RESUMO
In the original publication [...].
RESUMO
Bilateral traumatic dissections of the cervical internal carotid artery (ICA) are rare complications of polytrauma. A thorough literature review was performed, and data from selected studies were analyzed to assess the trends in clinical presentation, modes of trauma, management protocols, and clinical outcomes. The reported outcomes were categorized and graded into optimal, intermediate, and poor outcomes. We describe a rare case of bilateral dissection of ICA in a 31-year-old woman who was involved in a motor vehicle accident. She had a Glasgow Coma Scale score of 9 and right-sided hemiparesis. Radiological findings revealed left upper ICA dissection, arterial intramural thrombus, and stenosis of the upper segment of the right ICA. She improved on conservative management and had a good clinical outcome at a three-month follow-up. Emergency physicians must be knowledgeable about such cases, as more than half of these trauma victims are initially asymptomatic on initial presentation. Specific diagnostic and therapeutic modalities should be implemented based on low threshold clinical suspicion to avoid missing these potentially disabling injuries and reduce morbidity and mortality. Computed tomographic angiography is recommended in cases with atypical clinical presentations, unexplained neurological deficits, or delayed-onset clinical deterioration. While antiplatelet and anticoagulant therapies are the mainstays of conservative management, endovascular and surgical management are only used in severe cases when medical treatment has failed, the artery has been completely transected, or there is active bleeding. Generally, good outcomes were reported in about two-thirds of those patients.
RESUMO
A dry powder inhaled liposomal azithromycin formulation was developed for the treatment of chronic respiratory diseases such as cystic fibrosis and bronchiectasis. Key properties including liposome size, charge and encapsulation efficiency powder size, shape, glass transition temperature (Tg), water content and in vitro respiratory deposition were determined. Antimicrobial activity against cystic fibrosis (CF) respiratory pathogens was determined by MIC, MBC and biofilm assays. Cytotoxicity and cellular uptake studies were performed using A549 cells. The average liposome size was 105 nm, charge was 55 mV and encapsulation efficiency was 75 %. The mean powder particle size d[v,50] of 4.54 µm and Mass Median Aerodynamic Diameter (MMAD) was 5.23 µm with a mean Tg of 76ËC and water content of 2.1 %. These excellent physicochemical characteristics were maintained over one year. Liposomal loaded azithromycin demonstrated enhanced activity against P. aeruginosa clinical isolates grown in biofilm. The formulation was rapidly delivered into bacterial cells with > 75 % uptake in 1 h. Rapid uptake into A549 cells via a cholesterol-dependent endocytosis pathway with no cytotoxic effects apparent. These data demonstrate that this formulation could offer benefits over current treatment regimens for people with chronic respiratory infection.
Assuntos
Fibrose Cística , Infecções Respiratórias , Humanos , Azitromicina , Antibacterianos , Lipossomos/uso terapêutico , Pós , Fibrose Cística/tratamento farmacológico , Administração por Inalação , Infecções Respiratórias/tratamento farmacológico , Água , Tamanho da Partícula , Inaladores de Pó SecoRESUMO
Spinal dural arteriovenous fistulas account for the majority of spinal vascular malformations. They are typically located in the thoracolumbar region and are diagnosed in the middle-aged and elderly populations. Although spinal dural arteriovenous fistulas have been postulated to be acquired, their exact development remains uncertain. Typically, the arteriovenous shunt is situated close to the spinal nerve root, inside the dura mater, where the blood from the radiculomeningeal artery and radicular vein intermix. Throughout history, there have been multiple classification systems of spinal arteriovenous shunts since 1967. Those were mainly based on the evolution of diagnostic studies as well as the treatment of these lesions. Such classification systems have undergone significant changes over the years. Unlike intracranial dural arteriovenous fistula, spinal dural arteriovenous fistula is progressive in nature. The neurological manifestations, due to venous congestion, tend to be insidious as well as non-specific. These include sensory deficits, such as paresthesia, bilateral and/or unilateral radicular pain affecting the lower limbs, and gait disturbances. Spinal dural arteriovenous fistulas can be suspected on magnetic resonance imaging/magnetic resonance angiography and confirmed by digital subtraction angiography (DSA). The management includes surgery, endovascular therapy, and in selected cases, radiotherapy. The treatment goal of spinal dural arteriovenous fistula is to halt the progression of the disease. The prognosis depends on both the duration of symptoms as well as the clinical condition prior to therapy. The present article comprehensively reviews the pathophysiology, changes in classification systems, natural history, clinical manifestations, radiological features, management, and prognosis.
