RESUMEN
OBJECTIVES: To evaluate the longevity of cantilevered zirconia-based resin-bonded fixed partial dentures (RBFPDs) in replacing missing posterior teeth, as well as the quality of life and patient satisfaction experienced by those receiving zirconia RBFPDs. METHODS: A prospective single-arm uncontrolled clinical trial was conducted to replace one or more missing premolars or molars with a span of 5 to 8 mm using cantilevered zirconia RBFPDs. Thirty-six participants with 40 prostheses were recruited and underwent a 3-year clinical evaluation. The retainer designs included a minimum thickness of 0.8 mm, a minimum of 200° circumferential wraparound with an occlusal bar, and a connector dimension of 3 × 3 mm. Patient-reported outcomes, including patient satisfaction and Oral Health Impact Profile (OHIP), were assessed. RESULTS: The average age of participants was 45.8 years, and 72.5 % were women. The success rate of the posterior zirconia RBFPDs was 76.2 %, with an estimated mean success duration of 46.1 months. The survival rate was 88.1 %, with an estimated mean survival duration of 49.4 months. Participants were highly satisfied with the treatment, achieving an average satisfaction score of 80.8 ± 11.9. Participants' total OHIP scores decreased from 52.3 to 39.6 after 3 years, indicating a significant improvement in oral health-related quality of life (P = 0.009). CONCLUSIONS: After 3 years, a moderately high survival rate and favourable patient-reported outcomes of posterior cantilevered zirconia RBFPDs were achieved. Therefore, it can be recommended as a conservative treatment option to replace missing posterior teeth, provided that retainer design considerations are taken into account. CLINICAL SIGNIFICANCE: Cantilevered zirconia RBFPDs for posterior teeth can serve as a conservative treatment option that is both aesthetically pleasing and biocompatible. It offers a more cost-effective alternative compared to dental implants, which are often prohibitively expensive for the majority of patients. This approach has the potential to greatly improve patient-reported outcomes.
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Diseño de Dentadura , Dentadura Parcial Fija con Resina Consolidada , Diente Molar , Satisfacción del Paciente , Calidad de Vida , Circonio , Humanos , Circonio/química , Femenino , Estudios Prospectivos , Masculino , Persona de Mediana Edad , Adulto , Diente Premolar , Resultado del Tratamiento , Retención de Dentadura , Fracaso de la Restauración Dental , Materiales Dentales/química , AncianoRESUMEN
Amoxicillin, doxycycline, and clindamycin are among the commonly used antibiotics to treat bacterial infections. However, dosage forms of antibiotics for pediatric patients may not be as readily available as the formulations for adult patients. As such, it is anticipated that during a public health emergency, special instruction may need to be provided on home preparation and administration procedures to dose pediatric patients using available stockpiles of oral tablet and capsule dosage forms. Mixing crushed tablets or capsule contents with soft- or liquid- foods is one of the most common home preparation procedures. To gain knowledge for safe and effective use of prepared drug product instead of the intended intact dosage form, the impact of manipulation of the dosage form was studied. Capsule opening, capsule content assay and uniformity, dissolution, homogeneity, and stability studies of drug mixed with various liquid and soft foods were carried out using intact capsules of amoxicillin, doxycycline, and clindamycin. Higher recovery of capsule contents was achieved when using hands or knives to open capsules compared to using scissors. The capsules of all three antibiotic products contained the labeled amount of active pharmaceutical ingredients (API). The peanut butter-drug mixtures failed both United States Pharmacopeia (USP) assay and dissolution criteria because the peanut butter significantly affected the solubility of the drugs, and hence it was omitted from further study. All drug-food mixtures of the three antibiotic products and 15 selected foods exhibited fast dissolution (e.g., >80 % in 60 min) in the tested medium, except for the amoxicillin-chocolate pudding mixture. Three household containers (cups, plates, and bowls) and four mixing times (0.5 min, 1 min, 2 min, and 5 min) were found to be suitable for preparation of homogeneous mixtures of the antibiotics and foods. For practical purposes, 1 to 2 min mixing time is sufficient to produce homogeneous mixtures. The results of this study provided product quality data on the interactions between the antibiotics and the foods and can potentially support future development of home preparation instructions of antibiotics for pediatric patients or patients with swallowing difficulties.
