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1.
Ann Med Surg (Lond) ; 86(2): 1101-1105, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38333298

RESUMO

Introduction and importance: Epidermodysplasia verruciformis is a rare autosomal recessive genodermatosis. Clinical manifestations might be helpful in the diagnosis of this disease. However, the final diagnosis is made after a genetic and histological study. Acquired epidermodysplasia verruciformis is a form of epidermodysplasia verruciformis described in patients with compromised cell-mediated immunity. Case presentation: A 42-year-old female with a history of a pain and itch on the soles and palms started a year ago. There were multiple flat papules on the dorsal hands, scarring alopecia, malar rash, oral ulcers, Raynaud phenomenon, and palpable purpura. A histological examination confirmed the diagnosis of epidermodysplasia verruciformis. Clinical discussion: Epidermodysplasia verruciformis is an uncommon disease that affects the immune system. The coexistence of systemic lupus erythematosus and epidermodysplasia verruciformis is rarely reported in the medical literature. This paper reports a rare case in which these two diseases have coexisted. Conclusion: This publication aims to document this rare case and highlight the ideal criteria in diagnosing and treating epidermodysplasia verruciformis.

2.
Glob J Qual Saf Healthc ; 7(1): 22-27, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38406656

RESUMO

Introduction: Venous thromboembolism (VTE) prevention and management are susceptible issues that require specific rules to sustain and oversee their functioning, as preventing VTE is a vital patient safety priority. This paper aims to investigate and provide recommendations for VTE assessment and reassessment through policy enhancement and development. Methods: We reviewed different papers and policies to propose recommendations and theme analysis for policy modifications and enhancements to improve VTE prophylaxis and management. Results: Recommendations were set to enhance the overall work of VTE prophylaxis, where the current VTE protocols and policies must ensure high levels of patient safety and satisfaction. The recommendations included working through a well-organized multidisciplinary team and staff engagement to support and enhance VTE's work. Nurses', pharmacists', and physical therapists' involvement in setting up the plan and prevention is the way to share the knowledge and paradigm of experience to standardize the management. Promoting policies regarding VTE prophylaxis assessment and reassessment using electronic modules as a part of the digital health process was proposed. A deep understanding of the underlying issues and the incorporation of generic policy recommendations were set. Conclusion: This article presents recommendations for stakeholders, social media platforms, and healthcare practitioners to enhance VTE prophylaxis and management.

3.
Ann Med Surg (Lond) ; 86(1): 489-496, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38222680

RESUMO

Introduction and importance: Edward syndrome is a severe chromosomal defect that occurs as a result of non-disjunction through meiosis. It presents with cardiac septal defects, horseshoe kidneys, patent ductus arteriosus, central nervous system dysgenesis, distinctive craniofacial deformities, and overriding or overlapping fingers. Klinefelter syndrome (47, XXY) is found in 1 in 660 newborn males. It is considered to be one of the most common genetic causes of infertility. It manifests with small firm testes, androgen insufficiency, and azoospermia. Case presentation: A 2-month-old male infant with a history of weakness in feeding, frequent convulsions, and an increase in cyanosis two days ago. There were multiple skeletal deformities and a tendency to spasm in the extremities, left ventricular atrophy, mitral atresia, atrial septal defect, ventricular septal defect with dilated right cavities, tricuspid valve regurgitation, pulmonary valve stenosis; and the aorta exits in the right ventricle. There is a widening of the subdural space, which was observed in the left frontal-parietal side with cortical atrophy in that area and a widening of the Sylvian fissure. A karyotype test confirmed the presence of Edward and Klinefelter syndromes. Clinical discussion: Aneuploidy is a chromosomal issue characterized by an abnormal number of a chromosome copies. The coexistence of two aneuploidies is called "double aneuploidy" which is a rare occurrence. Herein, we report a case of a 2-month-old male with Edward syndrome and Klinefelter syndrome. Conclusion: This publication aims to highlight the challenges in diagnosing and treating a complicated genetic disease.

