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1.
Am J Hum Genet ; 109(9): 1667-1679, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-36055213

RESUMEN

African populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multi-generational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We find suggestive evidence for the rate of language transmission in matrilineal groups having been higher than that for patrilineal ones. We highlight both the diversity of variation within Africa as well as how within-Africa variation can be informative for broader variant interpretation; many variants that are rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity across Africa.


Asunto(s)
Variación Genética , Genética de Población , África Austral , Población Negra/genética , Estructuras Genéticas , Variación Genética/genética , Humanos
2.
N Engl J Med ; 387(2): 132-147, 2022 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-35660812

RESUMEN

BACKGROUND: In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown. METHODS: In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received lenalidomide until disease progression, unacceptable side effects, or both. The primary end point was progression-free survival. RESULTS: Among 357 patients in the RVD-alone group and 365 in the transplantation group, at a median follow-up of 76.0 months, 328 events of disease progression or death occurred; the risk was 53% higher in the RVD-alone group than in the transplantation group (hazard ratio, 1.53; 95% confidence interval [CI], 1.23 to 1.91; P<0.001); median progression-free survival was 46.2 months and 67.5 months. The percentage of patients with a partial response or better was 95.0% in the RVD-alone group and 97.5% in the transplantation group (P = 0.55); 42.0% and 46.8%, respectively, had a complete response or better (P = 0.99). Treatment-related adverse events of grade 3 or higher occurred in 78.2% and 94.2%, respectively; 5-year survival was 79.2% and 80.7% (hazard ratio for death, 1.10; 95% CI, 0.73 to 1.65). CONCLUSIONS: Among adults with multiple myeloma, RVD plus ASCT was associated with longer progression-free survival than RVD alone. No overall survival benefit was observed. (Funded by the National Heart, Lung, and Blood Institute and others; DETERMINATION ClinicalTrials.gov number, NCT01208662.).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia de Mantención , Mieloma Múltiple , Trasplante de Células Madre , Adulto , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Humanos , Lenalidomida/administración & dosificación , Lenalidomida/efectos adversos , Quimioterapia de Mantención/métodos , Melfalán/administración & dosificación , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/cirugía , Trasplante Autólogo
3.
Am J Hum Genet ; 108(4): 656-668, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33770507

RESUMEN

Genetic studies in underrepresented populations identify disproportionate numbers of novel associations. However, most genetic studies use genotyping arrays and sequenced reference panels that best capture variation most common in European ancestry populations. To compare data generation strategies best suited for underrepresented populations, we sequenced the whole genomes of 91 individuals to high coverage as part of the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study with participants from Ethiopia, Kenya, South Africa, and Uganda. We used a downsampling approach to evaluate the quality of two cost-effective data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole-genome sequencing data. We show that low-coverage sequencing at a depth of ≥4× captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5-1×) performed comparably to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation; 4× sequencing detects 45% of singletons and 95% of common variants identified in high-coverage African whole genomes. Low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, effectively identify novel variation particularly in underrepresented populations, and present opportunities to enhance variant discovery at a cost similar to traditional approaches.


Asunto(s)
Análisis Mutacional de ADN/economía , Análisis Mutacional de ADN/normas , Variación Genética/genética , Genética de Población/economía , África , Análisis Mutacional de ADN/métodos , Genética de Población/métodos , Genoma Humano/genética , Estudio de Asociación del Genoma Completo , Equidad en Salud , Humanos , Microbiota , Secuenciación Completa del Genoma/economía , Secuenciación Completa del Genoma/normas
4.
Compr Psychiatry ; 133: 152504, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38876004