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Antibacterianos , Preferencias Alimentarias , Adulto , Humanos , Niño , Clindamicina , Doxiciclina , Química Farmacéutica/métodos , Comprimidos , Amoxicilina , Solubilidad , CápsulasRESUMEN
BACKGROUND: The high mortality of systemic anthrax is likely a consequence of the severe central nervous system inflammation that occurs in anthrax meningitis. Effective treatment of such infections requires, at a minimum, adequate cerebrospinal fluid (CSF) antimicrobial concentrations. METHODS: We reviewed English medical literature and regulatory documents to extract information on serum and CSF exposures for antimicrobials with in vitro activity against Bacillus anthracis. Using CSF pharmacokinetic exposures and in vitro B. anthracis susceptibility data, we used population pharmacokinetic modeling and Monte Carlo simulations to determine whether a specific antimicrobial dosage would likely achieve effective CSF antimicrobial activity in patients with normal to inflamed meninges (ie, an intact to markedly disrupted blood-brain barrier). RESULTS: The probability of microbiologic success at achievable antimicrobial dosages was high (≥95%) for ciprofloxacin, levofloxacin (500â mg every 12 hours), meropenem, imipenem/cilastatin, penicillin G, ampicillin, ampicillin/sulbactam, doxycycline, and minocycline; acceptable (90%-95%) for piperacillin/tazobactam and levofloxacin (750â mg every 24â hours); and low (<90%) for vancomycin, amikacin, clindamycin, and linezolid. CONCLUSIONS: Prompt empiric antimicrobial therapy of patients with suspected or confirmed anthrax meningitis may reduce the high morbidity and mortality. Our data support using several ß-lactam-, fluoroquinolone-, and tetracycline-class antimicrobials as first-line and alternative agents for treatment of patients with anthrax meningitis; all should achieve effective microbiologic exposures. Our data suggest antimicrobials that should not be relied on to treat suspected or documented anthrax meningitis. Furthermore, the protein synthesis inhibitors clindamycin and linezolid can decrease toxin production and may be useful components of combination therapy.
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Carbunco , Antibacterianos , Bacillus anthracis , Meningitis Bacterianas , Humanos , Bacillus anthracis/efectos de los fármacos , Carbunco/tratamiento farmacológico , Meningitis Bacterianas/tratamiento farmacológico , Meningitis Bacterianas/microbiología , Meningitis Bacterianas/líquido cefalorraquídeo , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Método de Montecarlo , Pruebas de Sensibilidad MicrobianaRESUMEN
This report updates previous CDC guidelines and recommendations on preferred prevention and treatment regimens regarding naturally occurring anthrax. Also provided are a wide range of alternative regimens to first-line antimicrobial drugs for use if patients have contraindications or intolerances or after a wide-area aerosol release of: Bacillus anthracis spores if resources become limited or a multidrug-resistant B. anthracis strain is used (Hendricks KA, Wright ME, Shadomy SV, et al.; Workgroup on Anthrax Clinical Guidelines. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20:e130687; Meaney-Delman D, Rasmussen SA, Beigi RH, et al. Prophylaxis and treatment of anthrax in pregnant women. Obstet Gynecol 2013;122:885-900; Bradley JS, Peacock G, Krug SE, et al. Pediatric anthrax clinical management. Pediatrics 2014;133:e1411-36). Specifically, this report updates antimicrobial drug and antitoxin use for both postexposure prophylaxis (PEP) and treatment from these previous guidelines best practices and is based on systematic reviews of the literature regarding 1) in vitro antimicrobial drug activity against B. anthracis; 2) in vivo antimicrobial drug efficacy for PEP and treatment; 3) in vivo and human antitoxin efficacy for PEP, treatment, or both; and 4) human survival after antimicrobial drug PEP and treatment of localized anthrax, systemic anthrax, and anthrax meningitis. Changes from previous CDC guidelines and recommendations include an expanded list of alternative antimicrobial drugs to use when first-line antimicrobial drugs are contraindicated or not tolerated or after a bioterrorism event when first-line antimicrobial drugs are depleted or ineffective against a genetically engineered resistant: B. anthracis strain. In addition, these updated guidelines include new recommendations regarding special considerations for the diagnosis and treatment of anthrax meningitis, including comorbid, social, and clinical predictors of anthrax meningitis. The previously published CDC guidelines and recommendations described potentially beneficial critical care measures and clinical assessment tools and procedures for persons with anthrax, which have not changed and are not addressed in this update. In addition, no changes were made to the Advisory Committee on Immunization Practices recommendations for use of anthrax vaccine (Bower WA, Schiffer J, Atmar RL, et al. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices, 2019. MMWR Recomm Rep 2019;68[No. RR-4]:1-14). The updated guidelines in this report can be used by health care providers to prevent and treat anthrax and guide emergency preparedness officials and planners as they develop and update plans for a wide-area aerosol release of B. anthracis.
