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Background: Worldwide, 1.7 million children younger than 15 years were living with HIV in 2021. Only 52% of them had access to antiretrovirals (ARVs). Lack of age-appropriate ARV formulations (i.e. easy to swallow for young infants, acceptable taste) remains the main obstacle to the access to ARVs. Therefore, a strawberry-flavoured Abacavir/Lamivudine/Lopinavir/Ritonavir (30/15/40/10 mg) fixed-dose combination of granules in a capsule (4-in-1) for children living with HIV weighing 3-25 kg was developed. Objective: We assessed caregivers' perceived acceptability of the 4-in-1 compared with previous paediatric ARV formulations and factors influencing acceptability. Methods: This exploratory qualitative case study embedded in a phase I/II, open-label, randomized cross-over pharmacokinetic, safety and acceptability study (LOLIPOP) was conducted in three sites in Uganda (May 2019-October 2020). Thirty-six children weighing between 3 and 19.9 kg participated in the main study. We purposively sampled caregiver-child dyads according to weight bands, and conducted 20 semi-structured interviews with caregivers and 5 with healthcare providers. We triangulated these results with a quantitative acceptability questionnaire. We analysed interviews inductively using NVivo12 adopting a thematic analysis approach and acceptability questionnaires descriptively to assess concordance between them. Results: All caregivers found the 4-in-1 formulation highly acceptable and easier to use than previous formulations (i.e. pellets/tables/syrup). Appealing taste, ease of administration, easy storage and children's acceptance contributed to acceptability despite structural challenges of food shortage and HIV stigma. Visible improvements in children's health and comprehensive and tailored healthcare provider support to overcome initial difficulties such as vomiting increased caregivers' acceptance. Concordant results from questionnaire- and interview-data confirmed high acceptability. Conclusion: Caregivers of children in all weight bands in this sample found the 4-in-1 granules highly acceptable compared with the pellets/tablets combination. Healthcare providers' support to caregivers allowed for individual tailoring of drug administration despite challenges such as food shortage. This enabled short-term adherence. These findings informed further practical recommendations. Registration: Clinical trial number: NCT03836833.
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Autobiographical memory (AM) impairments influence both sense of identity and social functioning of patients with schizophrenia. However, cognitive remediation methods addressing these difficulties do not sufficiently consider the heterogeneity of this disorder and frequently face methodological limitations. The aim of the present study was to evaluate the efficacy of a method using a wearable camera (NarrativeClip®), through an alternating treatments design across two types of AM training. In parallel, repeated measures were used to appreciate the efficacy, specificity, and generalizability of the programme's benefits. Three patients were invited to wear the camera during 24 personal events. Ten of these events memories were trained by visual cueing (wearable camera condition), 10 others by verbal cueing (written diary condition) and 4 were not trained (control condition). Using pictures collected by the wearable camera seemed particularly relevant, since it promoted more detailed recalls than the diary method, from the first training session and until the end of a one-year follow-up. In addition, the repeated measures performed revealed (1) the efficacy (improvement in AM capacities after participating in the programme), (2) specificity (persistence of working memory deficits), and (3) generalizability (improvement in measures of episodic memory) of our cognitive remediation programme's effects.
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OBJECTIVES: Ethambutol protects against the development of resistance to co-administered drugs in the intensive phase of first-line anti-TB treatment in children. It is especially relevant in settings with a high prevalence of HIV or isoniazid resistance. We describe the population pharmacokinetics of ethambutol in children with TB to guide dosing in this population. METHODS: We pooled data from 188 intensively sampled children from the DATiC, DNDi and SHINE studies, who received 15-25â mg/kg ethambutol daily according to WHO guidelines. The median (range) age and weight of the cohort were 1.9 (0.3-12.6)â years and 9.6 (3.9-34.5)â kg, respectively. Children with HIV (HIV+; nâ=â103) received ART (lopinavir/ritonavir in 92%). RESULTS: Ethambutol pharmacokinetics were best described by a two-compartment model with first-order elimination and absorption transit compartments. Clearance was estimated to reach 50% of its mature value by 2â months after birth and 99% by 3â years. Typical steady-state apparent clearance in a 10â kg child was 15.9â L/h. In HIV+ children on lopinavir/ritonavir, bioavailability was reduced by 32% [median (IQR) steady-state Cmaxâ=â0.882 (0.669-1.28) versus 1.66 (1.21-2.15)â mg/L). In young children, bioavailability correlated with age. At birth, bioavailability was 73.1% of that in children 3.16â years or older. CONCLUSIONS: To obtain exposure within the 2-6â mg/L recommended range for Cmax, the current doses must be doubled (or tripled with HIV+ children on lopinavir/ritonavir) for paediatric patients. This raises concerns regarding the potential for ocular toxicity, which would require evaluation.
