subcutaneous methotrexate in the form of prefilled syringe in the period October 2018 - April 2019 completed a questionnaire evaluating their experience with this device. Subsequently, children received a one-month supply of pen autoinjector and completed the same questionnaire, regarding their experience with the new methotrexate delivery system. If the patient was not performing the injections himself the questionnaires were completed by the caregiver administrating MTX. The results obtained in both questionnaires were compared using the Wilcoxon matched-pairs signed-rank test. RESULTS: 82,6% patients and their caregivers voted for the prefilled pen as their preferred method of subcutaneous methotrexate administration. Moreover, the injection with the prefilled pen was reported as less painful in comparison to the prefilled syringe (p < 0.01). Side effects of methotrexate were less pronounced after the prefilled pen treatment, this difference was most prominent regarding gastrointestinal adverse events associated with the injection (p < 0.01). CONCLUSION: Administration of methotrexate using the pen device is a promising way of subcutaneous methotrexate delivery in children with juvenile idiopathic arthritis, as the injection is less painful and associated with fewer side effects.

The effects of combined intravenous cocaine and ethanol self-administration on the behavioral and amino acid profile of young adult rats.

Under paradigms of combined intravenous cocaine and ethanol self-administration, the effects on behavior have been poorly explored. Numerous studies have found sex differences in amino acids profile and behavioral responses to each drug, yet few have focused on the interactions between cocaine and ethanol. The main objective of this work was to explore the acquisition and maintenance of intravenous self-administration behavior with a combination of cocaine and ethanol in male and female young adult rats. Likewise, the amino acids profile in blood plasma was quantified 48 hours after the last self-administration session. Male and female 52 days old Wistar rats were randomly assigned to one of 3 groups: i) saline control, ii) cocaine (1 mg/kg bodyweight/injection) and iii) cocaine and ethanol (1 mg + 133 mg/kg bodyweight/ injection). After 24 self-administration sessions carried out on a fixed-ratio-1 schedule, with a limit of 15 doses per session, 14 plasma amino acids were quantified by mean Capillary Electrophoresis technique. The curve of cocaine and ethanol combined self-administration was similar to that associated with cocaine administration alone, with females acquiring self-administration criterion before males. The self-administration of cocaine and ethanol altered the plasma concentration and relative ratios of the amino acid L-Tyrosine. In our intravenous self-administration model, females appeared more vulnerable to acquire abusive consumption of the cocaine and ethanol combination, which altered plasma L-Tyrosine levels.

Device use errors with soft mist inhalers: A global systematic literature review and meta-analysis.

Inhaled bronchodilators are the cornerstone of treatment for chronic obstructive pulmonary disease (COPD). Soft mist inhalers (SMIs) are devices that deliver bronchodilators. Although correct device use is paramount to successful medication delivery, patient errors are common. This global systematic literature review and meta-analysis examined device use errors with SMIs among patients with obstructive lung diseases. PubMed, EMBASE, PsycINFO, Cochrane, and Google Scholar were searched to identify studies published between 2010 and 2019 that met the following inclusion criteria: (a) English language; (b) a diagnosis of COPD, bronchitis, or emphysema; and (c) reported device use errors among adults receiving long-acting bronchodilator treatment with Respimat® SMI (i.e. Spiriva®, Stiolto®, Spiolto®, and Striverdi®). Descriptive statistics examined sociodemographics, clinical characteristics, and device use errors. Meta-analysis techniques were employed with random-effects models to generate pooled mean effect sizes and 95% confidence intervals (CIs) for overall and step-by-step errors. The I2 statistic measured heterogeneity. Twelve studies (n = 1288 patients) were included in this meta-analysis. Eighty-eight percent of patients had COPD, and most had moderate/very severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease spirometric stages II to IV). Aggregate results revealed that 58.9% (95% CI: 42.4-75.5; I2 = 92.8%) of patients made ≥1 device use errors. Among 11 studies with step-by-step data, the most common errors were failure to (1) exhale completely and away from the device (47.8% (95% CI: 33.6-62.0)); (2) hold breath for up to 10 seconds (30.6% (95% CI: 17.5-43.7)); (3) take a slow, deep breath while pressing the dose release button (27.9% (95% CI: 14.5-41.2)); (4) hold the inhaler upright (22.6% (95% CI: 6.2-39.0)); and (5) turn the base toward the arrows until it clicked (17.6% (95% CI: 3.0-32.2)). Device use errors occurred in about 6 of 10 patients who used SMIs. An individualized approach to inhalation device selection and ongoing training and monitoring of device use are important in optimizing bronchodilator treatment.

