A primary care psychoeducational group intervention for patients with depression and physical comorbidity: A qualitative study with a gender perspective.

OBJECTIVE: To explore the experiences and emotions of individuals with depression and physical comorbidity within the context of psychoeducational group interventions led by primary care nurses in Catalunya (Spain). METHOD: A psychoeducational group intervention was conducted in the first semester of 2019 with 13 primary care teams (rural/urban) and 95 participants with depression and physical comorbidity. The qualitative research and phenomenological perspective were based on 13 field diaries and 7 semi-structured interviews carried out with the observer nurses. The interviews were recorded and transcribed. Codes were identified by segmenting the text into citations/verbatim accounts and emerging categories/subcategories by regrouping the codes. The results were triangulated among the researchers to identify and compare similarities and differences. RESULTS: Four major themes were found: (a) gender differences; (b) coping strategies and changes observed during the intervention; (c) functions of the group as a therapeutic element; and (d) the nurses' perceptions of the group experience. Gender differences were identified in relation to experiences and emotions. CONCLUSIONS: As some patients acquired skills/behaviours during the intervention that helped them initiate changes and the nurses were satisfied with the intervention, it is important to include this information when planning effective interventions for patients with this profile.

Synergistic Effects of Sanglifehrin-Based Cyclophilin Inhibitor NV651 with Cisplatin in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), commonly diagnosed at an advanced stage, is the most common primary liver cancer. Owing to a lack of effective HCC treatments and the commonly acquired chemoresistance, novel therapies need to be investigated. Cyclophilins-intracellular proteins with peptidyl-prolyl isomerase activity-have been shown to play a key role in therapy resistance and cell proliferation. Here, we aimed to evaluate changes in the gene expression of HCC cells caused by cyclophilin inhibition in order to explore suitable combination treatment approaches, including the use of chemoagents, such as cisplatin. Our results show that the novel cyclophilin inhibitor NV651 decreases the expression of genes involved in several pathways related to the cancer cell cycle and DNA repair. We evaluated the potential synergistic effect of NV651 in combination with other treatments used against HCC in cisplatin-sensitive cells. NV651 showed a synergistic effect in inhibiting cell proliferation, with a significant increase in intrinsic apoptosis in combination with the DNA crosslinking agent cisplatin. This combination also affected cell cycle progression and reduced the capacity of the cell to repair DNA in comparison with a single treatment with cisplatin. Based on these results, we believe that the combination of cisplatin and NV651 may provide a novel approach to HCC treatment.

Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV.

Duration of protection from SARS-CoV-2 infection in people living with HIV (PWH) following vaccination is unclear. In a substudy of the phase II/III the COV002 trial (NCT04400838), 54 HIV+ male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells > 350 cells/µL) received 2 doses of ChAdOx1 nCoV-19 (AZD1222) 4-6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and Meso Scale Discovery [MSD]), neutralization, ACE-2 inhibition, IFN-γ ELISpot, activation-induced marker (AIM) assay and T cell proliferation. We show that, 6 months after vaccination, the majority of measurable immune responses were greater than prevaccination baseline but with evidence of a decline in both humoral and cell-mediated immunity. There was, however, no significant difference compared with a cohort of HIV-uninfected individuals vaccinated with the same regimen. Responses to the variants of concern were detectable, although they were lower than WT. Preexisting cross-reactive T cell responses to SARS-CoV-2 spike were associated with greater postvaccine immunity and correlated with prior exposure to beta coronaviruses. These data support the ongoing policy to vaccinate PWH against SARS-CoV-2, and they underpin the need for long-term monitoring of responses after vaccination.

