Establishment and comparison of two methods to produce a rat model of mammary gland hyperplasia with hyperprolactinemia

Abstract This study aimed to establish and compare models of mammary gland hyperplasia (MGH) with hyperprolactinemia (HPRL) using two different methods. The models provide information on the relationship between mammary gland hyperplasia and associated hormones. Model A was constructed using intramuscular injections of estradiol benzoate injection (EBI), followed by progesterone (P), and then metoclopramide dihydrochloride (MDI). Model B was designed by administering MDI, follow by EBI, and then P intramuscularly. Model B showed higher MGH progression compared with model A. Notably, increase in estradiol (E2) was negatively correlated with prolactin (PRL) secretion. However, PRL levels in model B were significantly higher compared with the levels in model A. Estrogen (ER), prolactin receptor (PRLR), and progesterone receptor (PR) mRNA and protein expression levels in model B rats were positively correlated with changes in the corresponding hormone levels. However, E2, P, and PRL levels in model A showed no direct relationship with levels of the mRNAs of related hormones and protein expression levels. Our results suggest that model B is an appropriate model of MGH with HPRL that can be used to perform further studies about the interactions of the E2, P, and PRL hormones in this disorder.

Shotblocker Use in Emergency Care: A Randomized Clinical Trial.

This study was conducted to evaluate the effect of ShotBlocker on the intramuscular injection pain and satisfaction in emergency adult patients. This research was designed as a randomized controlled, double-blind, experimental study. The study was conducted with 74 patients who applied to the adult emergency department. Patients were randomized to ShotBlocker and control groups. Patient Assessment Form, Visual Analog Scale, and Visual Analog Patient Satisfaction Scale were used. The mean scores of postinjection pain and satisfaction level were analyzed between the groups; it was determined that while postinjection pain mean score of the experimental group was statistically significantly lower than that of the control group (p = 0.0001), satisfaction scores were statistically significantly higher in the experimental group than in the control group (p = 0.004). When the correlation between the intragroup Pain Scores (VAS) and the Satisfaction Scores (VAS) of the groups after injection was examined, a statistically significant and inverse correlation was found (p < 0.05). It was determined that ShotBlocker was effective in reducing intramuscular injection pain and increasing satisfaction levels.

Factors contributing to underuse of epinephrine autoinjectors in pediatric patients with food allergy.

BACKGROUND: Epinephrine autoinjectors (EAs) are the standard of care for severe food allergic reactions, although they are frequently underused or misused. OBJECTIVE: To understand the factors associated with underuse of EA by caregivers of pediatric patients with food allergy. METHODS: A survey was administered to 200 caregivers of pediatric patients with food allergies to assess most severe lifetime allergic reaction, EA education, and use and factors associated with incorrect use or underutilization. RESULTS: A total of 164 surveys were completed; of which 118 (72%) of lifetime most severe reactions warranted EA use, but the EA was used in only 45 (38.1%). Reasons caregivers indicated for not administering the EA included the following: reactions did not seem severe enough; it was the patient's first allergic reaction; use of other medication; and fear of using EA. CONCLUSION: Multiple factors contribute to underuse of EA in the treatment of severe allergic reactions. Results from this study highlight the need for continuous EA education in caregivers of and pediatric patients with food allergies, using a multipronged approach targeting clear symptom recognition and alleviation of fear of EA use.

Preclinical studies of non-stick thin film metallic glass-coated syringe needles.

Our objective in this study was to determine the biocompatibility and hemocompatibility of thin film metallic glass (TFMG) and its potential use in hypodermic needles for intramuscular or intravenous injection. Mouse and rabbit models were employed under approval from the Institutional Animal Care and Use Committee (n = 5/group, two groups in total for both animal models). Platelet-rich plasma (PRP) was collected from the whole blood of rabbits (ear vein) without anti-coagulant for use in in vitro coagulation tests. Histological analysis and optical microscopy were used to assess the endothelial structure of the inner lining of veins after being punctured with needles and detained for 3 days. Histological analysis of ear vein sections revealed that the extent of endothelial damage after puncturing with a TFMG-coated needle was 33% less than that produced by bare needles. Our results confirm that the deposition of a thin TFMG layer (e.g., Zr53Cu33Al9Ta5) on the surface of hypodermic needle can have remarkably clinical benefits, including anti-adhesion, reduced invasion, and minimal endothelial damage. Our results also confirm the good biocompatibility and hemocompatibility of the TFMG coatings.

Self-injectable epinephrine: doctors' attitude and patients' adherence in real-life.