RESUMO
BACKGROUND: Traumatic retroclival hematomas (RCHs) are infrequent occurrences among the pediatric population. The existing body of research pertaining to these hematomas primarily consists of case reports or small case series, which do not provide adequate guidance for managing this condition. OBJECTIVE: This study aims to present a report on four cases of RCHs. Additionally, we aim to conduct a systematic review to consolidate the existing literature on pediatric RCHs. METHODS: The authors conducted a systematic review in accordance with the PRISMA and CARE guidelines. A multivariate logistic regression model was developed to evaluate the potential impact of various clinical variables on clinical outcomes. The study also documented four of our cases, one of which was a rare occurrence of spontaneous subdural RCH. RESULTS: A total of 62 traumatic RCHs have been documented in the literature. We documented three cases of traumatic RCHs and one case of spontaneous RCH. A systematic analysis of 65 traumatic RCHs was performed. Of trauma cases, 64.6% demonstrated craniocervical junction instability with 83.3% ligamentous involvement. Thirty-five patients were males. 50.7% were aged between 5 and 9 years. Cranial nerve palsies occurred in 29 patients (27 had abducent palsy), 26 of which resolved within 6 months of trauma. 23.5% underwent surgery, and 76.5% were conservatively managed. Surgeries targeted hematomas, hydrocephalus, or craniocervical instability. Approaches to hematomas included transclival and far/extreme lateral suboccipital approaches. Clinical outcome was good in 75.4% and intermediate or poor in 24.6%. Logistic regression suggested an association between craniocervical junction injuries and poor or intermediate outcomes (OR 4.88, 95% CI (1.17, 27.19), p = 0.04). CONCLUSION: Pediatric RCHs are mostly traumatic and extradural. Children between 5 and 9 years old are most vulnerable. Craniocervical junction injuries, mainly ligamentous, are common in RCHs and are associated with intermediate or poor outcomes. Cervical MRI could be important in cases of trauma to rule out ligamentous injuries of the craniocervical junction. The small size of RCHs should not exempt the careful assessment of craniocervical junction instability. Cranial nerve palsies are common and usually resolve within 6 months. Conservative treatment is typical unless brainstem compression, hydrocephalus, or craniocervical junction instability exists.
Assuntos
Doenças dos Nervos Cranianos , Hidrocefalia , Traumatismos do Sistema Nervoso , Masculino , Humanos , Criança , Pré-Escolar , Feminino , Hematoma , Imageamento por Ressonância MagnéticaRESUMO
The majority of the Arab countries have high records of daily tobacco smoking. Electronic cigarettes (e-cigarettes) use has exponentially increased in the past decade in Arab countries. Consumers' willingness to quit smoking traditional cigarettes and their perception of e-cigarettes as a safer alternative to conventional cigarettes have increased the demand for these devices. This narrative review aimed to gather and discuss the available literature on the awareness, prevalence, and sales regulations of e-cigarettes in Arab countries. A search was conducted on electronic databases such as PubMed, Medline, Scopus, and Google Scholar with no time limits until the end of 2021. Some of the recent studies (2019-2021) considered in this review have reported that more than 25% of participants were e-cigarettes users. The prevalence of e-cigarettes has increased drastically with raised awareness of e-cigarettes among the population in these Arab countries. Most of the users of e-cigarettes are young males. In addition, an increase in e-cigarettes use has been reported in females. The policies which regulate trade and sale of e-cigarettes and related products were issued in only three Arab countries. In contrast, regulations for the trade and sale of traditional cigarette products are also applied in some countries to e-cigarette products, banning the sale of e-cigarettes to minors and/or amend smoke-free laws to restrict public use of e-cigarettes. There is a need for a concerted effort to assess the prevalence and significant rise of e-cigarettes consumption in Arab societies to help implement and improve harm reduction policies.