Novel Cyclophilin Inhibitor Decreases Cell Proliferation and Tumor Growth in Models of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), the most common primary liver cancer, is usually diagnosed in its late state. Tyrosine kinase inhibitors such as sorafenib and regorafenib are one of the few treatment options approved for advanced HCC and only prolong the patient's life expectancy by a few months. Therefore, there is a need for novel effective treatments. Cyclophilins are intracellular proteins that catalyze the cis/trans isomerization of peptide bonds at proline residues. Cyclophilins are known to be overexpressed in HCC, affecting therapy resistance and cell proliferation. In the present study, we explored the potential of cyclophilin inhibitors as new therapeutic options for HCC in vitro and in vivo. Our results showed that the novel cyclophilin inhibitor, NV651, was able to significantly decrease proliferation in a diverse set of HCC cell lines. The exposure of HCC cells to NV651 caused an accumulation of cells during mitosis and consequent accumulation in the G2/M phase of the cell cycle. NV651 reduced tumor growth in vivo using an HCC xenograft model without affecting the body weights of the animals. The safety aspects of NV651 were also confirmed in primary human hepatocytes without any cytotoxic effects. Based on the results obtained in this study, we propose NV651 as a potential treatment strategy for HCC.

Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial.

BACKGROUND: Data on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV. METHODS: In this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18-55 years with HIV were enrolled at two HIV clinics in London, UK. Eligible participants were required to be on antiretroviral therapy (ART), with undetectable plasma HIV viral loads (<50 copies per mL), and CD4 counts of more than 350 cells per µL. A prime-boost regimen of ChAdOx1 nCoV-19, with two doses was given 4-6 weeks apart. The primary outcomes for this substudy were safety and reactogenicity of the vaccine, as determined by serious adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and antibody-mediated live virus neutralisation. Cell-mediated immune responses were measured by ex-vivo IFN-γ enzyme-linked immunospot assay (ELISpot) and T-cell proliferation. All outcomes were compared with an HIV-uninfected group from the main COV002 study within the same age group and dosing strategy and are reported until day 56 after prime vaccination. Outcomes were analysed in all participants who received both doses and with available samples. The COV002 study is registered with ClinicalTrials.gov, NCT04400838, and is ongoing. FINDINGS: Between Nov 5 and Nov 24, 2020, 54 participants with HIV (all male, median age 42·5 years [IQR 37·2-49·8]) were enrolled and received two doses of ChAdOx1 nCoV-19. Median CD4 count at enrolment was 694·0 cells per µL (IQR 573·5-859·5). No serious adverse events occurred. Local and systemic reactions occurring during the first 7 days after prime vaccination included pain at the injection site (26 [49%] of 53 participants with available data), fatigue (25 [47%]), headache (25 [47%]), malaise (18 [34%]), chills (12 [23%]), muscle ache (19 [36%]), joint pain (five [9%]), and nausea (four [8%]), the frequencies of which were similar to the HIV-negative participants. Anti-spike IgG responses by ELISA peaked at day 42 (median 1440 ELISA units [EUs; IQR 704-2728]; n=50) and were sustained until day 56 (median 941 EUs [531-1445]; n=49). We found no correlation between the magnitude of the anti-spike IgG response at day 56 and CD4 cell count (p=0·93) or age (p=0·48). ELISpot and T-cell proliferative responses peaked at day 14 and 28 after prime dose and were sustained to day 56. Compared with participants without HIV, we found no difference in magnitude or persistence of SARS-CoV-2 spike-specific humoral or cellular responses (p>0·05 for all analyses). INTERPRETATION: In this study of people with HIV, ChAdOx1 nCoV-19 was safe and immunogenic, supporting vaccination for those well controlled on ART. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

Inhibition of mitotic kinase Mps1 promotes cell death in neuroblastoma.

Neuroblastoma is the most common paediatric cancer type. Patients diagnosed with high-risk neuroblastoma have poor prognosis and occasionally tumours relapse. As a result, novel treatment strategies are needed for relapse and refractory neuroblastoma patients. Here, we found that high expression of Mps1 kinase (mitotic kinase Monopolar Spindle 1) was associated with relapse-free neuroblastoma patient outcomes and poor overall survival. Silencing and inhibition of Mps1 in neuroblastoma or PDX-derived cells promoted cell apoptosis via the caspase-dependent mitochondrial apoptotic pathway. The mechanism of cell death upon Mps1 inhibition was dependent on the polyploidization/aneuploidization of the cells before undergoing mitotic catastrophe. Furthermore, tumour growth retardation was confirmed in a xenograft mouse model after Mps1-inhibitor treatment. Altogether, these results suggest that Mps1 expression and inhibition can be considered as a novel prognostic marker as well as a therapeutic strategy for the treatment of high-risk neuroblastoma patients.