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Vacunas contra el Carbunco , Carbunco , Antiinfecciosos , Antitoxinas , Bacillus anthracis , Meningitis , Adulto , Humanos , Femenino , Niño , Embarazo , Estados Unidos/epidemiología , Carbunco/diagnóstico , Carbunco/tratamiento farmacológico , Carbunco/prevención & control , Vacunas contra el Carbunco/uso terapéutico , Vacunas contra el Carbunco/efectos adversos , Antiinfecciosos/uso terapéutico , Antitoxinas/farmacología , Antitoxinas/uso terapéutico , Centers for Disease Control and Prevention, U.S. , Aerosoles/farmacología , Aerosoles/uso terapéutico , Meningitis/inducido químicamente , Meningitis/tratamiento farmacológicoRESUMEN
Epidermal growth factor receptor (EGFR)-targeted therapy is used to treat EGFR mutation-induced non-small cell lung cancer (NSCLC). However, its efficacy does not last beyond a certain period due to the development of primary and secondary resistance. First and second-generation inhibitors (e.g., gefitinib, erlotinib, and afatinib) induce EGFR T790M mutations, while third-generation inhibitors (e.g., osimertinib) induce C797S as a major target resistance mutation. Therefore, the C797S mutation is being actively researched. In this study, we investigated the structure-activity relationship of several synthesized compounds as fourth-generation inhibitors against the C797S mutation. We identified a compound 13k that displayed nanomolar potency and high selectivity. Moreover, we used a triple mutant xenograft mouse model to evaluate the in vivo efficacy of 13k in inhibiting EGFR C797S, which demonstrated exceptional profiles and satisfactory EGFR C797S inhibition efficacy. Based on its excellent in vitro and in vivo profiles, compound 13k can be considered a promising candidate for treating EGFR C797S mutations.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Mutación , Neoplasias Pulmonares/metabolismo , Receptores ErbB , Inhibidores de Proteínas Quinasas/farmacología , Resistencia a Antineoplásicos , Compuestos de Anilina/farmacologíaRESUMEN
During the 2022 multinational outbreak of monkeypox virus (MPXV) infection, the antiviral drug tecovirimat (TPOXX; SIGA Technologies, Inc., https://www.siga.com) was deployed in the United States on a large scale for the first time. The MPXV F13L gene homologue encodes the target of tecovirimat, and single amino acid changes in F13 are known to cause resistance to tecovirimat. Genomic sequencing identified 11 mutations previously reported to cause resistance, along with 13 novel mutations. Resistant phenotype was determined using a viral cytopathic effect assay. We tested 124 isolates from 68 patients; 96 isolates from 46 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of tecovirimat treatment, whereas most isolates identified by routine surveillance of patients not treated with tecovirimat remained sensitive. The frequency of resistant viruses remains relatively low (<1%) compared with the total number of patients treated with tecovirimat.
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Mpox , Humanos , Estados Unidos/epidemiología , Antivirales/farmacología , Antivirales/uso terapéutico , Benzamidas/uso terapéutico , Bioensayo , Monkeypox virusRESUMEN
Monkeypox (mpox) is a serious viral zoonosis endemic in west and central Africa. An unprecedented global outbreak was first detected in May 2022. CDC activated its emergency outbreak response on May 23, 2022, and the outbreak was declared a Public Health Emergency of International Concern on July 23, 2022, by the World Health Organization (WHO),* and a U.S. Public Health Emergency on August 4, 2022, by the U.S. Department of Health and Human Services. A U.S. government response was initiated, and CDC coordinated activities with the White House, the U.S. Department of Health and Human Services, and many other federal, state, and local partners. CDC quickly adapted surveillance systems, diagnostic tests, vaccines, therapeutics, grants, and communication systems originally developed for U.S. smallpox preparedness and other infectious diseases to fit the unique needs of the outbreak. In 1 year, more than 30,000 U.S. mpox cases were reported, more than 140,000 specimens were tested, >1.2 million doses of vaccine were administered, and more than 6,900 patients were treated with tecovirimat, an antiviral medication with activity against orthopoxviruses such as Variola virus and Monkeypox virus. Non-Hispanic Black (Black) and Hispanic or Latino (Hispanic) persons represented 33% and 31% of mpox cases, respectively; 87% of 42 fatal cases occurred in Black persons. Sexual contact among gay, bisexual, and other men who have sex with men (MSM) was rapidly identified as the primary risk for infection, resulting in profound changes in our scientific understanding of mpox clinical presentation, pathogenesis, and transmission dynamics. This report provides an overview of the first year of the response to the U.S. mpox outbreak by CDC, reviews lessons learned to improve response and future readiness, and previews continued mpox response and prevention activities as local viral transmission continues in multiple U.S. jurisdictions (Figure).