RESUMO
This study addresses the crucial aspect of childhood COVID-19 vaccination and its impact on parental decisions concerning learning modalities during the pandemic. This study aimed to gauge parental hesitancy towards vaccinating their children and its influence on choosing between distance and face-to-face learning options. Following STROBE guidelines for cross-sectional studies, this study surveyed 1973 parents in the United Arab Emirates using Google Forms during the COVID-19 pandemic. The results revealed that while more than half of the parents (51.6%) were willing to vaccinate their children if the COVID-19 vaccine was accessible and affordable, a significant majority (91.2%) expressed concerns about the rapid vaccine development process, which was the primary reason for vaccine rejection. Interestingly, a sizable portion (55.3%) had experienced online learning in the previous academic term, and, of those, 59.6% believed it negatively influenced their children's academic performance. Consequently, 66.4% expressed intent to shift their children back to face-to-face learning once feasible. Significantly, parents with medical backgrounds were more inclined (91.6%) to opt for face-to-face schooling compared to those without such backgrounds. Logistic regression analysis indicated associations between sociodemographic characteristics, educational level and background, and the decision to return children to face-to-face learning. Interestingly, when it comes to vaccine hesitancy, a noteworthy connection exists between the parents' reluctance to vaccinate their children and their preference for distance learning. In fact, parents who responded negatively to vaccinating their children against COVID-19, if the vaccine was available, showed a clear preference for the distance learning modality (p-value < 0.0001). This study underscores the complex interplay of factors and community perspectives shaping parental acceptance of childhood COVID-19 vaccination. The development pace of vaccines significantly influences parents' attitudes and beliefs about vaccination programs. Parents' medical backgrounds exhibit a clear correlation with their perceptions of sending children back to school safely. This highlights the potential impact of parental medical knowledge on decision making, emphasizing the need to consider parents' professional backgrounds when devising education- and vaccination-related policies.
RESUMO
Bacterial vaginosis (BV) is a common dysbiosis of the human vaginal microbiota characterized by depletion of hydrogen peroxide and lactic acid-producing Lactobacillus bacteria and an overgrowth of certain facultative anaerobic bacteria. Although short-term cure rates following treatment with frontline antibiotics (most notably oral metronidazole (MNZ), clindamycin vaginal cream, and MNZ vaginal gel) are generally high, longer-term recurrence rates are an issue. The development of vaginal formulations offering continuous/sustained administration of antibiotic drugs over one or more weeks might prove useful in reducing recurrence. Here, we report the manufacture and preclinical testing of matrix-type vaginal rings offering sustained release of four 5-nitroimidazole antimicrobial drugs either being used clinically or having potential in treatment of BV - MNZ, tinidazole (TNZ), secnidazole (SNZ) and ornidazole (ONZ). All four drugs showed good compatibility with a medical-grade addition-cure silicone elastomer based upon thermal analysis experiments, and matrix-type rings containing 250 mg (3.125 %w/w) of each drug were successfully manufactured by reaction injection molding. 28-day in vitro drug release studies demonstrated root-time kinetics, with daily release rates of 25, 22, 9 and 6 mg/day½ for SNZ, ONZ, MNZ and TNZ, respectively. The rank order of drug release from rings correlated with the simple molecular permeability parameter S/V, where S is the measured drug solubility in silicone fluid and V is the drug molecular volume. The relative merits of SNZ and ONZ over MNZ (the current reference treatment) are discussed. The data support development of vaginal rings for sustained release of 5-nitroimidazole compounds for treatment of BV.