Prevalence of congenital malformations and deformities of the osteomuscular system in live newborns in Mexico, 2008-2017.

BACKGROUND: From 2009 to 2010 in Mexico. CMDOMS prevalence was 27.4/10,000 births. The first places were congenital deformation of the feet with a prevalence of 8.0 and congenital deformation of the hip with 6.7/10,000 births. OBJECTIVE: To estimate for Mexico the national prevalence of CMDOMS in live births, by state and municipality, as well as to analyze spatial distribution by these same territorial delimitations. METHOD: A database of 20,175,422 newborns (NB) alive from 2008 to 2017 was integrated. Percentages and prevalence were calculated at the national level, federal entities and municipalities, with confidence intervals at 95%. Maps were made and prevalence was stratified. RESULTS: The congenital malformation prevalence rate was 77.8/10,000 NB. CMDOMS were in first place with 40.8% and a prevalence of 31.8/10,000 NB. Prevalence by federal entity presented a range of 8.0-75.8/10,000 NB, were stratified by states and municipalities for presentation on maps. CONCLUSION: In Mexico for the years 2008-2017 an increase in CMDOMS prevalence was observed globally and in particular of some specific causes.

ANTECEDENTES: En México, de 2009 a 2010, la prevalencia de las malformaciones y deformidades congénitas del sistema osteomuscular (MDCSOM) fue de 27.4 por 10,000 nacimientos. Los primeros lugares los ocuparon la deformación congénita de los pies, con una prevalencia de 8.0, y la deformación congénita de la cadera, con 6.7 por 10,000 nacimientos. OBJETIVO: Estimar para México la prevalencia nacional de MDCSOM en nacidos vivos (NV), por entidad federativa y municipio, y analizar su distribución espacial por esas mismas delimitaciones territoriales. MÉTODO: Se integró una base de datos de 20,175,422 NV en 2008-2017. Se calcularon porcentajes y prevalencias por ámbito nacional, entidades federativas y municipios, con intervalos de confianza al 95%. Se elaboraron mapas y se estratificaron las prevalencias. RESULTADOS: La tasa de prevalencia de malformaciones congénitas fue de 77.8 por 10,000 NV. Se ubicaron en el primer lugar las MDCSOM, con un 40.8% y una prevalencia de 31.8 por 10,000 NV. Las prevalencias por entidad federativa presentaron un rango de 8.0 a 75.8 por 10,000 NV; se estratificaron por estados y municipios para su presentación en mapas. CONCLUSIÓN: En México, para los años 2008-2017, se observa un incremento en las prevalencias de las MDCSOM en forma global y en particular por algunas causas específicas.

Demand for obstetric care and density of health resources for childbearing age Mexican women.

INTRODUCTION: In Mexico, there is an increase recorded in the number of C-sections, as well as inequity and inequality in the distribution of resources for obstetric care. OBJECTIVE: To identify the states and municipalities in Mexico that concentrate the demand for obstetric care and the C-section rates and their relationship with health resources and women of childbearing age (WCBA). METHOD: Births of the 2008-2017 period were recorded, grouped into five municipal strata, as well as 2017 health resources and WCBA. RESULTS: The 2008-2017 national rate of C-sections was 45.3/100 births; 95 and 97 % of births and C-sections were concentrated in the "very high" stratum, where 80 % or more of health resources were used, with overuse standing out. The density of health resources assigned to WCBAs reflected inequity and inequality. CONCLUSIONS: The high concentration of obstetric demand and health resources supply could entail a higher recurrence of C-sections. Policies for C-section reduction should consider proper organization and administration of health resources.