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Fármacos Anti-VIH , Infecciones por VIH , Fármacos Anti-VIH/uso terapéutico , Antituberculosos/farmacocinética , Antituberculosos/uso terapéutico , Niño , Preescolar , Etambutol/farmacocinética , Etambutol/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Humanos , Recién Nacido , Lopinavir/farmacocinética , Lopinavir/uso terapéutico , RitonavirRESUMEN
BACKGROUND: Antiretroviral options for neonates (younger than 28 days) should be expanded. We evaluated the pharmacokinetics, safety, and acceptability of the "4-in-1" fixed-dose pediatric granule formulation of abacavir/lamivudine/lopinavir/ritonavir (30/15/40/10 mg) in neonates. METHODS: The PETITE study is an ongoing phase I/II, open-label, single-arm, 2-stage trial conducted in South Africa. In stage 1, term neonates exposed to HIV on standard antiretroviral prophylaxis (nevirapine ± zidovudine) received single dose(s) of the 4-in-1 formulation, followed by intensive pharmacokinetic sampling and safety assessments. At each PK visit, blood was drawn after an observed dose at 1, 2, 4, 8, and 12 hours postdose. In this study, we have reported the planned interim pharmacokinetic and safety analysis after completion of the single-dose administration. RESULTS: Sixteen neonates, with a median (range) birth weight of 3130 g (2790-3590 g), completed 24 pharmacokinetic visits. The 4-in-1 formulation imposed relatively high doses of abacavir [8.6 mg/kg (6.6-11.4)] and lamivudine [4.3 mg/kg (3.3-5.7)] but lower doses of lopinavir [11.5 mg/kg (8.8-15.2)]. The geometric means (GM, 90% CI) AUC0-12 of abacavir, lamivudine, and lopinavir were 29.87 (26.29-33.93), 12.61 (10.72-14.83), and 3.49 (2.13-5.72) µg.h/mL, respectively. Lopinavir GM AUC0-12 was below the predefined target (20-100 µg.h/mL), and ritonavir concentrations were only detectable in 4 of the 120 (3%) samples. No adverse events were related to study drugs. No neonate had difficulty swallowing the 4-in-1 formulation. CONCLUSIONS: The high doses of abacavir and lamivudine (in mg/kg) and AUCs were safe, and the formulation was well tolerated; however, lopinavir/ritonavir exposures were extremely low, preventing its use in neonates use in neonates. Alternative pediatric solid antiretroviral formulations must be studied in neonates.
