Post hoc analysis of the SuperB and Zilverpass trials for treatment of long and complex superficial femoral artery lesions.

OBJECTIVE: In two randomized controlled trials, the outcomes of endovascular treatment of complex femoropopliteal arterial lesions were compared with bypass surgery and considered a valid alternative treatment. The aim of this study was to compare both endovascular treatment options with the hypothesis that implantation of heparin-bonded self-expanding covered stents (Viabahn [SECS]) or drug-eluting stents (ZilverPTX [DES]) are related to similar clinical outcomes at 1-year follow-up. METHODS: In a post-hoc analysis, the SuperB trial and Zilverpass databases were merged. Patients in the endovascular treatment arms were included, and data was analyzed in an intention-to-treat (ITT) and a per-protocol (PP) fashion. Data included baseline and lesion characteristics, procedural details, and follow-up data. The primary endpoint of this study was primary patency at 1-year follow-up. The secondary endpoints were secondary patency, target lesion revascularization (TLR), limb loss, and all-cause mortality. RESULTS: A total of 176 patients were included; 63 in the SECS arm and 113 in the DES arm. Through 1-year follow-up, there were no significant differences in primary patency (ITT: 63.4% vs 71.1%: P = .183 and PP: 60.8% vs 71.1%; P = .100). Secondary patency rates were not significantly different in the ITT analysis (86.5% vs 95.1%; P = .054), but in the PP analysis, there was a significant difference in favor of the DES group (SECS, 85.6% vs DES, 95.1%; P = .038). There was no significant difference in freedom from TLR between groups (79.6% vs 77.0%; P = .481). No major amputations were performed in the SECS group, and two were performed in the DES group (1.8%). Survival rate was 98.2% in the SECS group, and 91.3% in the DES group after 1-year follow-up (P = .106). Based on diagnosis (intermittent claudication vs chronic limb-threatening ischemia) no differences between patients with intermittent claudication and chronic limb-threatening ischemia were observed in primary patency, secondary patency and freedom from TLR. CONCLUSIONS: Treatment of complex femoropopliteal arterial disease with the heparin-bonded Viabahn endoprosthesis and the Zilver PTX drug-eluting stent are related to similar primary and secondary patency, and TLR rates at 1 year, except for secondary patency in the PP analysis. This study further supports the endovascular treatment of long complex lesions in the femoropopliteal artery.

Prevalence of chronic rhinosinusitis without/with nasal polyps according to severity in Spain.

BACKGROUND: The worldwide prevalence range of chronic rhinosinusitis (CRS) is 5-12%; from this, 20 % have nasal polyps. Due to the little epidemiological data about CRS in the Spanish population, this study analyses the prevalence and severity of CRS with (CRSwNP) or without (CRSsNP) nasal polyps, and their connection with other coexisting type 2 inflammatory diseases in Spain. METHODOLOGY: This is a retrospective, large-scale, nationwide, epidemiological study based on the electronic medical records from the BIG-PAC® database. Patients diagnosed of CRSsNP and CRSwNP were identified using specific disease codes. The severe form of the disease was defined as patients who received at least a long course of antibiotics in CRSsNP or ≥2 short courses of systemic corticosteroids in CRSwNP in ≤12 months during the last 2 years, and/or had previous sinus surgery. Physician-diagnosed prevalence, sociodemographic and clinical characteristics, and disease severity were assessed. RESULTS: Out of a cohort of 1,012,257 patients (≥18 years old), 42,863 and 7,550 patients with diagnosed CRSsNP and CRSwNP, respectively, were analysed. The overall prevalence of diagnosed CRS was 5.1%, being 4.3% and 0.8% for CRSsNP and CRSwNP, respectively. Patients with CRSwNP and severe forms of the disease were older and had higher levels of type 2 inflammatory biomarkers than CRSsNP patients and non-severe disease. CONCLUSIONS: Although CRSsNP was more prevalent than CRSwNP, the severe forms of CRS were more frequent in patients with CRSwNP. In addition, CRSwNP patients had a higher incidence of coexisting type 2 inflammatory diseases.