RESUMEN

BACKGROUND: The link between trauma exposure and psychotic disorders is well-established. Further, specific types of trauma may be associated with specific psychotic symptoms. Network analysis is an approach that can advance our understanding of the associations across trauma types and psychotic symptoms. METHODS: We conducted a network analysis with data from 16,628 adult participants (mean age [standard deviation] = 36.3 years [11.5]; 55.8% males) with psychotic disorders in East Africa recruited between 2018 and 2023. We used the Life Events Checklist and the Mini International Neuropsychiatric Interview to determine whether specific trauma types experienced over the life course and specific psychotic symptoms were connected. We used an Ising model to estimate the network connections and bridge centrality statistics to identify nodes that may influence trauma types and psychotic symptoms. RESULTS: The trauma type "exposure to a war zone" had the highest bridge strength, betweenness, and closeness. The psychotic symptom "odd or unusual beliefs" had the second highest bridge strength. Exposure to a war zone was directly connected to visual hallucinations, odd or unusual beliefs, passivity phenomena, and disorganized speech. Odd or unusual beliefs were directly connected to transportation accidents, physical assault, war, and witnessing sudden accidental death. CONCLUSION: Specific trauma types and psychotic symptoms may interact bidirectionally. Screening for psychotic symptoms in patients with war-related trauma and evaluating lifetime trauma in patients with odd or unusual beliefs in clinical care may be considered points of intervention to limit stimulating additional psychotic symptoms and trauma exposure. This work reaffirms the importance of trauma-informed care for patients with psychotic disorders.


Asunto(s)
Trastornos Psicóticos , Humanos , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/psicología , Trastornos Psicóticos/diagnóstico , Adulto , Masculino , Femenino , Persona de Mediana Edad , África Oriental/epidemiología , Trauma Psicológico/epidemiología , Trauma Psicológico/psicología , Alucinaciones/epidemiología , Alucinaciones/psicología , Alucinaciones/diagnóstico
5.
Chaos ; 34(5)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38809904

RESUMEN

We analyze a system of two uniformly magnetized spheres, one fixed and the other free to slide in frictionless contact with the surface of the first. The centers of the two magnets, and their magnetic moments, are restricted to a plane. We search for sets of initial conditions that yield finite-amplitude oscillatory periodic solutions. We extend two small-amplitude base modes, one with orbital and spin motions that are in phase and the other out of phase, to finite amplitudes and show that the motion for arbitrary oscillatory solutions can be considered to be a nonlinear superposition of these base modes. Some solutions are pure periodic finite-amplitude extensions of one base mode, while others are hybrid finite-amplitude superpositions of the two modes. Hybrid modes with rational frequency ratios are periodic and come in families defined by their frequency ratios. We further characterize hybrid periodic modes by identifying two symmetry classes that describe their relative phases. We see continuous transitions between one finite-amplitude base mode and the other, with one mode gradually transforming into the other. We also calculate frequency spectra of nonperiodic modes, show that the two base modes have well-defined frequencies even for nonperiodic states, and show that periodic solutions can give clues about the behavior of nearby nonperiodic solutions. In the limit of small amplitudes, we confirm that the computed frequencies of these modes agree with small-amplitude analytical results. We also generate a Lyapunov exponent heatmap that reflects periodic and nonperiodic regions of state space.

6.
Haematologica ; 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38031762

RESUMEN

Examination of the impact of race and ethnicity on multiple myeloma (MM) outcomes has yielded inconsistent results. This retrospective, real-world (RW) study describes patient, disease, and treatment characteristics (and associations with survival outcomes) among newly diagnosed MM patients of non-Hispanic (NH) Black/African American (AA) and NH White race/ethnicity in the United States. We included patients from the nationwide Flatiron Health electronic health record-derived de-identified database who initiated first line of therapy (LOT) for MM between January 1, 2016 and March 31, 2022. Of 4,614 patients in our study cohort, 23.3% were NH Black/AA. Non-Hispanic Black/AA patients were younger than NH White patients at diagnosis (median 68 vs 71 years) and more likely to be female (53.4% vs 43.5%). Rates of high-risk cytogenetics and 1q21+ were similar between races/ethnicities. The most common primary regimen used was lenalidomide-bortezomib-dexamethasone (50.1% of NH Black/AA and 48.1% of NH White patients). Receipt of stem cell transplantation during first LOT was less common among NH Black/AA (16.5%) than NH White (21.9%) patients. Unadjusted RW progression-free survival (rwPFS) and overall survival (rwOS) were similar between races/ethnicities. After multivariable adjustment, NH Black/AA race/ethnicity was associated with slightly inferior rwPFS (hazard ratio [HR] 1.13; 95% CI 1.01-1.27). The difference in rwOS (HR 1.12; 95% CI 0.98-1.28) was not statistically significant. In general, associations between risk factors for rwPFS and rwOS were consistent between races/ethnicities. Findings from this analysis help to inform clinicians about the impact of race/ethnicity on MM treatment paradigms and outcomes in the United States.