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Fármacos Anti-VIH , Infecciones por VIH , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/farmacocinética , Didesoxinucleósidos , Quimioterapia Combinada/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Humanos , Recién Nacido , Lamivudine/efectos adversos , Lamivudine/farmacocinética , Lopinavir/efectos adversos , Lopinavir/farmacocinética , Ritonavir/efectos adversos , Ritonavir/farmacocinéticaRESUMEN
INTRODUCTION: To achieve the elimination of hepatitis C virus (HCV), substantial scale-up in access to testing and treatment is needed. This will require innovation and simplification of the care pathway, through decentralisation of testing and treatment to primary care settings and task-shifting to non-specialists. The objective of this study was to evaluate the feasibility and effectiveness of decentralisation of HCV testing and treatment using rapid diagnostic tests (RDTs) in primary healthcare clinics (PHCs) among high-risk populations, with referral of seropositive patients for confirmatory viral load testing and treatment. METHODS: This observational study was conducted between December 2018 and October 2019 at 25 PHCs in three regions in Malaysia. Each PHC was linked to one or more hospitals, for referral of seropositive participants for confirmatory testing and pretreatment evaluation. Treatment was provided in PHCs for non-cirrhotic patients and at hospitals for cirrhotic patients. RESULTS: During the study period, a total of 15 366 adults were screened at the 25 PHCs, using RDTs for HCV antibodies. Of the 2020 (13.2%) HCV antibody-positive participants, 1481/2020 (73.3%) had a confirmatory viral load test, 1241/1481 (83.8%) were HCV RNA-positive, 991/1241 (79.9%) completed pretreatment assessment, 632/991 (63.8%) initiated treatment, 518/632 (82.0%) completed treatment, 352/518 (68.0%) were eligible for a sustained virological response (SVR) cure assessment, 209/352 (59.4%) had an SVR cure assessment, and SVR was achieved in 202/209 (96.7%) patients. A significantly higher proportion of patients referred to PHCs initiated treatment compared with those who had treatment initiated at hospitals (71.0% vs 48.8%, p<0.001). CONCLUSIONS: This study demonstrated the effectiveness and feasibility of a simplified decentralised HCV testing and treatment model in primary healthcare settings, targeting high-risk groups in Malaysia. There were good outcomes across most steps of the cascade of care when treatment was provided at PHCs compared with hospitals.
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Hepacivirus , Hepatitis C , Adulto , Antivirales/uso terapéutico , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Humanos , Malasia , Atención Primaria de SaludRESUMEN
BACKGROUND: In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV. METHODS: STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183. FINDINGS: Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment. INTERPRETATION: In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality. FUNDING: National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.
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Bencimidazoles/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Sofosbuvir/uso terapéutico , Valina/análogos & derivados , Proteínas no Estructurales Virales/antagonistas & inhibidores , Adulto , Anciano , Antivirales/administración & dosificación , Antivirales/efectos adversos , Antivirales/uso terapéutico , Bencimidazoles/administración & dosificación , Bencimidazoles/efectos adversos , Coinfección/epidemiología , Quimioterapia Combinada , Femenino , Genotipo , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Humanos , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/epidemiología , Cirrosis Hepática/etiología , Malasia/epidemiología , Masculino , Persona de Mediana Edad , ARN Viral/efectos de los fármacos , Seguridad , Sofosbuvir/administración & dosificación , Sofosbuvir/efectos adversos , Respuesta Virológica Sostenida , Tailandia/epidemiología , Resultado del Tratamiento , Valina/administración & dosificación , Valina/efectos adversos , Valina/uso terapéuticoRESUMEN
INTRODUCTION: In case of failure of non-operative treatment of isolated supraspinatus tear, tendon surgery can improve shoulder function and alleviate pain. The present study hypothesis was that isolated supraspinatus repair shows good healing, with improved clinical results. MATERIALS AND METHODS: A prospective multicentre study followed up 199 patients (mean age, 57 years) for one year. Inclusion criteria comprised: isolated full-thickness supraspinatus tear, retraction grade<3, with the same double-row arthroscopic technique. Clinical assessment used Constant score at 6 weeks and 3, 6 and 12 months. Ultrasound control checked tendon repair quality on the Sugaya criteria, types I-II-III being considered as healed. RESULTS: At one year, mean Constant score had increased by 26 points (p<0.001). Healing rate was 94% (n=187): Sugaya type I, 46% (n=92); type II, 41% (n=81); type III, 7% (n=14). Mean Constant score was significantly higher in case of healing: 81 vs. 70 points (p=0.002). Constant score progression was identical in both healing groups throughout follow-up. Univariate analysis showed no correlation between epidemiological or tear-related factors and tendon healing. CONCLUSION: Arthroscopic repair of isolated small supraspinatus tear provided 94% healing. Clinical results were better when healing was achieved. LEVEL OF EVIDENCE: I, prospective cohort study.