INTRODUCCIÓN: México registra aumento de las cesáreas e inequidad y desigualdad en la distribución de recursos para la atención obstétrica. OBJETIVO: Identificar las entidades y municipios en México que concentran la demanda de atención obstétrica y tasas de cesáreas y su relación con los recursos en salud y mujeres en edad fértil (MEF). MÉTODO: Se registraron los nacimientos del periodo 2008-2017, agrupados en cinco estratos municipales, y los recursos en salud y MEF de 2017. RESULTADOS: La tasa nacional de cesáreas 2008-2017 fue de 45.3/100 nacimientos; 95 y 97 % de los nacimientos y cesáreas se concentraron en el estrato "muy alto", en el cual se utilizó 80 % o más de los recursos en salud y destacó la sobreutilización. La densidad de recursos en salud destinados a las MEF reflejó inequidad y desigualdad. CONCLUSIONES: La alta concentración de la demanda obstétrica y oferta de los recursos en salud pudiera conllevar mayor recurrencia a la cesárea. En las políticas de reducción de cesáreas es necesario considerar la organización y administración adecuadas de los recursos en salud.

Preferential Killing of Tetraploid Colon Cancer Cells by Targeting the Mitotic Kinase PLK1.

BACKGROUND/AIMS: Chromosomal instability is a well-known factor in the progression of different types of cancer, including colorectal cancer. Chromosomal instability results in severely rearranged karyotypes and aneuploidy. Tetraploidy constitutes an intermediate phase during the polyploidy/aneuploidy cascade in oncogenesis, and tetraploid cells are particularly resistant to chemotherapy. Whether inhibition of the mitotic protein polo-like kinase 1 (PLK1) prevents the survival of tetraploid colon cancer cells is unknown. METHODS: Diploid and tetraploid cells were transfected with siPLK1 or treated with PLK1 inhibitor Bi2536 in combination with spindle poison. Cell toxicity was assessed via crystal violet staining and clonogenic assay. Flow cytometry assessment analyzed numerous cell apoptotic parameters and cell cycle phases. Synergistic activity between Bi2536 and paclitaxel, vincristine or colchicine was calculated using the CompuSyn software. RESULTS: Inhibition or abrogation of PLK1 prevented the survival of colon cancer cells, specifically tetraploid cells. The cell death induced by PLK inhibition was due to mitotic slippage, followed by the activation of the intrinsic pathway of apoptosis. We further demonstrated that co-treatment of the tetraploid colon cancer cells with a PLK1 inhibitor and the microtubule polymerisation inhibitor vincristine or colchicine, but not the microtubule depolymerisation inhibitor paclitaxel, provoked a lethal synergistic effect. CONCLUSION: PLK1 inhibition together with microtubule-targeting chemicals, serve as a potent therapeutic strategy for targeting tetraploid cancer cells.

Demanda de atención obstétrica y densidad de recursos en salud para mujeres mexicanas en edad fértil / Demand for obstetric care and density of health resources for childbearing age Mexican women

Resumen Introducción: México registra aumento de las cesáreas e inequidad y desigualdad en la distribución de recursos para la atención obstétrica. Objetivo: Identificar las entidades y municipios en México que concentran la demanda de atención obstétrica y tasas de cesáreas y su relación con los recursos en salud y mujeres en edad fértil (MEF). Método: Se registraron los nacimientos del periodo 2008-2017, agrupados en cinco estratos municipales, y los recursos en salud y MEF de 2017. Resultados: La tasa nacional de cesáreas 2008-2017 fue de 45.3/100 nacimientos; 95 y 97 % de los nacimientos y cesáreas se concentraron en el estrato “muy alto” (470 municipios), en el cual se utilizó 80 % o más de los recursos en salud y destacó la sobreutilización. La densidad de recursos en salud destinados a las MEF reflejó inequidad y desigualdad. Conclusiones: La alta concentración de la demanda obstétrica y oferta de los recursos en salud pudiera conllevar mayor recurrencia a la cesárea. En las políticas de reducción de cesáreas es necesario considerar la organización y administración adecuadas de los recursos en salud.