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Mpox , Minorías Sexuales y de Género , Masculino , Humanos , Estados Unidos/epidemiología , Homosexualidad Masculina , Mpox/epidemiología , Brotes de Enfermedades/prevención & control , Centers for Disease Control and Prevention, U.S.RESUMEN
Monkeypox (mpox) is a disease caused by infection with Monkeypox virus (MPXV), an Orthopoxvirus (OPXV) in the same genus as Variola virus, which causes smallpox. During 2022, a global outbreak involving mpox clade IIb was recognized, primarily among gay, bisexual, and other men who have sex with men.* Most affected patients have been immunocompetent and experienced ≤10 rash lesions (1). CDC has recommended supportive care including pain control. However, some patients have experienced severe mpox manifestations, including ocular lesions, neurologic complications, myopericarditis, complications associated with mucosal (oral, rectal, genital, and urethral) lesions, and uncontrolled viral spread due to moderate or severe immunocompromise, particularly advanced HIV infection (2). Therapeutic medical countermeasures (MCMs) are Food and Drug Administration (FDA)-regulated drugs and biologics that are predominantly stockpiled by the U.S. government; MCMs developed for smallpox preparedness or shown to be effective against other OPXVs (i.e., tecovirimat, brincidofovir, cidofovir, trifluridine ophthalmic solution, and vaccinia immune globulin intravenous [VIGIV]) have been used to treat severe mpox. During May 2022-January 2023, CDC provided more than 250 U.S. mpox consultations. This report synthesizes data from animal models, MCM use for human cases of related OPXV, unpublished data, input from clinician experts, and experience during consultations (including follow-up) to provide interim clinical treatment considerations. Randomized controlled trials and other carefully controlled research studies are needed to evaluate the effectiveness of MCMs for treating human mpox. Until data gaps are filled, the information presented in this report represents the best available information concerning the effective use of MCMs and should be used to guide decisions about MCM use for mpox patients.
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Infecciones por VIH , Mpox , Minorías Sexuales y de Género , Viruela , Animales , Masculino , Humanos , Homosexualidad MasculinaRESUMEN
Brain metastasis is a common complication in melanoma patients with BRAF and NRAS mutations and has a poor prognosis. Although BRAF inhibitors are clinically approved, their poor brain penetration limits their efficacy in brain metastasis. Thus, melanoma brain metastasis still requires better treatment. Belvarafenib, a pan-RAF inhibitor, has reported antitumor activity in melanoma with RAF and RAS mutations in animal models and patients. However, brain permeability and antitumor efficacy on brain metastasis have not been determined. This study confirmed the brain penetration of belvarafenib, the antitumor activity on BRAF and NRAS mutant melanoma, and the efficacy on melanoma within the brain. Belvarafenib strongly suppressed melanoma in BRAF V600E mutant A375SM tumor-bearing mice. It also significantly inhibited tumor growth in NRAS mutant SK-MEL-30 and K1735 tumor-bearing mice and synergized to enhance the antitumor activity combined with cobimetinib or atezolizumab. Belvarafenib was penetrated at considerable levels into the brains of mice and rats following oral administration. The exposure of belvarafenib in the brain was similar to or higher than that in plasma, and this high brain penetration differed significantly from that of other BRAF inhibitors with low brain penetration. Most importantly, belvarafenib strongly reduced tumor burden and markedly improved survival benefits in mice intracranially implanted with A375SM melanoma. These results demonstrated that belvarafenib, which has favorable BBB permeability, and potent antitumor activity on the tumors with BRAF/NRAS mutations, may be a promising therapeutic option for patients with BRAF/NRAS mutant melanoma brain metastasis.