Incidence of healthcare-associated Clostridioides difficile infection in a quaternary referral university hospital in Brazil.

Clostridioides difficile infection (CDI) is an important cause of diarrhea in hospitals worldwide. The incidence of CDI in Latin America has not yet been standardized. To fill this gap, the present study performed a daily active surveillance, for three months, between April to July of 2021, at a quaternary referral university hospital in Brazil. The incidence density was 9.2 cases per 10,000 patient-days. Cases were associated mostly with ribotypes 014 and 106 (44% and 22%, respectively). Ribotype 027 was not identified. The findings strongly reinforce the need for broad epidemiological studies on the incidence of CDI in Brazilian hospitals to increase the understanding, prevention, and treatment of this infection.

Metazoan parasites of white mullet Mugil curema Valenciennes, 1836 (Mugiliformes: Mugilidae) and new records of occurrence in the western Atlantic, Brazil.

Mugil curema is a pelagic fish species and it is considered the most common species of the Mugilidae family on the Brazilian coast. The objective of this study was to compile the existing information on the metazoan parasites of this host, as well as including new records from specimens captured in the Cabedelo city, state of Paraíba, Brazil. In the present study, we listed 81 taxa belonging to ten groups previously recorded for the host M. curema, and included 16 species recorded in the Cabedelo region. Eight out of 16 parasite taxa found in the Cabedelo region are first host records for M. curema: Ligophorus brasiliensis, Ligophorus sp.1, Ligophorus sp.2 (Monogenea), Fellodistomidae gen. sp., Bucephalidae gen. sp. (Digenea), Pharyngodonidae gen. sp. (Nematoda), Piscicolidae gen. sp. (Hirudinea) and Lernaeopodidae gen. sp. (Copepoda). Monogenea was the most abundant taxonomic group, followed by Copepoda. Despite the number of existing parasitological studies on this host species, new records of occurrence were made for the Cabedelo region and for the host, indicating that the knowledge about the parasites associated with this fish species is still under construction, especially because of its wide geographic distribution.

Milk lymphocyte profile and macrophage functions: new insights into the immunity of the mammary gland in quarters infected with Corynebacterium bovis.

BACKGROUNDS: The present study explored the viability of bovine milk macrophages, their intracellular production of reactive oxygen and nitrogen species (RONS), and their phagocytosis of Staphylococcus aureus, as well as the profile of lymphocytes, from healthy udder quarters and udder quarters infected by Corynebacterium bovis. The study included 28 healthy udder quarters from 12 dairy cows and 20 udder quarters infected by C. bovis from 10 dairy cows. The percentages of macrophages and lymphocytes were identified by flow cytometry using monoclonal antibodies. Macrophage viability, RONS production, and S. aureus phagocytosis were evaluated by flow cytometry. RESULTS: Milk samples from quarters infected with C. bovis showed a lower percentage of macrophages but an increased number of milk macrophages per mL and a higher percentage of macrophages that produced intracellular RONS and phagocytosed S. aureus. No effect of C. bovis infection on macrophage viability was found. Udder quarters infected by C. bovis showed a higher percentage of T cells and CD4+ T lymphocytes, but no effect was found on the percentage of CD8+ CD4- T, CD8- CD4- T, or B lymphocytes. CONCLUSIONS: Thus, our results corroborate, at least in part, the finding that intramammary infections by C. bovis may offer protection against intramammary infections by major pathogens.

Application of chemometric tools in the development and sensory evaluation of gluten-free cracknel biscuits with the addition of chia seeds and turmeric powder.