Abstract Introduction: In Mexico, there is an increase in the number of C-sections, as well as inequity and inequality in the distribution of resources for obstetric care. Objective: To identify the states and municipalities in Mexico that concentrate the demand for obstetric care and the C-section rates and their relationship with health resources and women of childbearing age (WCBA). Method: Births of the 2008-2017 period were recorded, grouped into five municipal strata, as well as 2017 health resources and WCBA. Results: The 2008-2017 national rate of C-sections was 45.3/100 births; 95 and 97 % of births and C-sections were concentrated in the “very high” stratum, where 80 % or more of health resources were used, with overuse standing out. The density of health resources assigned to WCBAs reflected inequity and inequality Conclusions: The high concentration of obstetric demand and health resources supply could entail a higher recurrence of C-sections. Policies for C-section reduction should consider proper organization and administration of health resources.

Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa.

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is a hereditary blistering disorder due to a lack of type VII collagen. At present, treatment is mainly supportive. OBJECTIVES: To determine whether intravenous allogeneic bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs) are safe in RDEB adults and if the cells improve wound healing and quality of life. METHODS: We conducted a prospective, phase I/II, open-label study recruiting 10 RDEB adults to receive 2 intravenous infusions of BM-MSCs (on day 0 and day 14; each dose 2-4 × 106 cells/kg). RESULTS: BM-MSCs were well tolerated with no serious adverse events to 12 months. Regarding efficacy, there was a transient reduction in disease activity scores (8/10 subjects) and a significant reduction in itch. One individual showed a transient increase in type VII collagen. LIMITATIONS: Open-label trial with no placebo. CONCLUSIONS: MSC infusion is safe in RDEB adults and can have clinical benefits for at least 2 months.

Evaluation of NV556, a Novel Cyclophilin Inhibitor, as a Potential Antifibrotic Compound for Liver Fibrosis.

Hepatic fibrosis can result as a pathological response to nonalcoholic steatohepatitis (NASH). Cirrhosis, the late stage of fibrosis, has been linked to poor survival and an increased risk of developing hepatocellular carcinoma, with limited treatment options available. Therefore, there is an unmet need for novel effective antifibrotic compounds. Cyclophilins are peptidyl-prolyl cis-trans isomerases that facilitate protein folding and conformational changes affecting the function of the targeted proteins. Due to their activity, cyclophilins have been presented as key factors in several stages of the fibrotic process. In this study, we investigated the antifibrotic effects of NV556, a novel potent sanglifehrin-based cyclophilin inhibitor, in vitro and in vivo. NV556 potential antifibrotic effect was evaluated in two well-established animal models of NASH, STAM, and methionine-choline-deficient (MCD) mice, as well as in an in vitro 3D human liver ECM culture of LX2 cells, a human hepatic stellate cell line. We demonstrate that NV556 decreased liver fibrosis in both STAM and MCD in vivo models and decreased collagen production in TGFß1-activated hepatic stellate cells in vitro. Taken together, these results present NV556 as a potential candidate for the treatment of liver fibrosis.

Cyclophilin Inhibitor NV556 Reduces Fibrosis and Hepatocellular Carcinoma Development in Mice With Non-Alcoholic Steatohepatitis.

Hepatocellular carcinoma (HCC), the third major cause of cancer mortality, can result from non-alcoholic steatohepatitis (NASH). Due to limited efficacy of drugs approved for HCC and no drug available yet for NASH, identification of new effective treatments is crucial. Here, we investigated whether NV556, a cyclophilin inhibitor derived from sanglifehrins, would decrease the development of NASH and HCC in a preclinical mouse model. For our experiment, male mice were administered streptozotocin to disrupt pancreatic cells and nourished with high-fat diet since 3 weeks of age. Afterward, NV556 or vehicle was orally administered daily for 6 weeks before the 14-week-old time point for the development of NASH, or 10 weeks before the 30-week-old time point for the establishment of HCC. Body weight, blood glucose level, and liver weight were recorded. Moreover, for NASH, livers were histologically examined for inflammation and steatosis. Collagen was measured by Sirius Red staining of hepatic tissues. Systemic cytokine levels in serum were detected by multiplex assays. For HCC, nodules of livers were measured and scored according to a developed system with number and size of nodules as criteria. NV556 significantly decreased collagen deposition (p = 0.0281), but did not alter inflammation, steatosis, body and liver weight, and systemic cytokine production compared to control mice with NASH symptoms. For HCC, NV556 statistically reduced the number (p = 0.0091) and diameter of tumorous nodules (p = 0.0264), along with liver weight (p = 0.0026) of mice.Our study suggests NV556 as a promising candidate for treatment of NASH-derived fibrosis and HCC.