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Lesiones del Manguito de los Rotadores , Manguito de los Rotadores , Artroscopía , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Estudios Prospectivos , Manguito de los Rotadores/diagnóstico por imagen , Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/cirugía , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
In children requiring lopinavir coformulated with ritonavir in a 4:1 ratio (lopinavir-ritonavir-4:1) and rifampin, adding ritonavir to achieve a 4:4 ratio with lopinavir (LPV/r-4:4) overcomes the drug-drug interaction. Possible drug-drug interactions within this regimen may affect abacavir concentrations, but this has never been studied. Children weighing <15 kg needing rifampin and LPV/r-4:4 were enrolled in a pharmacokinetic study and underwent intensive pharmacokinetic sampling on 3 visits: (i) during the intensive and (ii) continuation phases of antituberculosis treatment with LPV/r-4:4 and (iii) 1 month after antituberculosis treatment completion on LPV/r-4:1. Pharmacometric modeling and simulation were used to compare exposures across weight bands with adult target exposures. Eighty-seven children with a median (interquartile range) age and weight of 19 (4 to 64) months and 8.7 (3.9 to 14.9) kg, respectively, were included in the abacavir analysis. Abacavir pharmacokinetics were best described by a two-compartment model with first-order elimination and transit compartment absorption. After allometric scaling adjusted for the effect of body size, maturation could be identified: clearance was predicted to be fully mature at about 2 years of age and to reach half of this mature value at about 2 months of age. Abacavir bioavailability decreased 36% during treatment with rifampin and LPV/r-4:4 but remained within the median adult recommended exposure, except for children in the 3- to 4.9-kg weight band, in which the exposures were higher. The observed predose morning trough concentrations were higher than the evening values. Though abacavir exposure significantly decreased during concomitant administration of rifampin and LPV/r-4:4, it remained within acceptable ranges. (This study is registered in ClinicalTrials.gov under identifier NCT02348177.).
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Didesoxinucleósidos/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Lopinavir/farmacocinética , Rifampin/farmacocinética , Ritonavir/farmacocinética , Tuberculosis Pulmonar/tratamiento farmacológico , Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/uso terapéutico , Antituberculosos/farmacocinética , Antituberculosos/uso terapéutico , Disponibilidad Biológica , Niño , Preescolar , Didesoxinucleósidos/uso terapéutico , Combinación de Medicamentos , Interacciones Farmacológicas , Humanos , Lopinavir/uso terapéutico , Estudios Prospectivos , Rifampin/uso terapéutico , Ritonavir/uso terapéuticoRESUMEN
Viral hepatitis is a major public health threat and a leading cause of death worldwide. Annual mortality from viral hepatitis is similar to that of other major infectious diseases such as HIV and tuberculosis. Highly effective prevention measures and treatments have made the global elimination of viral hepatitis a realistic goal, endorsed by all WHO member states. Ambitious targets call for a global reduction in hepatitis-related mortality of 65% and a 90% reduction in new infections by 2030. This Commission draws together a wide range of expertise to appraise the current global situation and to identify priorities globally, regionally, and nationally needed to accelerate progress. We identify 20 heavily burdened countries that account for over 75% of the global burden of viral hepatitis. Key recommendations include a greater focus on national progress towards elimination with support given, if necessary, through innovative financing measures to ensure elimination programmes are fully funded by 2020. In addition to further measures to improve access to vaccination and treatment, greater attention needs to be paid to access to affordable, high-quality diagnostics if testing is to reach the levels needed to achieve elimination goals. Simplified, decentralised models of care removing requirements for specialised prescribing will be required to reach those in need, together with sustained efforts to tackle stigma and discrimination. We identify key examples of the progress that has already been made in many countries throughout the world, demonstrating that sustained and coordinated efforts can be successful in achieving the WHO elimination goals.
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Gastroenterología/organización & administración , Salud Global/economía , Hepatitis/prevención & control , Hepatitis/virología , Adolescente , Adulto , Niño , Preescolar , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/mortalidad , Costo de Enfermedad , Atención a la Salud/métodos , Femenino , Salud Global/normas , Infecciones por VIH/mortalidad , Accesibilidad a los Servicios de Salud , Hepacivirus/aislamiento & purificación , Hepatitis/epidemiología , Hepatitis/mortalidad , Hepatitis B/epidemiología , Hepatitis B/mortalidad , Hepatitis B/prevención & control , Hepatitis B/transmisión , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis C/epidemiología , Hepatitis C/mortalidad , Hepatitis C/prevención & control , Hepatitis C/transmisión , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Tuberculosis/mortalidad , Vacunación/normas , Organización Mundial de la Salud , Adulto JovenRESUMEN
In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI -16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI -29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View.