PURPOSE OF REVIEW: Epinephrine is the only life-saving treatment of anaphylaxis. Prescription and administration rates of self-injectable epinephrine are generally low. It is unclear whether this is because of availability, low prescription rates, fear of using epinephrine, or a combination of these issues. RECENT FINDINGS: This review focuses on what self-injectable epinephrine devices (SIED), such as auto-injectors and prefilled syringes, are preferred by patients and healthcare professionals (HCP). Our findings suggest that a device's ease to use, proper and frequent training on its operability, and availability have an impact on preferences and adherence to treatment with SIEDs. After prescribing a patient with a SIED, clinicians should emphasize its use in anaphylaxis, educate patients/caregivers to identify anaphylaxis and on how to use the SIED, and encourage constant practicing with training devices. SUMMARY: Epinephrine is the sole recommended anaphylaxis treatment and SIEDs are of critical usefulness in the community setting. Further studying of these devices is needed to optimize education for HCPs and patients and their accessibility to SIEDs.

Utilización rápida y segura de los autoinyectores de adrenalina. ¡Tenemos un problema / Rapid and safe use of adrenaline auto-injectors: We have a problem

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Autoinjector device for rapid administration of drugs and antidotes in emergency situations and in mass casualty management.

There are several situations such as medical emergencies and incidents involving mass casualties where drugs and antidotes have to be administered immediately along with other first aid at the site of the event. Self-administration by the affected person or by a companion is required as a life-saving measure. Autoinjector devices (AIDs) are useful for the rapid administration of drugs and antidotes and they can also be used by those who have not been medically trained. This makes them very convenient for emergency and mass casualty management. An AID has a drug cartridge with an embedded needle for subcutaneous or intramuscular injection, which is usually painless. The drugs are delivered slowly by the AID across a large area in the muscle, which increases the absorption and the drug effects are equal to that of intravenous administration. A variety of AIDs are available, such as atropine and pralidoxime for nerve agent poisoning, epinephrine for anaphylactic shock and allergy, diazepam for seizures, sumatriptan for migraine, amikacin for antibacterial treatment, buprenorphine for pain relief and monoclonal antibodies for a variety of diseases. This review describes the published peer-reviewed literature identified by online searches of journal databases.

Adrenaline Auto-injector injuries to digits; a systematic review and recommendations for emergency management.

AIMS: Accidental injury to digits with Adrenaline Auto-injectors (AAIs) is becoming increasingly common. Digital AAI injury causes painful ischaemia that can lead to necrosis and patient anxiety. There is a lack of understanding amongst surgeons regarding how to manage these injuries. We aimed to determine an optimal treatment algorithm for their management. METHODS: We conducted a systematic review using the search engines MEDLINE, PubMed, EMBASE, CINAHL, BNI, AMED, Google Scholar. Search items included ("epinephrine OR adrenaline") AND ("Digit" OR "Finger" OR "Thumb") AND ("Injury" OR "Accidental"). RESULTS: A total of 49 articles were identified describing 111 cases. In 58 cases; 52% of cases were managed with phentolamine, 24% were managed with nitroglycerine and 7% were treated with warm soaks. The remaining 17% of cases were managed with a variety of alternative treatments. Mean recovery time following treatment with phentolamine infiltration was 33 min, whilst symptoms persisted for several hours in some cases with observation/warm soaks and nitroglycerine. Phentolamine was more effective when injected into the AAI puncture site (mean resolution time: 17 min) in comparison to injection as a digital block (74 min). CONCLUSION: Phentolamine is the most effective method of reversing symptoms and treating ischaemic digits when compared to alternative therapies. Symptoms resolved much quicker when phentolamine was infiltrated into the site of injury compared to being infiltrated as a digital block. We propose a treatment algorithm for management of these injuries. Hand surgeons should be aware of AAI injuries and be able to advise on their management.

Anterolateral thigh measurements by ultrasound in neonates and young infants to ensure safe intramuscular injections during vaccination in low- and middle-income countries.