Safety and early efficacy outcomes for lentiviral fibroblast gene therapy in recessive dystrophic epidermolysis bullosa.

BACKGROUNDRecessive dystrophic epidermolysis bullosa (RDEB) is a severe form of skin fragility disorder due to mutations in COL7A1 encoding basement membrane type VII collagen (C7), the main constituent of anchoring fibrils (AFs) in skin. We developed a self-inactivating lentiviral platform encoding a codon-optimized COL7A1 cDNA under the control of a human phosphoglycerate kinase promoter for phase I evaluation.METHODSIn this single-center, open-label phase I trial, 4 adults with RDEB each received 3 intradermal injections (~1 × 106 cells/cm2 of intact skin) of COL7A1-modified autologous fibroblasts and were followed up for 12 months. The primary outcome was safety, including autoimmune reactions against recombinant C7. Secondary outcomes included C7 expression, AF morphology, and presence of transgene in the injected skin.RESULTSGene-modified fibroblasts were well tolerated, without serious adverse reactions or autoimmune reactions against recombinant C7. Regarding efficacy, there was a significant (P < 0.05) 1.26-fold to 26.10-fold increase in C7 mean fluorescence intensity in the injected skin compared with noninjected skin in 3 of 4 subjects, with a sustained increase up to 12 months in 2 of 4 subjects. The presence of transgene (codon-optimized COL7A1 cDNA) was demonstrated in the injected skin at month 12 in 1 subject, but no new mature AFs were detected.CONCLUSIONTo our knowledge, this is the first human study demonstrating safety and potential efficacy of lentiviral fibroblast gene therapy with the presence of COL7A1 transgene and subsequent C7 restoration in vivo in treated skin at 1 year after gene therapy. These data provide a rationale for phase II studies for further clinical evaluation.TRIAL REGISTRATIONClincalTrials.gov NCT02493816.FUNDINGCure EB, Dystrophic Epidermolysis Bullosa Research Association (UK), UK NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, and Fondation René Touraine Short-Exchange Award.

Estudio de variabilidad geográfica de las hospitalizaciones potencialmente evitables en México durante tres quinquenios.

INTRODUCCIÓN: Las enfermedades que motivan hospitalización potencialmente evitable tienen la característica de ser sensibles a la prevención, diagnóstico y control ambulatorio en atención primaria a la salud. OBJETIVOS: Identificar la tendencia nacional de la hospitalización potencialmente evitable entre 2001 y 2015 y analizar el patrón geográfico a nivel municipal y priorizar municipios. MÉTODO: Se usaron los egresos hospitalarios de la Secretaría de Salud. Se calcularon tasas de prevalencia nacionales y razones municipales, estandarizadas por edad y sexo. Se emplearon estadísticos de variabilidad para analizar y elaborar mapas. RESULTADOS: De los egresos hospitalarios, 10.39, 9.81 y 9.26 % se clasificaron como hospitalizaciones potencialmente evitables para cada periodo quinquenal. La tasa nacional se incrementó en el lapso estudiado: de 36.27 a 47.24 por 10 000 habitantes. La diabetes mellitus, las gastroenteritis y otras enfermedades de las vías respiratorias inferiores fueron las causas de mayor frecuencia. Los patrones geográficos en los tres periodos fueron semejantes. Se identificaron 487 municipios prioritarios, 174 con alto uso y 313 con sobreuso hospitalario, que concentraron 35.83 % de las hospitalizaciones evitables, 8.58 y 27.25 %, respectivamente. CONCLUSIONES: En México existe amplia variabilidad geográfica de la hospitalización potencialmente evitable con un patrón casi inmutable. INTRODUCTION: Diseases that motivate potentially preventable hospitalization (PH) have the characteristic of being sensitive to prevention, diagnosis and control on an outpatient basis in primary care. OBJECTIVES: To identify the national trend of potentially avoidable hospitalization between 2001 and 2015; to analyze its geographical pattern at the municipal level and prioritize municipalities. METHOD: Hospital discharge records from the Ministry of Health were used. National prevalence rates and municipal PH ratios, standardized by age and gender, were calculated. Variability statistics were used to analyze and generate maps. RESULTS: Among all hospital discharges, 10.39%, 9.81% and 9.26% were classified as PH for each period. The national PH rate did increase in the studied period: from 36.27 to 47.24 per 10,000 population. Diabetes mellitus, gastroenteritis and other diseases of the lower respiratory tract were the most common causes. Geographic patterns of PH were similar for the three periods. A total of 487 priority municipalities were identified, 174 with hospital high use and 313 with overuse, 35.83 % were avoidable hospitalizations, 8.58% and 27.25%, respectively. CONCLUSIONS: In Mexico there is wide geographical variability in PH, with an almost unchanging geographical pattern.