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Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Quimioterapia Combinada/métodos , Fluconazol/uso terapéutico , Flucitosina/uso terapéutico , Infecciones por VIH/mortalidad , Meningitis Criptocócica/tratamiento farmacológico , África/epidemiología , Anfotericina B/agonistas , Anfotericina B/provisión & distribución , Antifúngicos/economía , Antifúngicos/provisión & distribución , Coinfección , Cryptococcus neoformans/efectos de los fármacos , Cryptococcus neoformans/patogenicidad , Países en Desarrollo , Manejo de la Enfermedad , Esquema de Medicación , Quimioterapia Combinada/economía , Fluconazol/economía , Fluconazol/provisión & distribución , Flucitosina/economía , Flucitosina/provisión & distribución , Guías como Asunto , Infecciones por VIH/patología , Infecciones por VIH/virología , Humanos , Renta , Meningitis Criptocócica/microbiología , Meningitis Criptocócica/mortalidad , Meningitis Criptocócica/patología , Análisis de SupervivenciaRESUMEN
: A multicentric, retrospective case-series analysis (facility-based) in five sites across Kenya, Malawi, Mozambique, and Uganda screened HIV-positive adults for hepatitis C virus (HCV) antibodies using Oraquick rapid testing and viral confirmation (in three sites). The results reveal a substantially lower prevalence than previously reported for these countries, suggesting that targeted integration of HCV screening in African HIV programs may be more impactful than routine screening.
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Infecciones por VIH/complicaciones , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/epidemiología , Adolescente , Adulto , África del Sur del Sahara/epidemiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Adulto JovenRESUMEN
Objectives: We evaluated the usefulness of an Aspergillus fumigatus quantitative PCR assay performed in bronchoalveolar lavage fluid (BAL) for the diagnosis and prognosis of both invasive and non-invasive aspergillosis. Methods: This 4-year retrospective study involved 613 at-risk patients who had either hematological disorders or other immunosuppressive conditions, notably solid organ transplants. Thirty-five patients had proven/probable aspergillosis and thirteen had chronic non-invasive aspergillosis. We compared PCR, galactomannan index and mycological analysis of BAL. Results: For invasive aspergillosis (IA), PCR performed in BAL yielded 88.6% sensitivity and 95.5% specificity. Comparatively, galactomannan index and mycological examination yielded only 56.3 and 63.6% sensitivity and 97.6 and 94.5% specificity, respectively. Considering the 13 chronic aspergillosis cases, PCR, galactomannan index and mycological examination yielded 76.9, 15.4, and 84.6% sensitivity and 92.2, 94.9, and 93% specificity, respectively. Fungal load in BAL evaluated by PCR was able to discriminate between aspergillosis and contamination, but not between invasive and non-invasive forms. Finally, fungal load was predictive of 90-day mortality, with 23.1% mortality for patients with less than 500 copies/mL versus 68.4% for patients above that cut-off (p < 0.05). Conclusion: Our results indicate that Aspergillus PCR in BAL is of particular interest for both the diagnosis and the prognosis of IA. It is likewise an interesting tool for the diagnosis of non-invasive forms.