4.
Scand J Clin Lab Invest ; 83(8): 533-539, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38145316

RESUMO

Vitamin B12 deficiency and insufficiency can lead to both hematological and neurological impairments. This review examines nondisease causes and risk factors associated with dietary availability, such as eating habits, food processing, cooking techniques, and bioavailability, as well as increased physiological needs and iatrogenic factors linked to medication use or surgical procedures. As a result of these nondisease influences, groups at higher risk include vegans, vegetarians, older adults, individuals with limited diets, breastfed and preterm infants, and those who primarily consume foods prepared or cooked in ways that reduce vitamin B12 content, as well as individuals on certain medications or who have undergone specific surgeries. Recognizing these diverse risk factors helps develop strategies for prevention and intervention to minimize the adverse health effects related to B12 deficiency and insufficiency.


Assuntos
Deficiência de Vitamina B 12 , Vitamina B 12 , Recém-Nascido , Lactente , Humanos , Idoso , Dieta Vegetariana/efeitos adversos , Recém-Nascido Prematuro , Deficiência de Vitamina B 12/tratamento farmacológico , Deficiência de Vitamina B 12/etiologia , Fatores de Risco
5.
Clin Case Rep ; 11(11): e8255, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38028100

RESUMO

Key Clinical Message: Ectopic pituitary adenoma is a rare neoplasm located in the clivus and could mimic other clival tumors. Diagnosis and treatment could be challenging. It should be considered in the differential diagnosis of clival tumors. Abstract: Ectopic pituitary adenomas (EPAs) are isolated adenomas that can be located in variable locations outside the sella turcica and have a normal-appearing pituitary gland. These tumors are rare and are thought to often arise from embryological remnants along the route of Rathke's pouch migration. EPAs are associated with a wide range of clinical manifestations depending on hormonal activity and involvement of adjacent structures, which can represent a challenge in making the diagnosis and deciding on the most appropriate management. In this case study, we report a 47-year-old male who presented with visual disturbances, a headache, and generalized weakness. Magnetic resonance imaging showed a 2 cm mass located in the clivus invading the sphenoid sinus with an intact pituitary gland. The patient underwent endoscopic transsphenoidal surgery to eradicate the mass while maintaining the integrity of the pituitary gland, which was successful and uneventful. Pathological studies were consistent with prolactinoma, with no cytological malignant features. Post-surgery, symptoms notably improved, and serum prolactin levels significantly dropped, The patient's condition was satisfactory on follow-up with no long-term complications reported. This paper contributes to the existing literature by sharing the clinical management of a challenging and uncommon case.

6.
Ann Med Surg (Lond) ; 85(10): 5138-5144, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37811111

RESUMO

Background: Ectopic breast tissue (EBT) is normally found along the rudimentary mammary line, which is located from the axilla to the inguinal region and disappears during embryogenesis. Up to 6% of females around the world suffer from EBT. EBT cancer is rare, with only a few reports in the literature. The diagnosis, and treatment of these rare cases can be very difficult and complex. Case presentation: The authors report an interesting case of a 74-year-old female patient with a vulvar lump located on the mons pubis associated with ulceration, pain, and size increase. The histopathological study demonstrated an invasive ductal carcinoma grade 2 arising from EBT in the vulva. Within 4 months of follow-up, the patient's condition was stable. Clinical discussion and conclusions: Throughout this paper, the authors aim to highlight the diagnostic and therapeutic challenges since there are no current guidelines for treatment for such cases. Furthermore, this article describes this rare disease and includes surgical details, difficulties, diagnostic methods, and treatment options.

7.
ANS Adv Nurs Sci ; 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37655963

RESUMO

Arguably, the quest for a central, unifying paradigm in nursing has distracted from moving disciplinary knowledge forward in an accessible, meaningful manner. In this discursive philosophical article, we uphold that multiparadigmatic research teams and diverse approaches inform effective nursing praxis. We provide an overview of our worldviews (dialectical pluralism, critical realism, humanism, and pragmatism) and their philosophical assumptions and describe how they are commensurate with nursing. We present the Stadium Model in Nursing as a metaphor to illustrate how various worldviews function like different sections of a stadium to offer diverse, yet important vantages of our nursing phenomena of interest.