7.
Prev Sci ; 24(Suppl 1): 40-49, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36399222

RESUMEN

Given increasing opioid overdose mortality rates in the USA over the past 20 years, accelerating the implementation of prevention interventions found to be effective is critical. The Helping End Addiction Long-Term (HEAL) Prevention Cooperative (HPC) is a consortium of research projects funded to implement and test interventions designed to prevent the onset or escalation of opioid misuse among youth and young adults. The HPC offers a unique opportunity to synthesize and share lessons learned from participating research projects' varied implementation experiences, which can facilitate quicker integration of effective prevention interventions into practice. This protocol paper describes our hybrid approach to collecting and analyzing information about the implementation experiences of nine of the HPC research projects while they maintain their focus on assessing the effectiveness and cost-effectiveness of prevention interventions. To better understand implementation within this context, we will address five research questions: (1) What were the context and approach for implementing the prevention interventions, and how was the overall implementation experience? (2) How representative of the target population are the participants who were enrolled and retained in the research projects' effectiveness trials? (3) For what purposes and how were stakeholders engaged by the research projects? (4) What are the adaptable components of the prevention interventions? And finally, (5) how might implementation of the prevention interventions vary for non-trial implementation? This work will result in intervention-specific and general practical dissemination resources that can help potential adopters and deliverers of opioid misuse prevention make adoption decisions and prepare for successful implementation.


Asunto(s)
Conducta Adictiva , Sobredosis de Droga , Trastornos Relacionados con Opioides , Adolescente , Adulto Joven , Humanos , Sobredosis de Droga/prevención & control , Trastornos Relacionados con Opioides/prevención & control
8.
Anaesthesia ; 77(3): 293-300, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34861743

RESUMEN

Different introducers are available to assist with tracheal intubation. Subtle differences in the design of introducers can have a marked effect on safety and performance. The Difficult Airway Society's Airway Device Evaluation Project Team proposal states that devices should only be purchased for which there is at least a case-control study on patients assessing airway devices. However, resources are not currently available to carry out a case-control study on all introducers available on the market. This study comprised a laboratory and manikin-based investigation to identify introducers that could be suitable for clinical investigation. We included six different introducers in laboratory-based assessments (design characteristics) and manikin-based assessments involving the participation of 30 anaesthetists. Each anaesthetist attempted placement in the manikin's trachea with each of the six introducers in a random order. Outcomes included first-time insertion success rate; insertion success rate; number of attempts; time to placement; and distance placed. Each anaesthetist also completed a questionnaire. First-time insertion success rate depended significantly on the introducer used (p = 0.0016) and varied from 47% (Armstrong and P3) to 77% (Intersurgical and Frova). Median time to placement (including oesophageal placement) varied from 10 s (Eschmann and Frova) to 20 s (P3) (p = 0.0025). Median time to successful placement in the trachea varied from 9 s (Frova) to 22 s (Armstrong) (p = 0.037). We found that the Armstrong and P3 devices were not as acceptable as other introducers and, without significant improvements to their design and characteristics, the use of these devices in studies on patients is questionable. The study protocol is suitable for differentiating between different introducers and could be used as a basis for assessing other types of devices.


Asunto(s)
Manejo de la Vía Aérea/normas , Anestesistas/normas , Diseño de Equipo/normas , Intubación Intratraqueal/normas , Maniquíes , Encuestas y Cuestionarios , Manejo de la Vía Aérea/instrumentación , Competencia Clínica/normas , Diseño de Equipo/instrumentación , Humanos , Intubación Intratraqueal/instrumentación , Tráquea/anatomía & histología
9.
BMC Med Res Methodol ; 21(1): 73, 2021 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-33865324

RESUMEN

BACKGROUND: Recommendations within guidelines are developed by synthesising the best available evidence; when limited evidence is identified recommendations are generally based on informal consensus. However, there are potential biases in group decision making, and formal consensus methods may help reduce these. METHODS: We conducted a case study using formal consensus, to develop one set of recommendations within the Neonatal Parenteral Nutrition guideline being produced for the National Institute for Health and Care Excellence. Statements were generated through identification of published guidelines on several topics relating to neonatal parenteral nutrition. Ten high quality guidelines were included, and 28 statements were generated; these statements were rated by the committee via two rounds of voting. The statements which resulted in agreement were then used to develop the recommendations. RESULTS: The approach was systematic and provided transparency. Additionally, a number of lessons were learnt; including the value of selecting the appropriate topic, giving adequate time to the process, and ensuring methodologies are understood by the committee for their value and relevance. CONCLUSION: Formal consensus is a valuable option for use within guideline development when specific criteria are met. The approach provides transparent methodology, ensuring clarity on how recommendations are developed.