Usability of mepolizumab single-use prefilled autoinjector for patient self-administration.

Objective: To evaluate usability of mepolizumab as a liquid drug product self-administered via a single-use prefilled autoinjector (AI) by patients with severe eosinophilic asthma (SEA), or their caregivers, in-clinic and at home.Methods: This open-label, single-arm, Phase IIIa study (NCT03099096; GSK ID: 204959) included patients aged ≥12 years with SEA who were either receiving mepolizumab (100 mg subcutaneously [SC]) every 4 weeks (Q4W) for ≥12 weeks before screening or not receiving mepolizumab but met criteria indicative of SEA. Patients/caregivers self-administered mepolizumab (100 mg SC) via an AI Q4W for 12 weeks. The first (Week 0) and third (Week 8) doses were observed in-clinic; the second dose (Week 4) was administered unobserved at home. Primary and secondary endpoints were the proportion of patients who successfully self-administered their third and second doses, respectively (determined by investigator/site staff). Patient experience, mepolizumab trough concentrations, blood eosinophil count (BEC), and safety were also assessed.Results: Of 159 patients/caregivers who self-administered ≥1 dose of mepolizumab, 157 completed the study. Nearly all patients successfully self-administered their third mepolizumab dose in-clinic and second dose at home (≥98% and ≥96%, respectively); this was further confirmed by mepolizumab trough concentrations/BEC. At study end, ≥88% of patients were "very" or "extremely" confident about using the AI correctly. Incidence of on-treatment drug-related adverse events (AEs) was low (3%); no fatal AEs occurred.Conclusions: Patients/caregivers successfully self-administered mepolizumab via the AI both in-clinic and at home; no new safety concerns were identified.

Impact of pain associated with the subcutaneous administration of adalimumab.

BACKGROUND: There is limited information regarding the impact of patients' perception of injection pain on adherence to treatments, specifically in inflammatory bowel disease (IBD) patients. Therefore, we aimed to determine the impact of the pain associated with the subcutaneous administration of adalimumab in patients with IBD treated with the old formulation and the new low-volume/citrate-free formulation. METHODS: A specifically-designed questionnaire was completed by 76 patients with IBD, who started treatment with adalimumab before the availability of the low-volume/citrate-free formulation and were switched to this new formulation. Intensity of pain was measured by using visual analog scales (VAS). RESULTS: A total of 62 patients (82%) experienced injection-related pain with the initial formulation. The perception of pain was associated with a decreased adherence to the treatment (37%), an increase in pre-administration anxiety (25%) or, as a consequence, the patient required someone else to carry out the injection (21%). Younger age was the only factor associated with pain perception. After switching to the new formulation, perception of pain persisted only in 2 patients (3%). Among those who felt pain with the initial formulation, pre-administration anxiety disappeared in 44%; 32% and 42% stated that the new formulation eased adherence and self-administration. CONCLUSIONS: The perception of pain related to the subcutaneous administration of therapy negatively impacts on treatment adherence in IBD patients. Improved formulations for subcutaneous administration of drugs can positively impact patients' convenience and adherence.

Usability of mepolizumab single-use prefilled syringe for patient self-administration.