8.
J Chromatogr Sci ; 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37622601

RESUMO

N-nitrosamine pollutants are probable carcinogens. Regulatory agencies declared their presence in the drugs unsafe for human consumption and demanded their recall. Using ultra-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (UPLC-APCI-MS/MS) in tablet dosage form based on International Conference on Harmonization (ICH) tripartite guideline criteria, we aim to develop and test a new approach for identifying and validating nitrosamine-contaminants, N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) in irbesartan, olmesartan and metformin. The column was Phenomenex Luna-C18, 100 × 3.0 mm and 3.0 µm. A mobile gradient phase of formic acid in either water or methanol separated the impurities. NDMA and NDEA had retention times of 0.85 and 2.55 min, respectively. The detector's linearity was established at concentrations ranging from 0.6 to 100 ng/mL. R2 for NDMA and NDEA were 0.9996 and 0.9998, respectively, with a linear response function established at 0.6-100 ng/mL. Limit of detection and limit of quantification for NDMA and NDEA were 0.35, 0.29 and 0.55, 0.37 ng/mL, respectively. On average, recovery rates for NDMA and NDEA ranged from 96.0 to 98.4 and 96.2 to 98.0%, respectively. The relative standard deviation for NDMA and NDEA was 3.46 and 2.69, respectively. According to the ICH guidelines, the developed method was quick, sensitive and valid. The pharmaceutical formulations of irbesartan, olmesartan and metformin may be regularly examined using the approach provided here.

9.
Saudi J Gastroenterol ; 29(4): 251-255, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37282448

RESUMO

Background: Inflammatory bowel disease (IBD) patients are at increased risk of Clostridium difficile infection (CDI), causing significant morbidity and mortality. This study examined CDI's prevalence, predisposing factors, and clinical outcomes in Saudi hospitalized IBD patients. Methods: : A retrospective case-control study was conducted at a tertiary medical city in Riyadh, Saudi Arabia. All Saudi adult patients with IBD, admitted over the preceding four years were identified from the hospital's database. Eligible patients were divided into those with CDI and those without CDI. Binary logistic regression was used to determine the predisposing factors for CDI among admitted IBD patients. Results: During the study period, 95 patients were admitted with IBD. Crohn's disease (CD) was the predominant type (71.6%), whereas 28.4% of the patients were with ulcerative colitis (UC). Only 16 (16.8%) patients had positive CDI. CDI-positive patients tend to have hypertension and previous use of steroids. Patients with UC tend to have a higher risk of CDI than those with CD. Most patients recovered from the CDI (81.3%) with a median time to CDI clearance of 14 days. Three patients (18.8%) had recurrent CDI; among them, one died. Conclusion: The prevalence of CDI in Saudi IBD patients is similar to that reported elsewhere. UC, steroid treatment, and hypertension are risk factors for CDI in IBD patients. Recurrence of CDI in IBD patients is common and associated with a poor prognosis.


Assuntos
Infecções por Clostridium , Colite Ulcerativa , Doença de Crohn , Hipertensão , Doenças Inflamatórias Intestinais , Adulto , Humanos , Estudos de Casos e Controles , Estudos Retrospectivos , Prevalência , Arábia Saudita/epidemiologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Colite Ulcerativa/complicações , Doença de Crohn/epidemiologia , Fatores de Risco , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/complicações , Hipertensão/complicações
10.
East Mediterr Health J ; 29(3): 217-223, 2023 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-36987628