Assuntos
Dispositivos Anticoncepcionais Femininos , Ornidazol , Vaginose Bacteriana , Feminino , Humanos , Vaginose Bacteriana/tratamento farmacológico , Elastômeros de Silicone , Preparações de Ação Retardada/uso terapêutico , Administração Intravaginal , Metronidazol , Antibacterianos , Tinidazol , Ornidazol/uso terapêuticoRESUMO
T-activation polyagglutination can be caused by bacteria or viruses and has been associated with haemolytic anaemia. Coronavirus disease-19 (COVID-19) is also associated with haemolytic anaemia. The presented study aims to determine T activation polyagglutination in critically ill COVID-19 patients. Anti-T Arachis hypogaea lectin was incubated with the red blood cells of the COVID-19 patient and checked for agglutination. Thirty-four percent (34.3%) of COVID-19 patients in the intensive care unit (ICU) had potentially activated T cells and polyagglutinable red blood cells, as demonstrated by their cryptantigen exposure that caused agglutination. The study revealed a high prevalence of anti-T among ICU-admitted COVID-19 patients, suggesting that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause transient T activation, polyagglutination in critically ill COVID-19 patients in vitro and possibly haemolysis in vivo.
Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Estado Terminal , Anticorpos , Morte CelularRESUMO
Diabetic foot ulcers (DFUs) are a crucial complication of diabetes, as in a diabetic wound, each step of the physiological healing process is affected. This entails a more easily infectable wound, and delayed tissue regeneration due to the inflammation that occurs, leading to a drastic decrease in the overall patient's quality of life. As a strategy to manage DFUs, skin alternatives and wound dressings are currently receiving a lot of attention as they keep the wound environment "under control", while providing bioactive compounds that help to manage infection and inflammation and promote tissue repair. This has been made possible thanks to the advent of emerging technologies such as 3D Bioprinting to produce skin resembling constructs or microfluidics (MFs) that allows the manufacture of nanoparticles (NPs) that act as drug carriers, in a prompt and less expensive way. In the present proof-of-concept study, the possibility of combining two novel and appealing techniques in the manufacturing of wound dressings has been demonstrated for first time. The novelty of this work consists in the combination of liposomes (LPs) encapsulating the active pharmaceutical ingredient (API) into a hydrogel that is further printed into a three-dimensional scaffold for wound dressing; to the knowledge of the authors this has never been done before. A grid-shaped scaffold has been produced through the coaxial 3D bioprinting technique which has allowed to combine, in one single filament, two different bioinks. The inner core of the filament is a nanocomposite hydrogel consisting of hydroxyethyl cellulose (HEC) and PEGylated LPs encapsulated with thyme oil (TO) manufactured via MFs for the first time. The outer shell of the filament, instead, is represented by a hybrid hydrogel composed of sodium alginate/cellulose nanocrystals (SA/CNC) and enriched with free TO. This provides a combination of two different release ratios of the API, a bulk release for the first 24 h thanks to the free TO in the shell of the filament and a sustained release for up to 10 days provided from the API inside the LPs. Confocal Microscopy verified the actual presence of the LPs inside the scaffold after printing and evaluation using the zone of inhibition test proved the antibacterial activity of the manufactured scaffolds against both Gram-positive and Gram-negative bacteria.
Assuntos
Bioimpressão , Diabetes Mellitus , Pé Diabético , Humanos , Antibacterianos , Lipopolissacarídeos , Microfluídica , Qualidade de Vida , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Bandagens , Hidrogéis , Pé Diabético/tratamento farmacológico , Cicatrização , Inflamação , Celulose/uso terapêuticoRESUMO
BACKGROUND: Pityriasis rosea (PR) is an acute, self-limiting papulosquamous skin disease which predominantly affects children and young adults. Pityriasis rosea appears to be more common in West Africa. Reports about PR from northern Nigeria are few. OBJECTIVES: To present the relative prevalence, demographic and clinical characteristics of PR. METHODS: We conducted a retrospective review of records of consecutive patients attending two dermatology clinics in Kaduna, North-West Nigeria between September 2001 and November 2021. RESULTS: Of 39,037 patients, 922 (2.4%) presented with PR: Median age was 15 years (range 3 months to 63 years) and 24% < 10 years, 60% < 18 years, 87% < 30% years. 62% were female. In patients < 20 years, males were significantly more in number than females (69.6% vs. 60.9%, P = 0.007) while in those >20 years, females were more in number (39.1% vs. 30.4%, P = 0.007). The mean duration of disease at presentation was 14 days (range 1 - 240 days). Majority (60%) were seen during the rainy season. A herald patch was present in 67.8%, usually occurring 7 days before the main rash. The trunk was affected by the main rash in 94% while the neck and face were affected in 19.2% and 23.6%, respectively. Itching was reported by 80%. The classic disease constituted 80.2%. Oral involvement was rare. CONCLUSION: Pityriasis rosea is a common disease in Kaduna. It mostly affects children, adolescents and young adults. Clinical presentation is typical in the majority of patients. Rarely an atypical disease occurs. Oral involvement was rare.