Objective: A liquid mepolizumab formulation in a single-use prefilled syringe (PFS) is under development. We evaluated the usability of mepolizumab self-injected via PFS by patients with severe eosinophilic asthma (SEA), or their caregivers, in clinic and at home.Methods: This open-label, single-arm, Phase IIIa study included patients with SEA, aged ≥12 years, and receiving mepolizumab (100 mg subcutaneously) every 4 weeks for ≥12 weeks prior to screening. Patients with SEA not receiving mepolizumab at screening who met additional criteria were also included. Patients/caregivers self-administered mepolizumab (100 mg subcutaneously) via PFS every 4 weeks for 12 weeks. The first (Week 0) and third (Week 8) dose were observed in clinic; the second dose (Week 4) was unobserved at home. Primary and secondary endpoints were the proportion of patients who successfully self-administered their third and second doses, respectively. Injection success was determined by investigator/site staff. Patient experience, mepolizumab trough concentrations, blood eosinophil counts, and safety were also assessed.Results: Of the 56 patients/caregivers who self-administered ≥1 dose of mepolizumab, 55 completed the study. All patients were reported to have successfully self-administered their third mepolizumab dose in clinic (N = 55, 100%); this was further evidenced by trough concentrations/blood eosinophil counts. Most patients/caregivers found the PFS easy and convenient to use with 75% (n = 42) expressing little/no anxiety about using the device at home. Incidence of on-treatment drug-related adverse events was low (4%); none were fatal.Conclusions: Patients/caregivers successfully self-administered mepolizumab via the PFS both in clinic and at home, with no new safety concerns identified.

Home-based self-administered transcranial direct current stimulation in older adults with knee osteoarthritis pain: An open-label study.

Clinic-based transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that has been shown to improve pain. However, no published studies have reported using home-based self-administered tDCS in older adults with knee osteoarthritis (OA). The present study aimed to evaluate the preliminary efficacy and feasibility of home-based self-administered tDCS with real-time remote supervision on clinical pain, anxiety, depression, and sleep disturbances in older adults with knee OA. Twenty 50- to 85-year-old community-dwelling participants with knee OA received 10 daily home-based sessions of 2 mA tDCS for 20 min with real-time remote supervision. We measured clinical pain severity via the Visual Analog Scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Short-Form McGill Pain Questionnaire. We assessed anxiety, depression, and sleep disturbances using the Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety-short form, depression-short form, and sleep disturbance-short form, respectively. All 20 participants completed all 10 home-based tDCS sessions without serious adverse effects. Both clinical pain severity and sleep disturbances were improved after completion of the 10 tDCS sessions. Anxiety and depression scores were not significantly improved. We demonstrated that home-based self-administered tDCS with real-time remote supervision was feasible and beneficial in alleviating clinical pain in older adults with knee OA. These findings support future studies with larger samples and longer-term follow-up evaluations.

Dose-dependent effects of chronic alcohol drinking on peripheral immune responses.

It is well established that chronic heavy alcohol drinking (CHD) results in significant organ damage, increased susceptibility to infections, and poor outcomes following injury. In contrast, chronic moderate drinking (CMD) has been associated with improved cardiovascular health and immunity. These differential outcomes have been linked to alterations in both innate and adaptive branches of the immune system; however, the mechanisms remain poorly understood. To address this question, we determined the impact of chronic drinking on the transcriptional and functional responses of peripheral blood mononuclear cells (PBMC) collected from male rhesus macaques classified as CMD or CHD after 12 months of voluntary ethanol self-administration. Our analysis suggests that chronic alcohol drinking, regardless of dose alters resting transcriptomes of PBMC, with the largest impact seen in innate immune cells. These transcriptional changes are partially explained by alterations in microRNA profiles. Additionally, chronic alcohol drinking is associated with a dose dependent heightened inflammatory profiled at resting and following LPS stimulation. Moreover, we observed a dose-dependent shift in the kinetics of transcriptional responses to LPS. These findings may explain the dichotomy in clinical and immunological outcomes observed with moderate versus heavy alcohol drinking.

Expanding a woman's options to include home use of misoprostol for medical abortion up until 76 days: an observational study of efficacy and safety.