RESUMO

Background: The COVID-19 pandemic spread rapidly globally, making the WHO to declare it a public health emergency of international concern. The ability of health institutions to screen and test for COVID-19 has been critical in detecting, preventing, and managing the spread of the disease. Aims: This report documents lessons from the ambulatory care nursing for COVID-19 contact tracing at a tertiary care hospital. Methods: In March 2020, a multidisciplinary team consisting of staff of the Primary Healthcare Services, Ambulatory Care Center, Infection Prevention and Control Department, and Nursing Services at the Ministry of National Guard Health Affairs in Riyadh, Saudi Arabia, worked collaboratively to establish 2 dedicated COVID-19 contact tracing clinics away from hospital premises, one clinic established for the public and another for hospital staff. Surveillance system was established to detect and contain as many cases as possible. This report highlights the process of establishing and maintaining the structure and managing workflow of the contact tracing clinics. We calculated the number of nasopharyngeal swabs and the daily average number of patient visits for both clinics between March 2020 and March 2021. Results: Over the one-year period, the clinics served 79 146 visitors with an average of 52 visits for staff, 159 visits for adults, and 16 visits for children per day. The 2 clinics conducted 73 924 polymerase chain reaction tests. There was zero transmission of COVID-19 infection to staff working at both clinics. Conclusion: Despite the challenge of setting up contact tracing clinics, the decision to use separate geographic locations contributed to reducing the risk of infection exposure among staff of the clinics. Effective implementation of contact tracing interventions relies on interdepartmental cooperation and effective communication to contain the risk of viral spread.


Assuntos
COVID-19 , Enfermeiras e Enfermeiros , Adulto , Criança , Humanos , Busca de Comunicante , Pandemias/prevenção & controle , Centros de Atenção Terciária
11.
Influenza Other Respir Viruses ; 17(3): e13116, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36960162

RESUMO

Background: Type I interferons (IFNs) are essential antiviral cytokines induced upon respiratory exposure to coronaviruses. Defects in type I IFN signaling can result in severe disease upon exposure to respiratory viral infection and are associated with worse clinical outcomes. Neutralizing autoantibodies (auto-Abs) to type I IFNs were reported as a risk factor for life-threatening COVID-19, but their presence has not been evaluated in patients with severe Middle East respiratory syndrome (MERS). Methods: We evaluated the prevalence of type I IFN auto-Abs in a cohort of hospitalized patients with MERS who were enrolled in a placebo-controlled clinical trial for treatment with IFN-ß1b and lopinavir-ritonavir (MIRACLE trial). Samples were tested for type I IFN auto-Abs using a multiplex particle-based assay. Results: Among the 62 enrolled patients, 15 (24.2%) were positive for immunoglobulin G auto-Abs for at least one subtype of type I IFNs. Auto-Abs positive patients were not different from auto-Abs negative patients in age, sex, or comorbidities. However, the majority (93.3%) of patients who were auto-Abs positive were critically ill and admitted to the ICU at the time of enrollment compared to 66% in the auto-Abs negative patients. The effect of treatment with IFN-ß1b and lopinavir-ritonavir did not significantly differ between the two groups. Conclusion: This study demonstrates the presence of type I IFN auto-Abs in hospitalized patients with MERS.


Assuntos
COVID-19 , Interferon Tipo I , Humanos , Ritonavir/uso terapêutico , Lopinavir/uso terapêutico , Interferon beta-1b/uso terapêutico , Autoanticorpos
12.
J Biomol Struct Dyn ; 41(8): 3222-3233, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35261335