Asunto(s)
Consenso , Humanos , Recién Nacido
10.
Langmuir ; 36(21): 5902-5907, 2020 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-32378413

RESUMEN

Homogeneous platinum alloy nanoparticles (NPs) are of great interest to the electrocatalytic community for potential use in various fuel cell electrodes. Increasing the surface area available per unit mass by decreasing the size of NPs while maintaining or improving activity is one of the key tasks of fuel cell catalysis. Achieving both in a synthesis of multielement NPs is still a challenging workup. In this investigation, we report the use of glycine as a size control agent to make ultrasmall homogeneous trimetallic PtNiCu NPs within 2-5 nm range. The mechanistic roles of dimethyl formamide (DMF), formaldehyde, water, and glycine are explored to understand the formation of these small NPs. Interestingly, it was observed that these PtNiCu NPs exhibited substantially enhanced mass activities toward the electro-oxidation of ethanol in comparison to commercial Pt black.

11.
BJOG ; 127(1): 18-26, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31538709

RESUMEN

BACKGROUND: Anterior compartment prolapse is the most common pelvic organ prolapse (POP) with a range of surgical treatment options available. OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of surgical treatments for the repair of anterior POP. METHODS: We conducted a systematic review of randomised controlled trials comparing surgical treatments for women with POP. Network meta-analysis was possible for anterior POP, same-site recurrence outcome. A Markov model was used to compare the cost-utility of surgical treatments for the primary repair of anterior POP from a UK National Health Service perspective. MAIN RESULTS: We identified 27 eligible trials for the network meta-analysis involving eight surgical treatments tested on 3194 women. Synthetic mesh was the most effective in preventing recurrence at the same site. There was no evidence to suggest a difference between synthetic non-absorbable mesh, synthetic partially absorbable mesh, and biological mesh. The cost-utility analysis, which incorporated effectiveness, complications and cost data, found non-mesh repair to have the highest probability of being cost-effective. The conclusions were robust to model inputs including effectiveness, costs and utility values. CONCLUSIONS: Anterior colporrhaphy augmented with mesh appeared to be cost-ineffective in women requiring primary repair of anterior POP. There is a need for further research on long-term effectiveness and the safety of mesh products to establish their relative cost-effectiveness with a greater certainty. TWEETABLE ABSTRACT: New study finds mesh cost-ineffective in women with anterior pelvic organ prolapse.


Asunto(s)
Procedimientos Quirúrgicos Ginecológicos/economía , Prolapso de Órgano Pélvico/cirugía , Mallas Quirúrgicas/economía , Análisis Costo-Beneficio , Femenino , Procedimientos Quirúrgicos Ginecológicos/métodos , Humanos , Metaanálisis en Red , Prolapso de Órgano Pélvico/economía , Complicaciones Cognitivas Postoperatorias/economía , Años de Vida Ajustados por Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Prevención Secundaria/economía , Resultado del Tratamiento
12.
BJOG ; 127(1): 28-35, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31541614

RESUMEN

BACKGROUND: Mesh surgery for stress urinary incontinence or pelvic organ prolapse can result in complications such as mesh exposure, mesh extrusion, voiding dysfunction, dyspareunia, and pain. There is limited knowledge or guidance on the effective management for mesh-related complications. OBJECTIVE: To determine the best management of mesh complications; a systematic review was conducted as part of the national clinical guideline 'Urinary incontinence (update) and pelvic organ prolapse in women: management'. SEARCH STRATEGY: Search strategies were developed for each indication for referral. SELECTION CRITERIA: Relevant interventions included complete or partial mesh removal, mesh division, and non-surgical treatments such as vaginal estrogen. DATA COLLECTION AND ANALYSIS: Characteristics and outcome data were extracted, and as a result of the heterogeneous nature of the data a narrative synthesis was conducted. MAIN RESULTS: Twenty-four studies were included; five provided comparative data and four studies stated the indication for referral. Reported outcomes (including pain, dyspareunia, satisfaction, quality of life, incontinence, mesh exposure, and recurrence) and the reported incidences of these varied widely. CONCLUSIONS: The current evidence base is limited in quantity and quality and does not permit firm recommendations to be made on the most effective management for mesh-related complications. Robust data are needed so that mesh complications can be managed effectively in the future. TWEETABLE ABSTRACT: Systematic review demonstrates that the outcomes following mesh revision surgery are highly variable.