INTRODUCTION: Home use of misoprostol for medical abortion is increasingly being practiced. With gestational length up to 70 days, it is considered effective, safe and acceptable by women. Knowledge of safety and efficacy with longer gestations is limited and studies are required to expand women's options to include this method of abortion. MATERIAL AND METHODS: A retrospective cohort study was designed to compare home use of misoprostol for medical abortion at gestational length 64-76 days to its use at 57-63 days. Primary outcome was success rate. Success was defined as complete uterine evacuation without the need of surgical intervention due to incomplete abortion and no failed abortion with ongoing pregnancy. Secondary outcomes were rates of unscheduled return visits, telephone consultations, admissions to hospital, infections and the need for blood transfusion. RESULTS: We included 397 women, 270 within 57-63 days of gestation and 127 within 64-76 days of gestation at abortion. Success rate was 95.6% at 57-63 days and 93.7% at 64-76 days. The difference was not statistically significant (P = .431). The rate of unscheduled return visits was high overall but not significantly different in relation to gestational length at abortion (> 63 days; 20.5% vs < 64 days; 16.3%, P = .308). CONCLUSIONS: Our study indicates that home use of misoprostol for medical abortion at 64-76 days gestation may be as safe and effective as at 57-63 days. Further studies with larger sample sizes are needed to confirm our findings and to explore the acceptance of and experiences among women performing abortion at home at greater gestational length, before further implementation in clinical practice.

Unintentional Epinephrine Auto-injector Injuries: A National Poison Center Observational Study.

BACKGROUND: Epinephrine is the only first-line therapeutic agent used to treat life-threatening anaphylaxis. Epinephrine auto-injectors are commonly carried by patients at risk for anaphylaxis, and reported cases of unintentional auto-injector injury have increased over the last decade. Modifications of existing designs and release of a new style of auto-injector are intended to reduce epinephrine auto-injector misuse. STUDY QUESTION: The aim of the study was to characterize reported cases of unintentional epinephrine auto-injector exposures from 2013 to 2014 and compare demographics, auto-injector model, and anatomical site of such exposures. METHODS: The American Association of Poison Control Center's National Poison Data System was searched from January 1, 2013, to December 31, 2014, for cases of unintentional epinephrine auto-injector exposures. Anatomical site data were obtained from all cases reported to the Virginia Poison Center and participating regional poison center for Auvi-Q cases. RESULTS: A total of 6806 cases of unintentional epinephrine auto-injector exposures were reported to US Poison Centers in 2013 and 2014. Of these cases, 3933 occurred with EpiPen, 2829 with EpiPen Jr, 44 with Auvi-Q, and no case reported of Adrenaclick. The most common site of unintentional injection for traditional epinephrine auto-injectors was the digit or thumb, with 58% of cases for EpiPen and 39% of cases with EpiPen Jr. With Auvi-Q, the most common site was the leg (78% of cases). CONCLUSIONS: The number of unintentional epinephrine auto-injector cases reported to American Poison Centers in 2013-2014 has increased compared with previous data. Most EpiPen exposures were in the digits, whereas Auvi-Q was most frequently in the leg. Because of the limitations of Poison Center data, more research is needed to identify incidence of unintentional exposures and the effectiveness of epinephrine auto-injector redesign.

Successful prevention of follicular rupture at 45 h after hCG and GnRHa triggering by emergent administration of indomethacin: A case report.

OBJECTIVE: To report the management and prevention of pre-operative ovulation before oocyte retrieval with emergent administration of indomethacin. CASE REPORT: During in vitro fertilization (IVF) treatment, the patient described here mistakenly administered 6500 IU of hCG and 0.2 mg of triptorelin (GnRHa) 9 h earlier than scheduled triggering. To avoid emergent oocyte retrieval in the midnight, indomethacin was given (150 mg/day, there times a day) from 2 h after incorrect hCG and GnRHa injection to the night before ovum pickup. The oocyte retrieval was performed at originally scheduled time. The result showed that pre-operative ovulation was effectively prevented and we successfully collected the expected number Andersen et al., 1995 of oocytes at 45 h after triggering. CONCLUSION: The presented case demonstrates that indomethacin can be used safely and effectively as an emergent prescription to prevent and postpone ovulation till up to 45 h after hCG and GnRHa triggering.

Cerebrovascular Injury After Serial Exposure to Chronic Stress and Abstinence from Methamphetamine Self-Administration.