RESUMO

Many missense mutations/SNPs of the TCN2 gene (which yield Transcobalamin (TC)) were reported in the literature but no study is available about their effect on binding to vitamin B12(B12) at the structural level experimentally nor computationally. Predict the effect of TC missense mutations/SNPs on binding affinity to B12 and characterize their contacts to B12 at the structural level. TC-B12 binding energy difference from the wildtype (ΔΔGmut) was calculated for 378 alanine scanning mutations and 76 ClinVar missense mutations, repeated on two distinct X-ray structures of holoTC namely 2BB5 and 4ZRP. Destabilizing mutations then went through 100 ns molecular dynamics simulation to study their effect on TC-B12 binding at the structural level employing 2BB5 structure. Out of the studied 454 mutations (378 alanine mutations + 76 ClinVar mutations), 19 were destabilizing representing 17 amino acid locations. Mutation energy results show a neutral effect on B12 binding of several missense SNPs reported in the literature including I23V, G94S, R215W, P259R, S348F, L376S, and R399Q. Compared to the wildtype, all the destabilizing mutations have higher average RMSD-Ligand in the last 25% of the MD simulation trajectories and lower average hydrogen bond count while the other parameters vary. Previously reported TCN2 SNPs with an unknown effect on TC-B12 binding were found to have a neutral effect in the current study based on mutation energy calculations. Also, we reported 17 possible amino acids that destabilize TC-B12 binding upon mutation (four listed in ClinVar) and studied their structural effect computationally.


Assuntos
Polimorfismo de Nucleotídeo Único , Transcobalaminas , Humanos , Transcobalaminas/genética , Transcobalaminas/metabolismo , Mutação de Sentido Incorreto , Alanina/genética , Vitamina B 12/química , Vitamina B 12/metabolismo , Aminoácidos/genética
13.
Sci Rep ; 12(1): 18186, 2022 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-36307462

RESUMO

Animal and human data indicate variable effects of interferons in treating coronavirus infections according to inflammatory status and timing of therapy. In this sub-study of the MIRACLE trial (MERS-CoV Infection Treated with a Combination of Lopinavir-Ritonavir and Interferon ß-1b), we evaluated the heterogeneity of treatment effect of interferon-ß1b and lopinavir-ritonavir versus placebo among hospitalized patients with MERS on 90-day mortality, according to cytokine levels and timing of therapy. We measured plasma levels of 17 cytokines at enrollment and tested the treatment effect on 90-day mortality according to cytokine levels (higher versus lower levels using the upper tertile (67%) as a cutoff point) and time to treatment (≤ 7 days versus > 7 days of symptom onset) using interaction tests. Among 70 included patients, 32 received interferon-ß1b and lopinavir-ritonavir and 38 received placebo. Interferon-ß1b and lopinavir-ritonavir reduced mortality in patients with lower IL-2, IL-8 and IL-13 plasma concentrations but not in patients with higher levels (p-value for interaction = 0.09, 0.07, and 0.05, respectively) and with early but not late therapy (p = 0.002). There was no statistically significant heterogeneity of treatment effect according to other cytokine levels. Further work is needed to evaluate whether the assessment of inflammatory status can help in identifying patients with MERS who may benefit from interferon-ß1b and lopinavir-ritonavir. Trial registration: This is a sub-study of the MIRACLE trial (ClinicalTrials.gov number, NCT02845843).


Assuntos
Infecções por Coronavirus , Ritonavir , Animais , Humanos , Antivirais/uso terapêutico , Citocinas/uso terapêutico , Interferons/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico
14.
Sci Rep ; 12(1): 3900, 2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35273262

RESUMO

Catheter-associated urinary tract infections (CAUTIs) are nosocomial infections causing more than one million hospital cases annually. The progress of CAUTIs leads to severe health complications. Infections result in blockage of the medical device due to biofilm formation, which necessitates the replacement of the device. The objective of this study is to improve urological biomaterials to minimize microbial growth and reduce the incidence of CAUTIs. Challenges from mixed biofilm are crucial and need to be addressed in the development of new coating materials. Herein, an investigation highlighted the reduction of mixed biofilm overgrowth and attachment tendency on poly-2-hydroxyethyl methacrylate (p-HEMA) surface by loading the hydrogel with rifampicin (RIF), cefixime trihydrate (CFX), and combined ratios of RIF and CFX. Mixed biofilm-formation ability in (3:1) RIF: CFX-loading p-HEMA (F6) surface showed best tendency to resist form biofilm. Persistent antimicrobial activity increased in p-HEMA loaded with combined ratios of RIF and CFX surface compared to p-HEMA alone, antimicrobial activity lasted for 8 days. All fabricated films exhibited %cell viability higher than 75% on HEK 293 cells. The addition of RIF and CFX may improve the duration of urological device employment before replacement.