Asunto(s)
Prolapso de Órgano Pélvico/cirugía , Mallas Quirúrgicas/efectos adversos , Incontinencia Urinaria de Esfuerzo/cirugía , Adolescente , Adulto , Anciano , Pérdida de Sangre Quirúrgica , Dispareunia/etiología , Femenino , Humanos , Complicaciones Intraoperatorias/etiología , Persona de Mediana Edad , Satisfacción del Paciente , Complicaciones Posoperatorias/etiología , Calidad de Vida , Recurrencia , Disfunciones Sexuales Fisiológicas/etiología , Resultado del Tratamiento , Adulto Joven
13.
J Appl Microbiol ; 128(1): 280-291, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31563150

RESUMEN

AIMS: To determine the composition and temporal stability of the gut (faecal) microbiota of sheep (Ovis aries). METHODS AND RESULTS: Microbial population dynamics was conducted using ARISA (28 sheep) and 16S rRNA sequencing (11 sheep). Firmicutes and Bacteroidetes were the predominant bacterial phyla, constituting ~80% of the total population. The core faecal bacterial microbiota of sheep consisted of 67 of 136 detected families and 91 of 215 detected species. Predominant microbial taxa included Ruminococcaceae, unassigned families in Bacteroidales and Clostridiales, Verrucomicrobiaceae and Paraprevotellaceae. Diversity indices and core microbiota composition demonstrated the stability of the core microbiota over 2-4 weeks. The core microbiota remained similar over ~5 months. CONCLUSIONS: Temporal stability of the sheep microbiota is high over 2-4 weeks in the absence of experimental variables. The core microbiota of Merino sheep shares taxa found in other breeds of sheep and other ruminants. SIGNIFICANCE AND IMPACT OF THE STUDY: Numerous studies seek to investigate the impact of experimental variables on gut microbiota composition. To do so, knowledge of the innate stability (or instability) of the microbiota over an experimental time course is required, independent of other variables. We have demonstrated high stability of the gut microbiota in sheep over 3-4 weeks, with moderate stability over ~5 months.


Asunto(s)
Heces/microbiología , Microbioma Gastrointestinal , Oveja Doméstica/microbiología , Animales , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética
14.
Phys Rev Lett ; 122(2): 022002, 2019 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-30720291

RESUMEN

The Spin Asymmetries of the Nucleon Experiment measured two double spin asymmetries using a polarized proton target and polarized electron beam at two beam energies, 4.7 and 5.9 GeV. A large-acceptance open-configuration detector package identified scattered electrons at 40° and covered a wide range in Bjorken x (0.3

15.
J Public Health (Oxf) ; 40(1): 82-89, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-28069992

RESUMEN

Background: Incorporating physical activity into daily activities is key for the effectiveness of lifestyle education interventions aimed at improving health outcomes; however, consideration of the environmental context in which individuals live is not always made. Walkability is a characteristic of the physical environment, and may be a potential facilitator to changing physical activity levels. Methods: Using data collected during the Walking Away from Diabetes randomized controlled trial, we examined the association between the walkability of the home neighbourhood and physical activity of participants. We also determined whether home neighbourhood walkability of participants was associated with the intervention effect of the education programme. Results: Data from 706 participants were available for analysis. Neighbourhood walkability was not significantly associated with any of the physical activity measures at baseline, or at 12, 24 or 36 months following the intervention (P > 0.05 for all). There was no association between walkability and change in purposeful steps/day from baseline to 36 months in the usual care or intervention arm; 25.77 (-99.04, 150.58) and 42.97 (-327.63, 413.45), respectively. Conclusion: Neighbourhood walkability appeared to have no association with objectively measured physical activity in this population. Furthermore, the walkability of participant's neighbourhood did not influence the effectiveness of a lifestyle programme.