Cerebrovascular damage caused by either exposure to stress or the widely abused drug, methamphetamine (Meth) is known but stress and drug abuse frequently occur in tandem that may impact their individual cerebrovascular effects. This study examined their co-morbid cerebrovascular effects during abstinence from self-administered Meth after the exposure to chronic unpredictable stress (CUS). Exposure to CUS prior to unrestricted Meth self-administration had no effect on Meth intake in rats; however, the pro-inflammatory mediator cyclooxygenase-2 (COX-2) and the breakdown of cell-matrix adhesion protein ß-dystroglycan in isolated cerebral cortical capillaries were increased after 3 days of abstinence and persisted for 7 days. These changes preceded decreases in occludin, a key structural protein component of the blood-brain barrier. The decrease in occludin was blocked by the COX-2 specific inhibitor nimesulide treatment during abstinence from Meth. The changes in COX-2, ß-dystroglycan, and occludin were only evident following the serial exposure to stress and Meth but not after either one alone. These results suggest that stress and voluntary Meth intake can synergize and disrupt cerebrovasculature in a time-dependent manner during abstinence from chronic stress and Meth. Furthermore, COX-2 inhibition may be a viable pharmacological intervention to block vascular changes after Meth exposure.

Inyección accidental de adrenalina en un dedo / Accidental injection of adrenaline into a finger

Presentamos un caso de inyección accidental en un dedo de la mano en personal sanitario resuelto con inmersión del dedo en agua caliente y aplicación tópica de pomada nitroglicerina. Los síntomas más habituales son el dolor, palidez y frialdad a nivel local, aunque se han descrito complicaciones graves por vasoconstricción severa como la necrosis isquémica, que obliga a tratamientos más agresivos como la administración de fentolamina. El uso cada vez más extendido de autoinyectores de adrenalina para el tratamiento de reacciones anafilácticas severas ha hecho que aumenten los casos de inyección accidental de estos dispositivos, siendo recomendable el conocimiento del manejo de estas situaciones por los profesionales de Atención Primaria y de los Servicios de Urgencia (AU)

We present the case of an accidental injection of adrenaline into a digital finger in health personnel, solved by immersion of the finger in warm water and topical application of nitroglycerine intment. Most common symptoms are local pain, pallor and coldness, although some cases may present serious complications due to severe vasoconstriction, such as ischemic necrosis, which requires more aggressive treatments, including administration of phentolamine. The increased use of adrenaline auto-injectors for the treatment of severe anaphylactic reactions has caused an increasing incidence of accidental injection from these devices. It is therefore advisable that Primary Care and Emergency Department professionals are knowledgeable about the management of these situation (AU)

Injecting without pressing a button: An exploratory study of a shield-triggered injection mechanism.

AIMS: To evaluate the injection success and user perception of a shield-triggered pen-injector mechanism. METHODS: The trial (ClinicalTrials.gov NCT02627287) was an exploratory, two-centre, one-visit, open-label, randomized controlled trial conducted in Germany in 150 injection-experienced individuals with type 1 or type 2 diabetes. Participants self-administered subcutaneous injections of a placebo solution using a prototype shield-triggered pen-injector, DV3316 (Novo Nordisk, Bagsvaerd, Denmark), and FlexPen (Novo Nordisk, Bagsvaerd, Denmark). Injection success was evaluated on a yes/no basis by the investigator. Participant confidence, leakage of fluid and pain were evaluated after each injection. Pain and device experience were assessed after completion of all injections with each pen-injector. Overall preference was assessed after completion of all injections with both pen-injectors. RESULTS: Injection success was high with both pen-injectors (97.0%, DV3316 vs 99.7%, FlexPen). Participant confidence in dose delivery was similar for the two devices (88% of injections with DV3316 vs 81% with FlexPen were scored as "extremely confident"). The median injection pain score on a visual analogue scale (0-100) was 3 with DV3316 vs 4 with FlexPen after each injection, and 4 with DV3316 vs 5 with FlexPen after all injections with each device. After all injections were completed, 55% of participants reported an overall preference for DV3316 vs 21% for FlexPen. CONCLUSION: This study demonstrates that injection-experienced individuals can achieve a high injection success rate with a shield-triggered pen-injector, with similar patient confidence and injection pain compared with FlexPen.