CONTEXTE: Le pityriasis rosé (PR) est une dermatose papulosquameuse aiguë spontanément résolutive qui touche principalement les enfants et les jeunes adultes. Le pityriasis rosea semble être plus courant en Afrique de l'Ouest. Les rapports sur la RP du nord du Nigeria sont peu nombreux. OBJECTIFS: Présenter la prévalence relative, les caractéristiques démographiques et cliniques de la RP. METHODES: Nous avons effectué un examen rétrospectif des dossiers de patients consécutifs fréquentant deux cliniques de dermatologie à Kaduna, dans le nord-ouest du Nigeria, entre septembre 2001 et novembre 2021. RESULTATS: Sur 39 037 patients, 922 (2,4 %) ont présenté une RP : l'âge médian était de 15 ans (intervalle de 3 mois à 63 ans) et 24 % < 10 ans, 60 % < 18 ans, 87 % < 30 % ans. 62 % étaient des femmes. Chez les patients de < 20 ans, les hommes étaient significativement plus nombreux que les femmes (69,6 % contre 60,9 %, P = 0,007) tandis que chez ceux de > 20 ans, les femmes étaient plus nombreuses (39,1 % contre 30,4 %, P = 0,007) . La durée moyenne de la maladie au moment de la présentation était de 14 jours (fourchette de 1 à 240 jours). La majorité (60%) ont été observées pendant la saison des pluies. Un patch annonciateur était présent chez 67,8%, survenant généralement 7 jours avant l'éruption principale. Le tronc était touché par l'éruption principale dans 94 % tandis que le cou et le visage étaient touchés dans 19,2 % et 23,6 %, respectivement. Des démangeaisons ont été signalées par 80 %. La maladie classique constituait 80,2 %. L'atteinte orale était rare. CONCLUSION: Le pityriasis rosé est une maladie courante à Kaduna. Elle touche principalement les enfants, les adolescents et les jeunes adultes. La présentation clinique est typique chez la majorité des patients. Rarement une maladie atypique survient. L'atteinte orale était rare. Mots clés: Pityriasis rosé, Kaduna-Nigeria, Épidémiologie, Présentation clinique, Africains.
Assuntos
Exantema , Pitiríase Rósea , Criança , Masculino , Adolescente , Adulto Jovem , Humanos , Feminino , Lactente , Pitiríase Rósea/epidemiologia , Nigéria/epidemiologia , Prurido , África OcidentalRESUMO
BACKGROUND: Low back pain is a prevalent and debilitating condition that affects a significant proportion of the adult population. Medical students are particularly vulnerable due to the demands of their rigorous curriculum. Therefore, this study aims to investigate the prevalence and risk factors associated with low back pain among medical students. METHODS: A cross-sectional survey was conducted among medical students and interns at King Faisal University in Saudi Arabia using a convenience sampling technique. An online questionnaire was distributed via social media applications to explore the prevalence and risk factors for low back pain. RESULTS: Out of 300 medical students who participated in the study, 94% reported experiencing low back pain, with a mean pain score of 3.91 ± 2.0 out of 10. The most common factor that aggravated the pain was prolonged sitting. Logistic regression analysis revealed that sitting for more than eight hours (OR=5.61; 95% CI: 2.92-21.42) and not engaging in physical exercise (OR=3.10; 95% CI: 1.34-6.57) were independently associated with a higher prevalence of low back pain. These findings highlight the increased risk of low back pain among medical students due to prolonged sitting and a lack of physical activity. CONCLUSION: This study provides evidence of the high prevalence of low back pain among medical students and identifies significant risk factors that exacerbate the condition. It emphasizes the need for targeted interventions to promote physical activity, reduce prolonged sitting, manage stress, and encourage good posture among medical students. The implementation of such interventions could help alleviate the burden of low back pain and improve the quality of life for medical students.