Gluten-free biscuits were developed with the addition of chia seeds (Salvia hispanica L.) and turmeric powder. An experimental design 22 were employed in the formulation optimization that promotes better sensory acceptance through acceptance test with a hedonic scale of 9 points. For characterization purposes, the centesimal composition from chia seeds and the turmeric powder were determined. The biscuits were produced from an optimized formulation with and without chia seeds and turmeric powder with microbiological results safe for consumption by evaluation Salmonella sp., positive coagulase Staphylococcus, and Coliforms to 45 °C. The Principal Components Analysis (PCA) was used in the investigation of sensory results (color, flavor, texture, smell, appearance, overall impression). It was also considered the habits of consuming food with/without gluten, purchase intentions, including age and gender. The results show that there is no distinction between the biscuits with the addition of chia seeds and turmeric powder. A statistical test using the confidence ellipse confirms that there no significant difference, at a 95% confidence level, among the sensory results for the biscuits with and without chia seeds and turmeric powder.

The Use of Bone Marrow-Derived Stem Cells in the Treatment of a Comminuted Tibiotarsal Fracture in a Juvenile Red-legged Seriema (Cariama cristata).

An adult red-legged seriema (Cariama cristata) presented with a comminuted fracture of the tibiotarsus and fibula. Surgery was performed, and a type II external fixator, with 2 distal and 2 proximal pins, was used to stabilize the fracture. After a 10-day stabilization period, the bird developed a second fracture on the same bone, proximal to the first fracture site. Another surgery was performed on the seriema similar to the first one. However, in this second surgical procedure a single pin, instead of 2 perpendicular pins, was placed proximally to the fracture site. After the second surgical procedure, bone marrow stem cells (BMSCs) from the seriema's left ulna were collected. Twenty-seven days after the second surgery, the BMSCs were transplanted, into the fracture sites. Twenty-four days after the stem cells were injected into the fractures (51 days after the second surgical procedure), radiographic images revealed healing bone calluses at the fracture sites. The fracture healing was relatively long for this case (a total of 75 days). The addition of bone marrow stem cell therapy to the use of external fixation may have contributed to the healing observed radiographically 24 days after administration; therefore, bone marrow stem cell therapy, in addition to traditional surgical fracture reduction and stabilization, may be a promising therapeutic approach for avian cases with similar injuries and bone anatomy. However, as this is a single case, this therapeutic modality deserves further application and study. Moreover, we suggest modifications in the bone marrow stem cell collection and therapy, which may be useful for future studies and application involving birds.

Diversity and genetic stability in banana genotypes in a breeding program using inter simple sequence repeats (ISSR) markers.

Banana (Musa spp) is a fruit species frequently cultivated and consumed worldwide. Molecular markers are important for estimating genetic diversity in germplasm and between genotypes in breeding programs. The objective of this study was to analyze the genetic diversity of 21 banana genotypes (FHIA 23, PA42-44, Maçã, Pacovan Ken, Bucaneiro, YB42-47, Grand Naine, Tropical, FHIA 18, PA94-01, YB42-17, Enxerto, Japira, Pacovã, Prata-Anã, Maravilha, PV79-34, Caipira, Princesa, Garantida, and Thap Maeo), by using inter-simple sequence repeat (ISSR) markers. Material was generated from the banana breeding program of Embrapa Cassava & Fruits and evaluated at Embrapa Coastal Tablelands. The 12 primers used in this study generated 97.5% polymorphism. Four clusters were identified among the different genotypes studied, and the sum of the first two principal components was 48.91%. From the Unweighted Pair Group Method using Arithmetic averages (UPGMA) dendrogram, it was possible to identify two main clusters and subclusters. Two genotypes (Garantida and Thap Maeo) remained isolated from the others, both in the UPGMA clustering and in the principal cordinate analysis (PCoA). Using ISSR markers, we could analyze the genetic diversity of the studied material and state that these markers were efficient at detecting sufficient polymorphism to estimate the genetic variability in banana genotypes.

Genetic diversity in natural populations of mangaba in Sergipe, the largest producer State in Brazil.