Assuntos
Rifampina , Infecções Urinárias , Antibacterianos/farmacologia , Biofilmes , Cefixima/farmacologia , Feminino , Células HEK293 , Humanos , Hidrogéis/farmacologia , Masculino , Metacrilatos , Rifampina/farmacologia , Infecções Urinárias/tratamento farmacológico
15.
Nurs Leadersh (Tor Ont) ; 35(3): 32-47, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36735388

RESUMO

The year 2020 was unpredictable and brought about unimaginable change for our world, disrupting operations within the nursing profession and healthcare systems at large. In this discussion paper, we revisit a report from the Canadian Nurses Association, Toward 2020: Visions for Nursing (Villeneuve and MacDonald 2006), from a graduate student perspective. In this 2006 report, the authors presented a series of predictions for the preferred future of nursing in Canada in 2020. Even without the pandemic, the pre-existing trends in healthcare and nursing did not favour success for the visions presented in this national nursing report. Now, two years after 2020, we examine the extent to which these predictions held true in the following areas: health systems, nursing practice, nursing workforce, nursing education and nursing regulation. We conclude that most of the preferred scenarios were unmet or partially met, and argue that it is critical to enact relevant preferred scenarios now. While the deleterious effects of the pandemic will be felt by the nursing profession for years, these experiences did not hinder our collective ability to lead change in Canada. We offer insights to provide recommendations for nursing actions toward a healthier future for Canadians. The best of nursing in Canada is within sight.


Assuntos
Educação em Enfermagem , Humanos , Canadá , Atenção à Saúde , Estudantes , Recursos Humanos
16.
N Engl J Med ; 383(17): 1645-1656, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33026741

RESUMO

BACKGROUND: Whether combined treatment with recombinant interferon beta-1b and lopinavir-ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear. METHODS: We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir-ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results. RESULTS: A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of -19 percentage points (upper boundary of the 97.5% confidence interval [CI], -3; one-sided P = 0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group. CONCLUSIONS: A combination of recombinant interferon beta-1b and lopinavir-ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset. (Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843.).


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Interferon beta-1b/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Administração Oral , Adulto , Idoso , Infecções por Coronavirus/mortalidade , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Injeções Subcutâneas , Interferon beta-1b/efeitos adversos , Estimativa de Kaplan-Meier , Lopinavir/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ritonavir/efeitos adversos , Estatísticas não Paramétricas , Tempo para o Tratamento
17.
Pharmaceutics ; 12(9)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867015

RESUMO

Thymoquinone (TQ) is a water-insoluble natural compound isolated from Nigella sativa that has demonstrated promising chemotherapeutic activity. The purpose of this study was to develop a polymeric nanoscale formulation for TQ to circumvent its delivery challenges. TQ-encapsulated nanoparticles (NPs) were fabricated using methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) copolymers by the nanoprecipitation technique. Formulation variables included PCL chain length and NP architecture (matrix-type nanospheres or reservoir-type nanocapsules). The formulations were characterized in terms of their particle size, polydispersity index (PDI), drug loading efficiency, and drug release. An optimized TQ NP formulation in the form of oil-filled nanocapsules (F2-NC) was obtained with a mean hydrodynamic diameter of 117 nm, PDI of 0.16, about 60% loading efficiency, and sustained in vitro drug release. The formulation was then tested in cultured human cancer cell lines to verify its antiproliferative efficacy as a potential anticancer nanomedicine. A pilot pharmacokinetic study was also carried out in healthy mice to evaluate the oral bioavailability of the optimized formulation, which revealed a significant increase in the maximum plasma concentration (Cmax) and a 1.3-fold increase in bioavailability compared to free TQ. Our findings demonstrate that the versatility of polymeric NPs can be effectively applied to design a nanoscale delivery platform for TQ that can overcome its biopharmaceutical limitations.