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INTRODUCTION: Worldwide, 71 million people are infected with hepatitis C virus (HCV), which, without treatment, can lead to liver failure or hepatocellular carcinoma. HCV co-infection increases liver- and AIDS-related morbidity and mortality among HIV-positive people, despite ART. A 12-week course of HCV direct-acting antivirals (DAAs) usually cures HCV - regardless of HIV status. However, patents and high prices have created access barriers for people living with HCV, especially people who inject drugs (PWID). Inadequate access to and coverage of harm reduction interventions feed the co-epidemics of HIV and HCV; as a result, the highest prevalence of HCV is found among PWID, who face additional obstacles to treatment (including stigma, discrimination and other structural barriers). The HIV epidemic occurred during globalization of intellectual property rights, and highlighted the relationship between patents and the high prices that prevent access to medicines. Indian generic manufacturers produced affordable generic HIV treatment, enabling global scale-up. Unlike HIV, donors have yet to step forward to fund HCV programmes, although DAAs can be mass-produced at a low and sustainable cost. Unfortunately, although voluntary licensing agreements between originators and generic manufacturers enable low-income (and some lower-middle income countries) to buy generic versions of HIV and HCV medicines, most middle-income countries with large burdens of HCV infection and HIV/HCV co-infection are excluded from these agreements. Our commentary presents tactics from the HIV experience that treatment advocates can use to expand access to DAAs. DISCUSSION: A number of practical actions can help increase access to DAAs, including new research and development (R&D) paradigms; compassionate use, named-patient and early access programmes; use of TRIPS flexibilities such as compulsory licences and patent oppositions; and parallel importation via buyers' clubs. Together, these approaches can increase access to antiviral therapy for people living with HIV and viral hepatitis in low-, middle- and high-income settings. CONCLUSIONS: The HIV example provides helpful parallels for addressing challenges to expanding access to HCV DAAs. HCV treatment access - and harm reduction - should be massively scaled-up to meet the needs of PWID, and efforts should be made to tackle stigma and discrimination, and stop criminalization of drug use and possession.
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Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Accesibilidad a los Servicios de Salud , Hepatitis C/tratamiento farmacológico , Renta , Fármacos Anti-VIH/economía , Fármacos Anti-VIH/uso terapéutico , Antivirales/economía , Epidemias , Infecciones por VIH/epidemiología , Reducción del Daño , Hepatitis C/epidemiología , Humanos , PrevalenciaRESUMEN
BACKGROUND: Innovation contests are a novel approach to elicit good ideas and innovative practices in various areas of public health. There remains limited published literature on approaches to deliver hepatitis testing. The purpose of this innovation contest was to identify examples of different hepatitis B and C approaches to support countries in their scale-up of hepatitis testing and to supplement development of formal recommendations on service delivery in the 2017 World Health Organization hepatitis B and C testing guidelines. METHODS: This contest involved four steps: 1) establishment of a multisectoral steering committee to coordinate a call for contest entries; 2) dissemination of the call for entries through diverse media (Facebook, Twitter, YouTube, email listservs, academic journals); 3) independent ranking of submissions by a panel of judges according to pre-specified criteria (clarity of testing model, innovation, effectiveness, next steps) using a 1-10 scale; 4) recognition of highly ranked entries through presentation at international conferences, commendation certificate, and inclusion as a case study in the WHO 2017 testing guidelines. RESULTS: The innovation contest received 64 entries from 27 countries and took a total of 4 months to complete. Sixteen entries were directly included in the WHO testing guidelines. The entries covered testing in different populations, including primary care patients (n = 5), people who inject drugs (PWID) (n = 4), pregnant women (n = 4), general populations (n = 4), high-risk groups (n = 3), relatives of people living with hepatitis B and C (n = 2), migrants (n = 2), incarcerated individuals (n = 2), workers (n = 2), and emergency department patients (n = 2). A variety of different testing delivery approaches were employed, including integrated HIV-hepatitis testing (n = 12); integrated testing with harm reduction and addiction services (n = 9); use of electronic medical records to support targeted testing (n = 8); decentralization (n = 8); and task shifting (n = 7). CONCLUSION: The global innovation contest identified a range of local hepatitis testing approaches that can be used to inform the development of testing strategies in different settings and populations. Further implementation and evaluation of different testing approaches is needed.