A Paper-Based Test for Screening Newborns for Sickle Cell Disease.

The high cost, complexity and reliance on electricity, specialized equipment and supplies associated with conventional diagnostic methods limit the scope and sustainability of newborn screening for sickle cell disease (SCD) in sub-Saharan Africa and other resource-limited areas worldwide. Here we describe the development of a simple, low-cost, rapid, equipment- and electricity-free paper-based test capable of detecting sickle hemoglobin (HbS) in newborn blood samples with a limit of detection of 2% HbS. We validated this newborn paper-based test in a cohort of 159 newborns at an obstetric hospital in Cabinda, Angola. Newborn screening results using the paper-based test were compared to conventional isoelectric focusing (IEF). The test detected the presence of HbS with 81.8% sensitivity and 83.3% specificity, and identified SCD newborns with 100.0% sensitivity and 70.7% specificity. The use of the paper-based test in a two-stage newborn screening process could have excluded about 70% of all newborns from expensive confirmatory testing by IEF, without missing any of the SCD newborns in the studied cohort. This study demonstrates the potential utility of the newborn paper-based test for reducing the overall cost of screening newborns for SCD and thus increasing the practicality of universal newborn SCD screening programs in resource-limited settings.

[Percentage of births and fertility rates in adolescents in Mexico (2008-2012): stratification and priorization of municipalities with high risk]. / Porcentaje de nacimientos y tasas de fecundidad en adolescentes de México (2008-2012): estratificación y priorización de municipios con alto riesgo.

BACKGROUND: Mexico in 2008 was designed as the first place of adolescent pregnancy at the Organization for Economic Cooperation and Development, with specific fertility rate (SFR) for 15-1 9years of age of 64.2/1,000 woman at the same age. OBJECTIVE: Estimate of percentage births and SFR in adolescent population at national, state and municipal level in Mexico in 2008-2012 at the total group of adolescents 10 to 1 9 years old and by subgroups of 10-14 and 15 tol 9 years old, identifying the priority municipalities with adolescence pregnancies. MATERIAL AND METHOD: Data bases of certificates of live birth and fetal death with gestational age of 22-45 weeks were joined in 2008-2012. RESULTS: A data base of 1 0'585,032 births in 2008-2012 was obtained, 98.9% were live births and 1.1% was stillbirths. The SFR nationwide for the period 2008-2012 were of the order of 3.l for the group of 10-1 4years, 75.3 for 15-19, 39.6 for the total group of 10-19 years and 66.1 for 20 to 49 years per 1000 women for the same age. CONCLUSION: In the last decade it has increased teen pregnancy as well as the percentage of births and the fertility rate in this age group, worrying situation for the high risk of biological, psychological and social damage that pregnancy early.