Abstract
Objectives
To evaluate the efficacy and safety of the two-pill regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat as a switching strategy in ...heavily treatment-experienced people living with HIV (PLWH).
Methods
Multicentre, prospective, single-arm pilot clinical trial. Participants were virologically suppressed adults receiving a stable antiretroviral regimen of at least three pills from at least three drug families due to previous virological failures and/or toxicities with no documented resistance to integrase strand transfer inhibitors or darunavir (≥15 points, Stanford). Clinical and laboratory assessments were performed at 0, 4, 12, 24, 36 and 48 weeks. HIV-1 proviral DNA was amplified and sequenced by Illumina at baseline. Plasma bictegravir concentrations were determined in 22 patients using UHPLC-MS/MS. The primary study endpoint was viral load (VL)< 50 copies/mL at Week 48 (ITT).
Results
We enrolled 63 participants (92% men) with median baseline CD4 count of 515 cells/mm3 (IQR: 334.5–734.5), 24 years on ART (IQR: 15.9–27.8). The median number of pills was 4 (range: 3–10). At baseline, proviral DNA was amplified in 39 participants: 33/39 had resistance mutations. Three participants discontinued owing to toxicity. At 48 weeks, 95% had VL < 50 copies/mL by ITT and 100% by PP analysis. A modest increase was observed in the bictegravir plasma concentration, and a significant decrease in estimated glomerular filtration rate was observed only at Week 4, probably related to interaction with renal transporters.
Conclusions
Our data suggest that BIC/FTC/TAF + darunavir/cobicistat is an effective, well-tolerated regimen that may improve convenience and, potentially, long-term success in stable heavily pre-treated PLWH.
Facial feminization surgery covers a broad spectrum of procedures across both hard and soft tissues. Despite the fact that this is a decidedly predictable surgery, because of the high demand for the ...procedures, a growing number of patients are requiring revision surgery, whether to correct unexpected results or to treat mid-term to long-term functional and aesthetic complications. This Special Topic article categorizes unsatisfactory outcomes encountered after forehead surgery, lower jaw surgery, and thyroid chondroplasty; key steps to avoid these pitfalls; and strategies for structured analysis and operative planning in revision cases.
Ceftobiprole is a fifth-generation cephalosporin that has been approved in Europe solely for the treatment of community-acquired and nosocomial pneumonia. The objective was to analyze the use of ...ceftobiprole medocaril (Cefto-M) in Spanish clinical practice in patients with infections in hospital or outpatient parenteral antimicrobial therapy (OPAT).
This retrospective, observational, multicenter study included patients treated from 1 September 2021 to 31 December 2022.
A total of 249 individuals were enrolled, aged 66.6 ± 15.4 years, of whom 59.4% were male with a Charlson index of four (IQR 2-6), 13.7% had COVID-19, and 4.8% were in an intensive care unit (ICU). The most frequent type of infection was respiratory (55.8%), followed by skin and soft tissue infection (21.7%). Cefto-M was administered to 67.9% of the patients as an empirical treatment, in which was administered as monotherapy for 7 days (5-10) in 53.8% of cases. The infection-related mortality was 11.2%. The highest mortality rates were identified for ventilator-associated pneumonia (40%) and infections due to methicillin-resistant
(20.8%) and
(16.1%). The mortality-related factors were age (OR: 1.1, 95%CI (1.04-1.16)), ICU admission (OR: 42.02, 95%CI (4.49-393.4)), and sepsis/septic shock (OR: 2.94, 95%CI (1.01-8.54)).
In real life, Cefto-M is a safe antibiotic, comprising only half of prescriptions for respiratory infections, that is mainly administered as rescue therapy in pluripathological patients with severe infectious diseases.
Background
Parenteral anticoagulants and vitamin K antagonists (VKAs) have constituted the cornerstone of venous thromboembolism (VTE) treatment. Meanwhile, direct oral anticoagulants (DOACs) provide ...physicians with an alternative. The Global Anticoagulant Registry in the FIELD (GARFIELD)‐VTE observes real‐world treatment practices.
Objectives
Describe initial anticoagulation (AC) treatment patterns in VTE patients who received parenteral AC, VKAs, and/or DOACs within ±30 days of diagnosis.
Methods
VTE patients were categorized into parenteral AC only, parenteral AC with transition to VKA, VKA only, parenteral AC with transition to DOAC, and DOAC only.
Results
A total of 9647 patients were initiated on AC treatment alone. 4781 (49.6%) patients received DOACs ± parenteral ACs; 3187 (33.0%), VKA ± parenteral ACs; and 1679 (17.4%) parenteral ACs alone. Rivaroxaban was the most frequently used DOAC (79.4%). DOACs were more frequently used in North America/Australia (58.1%), Europe (52.2%), and Asia (47.6%) than in Latin America (29.7%) and the Middle East/South Africa (32.5%). In patients with suspected VTE, most received parenteral AC monotherapy (67.7%). Patients with deep vein thrombosis were more likely to receive DOACs alone than those with pulmonary embolism with or without deep vein thrombosis (36.2% vs 25.9%). Active cancer patients received parenteral AC alone (58.9%), with 25.5% receiving DOAC ± parenteral AC and 12.8% parenteral AC and VKA. A total of 46.5% of pregnant patients received parenteral AC monotherapy, 34.0% were treated with VKA ± parenteral AC, and 19.5% received a DOAC (± parenteral AC).
Conclusion
AC treatment patterns vary by patient population, geographic region and site of VTE. Guidelines for AC therapy are not always adhered to.
Keratitis‐ichthyosis‐deafness (KID) syndrome is a rare genetic disease caused by pathogenic variants in connexin 26 (gene GJB2), which is part of the transmembrane channels of the epithelia. Connexin ...26 is expressed mainly in the cornea, the sensory epithelium of the inner ear, and in the skin keratinocytes, which are the three main target organs in KID syndrome. Approximately a dozen pathogenic variants have been described to date, including some lethal forms. Patients with lethal pathogenic variants present with severe symptoms from birth and die from sepsis during the first year of life. We present a premature female patient with KID syndrome carrying the lethal p.Ala88Val pathogenic variant in GJB2. In addition to the respiratory distress associated with this variant, our patient presented severe hypercalcemia of unexplained origin refractory to treatment. This abnormality has not been reported earlier in other patients with KID syndrome with the same variant.
The article provides an empirical analysis on the impact of renewable energy development on the unemployment rate, agricultural output and relative rural population in Ecuador. Using an empirical ...approach, the study examined how the production and consumption of this energy affects the labor market in rural regions. To this end, relevant data on the development of renewable energies in the context of Ecuador were collected, and statistical analyses were carried out to evaluate the relationships between these and the variables of interest. The results obtained indicate that the development of renewable energies has can reduce the unemployment rate and has a positive effect on the relative population of rural regions, however, it does not seem to significantly affect agricultural production. These findings support the idea that the production and consumption of renewable energies can generate jobs directly, due to the need for workers for the construction and maintenance of these technologies, and indirectly, through cheaper energy, increased productive efficiency and better conditions for the expansion of companies. The study offers a significant contribution to the field of energy economics in developing countries and highlights the importance of the adoption of renewable energy sources for rural regions.
PDF