Asunto(s)
Planificación Ambiental , Caminata , Adulto , Anciano , Diabetes Mellitus Tipo 2/terapia , Ejercicio Físico , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Conducta de Reducción del Riesgo
16.
Int J Obes (Lond) ; 41(6): 909-916, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28262676

RESUMEN

BACKGROUND: Bariatric surgery is effective for the treatment of stage II and III obesity and its related diseases, although increasing evidence is showing weight regain ~12-24 months postsurgery. Weight regain increases the risk of physical function decline, which negatively affects an individual's ability to undertake activities of daily living. The study assessed the effects of a 12-week supervised exercise intervention on physical function and body composition in patients between 12 and 24 months post bariatric surgery. METHODS: Twenty-four inactive adult bariatric surgery patients whose body mass index remained ⩾30 kg m2 12 to 24 months post surgery were randomised to an exercise intervention (n=12) or control group (n=12). Supervised exercise consisted of three 60-min gym sessions per week of moderate intensity aerobic and resistance training for 12 weeks. Control participants received usual care. The incremental shuttle walk test (ISWT) was used to assess functional walking performance after the 12-week exercise intervention, and at 24 weeks follow-up. Measures of anthropometric, physical activity, cardiovascular and psychological outcomes were also examined. Using an intention-to-treat protocol, independent t-tests were used to compare outcome measures between groups. RESULTS: Significant improvements in the exercise group were observed for the ISWT, body composition, physical function, cardiovascular and self-efficacy measures from baseline to 12 weeks. A large baseline to 12-week change was observed for the ISWT (exercise: 325.00±117.28 m; control: 355.00±80.62 m, P<0.001). The exercise group at 24 weeks recorded an overall mean improvement of 143.3±86.6 m and the control group recorded a reduction of -32.50±75.93 m. Findings show a 5.6 kg difference between groups in body mass change from baseline to 24 weeks favouring the exercise group. CONCLUSIONS: A 12-week supervised exercise intervention led to significant improvements in body mass and functional walking ability post intervention, with further improvements at the 24-week follow-up.


Asunto(s)
Cirugía Bariátrica , Composición Corporal , Mantenimiento del Peso Corporal/fisiología , Terapia por Ejercicio , Ejercicio Físico , Obesidad/cirugía , Cuidados Posoperatorios , Actividades Cotidianas , Índice de Masa Corporal , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Obesidad/fisiopatología , Periodo Posoperatorio , Calidad de Vida , Factores de Tiempo , Resultado del Tratamiento , Reino Unido , Aumento de Peso/fisiología , Pérdida de Peso/fisiología
17.
Molecules ; 22(10)2017 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-28994722

RESUMEN

Copper-catalyzed azide-alkyne cycloadditions (CuAAC or click chemistry) are convenient methods to easily couple various pharmacophores or bioactive molecules. A new series of 1,2,3-triazole-linked nucleoside-amino acid conjugates have been designed and synthesized in 57-76% yields using CuAAC. The azido group was introduced on the 5'-position of uridine or the acyclic analogue using the tosyl-azide exchange method and alkylated serine or proparylglycine was the alkyne. Modeling studies of the conjugates in the active site of LpxC indicate they have promise as antibacterial agents.


Asunto(s)
Aminoácidos/química , Antibacterianos/química , Nucleósidos/química , Triazoles/química , Alquinos/química , Azidas/química , Catálisis , Química Clic , Cobre/química , Reacción de Cicloadición , Modelos Químicos , Estructura Molecular
18.
Haemophilia ; 22(2): 285-291, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26422253

RESUMEN

INTRODUCTION: In a minority of patients with a significant bleeding history no cause is found despite extensive testing and we diagnose such cases as unclassified bleeding disorders (UBD). UBDs may have diverse underlying causes and currently no standard management strategy exists in the event of a haemorrhage or to cover surgery. AIM: To document the clinical characteristics and response to treatment of UBDs. METHODS: We performed a retrospective chart review of all patients with UBDs who had an invasive procedure at our centre between 1998 and 2014. RESULTS: The commonest symptoms were menorrhagia (89%) and bleeding at the time of surgery (88%) or dental extraction (85%). A total of 33 patients underwent 78 minor and major haemostatic challenges. Haemostatic cover was provided in 28 procedures with tranexamic acid alone, two with desmopressin and 45 with both agents in combination. A successful haemostatic outcome was observed in 70/78 (90%) cases. No patient required additional surgical intervention to achieve haemostasis, but one patient required a platelet transfusion to control postoperative bleeding. CONCLUSIONS: This is the first study to report on the investigation and treatment of UBD. Future studies are needed to further our understanding of the bleeding phenotype and identify any underlying causes.