Mangaba (Hancornia speciosa Gomes) is found in areas of coastal tablelands in the Brazilian Northeast and Cerrado regions. This species has been subjected to habitat fragmentation that is mainly due to human activity, and requires conservation strategies. The aim of this study was to analyze the structure and inter- and intrapopulation genetic diversity of natural populations of H. speciosa Gomes using inter-simple sequence repeat (ISSR) molecular markers. A total of 155 individuals were sampled in 10 natural populations (ITA, PAC, IND, EST, BC, PIR, JAP, BG, NEO, and SANT) in the State of Sergipe, Brazil. Fifteen primers were used to generate 162 fragments with 100% polymorphism. Genetic analysis showed that the variability between populations (77%) was higher than within populations (23%). It was possible to identify five different groups by the unweighted pair group method with arithmetic mean and principal coordinate analysis, and only one individual (E10) remained isolated. Using ISSR markers it was possible to obtain a molecular profile of the populations evaluated, showing that these markers were effective and exhibited sufficient polymorphism to estimate the genetic variability of natural populations of H. speciosa Gomes.

Management of BU-HIV co-infection.

BACKGROUND: Buruli Ulcer (BU)-HIV co-infection is an important emerging management challenge for BU disease. Limited by paucity of scientific studies, guidance for management of this co-infection has been lacking. METHODS: Initiated by WHO, a panel of experts in BU and HIV management developed guidance principles for the management of BU-HIV co-infection based on review of available scientific evidence, current treatment experience, and global recommendations established for management of HIV infection and tuberculosis. RESULTS: The expert panel agreed that all BU patients should be offered quality provider-initiated HIV testing and counselling. In areas with high prevalence of malaria and/or bacterial infections, all patients with HIV co-infection should be started on cotrimoxazole preventative therapy. Combination antibiotic treatment for BU should be commenced before starting antiretroviral therapy (ART) and provided for 8 weeks duration. The suggested combination is rifampicin (10 mg/kg daily up to a maximum of 600 mg/day) plus streptomycin (15 mg/kg daily). An alternative regimen is rifampicin plus clarithromycin (7.5 mg/kg twice daily up to a maximum of 1000 mg daily) although due to drug interactions with antiretroviral drugs this regimen should be used with caution. ART should be initiated in all BU-HIV co-infected patients with symptomatic HIV disease (WHO clinical stage 3 or 4) regardless of CD4 cell count and in asymptomatic individuals with CD4 count ≤500 cells/mm(3) . If CD4 count is not available, BU-HIV co-infected individuals with category 2 or 3 BU disease should be offered ART. For eligible individuals, ART should be commenced as soon as possible within 8 weeks after commencing BU treatment, and as a priority in those with advanced HIV disease (CD4 ≤ 350 cells/mm(3) or WHO stage 3 or 4 disease). All co-infected patients should be actively screened for tuberculosis before commencing BU treatment and before starting ART. Programmes should implement a monitoring and reporting system to document the outcomes of BU-HIV interventions. CONCLUSIONS: Knowledge of the clinical and epidemiological interactions between BU and HIV disease is limited. While awaiting more urgently needed evidence, current management practice of both diseases has been useful to build simple 'common sense' preliminary guidance on how to manage BU-HIV co-infection.

Stakeholder Analysis as a strategic tool in framing collaborative governance arenas for marine litter monitoring.

Monitoring and assessment of marine litter requires multi-stakeholder involvement at national and subnational levels. Collaborative governance approaches are important, but often fail without adequate effort towards identifying and engaging stakeholders with appropriate profiles for the issue at stake. Stakeholder Analysis (SA) is increasingly used to ensure efficient governance arrangements. Our hypothesis is that SA contributes to collaborative governance processes for marine litter policies. We explored a pioneer participatory process in Brazil, where SA was applied to identify, categorize, and prioritize stakeholders, and analyze their power and interest, for the Strategic Plan for Monitoring and Assessing Marine Litter in the state of São Paulo. A top-down/bottom-up approach revealed that snowball sampling complemented the stakeholder assemblage identified by the consultation of experts. Prioritization of data-related stakeholders streamlined the participatory process. The interest-power matrix evaluated stakeholders' influences, guiding specific engagement strategies. We highlight the significance of SA in collaborative governance and mobilizing key stakeholders for effective marine litter monitoring initiatives, contributing to the global agenda to combat marine pollution.