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Neoplasias Encefálicas , Melanoma , Neoplasias Cutáneas , Ratones , Ratas , Animales , Proteínas Proto-Oncogénicas B-raf/genética , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Mutación , Línea Celular Tumoral , Neoplasias Cutáneas/patologíaRESUMEN
JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) is recommended in the United States for persons exposed to or at high risk for exposure to Monkeypox virus during the 2022 monkeypox (mpox) outbreak (1). JYNNEOS is a live, nonreplicating viral vaccine licensed for the prevention of smallpox and mpox in adults aged ≥18 years, administered as a 0.5-mL 2-dose series given 28 days apart by subcutaneous injection (2). On August 9, 2022, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for administration of 0.1 mL doses by intradermal injection for adults aged ≥18 years as a strategy to increase vaccine supply, and administration of 0.5 mL doses subcutaneously for persons aged <18 years (3). During May 22-October 21, 2022, a total of 987,294 JYNNEOS vaccine doses were administered in the United States. CDC has monitored JYNNEOS vaccine safety using the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for vaccine recipients of all ages, and through single-patient emergency Investigational New Drug (EIND) procedures for persons aged <18 years vaccinated before August 9, 2022. The most common adverse health events reported to VAERS for adults were nonserious and included injection site reactions, which was consistent with the prelicensure studies. Adverse health events were reported at similar rates for doses received by intradermal and subcutaneous administration. Serious adverse events were rare in adults, and no serious adverse events have been identified among persons aged <18 years. Overall, postlicensure and postauthorization surveillance to date support JYNNEOS vaccine safety.
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Mpox , Vacuna contra Viruela , Adulto , Humanos , Mpox/prevención & control , Vacuna contra Viruela/administración & dosificación , Vacuna contra Viruela/efectos adversos , Vigilancia de Productos ComercializadosRESUMEN
As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.§ Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox¶ during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.§§ Engaging all persons with HIV in sustained care remains a critical public health priority.
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Infecciones por VIH , Mpox , Minorías Sexuales y de Género , Estados Unidos/epidemiología , Humanos , Masculino , Adolescente , Adulto , Femenino , Infecciones por VIH/diagnóstico , Homosexualidad Masculina , Etnicidad , Vigilancia de la Población , Grupos Minoritarios , Mpox/epidemiologíaRESUMEN
Currently, no Food and Drug Administration (FDA)-approved treatments for human monkeypox are available. Tecovirimat (Tpoxx), however, is an antiviral drug that has demonstrated efficacy in animal studies and is FDA-approved for treating smallpox. Use of tecovirimat for treatment of monkeypox in the United States is permitted only through an FDA-regulated Expanded Access Investigational New Drug (EA-IND) mechanism. CDC holds a nonresearch EA-IND protocol that facilitates access to and use of tecovirimat for treatment of monkeypox.§ The protocol includes patient treatment and adverse event reporting forms to monitor safety and ensure intended clinical use in accordance with FDA EA-IND requirements. The current multinational monkeypox outbreak, first detected in a country where Monkeypox virus infection is not endemic in May 2022, has predominantly affected gay, bisexual, and other men who have sex with men (MSM) (1,2). To describe characteristics of persons treated with tecovirimat for Monkeypox virus infection, demographic and clinical data abstracted from available tecovirimat EA-IND treatment forms were analyzed. As of August 20, 2022, intake and outcome forms were available for 549 and 369 patients, respectively; 97.7% of patients were men, with a median age of 36.5 years. Among patients with available data, 38.8% were reported to be non-Hispanic White (White) persons, 99.8% were prescribed oral tecovirimat, and 93.1% were not hospitalized. Approximately one half of patients with Monkeypox virus infection who received tecovirimat were living with HIV infection. The median interval from initiation of tecovirimat to subjective improvement was 3 days and did not differ by HIV infection status. Adverse events were reported in 3.5% of patients; all but one adverse event were nonserious. These data support the continued access to and treatment with tecovirimat for patients with or at risk for severe disease in the ongoing monkeypox outbreak.
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Infecciones por VIH , Mpox , Minorías Sexuales y de Género , Adulto , Animales , Antivirales/uso terapéutico , Drogas en Investigación/uso terapéutico , Femenino , Infecciones por VIH/tratamiento farmacológico , Homosexualidad Masculina , Humanos , Masculino , Mpox/tratamiento farmacológico , Mpox/epidemiología , Monkeypox virus , Estados UnidosRESUMEN
Monkeypox is a rare, sometimes life-threatening zoonotic infection that occurs in west and central Africa. It is caused by Monkeypox virus, an orthopoxvirus similar to Variola virus (the causative agent of smallpox) and Vaccinia virus (the live virus component of orthopoxvirus vaccines) and can spread to humans. After 39 years without detection of human disease in Nigeria, an outbreak involving 118 confirmed cases was identified during 2017-2018 (1); sporadic cases continue to occur. During September 2018-May 2021, six unrelated persons traveling from Nigeria received diagnoses of monkeypox in non-African countries: four in the United Kingdom and one each in Israel and Singapore. In July 2021, a man who traveled from Lagos, Nigeria, to Dallas, Texas, became the seventh traveler to a non-African country with diagnosed monkeypox. Among 194 monitored contacts, 144 (74%) were flight contacts. The patient received tecovirimat, an antiviral for treatment of orthopoxvirus infections, and his home required large-scale decontamination. Whole genome sequencing showed that the virus was consistent with a strain of Monkeypox virus known to circulate in Nigeria, but the specific source of the patient's infection was not identified. No epidemiologically linked cases were reported in Nigeria; no contact received postexposure prophylaxis (PEP) with the orthopoxvirus vaccine ACAM2000.