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Hepatitis B/diagnóstico , Hepatitis C/diagnóstico , Guías como Asunto , Hepatitis B/economía , Hepatitis C/economía , Humanos , Tamizaje Masivo/economía , Atención Primaria de Salud/economía , Salud Pública/economía , Organización Mundial de la SaludRESUMEN
The International AIDS Society convened the 3rd International HIV/Viral Hepatitis Co-Infection Meeting on 17 July 2016 as part of the pre-conference program preceding the 21st International AIDS Conference held in Durban, South Africa. The meeting brought together a diversity of scientific, technical and community interests to discuss opportunities and challenges for increased prevention, diagnosis and treatment of viral hepatitis in people living with HIV, particularly in low- and middle-income settings. The objectives of the meeting were:i.To review the latest therapeutic developments in viral hepatitis;ii.To identify challenges such as high cost of medications for hepatitis C virus (HCV) and risk of developing viral resistance, and successes, such as the provision of HCV treatment in community-based settings, movements to reduce drug costs and increasing access, in relation to scaling up diagnosis, screening, antiviral treatment and prevention of viral hepatitis;iii.To advance the agenda for elimination of viral hepatitis as a public health problem. Discussions centred around the six key interventions outlined by the World Health Organization Global Health Sector Strategy on Viral Hepatitis 2016-2021: hepatitis B virus (HBV) vaccination (including birth dose); safe injection practices plus safe blood; harm reduction among people who inject drugs; safer sex practices; hepatitis B treatment; and hepatitis C cure. This article summarizes the main issues and findings discussed during the pre-conference meeting. One of the recommendations from the meeting delegates is universal implementation of birth dose vaccination for HBV without further delay to prevent mother-to-child transmission of infection. There is also the need to implement screening and treatment of hepatitis among pregnant women. A call was made for concerted efforts to be put together by all stakeholders towards addressing some of the structural barriers, including criminalization of drug use, discrimination and stigma that people living with viral hepatitis face. Finally, the need for greater advocacy was highlighted to enable access to therapy of viral hepatitis at lower cost than currently prevails. Implementation of these resolutions will help in achieving the target of eliminating viral hepatitis as a public health threat.
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Body image disturbances and massive weight loss are major clinical symptoms of anorexia nervosa (AN). The aim of the present study was to examine the influence of body changes and eating attitudes on self-face recognition ability in AN. Twenty-seven subjects suffering from AN and 27 control participants performed a self-face recognition task (SFRT). During the task, digital morphs between their own face and a gender-matched unfamiliar face were presented in a random sequence. Participants' self-face recognition failures, cognitive flexibility, body concern and eating habits were assessed with the Self-Face Recognition Questionnaire (SFRQ), Trail Making Test (TMT), Body Shape Questionnaire (BSQ) and Eating Disorder Inventory-2 (EDI-2), respectively. Subjects suffering from AN exhibited significantly greater difficulties than control participants in identifying their own face (p = 0.028). No significant difference was observed between the two groups for TMT (all p > 0.1, non-significant). Regarding predictors of self-face recognition skills, there was a negative correlation between SFRT and body mass index (p = 0.01) and a positive correlation between SFRQ and EDI-2 (p < 0.001) or BSQ (p < 0.001). Among factors involved, nutritional status and intensity of eating disorders could play a part in impaired self-face recognition.
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Anorexia Nerviosa/psicología , Trastorno Dismórfico Corporal/psicología , Imagen Corporal/psicología , Conducta Alimentaria/psicología , Reconocimiento en Psicología/fisiología , Adolescente , Adulto , Anorexia Nerviosa/complicaciones , Trastorno Dismórfico Corporal/complicaciones , Índice de Masa Corporal , Cognición/fisiología , Femenino , Humanos , Persona de Mediana Edad , Pruebas Neuropsicológicas , Autoimagen , Adulto JovenRESUMEN
BACKGROUND: Neoscytalidium species (formerly Scytalidium species) are black fungi that usually cause cutaneous infections mimicking dermatophytes lesions. Very few publications have reported invasive or disseminated infections. CASE PRESENTATION: In this paper, we report the clinical presentations, treatments and outcomes of five cases of invasive Neoscytalidium infections with cutaneous involvement, including two cases with disseminated infection, in five renal transplant recipients. To our knowledge, this is the first report of a series-albeit small-of renal transplant patients in whom this infection was identified. All cases occurred in a single hospital in Paris, France, between 2001 and 2011. Patients all originate from tropical area. CONCLUSION: Treatments of Neoscytalidium infection varied greatly, underlining the lack of a recommendation for a standardized treatment. All patients were cured after long-term antifungal therapy and/or surgical excision. Interestingly, one patient with disseminated infection involving the left elbow, the right leg, the lungs and the nasal septum was cured by medical therapy only without surgery. This may suggest that in contrast to others mycoses (such as mucormycosis), an adequate medical treatment could be sufficient for treating Neoscytalidium. We also point out the difficulties we had in diagnosing two patients with Kaposi's sarcoma because of the similarity of the lesions. Furthermore, our report underlines the need to check for this rare infection in immunocompromised kidney transplant recipients originating from tropical areas.
