ABSTRACT
Cervarix vaccine was included in the National Immunization Program of Argentina in 2011 but data about the local distribution of human papillomavirus (HPV) infection in women exposed to the virus are scarce. This cross-sectional study determined the prevalence and type distribution of HPV infection in unvaccinated women attending routine gynecological screening in two public hospitals located in Buenos Aires and Santa Fe, Argentina. Socio-demographic, sexual behavior, and co-factors information was obtained from all participants (Buenos Aires, n = 429; Santa Fe, n = 433). Cervicovaginal swabs were tested with an MY11/09 primer-based assay and with the CUT primer system targeting mucosal/cutaneous HPVs. Participants from Buenos Aires showed significantly higher rates of HPV infection (52.4% vs. 40.6%), of multiple infections (24.2% vs. 16.4%), and of low-risk (20.3% vs. 13.9%) and high-risk types (44.1% vs. 33.3%) than those from Santa Fe. HPV-66 (Buenos Aires: 17%) and HPV-16 (Santa Fe: 8.5%) were the most prevalent types. Novel HPV-66 putative subtype and variants were identified. Vaccine types 16 and 18 were frequent (Buenos Aires: 13.5%; Santa Fe: 10.2%) but few participants had co-infections with both (Buenos Aires: 1.4%; Santa Fe: 0.2%). A common risk factor for HPV infection was having a new sexual partner in the last year (Buenos Aires: OR 2.53, P < 0.001; Santa Fe: OR 1.85, P = 0.04). This study provides valuable baseline data for future assessment of the impact of massive vaccination in Argentina and it underlines the use of additional HPV testing strategies, such as the CUT system, for surveillance and vaccinology.
Subject(s)
Papillomaviridae/classification , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Adolescent , Adult , Aged , Argentina/epidemiology , Cross-Sectional Studies , DNA, Viral/chemistry , DNA, Viral/genetics , Female , Genotype , Hospitals , Humans , Middle Aged , Molecular Epidemiology , Molecular Sequence Data , Papillomaviridae/genetics , Prevalence , Sequence Analysis, DNA , Young AdultABSTRACT
BACKGROUND: Sudden death (SD) in the young usually has an underlying genetic cause. In many cases, autopsy reveals unspecific and inconclusive results, like idiopathic left ventricular hypertrophy (LVH), nonsignificant coronary atherosclerosis (CA), and primary myocardial fibrosis (PMF). Their pathogenicity and their relation to SD cause is unknown. This study aims to evaluate the diagnostic yield of genetic testing in these cases. METHODS: SD cases, between 1 and 50 years old, with findings of uncertain significance (idiopathic LVH, nonsignificant CA and PMF) on autopsy were evaluated prospectively, including information about medical and family history and circumstances of death. Genetic testing was performed. RESULTS: In a series of 195 SD cases, we selected 31 cases presenting idiopathic LVH (n = 16, 51.61%), nonsignificant CA (n = 17, 54.84%), and/or PMF (n = 24, 77.42%) in the autopsy. Mean age was 41 ± 7.2 years. Diagnostic yield of genetic test was 67.74%, considering variants of unknown significance (VUS), pathogenic variants (PV) and likely pathogenic variants (LPV); 6.45% including only PV and LPV. Structural genes represented 41,93% (n = 13) of cases, while 38,7% (n = 12) were related to channelopathies. CONCLUSION: Molecular autopsy in SD cases between 1 and 50 years old, with findings of uncertain significance, has a low diagnostic yield, being VUS the most frequent variant observed.