18.
Trials ; 21(1): 8, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900204

RESUMO

The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-ß1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-ß1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02845843. Registered on 27 July 2016.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Interferon beta-1b/uso terapêutico , Lopinavir/uso terapêutico , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Ritonavir/uso terapêutico , Antivirais/efeitos adversos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Interpretação Estatística de Dados , Método Duplo-Cego , Combinação de Medicamentos , Interações Hospedeiro-Patógeno , Humanos , Interferon beta-1b/efeitos adversos , Lopinavir/efeitos adversos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritonavir/efeitos adversos , Arábia Saudita , Fatores de Tempo , Resultado do Tratamento
19.
Anal Bioanal Chem ; 412(1): 171-179, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31832708

RESUMO

Many gas chromatography-flame ionization detection (GC/FID) studies are dealing with response behavior of analytes such as alcohols and alkanes. Studies in the field of liquid chromatography (LC)/FID mainly focused on volatile analytes. In contrast, studies on LC/FID by conveyor type interface covered high molecular weight non-volatile biopolymers, whereby no response factors were calculated. With this study, we fill the gap and present response factors of volatile and non-volatile analytes by LC/FID in terms of flow injection (FIA) measurements of the single compounds without an analytical separation by an LC column. In the present study, 56 different compounds such as carboxylic acids, N-heterocycles, halogenated acids, pharmaceuticals, and other compounds were investigated. In some cases, the obtained response factor data confirmed aspects known from GC/FID studies. But this study also disproves several assumptions done in previous response studies as well as the prediction models based upon the experimental data and literature. Especially the response factors and effective carbon number (ECN) values of structural isomers such as pyrazine, pyridazine, and pyrimidine are assumed to be equal in current response prediction models. Contradictory to these assumptions, the experimental response factors and ECN values of, e.g., the structural isomers pyrazine (RFExp = 0.59; ECNExp = 3.66), pyridazine (RFExp = 0.66; ECNExp = 4.1), and pyrimidine (RFExp = 0.63; ECNExp = 3.93) reveal different experimental response factors and ECN than proposed by response factor prediction models (RFExp = 0.64; ECNExp = 4). Graphical abstract Graphical abstract.

20.
BMJ Open ; 9(10): e031305, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641002

RESUMO

OBJECTIVES: Clinical trials (CTs) are considered an important method for developing new treatments and providing access to potentially effective drugs that are still under investigation. Measuring the public's knowledge of and attitudes toward CTs is important for assessing their readiness for and acceptance of human drug testing, which has previously not been assessed in the Kingdom of Saudi Arabia (KSA). The objective of this study is to explore the Saudi public's knowledge of and attitudes toward CTs as well as participation in trials to test new or approved drugs. DESIGN: Cross-sectional. SETTING: The 2016 Al Jenadriyah cultural/heritage festival in Riyadh, KSA. PARTICIPANTS: Participating booths and exhibition halls, as well as festival visitors, were approached to participate in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: Knowledge of and attitudes toward CTs. RESULTS: The final number of participants was 938. The responses were converted to a percentage mean score (out of 100) for each knowledge-related response and attitude. The total mean knowledge score was 56.8±24.8 and the attitude-related score was 61.5±28.0. Although most of the participants supported testing approved or off-label and new drugs on adult and paediatric patients, only a third (30.5%) agreed that new drugs could be tested on healthy volunteers. The results indicated that gender, educational level, income, medical background, age and health insurance were independently associated with the level of knowledge of CTs. In terms of attitudes toward CTs, the factors that were independently associated were gender, educational level and medical background. CONCLUSIONS: The Saudi public has a low level of knowledge and a moderately positive attitude toward CTs. There is a moderate positive correlation between the two factors such that as knowledge of CTs increases, the Saudi public will hold more positive attitudes toward CTs.


Assuntos
Ensaios Clínicos como Assunto/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Arábia Saudita , Experimentação Humana Terapêutica , Adulto Jovem
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