RESUMO
A Loss-of-function variant in ZNF808 is associated with non-syndromic neonatal diabetes in a consanguineous family with three affected siblings.
Assuntos
Diabetes Mellitus , Humanos , Recém-Nascido , Consanguinidade , Diabetes Mellitus/genética , Genes Recessivos , Linhagem , IrmãosRESUMO
Focused bis-pyridinium based-ionic liquids were successfully synthesized through the quaternization of the selected 1,2-di(pyridin-4-yl)ethane followed by metathetical anion exchange. The synthesized pyridinium derivatives were fully characterized using various NMR-spectroscopic techniques including 1H, 13C, 11B, 31P and 19F NMR. The synthesized compounds were tested for their potential effect against Toxoplasma gondii. It was revealed that compound 5 had higher antiparasitic activity compared to other compounds. Parasitic reduction percentage reached 38, 50, 77 and 79 for groups III, IV, V and VI respectively in the liver with noticed distortion and deformation in tachyzoites' shape. Surprisingly there was no statistically significant difference between the synthesized compound 5 and the known anti-toxoplasmosis drug pyrimethamine. Histopathological study proved the effectiveness of the synthesized compound 5 on liver, spleen and brain tissues with observed better histological features compared to pyrimethamine treated group. The present investigation may pave the way to the possible use of compound 5 to replace the known drug pyrimethamine with better antiparasitic profile and fewer side effects.
RESUMO
INTRODUCTION: Vein of Galen malformation (VOGM) is an exceptionally uncommon form of congenital intracranial vascular malformations. It is highly unusual for this lesion to spontaneously thrombose. The clinical presentation of a patient may range from being asymptomatic to critically ill. The underlying pathophysiological mechanisms that cause spontaneous thrombosis are still poorly understood. METHODS AND RESULTS: The literature on spontaneous thrombosis of VOGM was systematically reviewed, analyzed, and summarized with a focus on its pathophysiology, types, clinical presentations, diagnosis, management, and outcomes. It was also illustrated with a case presentation. The case presents an unusual presentation and location of a VOGM in a 2-year-old boy who was successfully treated with surgical resection. CONCLUSIONS: A handful of cases of thrombosed VOGM have been reported worldwide where surgery was used to treat the condition. Low-flow fistulas of the mural type are prone to spontaneous thrombosis, have delayed clinical presentations, and are typically diagnosed in young children. Among the many possible manifestations, hydrocephalus is by far the most common. In the absence of blood flow, MRI is the diagnostic test of choice. Depending on the patient's symptoms, surgery to either remove the aneurysm or divert the cerebrospinal fluid usually results in a good prognosis.
Assuntos
Veias Cerebrais , Trombose , Malformações da Veia de Galeno , Criança , Masculino , Humanos , Pré-Escolar , Malformações da Veia de Galeno/complicações , Malformações da Veia de Galeno/diagnóstico por imagem , Malformações da Veia de Galeno/cirurgia , Veias Cerebrais/diagnóstico por imagem , Veias Cerebrais/cirurgia , Veias Cerebrais/patologia , Imageamento por Ressonância Magnética , Angiografia CerebralRESUMO
Inherited cardiomyopathies are a prevalent cause of heart failure and sudden cardiac death. Both hypertrophic (HCM) and dilated cardiomyopathy (DCM) are genetically heterogeneous and typically present with an autosomal dominant mode of transmission. Whole exome sequencing and autozygosity mapping was carried out in eight un-related probands from consanguineous Middle Eastern families presenting with HCM/DCM followed by bioinformatic and co-segregation analysis to predict the potential pathogenicity of candidate variants. We identified homozygous missense variants in TNNI3K, DSP, and RBCK1 linked with a dilated phenotype, in NRAP linked with a mixed phenotype of dilated/hypertrophic, and in KLHL24 linked with a mixed phenotype of dilated/hypertrophic and non-compaction features. Co-segregation analysis in family members confirmed autosomal recessive inheritance presenting in early childhood/early adulthood. Our findings add to the mutational spectrum of recessive cardiomyopathies, supporting inclusion of KLHL24, NRAP and RBCK1 as disease-causing genes. We also provide evidence for novel (recessive) modes of inheritance of a well-established gene TNNI3K and expand our knowledge of the clinical heterogeneity of cardiomyopathies. A greater understanding of the genetic causes of recessive cardiomyopathies has major implications for diagnosis and screening, particularly in underrepresented populations, such as those of the Middle East.