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Mpox , Humanos , Masculino , Mpox/diagnóstico , Mpox/epidemiología , Mpox/prevención & control , Monkeypox virus/genética , Nigeria/epidemiología , Texas/epidemiologíaRESUMEN
BACKGROUND/AIM: Using a rat model of collagen-induced arthritis (CIA), we evaluated the therapeutic effects of HM71224 (BTKi), as well as the drug-drug interactions in combined therapy with methotrexate (MTX) based on both drugs' pharmacological role in immune regulation and antiinflammation. MATERIALS AND METHODS: Arthritis in rats was induced using type II collagen and incomplete Freund's adjuvant. The therapeutic effects of HM71224 (alone or in combination with MTX) were evaluated by arthritis score, paw volume, body weight, and histopathological examination (H&E and Safranin-O staining). The drug-drug interactions between HM71224 and MTX were investigated by measuring plasma, liver enzyme and creatinine levels and blood cell counts. RESULTS: HM71224 reduced the clinical signs of arthritis, paw volume, and body weight loss in CIA rats. ED50 and ED90 were 1.0 and 2.5 mg/kg, respectively. HM71224 combined with MTX decreased the arthritis score, bone erosion, synovitis, and cartilage degradation without apparent interaction. CONCLUSION: The combination of HM71224 and MTX improved the therapeutic effect with no drug-drug interactions in RA.
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Artritis Experimental , Metotrexato , Animales , Antiinflamatorios/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Quimioterapia Combinada , Metotrexato/farmacología , Metotrexato/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , RatasRESUMEN
This report summarizes the recommendations of the Advisory Committee on Immunization Practices (ACIP) for use of the rVSVΔG-ZEBOV-GP Ebola vaccine (Ervebo) in the United States. The vaccine contains rice-derived recombinant human serum albumin and live attenuated recombinant vesicular stomatitis virus (VSV) in which the gene encoding the glycoprotein of VSV was replaced with the gene encoding the glycoprotein of Ebola virus species Zaire ebolavirus. Persons with a history of severe allergic reaction (e.g., anaphylaxis) to rice protein should not receive Ervebo. This is the first and only vaccine currently licensed by the Food and Drug Administration for the prevention of Ebola virus disease (EVD). These guidelines will be updated based on availability of new data or as new vaccines are licensed to protect against EVD.ACIP recommends preexposure vaccination with Ervebo for adults aged ≥18 years in the U.S. population who are at highest risk for potential occupational exposure to Ebola virus species Zaire ebolavirus because they are responding to an outbreak of EVD, work as health care personnel at federally designated Ebola treatment centers in the United States, or work as laboratorians or other staff at biosafety level 4 facilities in the United States. Recommendations for use of Ervebo in additional populations at risk for exposure and other settings will be considered and discussed by ACIP in the future.
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Vacunas contra el Virus del Ébola/administración & dosificación , Fiebre Hemorrágica Ebola/prevención & control , Adulto , Comités Consultivos , Fiebre Hemorrágica Ebola/epidemiología , Humanos , Estados Unidos/epidemiología , United States Food and Drug AdministrationRESUMEN
Eflapegrastim (Rolontis) is a long-acting granulocyte colony-stimulating factor (G-CSF) with an IgG4 Fc fragment and short polyethylene glycol linker. Current G-CSF products are administered 24 hours after chemotherapy. The present study compares the duration of neutropenia (DN) with eflapegrastim or pegfilgrastim at 0, 2, 5, or 24 hours post chemotherapy. Eflapegrastim was evaluated by G-CSF receptor binding and bone marrow cell proliferation assays in vitro. Eflapegrastim-Fc component binding to Fcγ receptors C1q and FcRn was assessed by enzyme-linked immunosorbent assay. Neutropenia was induced in rats via intraperitoneal cyclophosphamide or docetaxel/cyclophosphamide. Rats received chemotherapy followed by vehicle, pegfilgrastim, or eflapegrastim at 2, 5, or 24 hours. The difference in DN after treatment was assessed. In vitro binding to G-CSF receptor of both agents was similar. Binding to FcRn and no binding to Fcγ receptors or C1q were observed with eflapegrastim. Studies in chemotherapy-induced neutropenic rats revealed shorter DN with eflapegrastim versus pegfilgrastim. Increased levels of G-CSF in serum and marrow were observed in groups treated with eflapegrastim versus those treated with pegfilgrastim. Although eflapegrastim and pegfilgrastim have similar in vitro binding affinity, the Fc fragment in eflapegrastim increases the uptake into bone marrow, resulting in increased therapeutic potential for chemotherapy-induced neutropenia. Eflapegrastim's greater marrow resident time provided a pharmacodynamic advantage over pegfilgrastim, translating into shortened duration of neutropenia. Our findings support eflapegrastim same-day administration with chemotherapy, warranting further evaluation in patients undergoing myelosuppressive chemotherapy.