BACKGROUND: Use of same length needle for intramuscularly administered vaccines had been reported to cause under-and over-penetration among infants due to their different body weights and underlying variations in the fat and muscle thickness. Normative data regarding thigh compartment thickness are, however, lacking among neonates and infants aged ≤12 weeks particularly in low- and middle-incoming countries with high burden of low birth weight/growth restricted infants. METHODS: Present study investigated skin to muscle and skin to bone (STBD) distances of anterolateral thigh of babies (n = 300) aged ≤12 weeks (1-80 days) with different weight groups (<3 kg, 3-4 kg and >4 kg) by ultrasonography during their intramuscular vaccinations. RESULTS: Overall, mean [standard deviation (SD)] STBD was 17.04 (2.66) mm with range of 10.60-23.30 mm. Stratifying by current body weight, mean (SD) STBD in infants weighing less than 3 kg was 14.39 (1.23) mm. For infants weighing between 3-4 kg and >4 kg, the mean (SD) STBD were 16.69 (1.43) mm and 17.04 (2.66) mm, respectively. Estimated safety (no risk of over-penetration) of 16 mm was observed in 57.33% (172) infants whereas 25 mm needle had 100% over-penetration risk in the study cohort. Current body weight of infants was a significant predictor of safe injection [area under the receiver operating characteristic (ROC) curve 0.95; 95% CI 0.92-0.97]. CONCLUSIONS: Our study offers objective normative measurements of anterolateral thigh for safe intramuscular vaccination in young infants especially for low birth weight and growth restricted infants in low- and middle-income countries.

Tolerability of IM penicillin G benzathine diluted or not with local anesthetics, or different gauge needles for syphilis treatment: a randomized clinical trial.

BACKGROUND: Penicillin G Benzathine (PGB) is the cornerstone of syphilis treatment. However, its intramuscular (IM) administration is associated with pain at the site of injection. The dilution of PGB with local anesthetics is recommended in some guidelines, but the evidence that supports it, particularly in adults and in HIV infection, is scarce. Preliminary clinical experience also suggests that the IM administration of PGB through increased needle gauges might improve its tolerability. The aim of the study to identify less painful ways of administering IM PGB in the treatment of syphilis in adults. METHODS: Multicenter, randomized, double-blinded clinical trial in patients diagnosed with primary syphilis that required a single IM injection of PGB 2400,00 IU. Patients were randomized to receive PGB diluted with 0.5 mL mepivacaine 1% (MV) or PGB alone, and both groups either with a long 19G or short 21G IM needle. The primary objective was the effect on local pain immediately after the administration through a visual scale questionnaire on pain (0 to 10). RESULTS: One hundred eight patients were included, 27 in each group. Ninety-four (94.4%) were male, and 41.7% were also HIV-infected. Mean age 36.6 years (SD 11). Significant differences in immediate pain intensity were observed when comparing the long 19G group with anesthesia (mean pain intensity, [MPI] 2.92 [CI 95% 1.08-4.07]) vs long 19G without anesthesia (MPI 5.56 [CI 95% 4.39-6.73), p < 0.001; and also between short 21G group with anesthesia (MPI 3.36 [CI 95% 2.22-4.50]) vs short 21G without anesthesia (MPI 5.06 [CI 95% 3.93-6.19]), p = 0.015). No significant differences in immediate pain were observed between 19G and 21G in the presence or absence of anesthesia (p = 1.0 in both cases). No differences were found between study arms after 6 and 24 h. CONCLUSIONS: The IM administration of 1% mepivacaine-diluted PGB induces significantly less immediate local pain as compared to PGB alone. The needle gauge did not have any effect on the pain. Based on these results, we suggest anesthetic-diluted IM PGB as the standard treatment for primary syphilis. TRIAL REGISTRATION: EudraCT 2014-003969-24 (Date of registration 18/09/2014).

Comparison of the efficacy of ShotBlocker and cold spray in reducing intramuscular injection-related pain in adults. A prospective, randomized, controlled trial.

OBJECTIVES: To compare the efficacy of ShotBlocker and cold spray in reducing intramuscular (IM) injection-related pain in adults. Methos: A prospective, randomized, controlled study carried out between January 2018 and March 2018 at the Department of Emergency Medicine, Acibadem Mehmet Ali Aydinlar University, School of Medicine, Istanbul, Turkey. Adult patients receiving IM injection of diclofenac sodium (75 mg/3 ml) were included. The patients were randomized into 3 groups: ShotBlocker, cold spray, and control. Each group comprised 40 patients. Patients were instructed to rate the intensity of IM injection-related pain using a 100-mm visual analog scale (VAS). Visual analog scale scores of the patients were statistically analyzed. Results: Visual analog scale scores were lower in the ShotBlocker (11 mm) and cold spray (10 mm) groups than in the control group (31 mm) (p=0.001). There were no significant differences in VAS scores between the ShotBlocker and cold spray groups. The operators' responses revealed that ShotBlocker was more difficult to administer than cold spray. Conclusion: ShotBlocker is an effective non-pharmacological method that reduces IM injection-related pain and is similar in efficacy, to cold spray.