Assuntos
Cardiomiopatias , Cardiomiopatia Dilatada , Pré-Escolar , Humanos , Consanguinidade , Cardiomiopatias/genética , Cardiomiopatia Dilatada/genética , Mutação , Mutação de Sentido Incorreto , Proteínas Serina-Treonina Quinases/genéticaRESUMO
Previously reported in vitro release test methods for drug-releasing vaginal rings containing poorly water-soluble drugs have described use of water-alcohol systems or surfactant solutions in efforts to maintain sink conditions. Here, as part of efforts to more closely match in vitro and in vivo release for the 25 mg dapivirine matrix-type silicone elastomer vaginal ring for HIV prevention, we have investigated alternatives to the 1:1 v/v water/isopropanol medium described previously. Specifically, we evaluated dapivirine release from rings into (i) monophasic water/isopropanol mixtures of varying compositions and (ii) biphasic buffer/octanol systems using pH 4.2 and pH 7.0 buffers. The rate and mechanism of dapivirine release were dependent upon the isopropanol concentration in the release medium, in accordance with the observed trend in drug solubility. At 0 and 10% v/v isopropanol concentrations, dapivirine release followed a partition-controlled mechansim. For media containing ≥ 20% v/v isopropanol, in vitro release of dapivirine was significantly increased and obeyed permeation-controlled kinetics. Cumulative release of ~3.5 mg dapivirine over 28 days was obtained using a water isopropanol mixture containing 20% v/v isopropanol, similar to the ~4 mg dapivirine released in vivo. Dapivirine release into the biphasic buffer/octanol system (intended to mimic the fluid/tissue environment in vivo) was constrained by the limited solubility of dapivirine in the buffer component in which the ring resided, such that cumulative dapivirine release was consistently lower than that observed with the 20% v/v isopropanol in water medium. Release into the biphasic system was also pH dependent, in line with dapivirine's pKa and with potential implications for in vivo release and absorption in women with elevated vaginal pH.
Assuntos
Fármacos Anti-HIV , Dispositivos Anticoncepcionais Femininos , Infecções por HIV , Humanos , Feminino , Fármacos Anti-HIV/química , 2-Propanol/análise , Vagina , Infecções por HIV/prevenção & controleRESUMO
BACKGROUND: The association of various morphological features of facet diastasis with posterior ligamentous complex (PLC) injury has not been previously described. This study aims to determine the diagnostic value of facet diastasis subtypes for diagnosing thoracolumbar PLC injury. METHODS: We retrospectively reviewed 337 consecutive patients with acute thoracolumbar fractures who had computed tomography (CT) and magnetic resonance imaging (MRI) within 10 days of injury. Three and 5 reviewers evaluated MRI and CT images, respectively. Facet diastasis was subclassified as follows: Dislocated, no articular surface apposition; subluxed, incomplete articular surface apposition; and facet fracture articular process fractures which may be displaced ≥2 mm or otherwise undisplaced, facet joint widening (FJW) ≥ 3 mm. We examined the diagnostic accuracy and the multivariate associations of facet diastasis subtypes with PLC injury in MRI. RESULTS: Facet dislocation, subluxation, and displaced facet fracture yielded a high positive predictive value (PPV) for PLC injury (96%, 88%, and 94%, respectively). In contrast, undisplaced facet fracture and FJW yielded a moderate PPV for PLC injury (78%, and 45%, respectively). Facet dislocation, subluxation, and displaced facet fracture showed independent associations with PLC injury (adjusted odds ratio [AOR] = 38.4, 17.1, 13.4, respectively; P < 0.05). Undisplaced facet fracture and FJW were not associated with PLC injury (AOR = 3.9 [95% confidence interval, 0.49-38.4], P = 0.20) and (AOR = 1.94 [95% confidence interval, 0.48-7.13]; P = 0.20; P = 0.33), respectively. CONCLUSIONS: Facet dislocation, subluxation, and displaced facet fracture, but not undisplaced facet fracture or FJW, were independently associated with PLC injury. Therefore, we propose to define facet diastasis as a surrogate marker of PLC injury in MRI based on these morphologies.