19.
J Public Health (Oxf) ; 38(3): 534-542, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-26315996

RESUMEN

BACKGROUND: The NHS Health Check Programme was introduced in 2009 to improve primary prevention of coronary heart disease, stroke, diabetes and chronic kidney disease; however, there has been debate regarding the impact. We present a retrospective evaluation of Leicester City Clinical Commissioning Group. METHODS: Data are reported on diagnosis of type 2 diabetes, hypertension, chronic kidney disease, high risk of type 2 diabetes and high risk of cardiovascular disease. Data on management following the Health Check are also reported. RESULTS: Over a 5-year period, 53 799 health checks were performed, 16 388 (30%) people were diagnosed with at least one condition when diagnosis of being at high risk of cardiovascular disease was defined as ≥20%. This figure increased to 43% when diagnosis of high cardiovascular risk ≥10% was included. Of the 3063 (5.7%) individuals diagnosed with type 2 diabetes, 54% were prescribed metformin and 26% were referred for structured education. Of the 5797 (10.8%) individuals diagnosed at high risk of cardiovascular disease (≥20%), 64% were prescribed statins. CONCLUSIONS: A high proportion of new cases of people at risk of cardiovascular disease were identified by the NHS Health Check Programme. Data suggest that this has translated into appropriate preventative measures.


Asunto(s)
Prevención Primaria/métodos , Adulto , Anciano , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/prevención & control , Inglaterra/epidemiología , Femenino , Humanos , Hipertensión/epidemiología , Hipertensión/prevención & control , Masculino , Persona de Mediana Edad , Prevención Primaria/organización & administración , Evaluación de Programas y Proyectos de Salud , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/prevención & control , Estudios Retrospectivos , Factores de Riesgo , Medicina Estatal
20.
J R Army Med Corps ; 162(1): 50-5, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26045484

RESUMEN

INTRODUCTION: Exercise ASKARI SERPENT (Ex AS) is a British Army exercise that provides primary healthcare (PHC) to Kenyan civilians in support of local health authorities. It is conducted in partnership with the Kenya Defence Force Medical Services (KDFMS). Accurate epidemiological data is critical in planning the exercise and for any future short-notice contingency operations in similar environments. This paper reports epidemiological data for Ex AS using a novel data collection system. METHODS: PHC on Ex AS was delivered by trained and validated combat medical technicians (CMTs) using a set of Read-coded protocols. The CMTs were also directly supported and supervised by medical officers and nurses. RESULTS: A total of 3093 consultations were conducted over a 16-day period. Of these, 2707 (87.5%) consultations fell within the remit of the CMT protocols, with only 386 consultations (12.5%) being conducted exclusively by the medical officers or nurses. DISCUSSION: A Read-coded matrix built on CMT protocols is a simple and useful tool, particularly in civilian populations, for collecting morbidity data with the vast majority of conditions accounted for in the protocols. It is anticipated that such a system can better inform training, manning, medical material and pharmaceutical procurement than current category-based morbidity surveillance systems such as EPINATO (NATO epidemiological data). There is clear advantage to directly linking data capture to treatment algorithms. Accuracy, both in terms of numbers and condition, is likely improved. Data is also captured contemporaneously rather than after indeterminate time. Read coding has the added benefit of being an established electronic standard. In addition, the system would support traditional reporting methods such as EPINATO by providing increased assurance.


Asunto(s)
Recolección de Datos/métodos , Planificación en Salud/métodos , Planificación en Salud/normas , Medicina Militar , Humanos , Kenia , Medicina Militar/métodos , Medicina Militar/organización & administración , Medicina Militar/normas , Reino Unido
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