Cost-Effectiveness of Stock Epinephrine Autoinjectors on Commercial Aircraft.

BACKGROUND: In-flight food-allergic reactions are rare events, but given increasing reports, grass-root advocates have lobbied to replace aircraft emergency kit epinephrine ampules with autoinjectors. OBJECTIVE: To evaluate the cost-effectiveness of stock epinephrine on commercial aircraft. METHODS: We conducted a Markov model with microsimulation of food-allergic individuals over an 80-year time horizon to evaluate the cost-effectiveness of supplementing airline medical kits with epinephrine autoinjectors (eg, providing autoinjector twin-packs in addition to the epinephrine ampule in the medical kit), versus not doing so, using a per-plane annual value-based cost ceiling of $338 (the value-based ceiling for school stock epinephrine). We assumed that autoinjector availability reduced fatality risk by 10%. RESULTS: Equipping all commercial aircraft with autoinjectors cost $2,470,422/year ($0.08/passenger-at-risk), from a societal perspective and when distributed over all at-risk travelers. Over the model horizon, the supplemental autoinjector strategy cost $32,329.29 (standard deviation [SD], $4024.32) versus $32,326.70 (SD $4024.29), produced 26.8917 quality-adjusted life-years (QALYs) (SD, 2.9720) versus 26.8915 (SD, 2.9725), with a lower fatality rate (0.00012; SD, 0.01095 vs 0.00015; SD, 0.1225) versus the ampule-only strategy. The incremental cost-effectiveness ratio of supplemental airline epinephrine autoinjectors was $10,766/QALY in the base-case analysis. The supplemental model remained cost-effective at a willingness to pay threshold of $100,000/QALY if it produced a minimum 1.4% annual food allergy fatality risk reduction, and dominated if it lowered diversion risk or event-related medical care costs-per-event by 10%, respectively. CONCLUSIONS: Under base-case scenarios, an airline supplemental stock epinephrine model is cost-effective, with a high value-based cost-ceiling and low annual cost per passenger-at-risk of $0.08.

Immunogenicity of full and fractional dose of inactivated poliovirus vaccine for use in routine immunisation and outbreak response: an open-label, randomised controlled trial.

BACKGROUND: Intradermal administration of fractional inactivated poliovirus vaccine (fIPV) is a dose-sparing alternative to the intramuscular full dose. We aimed to compare the immunogenicity of two fIPV doses versus one IPV dose for routine immunisation, and also assessed the immunogenicity of an fIPV booster dose for an outbreak response. METHODS: We did an open-label, randomised, controlled, inequality, non-inferiority trial in two clinics in Dhaka, Bangladesh. Healthy infants were randomly assigned at 6 weeks to one of four groups: group A received IPV at age 14 weeks and IPV booster at age 22 weeks; group B received IPV at age 14 weeks and fIPV booster at age 22 weeks; group C received IPV at age 6 weeks and fIPV booster at age 22 weeks; and group D received fIPV at 6 weeks and 14 weeks and fIPV booster at age 22 weeks. IPV was administered by needle-syringe as an intramuscular full dose (0·5 mL), and fIPV was administered intradermally (0·1 mL of the IPV formulation was administered using the 0·1 mL HelmJect auto-disable syringe with a Helms intradermal adapter). Both IPV and fIPV were administered on the outer, upper right thigh of infants. The primary outcome was vaccine response to poliovirus types 1, 2, and 3 at age 22 weeks (routine immunisation) and age 26 weeks (outbreak response). Vaccine response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (≥1:8) or four-fold increase in reciprocal antibody titres adjusted for maternal antibody decay and was assessed in the modified intention-to-treat population (infants who received polio vaccines per group assignment and polio antibody titre results to serotypes 1, 2, and 3 at 6, 22, 23, and 26 weeks of age). The non-inferiority margin was 12·5%. This trial is registered with ClinicalTrials.gov, number NCT02847026. FINDINGS: Between Sept 1, 2016 and May 2, 2017, 1076 participants were randomly assigned and included in the modified intention-to-treat analysis: 271 in Group A, 267 in group B, 268 in group C, and 270 in group D. Vaccine response at 22 weeks to two doses of fIPV (group D) was significantly higher (p<0·0001) than to one dose of IPV (groups A and B) for all three poliovirus serotypes: the type 1 response comprised 212 (79% [95% CI 73-83]) versus 305 (57% [53-61]) participants, the type 2 response comprised 173 (64% [58-70]) versus 249 (46% [42-51]) participants, and the type 3 response comprised 196 (73% [67-78]) versus 196 (36% [33-41]) participants. At 26 weeks, the fIPV booster was non-inferior to IPV (group B vs group A) for serotype 1 (-1·12% [90% CI -2·18 to -0·06]), serotype 2 (0·40%, [-2·22 to 1·42]), and serotype 3 (1·51% [-3·23 to -0·21]). Of 129 adverse events, 21 were classified as serious including one death; none were attributed to IPV or fIPV. INTERPRETATION: fIPV appears to be an effective dose-sparing strategy for routine immunisation and outbreak responses. FUNDING: US Centers for Disease Control and Prevention.