Assuntos
Fraturas Ósseas , Luxações Articulares , Fraturas da Coluna Vertebral , Humanos , Estudos Retrospectivos , Ligamentos Longitudinais/patologia , Fraturas da Coluna Vertebral/diagnóstico , Vértebras Lombares/lesões , Vértebras Torácicas/lesões , Imageamento por Ressonância Magnética/métodos , Luxações Articulares/patologia , Fraturas Ósseas/patologiaRESUMO
Purpose: The early diagnosis of sickle cell disease (SCD) patients and getting appropriate treatment are crucial for improving clinical outcomes. This study aims to assess the use of hydroxyurea among patients diagnosed with SCD and assess factors influencing the attitude toward the medication and the reasons for discontinuation. Methods: This study was a cross-sectional investigation targeting parents or caregivers of children diagnosed with SCD in the Jazan region of Saudi Arabia. Data were collected from tertiary healthcare hospitals via a self-administered questionnaire. The questionnaire was composed of sections measuring the participants' demographics, the number of children diagnosed with SCD, the use of hydroxyurea, and the parents' beliefs about hydroxyurea. Results: There were 301 parents or caregivers recruited. The majority of the recruited participants were mothers (54.5%), and nearly half of the sample were older than 35. More than 80% of the participants declare that one or more of their children are receiving hydroxyurea to manage SCD. The majority of participants declared that using hydroxyurea reduced the frequency of body pain episodes, emergency department visits, and hospital admissions. Participants' major concern about the use of hydroxyurea was related to the fear of weakening their immunity (29.5%) and hydroxyurea's perceived effect on fertility (16.8%). Furthermore, 52 (18%) of the participants declared that the use of hydroxyurea to manage the disease was stopped; the main reasons for stopping was their belief that hydroxyurea had side effects and its impact on weakening of their immune system. Conclusion: The findings indicate the importance of increasing the role of clinicians in educating patients and caregivers about the use of hydroxyurea and its benefits.
RESUMO
Background: Low back pain (LBP) is one of the most common health problems. Red flags (RFs) of LBP are risk factors that are reported during clinical assessment to determine serious illness. This study aimed to assess primary health-care physicians' knowledge of and practices for RFs of LBP and identify variables associated with a high level of knowledge and awareness about it. Methods: An observational cross-sectional survey was conducted in 2021 among a random sample of 261 primary health care (PHC) physicians in the Jazan Region in southwest Saudi Arabia. A web-based questionnaire was used to collect data on LBP red flags awareness and practices. Descriptive (frequency and percentage) and inferential statistics were used for data analysis. Results: The overall mean score of RFs knowledge among physicians was 82.33 ± 36.3, with 95% confidence interval (CI); (77.7-86.9). Regarding the Physician's practices, more than 95% of the participants would refer patients to higher levels in the presence of symptoms or signs of RFs. General practitioners and residents were significantly more likely to ask for an Xray, even with symptoms that had persisted for less than 2 weeks without RF signs (p = 0.006). The overall percentage of patients with nonspecific LBP referrals was as high as 57.8%. The number of patients with LBP seen per month (fewer than 15) and female physician were associated with an increased level of knowledge (OR = 2.2, 95%, P < 0.05) and (OR = 2.2, 95%, P < 0.05) respectively. Conclusion: Overall, awareness of RFs for LBP and referring critical patients who present with LBP is good among PHC physicians in the Jazan Region. Junior physicians have a low threshold to request images. The referral rate for nonspecific LBP is still high, which could overwhelm spinal clinics. Further educational programs for back pain management are recommended.