ABSTRACT
Bictegravir is a novel integrase strand transfer inhibitor, administrated in co-formulation with tenofovir alafenamide and emtricitabine (Biktarvy®), indicated in the management of HIV-1 infection in patients not previously treated with antiretroviral therapy. Bictegravir is highly bound to plasma proteins, and this significantly determines its clearance, solubility, and activity. These characteristics are crucial determinants of bictegravir penetration into human body compartments, as the central nervous system. We developed and validated UHPLC-MS/MS procedures to measure total and unbound bictegravir concentrations in plasma and cerebrospinal fluid. Simple protein precipitation with acetonitrile was implemented to prepare plasma and cerebrospinal fluid samples. Sample preparation was preceded by ultrafiltration for measuring unbound bictegravir concentrations. Chromatographic separations were achieved on an Acquity® UHPLC® BEHTM (2.1â¯×â¯100â¯mm id, 1.7⯵m) reverse-phase C18 column using an isocratic mobile phase 20:80 (v/v) water/acetonitrile with 0.1% formic. Bictegravir and its internal standard (bictegravir-15N d2) were detected by electrospray ionization mass spectrometry in positive and multiple reaction monitoring modes, using transitions of 450.2â289.2/145.4 and 453.2â289.2, respectively. Ultrafiltration procedures presented non-specific bindings of (8.6⯱â¯1.2) % for bictegravir in plasma and (26.6⯱â¯3.1) % for bictegravir in cerebrospinal fluid. Linearity was observed between (10.70-8560)⯵g/L, (1.07-856.0)⯵g/L for total and unbound bictegravir in plasma, and 0.107-26.75⯵g/L for total and unbound bictegravir in cerebrospinal fluid. Imprecisions, absolute relative biases, normalized-matrix factors, and normalized-recoveries were ≤14.4%, ≤13.8%, (97.4-102.5) %, and (99.8-105.1) %, respectively. No significant interferences and carry-over were observed. The validated UHPLC-MS/MS procedures could be useful for pharmacokinetic and pharmacodynamic studies.
Subject(s)
Drug Monitoring/methods , HIV Infections/drug therapy , HIV Integrase Inhibitors/analysis , Heterocyclic Compounds, 4 or More Rings/analysis , Adult , Amides , Chemistry, Pharmaceutical/methods , Chromatography, High Pressure Liquid/methods , Feasibility Studies , Female , HIV Infections/blood , HIV Infections/cerebrospinal fluid , HIV Integrase Inhibitors/pharmacokinetics , HIV Integrase Inhibitors/therapeutic use , Heterocyclic Compounds, 3-Ring , Heterocyclic Compounds, 4 or More Rings/pharmacokinetics , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Humans , Male , Middle Aged , Piperazines , Pyridones , Reproducibility of Results , Tandem Mass Spectrometry/methods , Ultrafiltration/methodsABSTRACT
La búsqueda de tratamientos eficaces contra la pandemia actual por COVID-19 ha supuesto un desafïo enorme para la comunidad científica. De hecho, no existe todavía un tratamiento claramente efectivo, además de las medidas de soporte, contra el SARS-CoV-2. Los esfuerzos se han centrado en recuperar fármacos antivirales empleados previamente contra otras infecciónes viricas y en el uso de antiinflamatorios, dado el estado hiperinflamatorio que pueden sufrir los pacientes con COVID-19 y que se asocia con un peor pronóstico de la enfermedad. Sin embargo, estos fármacos, usados en ocasiones de manera compasiva, pueden causar efectos secundarios graves o interacciones farmacológicas que se debe conocer. El objetivo de este artículo es revisar el estado actual del conocimiento sobre los tratamientos farmacológicos más usados contra la COVID-19 en nuestro medio, prestando una especial atención a los efectos secundarios y las interacciones farmacológicas relacionadas con el sistema cardiovascular
The search for effective treatments against COVID-19 in the current pandemic has presented the scientific community with an enormous challenge. In fact, there is still no effective treatment for SARS-CoV-2 infection, apart from supportive measures. Research has focused on re-examining antiviral drugs that were previously used against other viral infections and on the use of anti-inflammatories, since COVID-19 patients can develop a hyperinflammatory state, which is associated with a poorer disease prognosis. However, these drugs, sometimes administered on a compassionate-use basis, can cause serious side effects or drug interactions that we should be aware of. The aim of this article is to provide an overview of what is currently known about the pharmacological therapies most frequently used against COVID-19 in our field, while paying particular attention to the adverse events and drug interactions that can affect the cardiovascular system
Subject(s)
Humans , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Pandemics , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Cardiovascular System/drug effects , Drug InteractionsSubject(s)
Humans , Male , Aged , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/surgery , Amyloidosis, Familial/diagnosis , Amyloidosis, Familial/surgery , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/genetics , SpainABSTRACT
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