Nutrition risk prevalence and screening tools' validity in pediatric patients: A systematic review.

Nutrition screening (NS) allows health professionals to identify patients at nutritional risk (NR), enabling early nutrition intervention. This study aimed to systematically review the criterion validity of NS tools for hospitalized non-critical care pediatric patients and to estimate the prevalence of NR in this population. This research was performed using PubMed, Embase, and Scopus databases until June 2021. The reviewers extracted the studies' general information, the population characteristics, the NR prevalence, and the NS tools' concurrent and predictive validity data. Quality evaluation was performed using the Newcastle-Ottawa Scale, adapted Newcastle-Ottawa Scale, and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The primary studies were qualitatively analyzed, and descriptive statistics were calculated to describe the NR prevalence. Of the total 3944 studies found, 49 met the inclusion criteria. Ten different pediatric NS tools were identified; the most frequently used were Screening Tool for Risk on Nutritional Status and Growth (STRONGkids), Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP), and Pediatric Yorkhill Malnutrition Score (PYMS). The mean NR prevalence was 59.85% (range, 14.6%-96.9%). Among all NS tools analyzed, STRONGkids and PYMS showed the best diagnostic performance. STRONGkids had the most studies of predictive validity showing that the NR predicted a higher hospital length of stay (odds ratio [OR], 1.96-8.02), health complications during hospitalization (OR, 3.4), and the necessity for nutrition intervention (OR, 18.93). Considering the diagnostic accuracy, robust and replicated findings of predictive validity, and studies' quality, STRONGkids performed best in identifying NR in the pediatric population among the tools identified.

Fast and efficient electrochemical thinning of ultra-large supported and free-standing MoS2 layers on gold surfaces.

Molybdenum disulfide (MoS2) is a very promising layered material for electrical, optical, and electrochemical applications because of its unique and outstanding properties. To unlock its full potential, among different preparation routes, electrochemistry has gain interest due to its simple, fast, scalable and simple instrumentation. However, obtaining large-area monolayer MoS2 that will enable the fabrication of novel electronic and electrochemical devices is still challenging. In this work, we reported a simple and fast electrochemical thinning process that results in ultra-large MoS2 down to monolayer on Au surfaces. The high affinity of MoS2 by Au surfaces enables the removal of bulk layers while preserving the first layer attached to the electrode. With a proper choice of the applied potential, more than 90% of the bulk regions can be removed from large-area MoS2 crystals, as confirmed by atomic force microscopy, photoluminescence, and Raman spectroscopy. We further address a set of contributions that are helpful to elucidate the features of MoS2, namely, the hyphenation of electrochemistry and optical microscopy for real-time observation of the thinning process that was revealed to occur from the edges to the center of the flake, an image treatment to estimate the thinning area and thinning rate, and the preparation of free-standing MoS2 layers by electrochemically thinning bulk flakes on microhole-structured Ni/Au meshes.

Biocompatible Wearable Electrodes on Leaves toward the On-Site Monitoring of Water Loss from Plants.

Impedimetric wearable sensors are a promising strategy for determining the loss of water content (LWC) from leaves because they can afford on-site and nondestructive quantification of cellular water from a single measurement. Because the water content is a key marker of leaf health, monitoring of the LWC can lend key insights into daily practice in precision agriculture, toxicity studies, and the development of agricultural inputs. Ongoing challenges with this monitoring are the on-leaf adhesion, compatibility, scalability, and reproducibility of the electrodes, especially when subjected to long-term measurements. This paper introduces a set of sensing material, technological, and data processing solutions that overwhelm such obstacles. Mass-production-suitable electrodes consisting of stand-alone Ni films obtained by well-established microfabrication methods or ecofriendly pyrolyzed paper enabled reproducible determination of the LWC from soy leaves with optimized sensibilities of 27.0 (Ni) and 17.5 kΩ %-1 (paper). The freestanding design of the Ni electrodes was further key to delivering high on-leaf adhesion and long-term compatibility. Their impedances remained unchanged under the action of wind at velocities of up to 2.00 m s-1, whereas X-ray nanoprobe fluorescence assays allowed us to confirm the Ni sensor compatibility by the monitoring of the soy leaf health in an electrode-exposed area. Both electrodes operated through direct transfer of the conductive materials on hairy soy leaves using an ordinary adhesive tape. We used a hand-held and low-power potentiostat with wireless connection to a smartphone to determine the LWC over 24 h. Impressively, a machine-learning model was able to convert the sensing responses into a simple mathematical equation that gauged the impairments on the water content at two temperatures (30 and 20 °C) with reduced root-mean-square errors (0.1% up to 0.3%). These data suggest broad applicability of the platform by enabling direct determination of the LWC from leaves even at variable temperatures. Overall, our findings may help to pave the way for translating "sense-act" technologies into practice toward the on-site and remote investigation of plant drought stress. These platforms can provide key information for aiding efficient data-driven management and guiding decision-making steps.