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Ascomicetos , Trasplante de Riñón/efectos adversos , Feohifomicosis/etiología , Receptores de Trasplantes , Anciano , Ascomicetos/aislamiento & purificación , Ascomicetos/patogenicidad , Emigrantes e Inmigrantes , Femenino , Francia , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Hongos Mitospóricos/aislamiento & purificación , Hongos Mitospóricos/patogenicidad , Feohifomicosis/tratamiento farmacológico , Feohifomicosis/patología , Sarcoma de Kaposi/diagnóstico , Clima TropicalRESUMEN
Of the estimated 130-150 million people who are chronically infected with hepatitis C virus, around 90% reside in low- and middle-income countries. People who inject drugs are disproportionately affected by HCV, with a global estimated prevalence (based on serological reports of HCV antibodies) of 67%; world-wide over 10 million people who inject drugs are infected with HCV. Treatment for HCV has improved dramatically in recent years with the arrival of new direct acting antivirals (DAAs) and this is stimulating considerable efforts to scale up access to treatment. However, treatment coverage among the general population is less than 10% in most countries, and coverage for people who inject drugs is generally much lower. It is estimated that globally around 2 million people who inject drugs need treatment for HCV. The DAAs offer significant potential to rapidly expand access to treatment for HCV. While the ideal combination therapy remains to be established, key characteristics include high efficacy, tolerability, pan-genotypic activity, short treatment duration, oral therapy, affordability, limited drug-drug interactions, and availability as fixed-dose combinations and once daily treatments. This paper outlines 10 key priorities for improving access to HCV treatment for people who inject drugs: (1) affordable access to direct acting antivirals; (2) increased awareness and testing; (3) standardization of treatment; (4) simplification of service delivery; (5) integration of services; (6) peer support; (7) treatment within a framework of comprehensive prevention; (8) tracking progress; (9) dedicated funding; and (10) enabling policies.
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Antivirales/uso terapéutico , Atención a la Salud/métodos , Países en Desarrollo/estadística & datos numéricos , Hepatitis C/tratamiento farmacológico , Abuso de Sustancias por Vía Intravenosa/complicaciones , Antivirales/efectos adversos , Antivirales/economía , Atención a la Salud/normas , Política de Salud , Accesibilidad a los Servicios de Salud , Hepatitis C/economía , Hepatitis C/epidemiología , Humanos , Abuso de Sustancias por Vía Intravenosa/rehabilitaciónRESUMEN
BACKGROUND: In 2013, an estimated 686,000 people died from hepatitis B virus (HBV) infection worldwide. Mass treatment programmes for hepatitis B will require very low drug costs. International treatment guidelines recommend first-line monotherapy with either entecavir or tenofovir disoproxil fumarate (TDF). While the basic patent on TDF expires in 2017/8, entecavir is already generic in several countries, including the US. The chemical structure of entecavir is related to abacavir, which costs <$200 per person-year in low-income countries. METHODS: The clinical efficacy, chemical structures, daily doses, routes of chemical synthesis, costs of raw materials and patent expiry dates were analysed for entecavir and TDF. Costs of sustainable, generic production were calculated for entecavir, and compared with published originator and generic prices in high- and low-income countries. RESULTS: With a daily dose of 0.5 mg, one year's supply of entecavir treatment requires <0.2 g of active pharmaceutical ingredient (API) per person, estimated to cost $4/year, based on quotations of API production from generic suppliers. With an additional $20 per year for formulation/packaging and a 50% profit margin, entecavir was estimated to cost a minimum of $36/person-year, substantially lower than current originator and generic prices. Entecavir is no longer under patent protection in the USA, China, Brazil and South Africa, with European expiry in 2017. Given differences in daily dosing, production volumes for entecavir would be 600 times lower than TDF (300 mg once daily) for treating the same numbers of patients. CONCLUSIONS: Mass treatment for hepatitis B with generic entecavir could be achieved at very low cost in all countries, provided that important projections can be met in terms of pricing for the API and finished dosage form.