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Filgrastim , Neutropenia/sangre , Neutropenia/tratamiento farmacológico , Polietilenglicoles , Animales , Ciclofosfamida/efectos adversos , Ciclofosfamida/farmacología , Docetaxel/efectos adversos , Docetaxel/farmacología , Filgrastim/farmacocinética , Filgrastim/farmacología , Antígenos de Histocompatibilidad Clase I/sangre , Humanos , Masculino , Ratones , Neutropenia/inducido químicamente , Neutropenia/patología , Polietilenglicoles/farmacocinética , Polietilenglicoles/farmacología , Ratas , Ratas Sprague-Dawley , Receptores Fc/sangre , Células U937RESUMEN
In the 1930s, Stalin established Pavlovian theory as a socialist medical theory, criticized bourgeois science and ideology, and consolidated his dictatorship. Stalin used Pavlov's theory to emphasize the interaction between man and environment and the inheritance of acquired characteristics, trying to ensure the legitimacy of the socialist system reform in politics and society. Therefore, if the Soviet scientists and doctors did not conform to Pavlov's theory, their research would be strictly controlled, making free and creative research impossible. In the 1950s, China and North Korea, which accepted the socialist political model of the Soviet Union, also had this dogmatic tendency. In 1950, China signed the "The Sino-Soviet Treaty of Friendship," initiated the movement of learning from the Soviet Union in politics, economy, society, education, law, science, medical care, and other aspects, and established a socialist country based on the Soviet model. In Chinese medical circles, through the "Pavlov Learning Movement," they accepted the health care system and medical technology of the Soviet Union without any criticism, and carried out the ideological transformation of intellectuals to wipe out the influence of western capitalism. Moreover, Virchow's 'Cellular Pathology' and Mendel's 'Genetics' were denounced as reactionary bourgeoisie theory, and Pavlov's theory became a socialist medical theory based on dialectical materialism. As a result, the Communist Party of China reorganized the medical and scientific knowledge system based on Pavlov's theory, and took it as an important ideological tool to establish the socialist medical system. In the 1950s, Chinese medical workers strengthened ideological education through the "Pavlov's learning movement," applied this theory to clinical practice, and implemented new treatment methods such as "Sleep Therapy" and "PPM(Psychoprophylactic Painless childbirth Method)." In addition, hospitals implemented the "Protective Medical System" and established the socialist medical system. The goal of the protective medical system was to eliminate the negative stimulation which has adverse effects on the treatment of patients and to establish a patient-centered medical system. Therefore, the hospital launched a comprehensive effort to create a clean environment, eliminate all kinds of noise, cultivate a friendly working attitude, and improve nutrition. As a result, the hospital environment and the working attitude of medical staff improved and the treatment rate of diseases also improved, while the mortality rate of patients decreased. At the same time, with the strengthening of political education for doctors, nurses and patients in hospitals, hospitals have become places to educate socialist laws and ideology. In addition, in order to prove the superiority of Pavlov's theory, medical workers carried out unscientific sleep therapy on patients, so people's body became an experimental space for of socialism. Moreover, in the implementation of PPM, women could not tell the pain of childbirth, but under medical control, they were in a contradictory situation of enduring labor pain. The Communist Party of China has established its national identity by promoting its image of "rescuer", which liberates the patients from the pain of disease, and the "welfare" image of taking good care of the people's body. The Communist Party of China has reconstructed the metaphors of "sickness" and "labor pain", making it an indispensable medium for the concepts of socialism, women's Liberation and medical welfare to be engraved on the people's body. Therefore, through the clinical practice of sleep therapy and PPM, we can understand how the Communist Party of China controlled the people's body, and such policies and systems demonstrate the "medical" governance mode of socialist control over the people.