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update.

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

Bifunctional Metal Meshes Acting as a Semipermeable Membrane and Electrode for Sensitive Electrochemical Determination of Volatile Compounds.

The monitoring of toxic inorganic gases and volatile organic compounds has brought the development of field-deployable, sensitive, and scalable sensors into focus. Here, we attempted to meet these requirements by using concurrently microhole-structured meshes as (i) a membrane for the gas diffusion extraction of an analyte from a donor sample and (ii) an electrode for the sensitive electrochemical determination of this target with the receptor electrolyte at rest. We used two types of meshes with complementary benefits, i.e., Ni mesh fabricated by robust, scalable, and well-established methods for manufacturing specific designs and stainless steel wire mesh (SSWM), which is commercially available at a low cost. The diffusion of gas (from a donor) was conducted in headspace mode, thus minimizing issues related to mesh fouling. When compared with the conventional polytetrafluoroethylene (PTFE) membrane, both the meshes (40 µm hole diameter) led to a higher amount of vapor collected into the electrolyte for subsequent detection. This inedited fashion produced a kind of reverse diffusion of the analyte dissolved into the electrolyte (receptor), i.e., from the electrode to bulk, which further enabled highly sensitive analyses. Using Ni mesh coated with Ni(OH)2 nanoparticles, the limit of detection reached for ethanol was 24-fold lower than the data attained by a platform with a PTFE membrane and placement of the electrode into electrolyte bulk. This system was applied in the determination of ethanol in complex samples related to the production of ethanol biofuel. It is noteworthy that a simple equation fitted by machine learning was able to provide accurate assays (accuracies from 97 to 102%) by overcoming matrix effect-related interferences on detection performance. Furthermore, preliminary measurements demonstrated the successful coating of the meshes with gold films as an alternative raw electrode material and the monitoring of HCl utilizing Au-coated SSWMs. These strategies extend the applicability of the platform that may help to develop valuable volatile sensing solutions.

Development and evaluation of naproxen-loaded sericin/alginate beads for delayed and extended drug release using different covalent crosslinking agents.

Different polymer matrix compositions based on sericin and alginate blend (using or not the covalent crosslinking agents dibasic sodium phosphate, polyvinyl alcohol and polyethylene glycol) were evaluated to entrap naproxen. Sericin has been shown to be essential for improving incorporation efficiency. Comparing the formulations with and without crosslinking agent, the best results were obtained for that composed only of sericin and alginate, with satisfactory values of entrapment efficiency (>80%) and drug loading capacity (>20%). In this case, delayed release (<10% in acid medium) and prolonged release (~360 min) were achieved, with a complex release mechanism involving swelling and polymer chain relaxation. The incorporation of the drug could be confirmed by the techniques of characterization of X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), as well as drug compatibility with the polymer matrix. In addition, particles of suitable size for multiparticulate systems were obtained and with higher thermal stability when compared to the pure drug.

Incidence and predictors of death, retention, and switch to second-line regimens in antiretroviral- treated patients in sub-Saharan African Sites with comprehensive monitoring availability.