Implications of variation of epinephrine auto-injector needle length.

BACKGROUND: The variation of needle lengths of epinephrine auto-injectors (EAIs) has not been investigated. OBJECTIVE: To investigate the impact of the variation of the needle length of EAIs. METHODS: Skin-to-muscle (STMD) and skin-to-bone distances (STBD) were measured for 303 children and adolescents and 99 adults. Distance was determined by ultrasound, applying high or low pressure on the probe. The risk of subcutaneous and periosteal/intraosseous injection was calculated using the lower and upper acceptance limits for length of EAI needles as provided for 3 high-pressure EAIs (HPEAI) and 1 low-pressure EAI (LPEAI). RESULTS: The variation in needle length of the HPEAIs are for Epipen Jr/Epipen 5 mm, for Jext 2 mm, for Auvi-Q 2.5 mm, and for the LPEAI, Emerade, 1.5 mm. When using the longest acceptable needles for Epipen Jr, the risk of intraosseous/periosteal penetration was highest in children weighing less than 15 kg at 60% and for Jext at 43%. The risk was low for Auvi-Q and Emerade. The risk of subcutaneous injection was greatest with the shortest needles of the Auvi-Q 0.1 mg at 94% in children weighing less than 15 kg. In adults, the risk of subcutaneous injection using the shortest needles was for Epi-Pen at 41%, Jext at 36%, Auvi-Q at 38%, and Emerade at 12%. CONCLUSION: The variation in needle length of EAIs influences the risk of subcutaneous and intraosseous/periosteal injections. Compared with Epipen Jr, the Auvi-Q 0.1 mg for children weighing less than 15 kg had a low risk of intraosseous/periosteal injection but a very high risk of subcutaneous injection. For adults, there is a significant risk of subcutaneous injection.

Changes in Emergency Department Concordance with Guidelines for the Management of Food-Induced Anaphylaxis: 1999-2001 versus 2013-2015.

BACKGROUND: Awareness about food allergy and food-induced anaphylaxis (FIA) has increased dramatically over the past decade. It remains unclear, however, whether concordance with guidelines for FIA management has improved over time. OBJECTIVE: Our objective was to describe changes in emergency department (ED) concordance with guidelines for FIA management. METHODS: We analyzed data from 2 multicenter retrospective studies of patients with food-related acute allergic reactions seen in 1 of 17 EDs during 2 time periods: 1999 to 2001 and 2013 to 2015. Visits were identified similarly across years-for example, using International Classification of Diseases, Ninth Revision, Clinical Modification codes 693.1, 995.60, 995.61-995.69, 995.0, and 995.3. Anaphylaxis was defined as an acute allergic reaction with involvement of 2+ organ systems or hypotension. We compared concordance between time periods for 4 guideline recommendations: (1) treatment with epinephrine, (2) discharge prescription for an epinephrine autoinjector (EAI), (3) referral to an allergist/immunologist, and (4) instructions to avoid offending allergen. RESULTS: We compared 290 patients with FIA during 1999 to 2001 and 459 during 2013 to 2015. Any treatment with epinephrine (pre-ED or in the ED) for patients with FIA increased over time (38% vs 56%; P < .001). Prescriptions for EAI at discharge (24% vs 54%; P < .001) and documentation for referral to an allergist/immunologist (14% vs 24%; P = .001) approximately doubled, whereas instructions to avoid the offending allergen did not change significantly (37% vs 43%; P = .08). Receipt of 3+ guideline recommendations remained low but almost quadrupled over the study interval (6% vs 23%; P < .001). CONCLUSIONS: Over the nearly 15-year study interval, we observed clinically and statistically significant increases in ED concordance with epinephrine-related guidelines for FIA. Management gaps remain and interventions to standardize care still appear warranted.