Asunto(s)
Comunismo , Socialismo , China , Femenino , Humanos , Dolor , Sistemas Políticos , Política , EmbarazoRESUMEN
BACKGROUND: The safety profile of antimicrobials used during pregnancy is one important consideration in the decision on how to treat and provide postexposure prophylaxis (PEP) for plague during pregnancy. METHODS: We searched 5 scientific literature databases for primary sources on the safety of 9 antimicrobials considered for plague during pregnancy (amikacin, gentamicin, plazomicin, streptomycin, tobramycin, chloramphenicol, doxycycline, sulfadiazine, and trimethoprim-sulfamethoxazole [TMP-SMX]) and abstracted data on maternal, pregnancy, and fetal/neonatal outcomes. RESULTS: Of 13â 052 articles identified, 66 studies (case-control, case series, cohort, and randomized studies) and 96 case reports were included, totaling 27â 751 prenatal exposures to amikacin (nâ =â 9), gentamicin (nâ =â 345), plazomicin (nâ =â 0), streptomycin (nâ =â 285), tobramycin (nâ =â 43), chloramphenicol (nâ =â 246), doxycycline (nâ =â 2351), sulfadiazine (nâ =â 870), and TMP-SMX (nâ =â 23â 602). Hearing or vestibular deficits were reported in 18/121 (15%) children and 17/109 (16%) pregnant women following prenatal streptomycin exposure. First trimester chloramphenicol exposure was associated with an elevated risk of an undescended testis (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2-28.7). Doxycycline was associated with cardiovascular malformations (OR 2.4, 95% CI 1.2-4.7) in 1 study and spontaneous abortion (OR 2.8, 95% CI 1.9-4.1) in a separate study. First trimester exposure to TMP-SMX was associated with increased risk of neural tube defects (pooled OR 2.5, 95% CI 1.4-4.3), spontaneous abortion (OR 3.5, 95% CI 2.3-5.6), preterm birth (OR 1.5, 95% CI 1.1-2.1), and small for gestational age (OR 1.6, 95% CI 1.2-2.2). No other statistically significant associations were reported. CONCLUSIONS: For most antimicrobials reviewed, adverse maternal/fetal/neonatal outcomes were not observed consistently. Prenatal exposure to streptomycin and TMP-SMX was associated with select birth defects in some studies. Based on limited data, chloramphenicol and doxycycline may be associated with adverse pregnancy or neonatal outcomes; however, more data are needed to confirm these associations. Antimicrobials should be used for treatment and PEP of plague during pregnancy; the choice of antimicrobials may be influenced by these data as well as information about the risks of plague during pregnancy.
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Aborto Espontáneo , Antiinfecciosos , Peste , Nacimiento Prematuro , Niño , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Combinación Trimetoprim y Sulfametoxazol/efectos adversosRESUMEN
This report updates the 2009 recommendations from the CDC Advisory Committee on Immunization Practices (ACIP) regarding use of anthrax vaccine in the United States (Wright JG, Quinn CP, Shadomy S, Messonnier N. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices [ACIP)], 2009. MMWR Recomm Rep 2010;59[No. RR-6]). The report 1) summarizes data on estimated efficacy in humans using a correlates of protection model and safety data published since the last ACIP review, 2) provides updated guidance for use of anthrax vaccine adsorbed (AVA) for preexposure prophylaxis (PrEP) and in conjunction with antimicrobials for postexposure prophylaxis (PEP), 3) provides updated guidance regarding PrEP vaccination of emergency and other responders, 4) summarizes the available data on an investigational anthrax vaccine (AV7909), and 5) discusses the use of anthrax antitoxins for PEP. Changes from previous guidance in this report include the following: 1) a booster dose of AVA for PrEP can be given every 3 years instead of annually to persons not at high risk for exposure to Bacillus anthracis who have previously received the initial AVA 3-dose priming and 2-dose booster series and want to maintain protection; 2) during a large-scale emergency response, AVA for PEP can be administered using an intramuscular route if the subcutaneous route of administration poses significant materiel, personnel, or clinical challenges that might delay or preclude vaccination; 3) recommendations on dose-sparing AVA PEP regimens if the anthrax vaccine supply is insufficient to vaccinate all potentially exposed persons; and 4) clarification on the duration of antimicrobial therapy when used in conjunction with vaccine for PEP.These updated recommendations can be used by health care providers and guide emergency preparedness officials and planners who are developing plans to provide anthrax vaccine, including preparations for a wide-area aerosol release of B. anthracis spores. The recommendations also provide guidance on dose-sparing options, if needed, to extend the supply of vaccine to increase the number of persons receiving PEP in a mass casualty event.