BACKGROUND: Antiretroviral treatment programs in sub-Saharan Africa have high rates of early mortality and loss to follow-up. Switching to second-line regimens is often delayed because of limited access to laboratory monitoring. METHODS: Retrospective analysis was performed of a cohort of adults who initiated a standard first-line antiretroviral treatment at 5 public sector sites in 3 African countries. Monitoring included routine CD4 cell counts, human immunodeficiency virus RNA measures, and records of whether appointments were kept. Incidence and predictors of death, loss to follow-up, and switch to second-line regimens were analyzed by time-to-event approaches. RESULTS: A total of 3749 patients were analyzed; at baseline, 37.1% were classified as having World Health Organization disease stage 3 or 4, and the median CD4 cell count was 192 cells/mL. First-line regimens were nevirapine based in 96.5% of patients; 17.7% of patients attended <95% of their drug pickup appointments. During 4545 person-years of follow-up, mortality was 8.6 deaths per 100 person-years and was predicted by lower baseline CD4 cell count, lower hemoglobin level, and lower body mass index (calculated as weight in kilograms divided by the square of height in meters); more-advanced clinical stage of infection; male sex; and more missed drug pickup appointments. Dropouts (which accrued at a rate of 2.1 dropouts per 100 person-years) were predicted by a lower body mass index, more missed visits and missed drug pickup appointments, and later calendar year. Incidence of switches to second-line regimens was 4.9 per 100 person-years; increased hazards were observed with lower CD4 cell count and earlier calendar year at baseline. In patients who switched, virological failure was predicted by combined clinical and CD4 criteria with 74% sensitivity and 30% specificity. CONCLUSIONS: In an antiretroviral treatment program employing comprehensive monitoring, the probability of switching to second-line therapy was limited. Regular pickup of medication was a predictor of survival and was also strongly predictive of patient retention.

Management of HIV-infected patients with MDR- and XDR-TB in resource-limited settings.

The emergence of extensively drug-resistant tuberculosis (XDR-TB) poses a significant public health threat for human immunodeficiency virus (HIV) programmes and tuberculosis (TB) control efforts. Recent reports demonstrate high mortality rates among HIV-infected multidrug-resistant (MDR) and XDR-TB patients compared to those without HIV infection. Transmission of these highly resistant TB strains is occurring both within health facilities and in the community. We review the principles of a sound public health approach to this problem, including early diagnosis, treatment for suspected disease, patient support and adherence and sound infection control measures. In the context of drug-resistant TB, we elaborate on current World Health Organization antiretroviral guidelines addressing management issues related to timing of antiretroviral treatment (ART), drug interactions and drug toxicities among patients receiving both ART and second-line TB regimens. We highlight the important research agenda that exists at the intersection of MDR- and XDR-TB and HIV disease.

Genotyping of Mycobacterium tuberculosis over two periods: a changing scenario for tuberculosis transmission.

OBJECTIVE: To evaluate changes in the molecular epidemiology of tuberculosis (TB) in Zaragoza, Spain, over a decade that has seen large social and health changes, including the attenuation of the human immunodeficiency virus (HIV) epidemic and increased immigration. DESIGN: A population-based molecular study was conducted using standard restriction fragment length polymorphism IS6110 typing that included all patients with bacteriologically confirmed TB living in the Zaragoza area from 2001 to 2004. The current situation was compared with that described in a previous study from 1993 to 1995. RESULTS: A total of 454 Mycobacterium tuberculosis isolates were genotyped; 239 (52.6%) were grouped in 45 clusters composed of 2 to 85 isolates. Independent risk factors for clustering were identified. The main differences with the previous study were the increase of TB cases among immigrants, a decrease in HIV-TB co-infected patients and the occurrence of a large TB outbreak involving 85 patients (M. tuberculosis Zaragoza [MTZ] strain). CONCLUSION: A change in the epidemiological pattern of TB has been observed in the last years. TB transmission is more common among the Spanish-born population, while foreign birth is significantly less associated with clustering. A single epidemic strain caused 18.7% of all TB cases.