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1.
Colorectal Dis ; 26(4): 675-683, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38424669

RESUMEN

AIM: Faecal immunochemical testing (FIT) is used in the detection of colorectal cancer (CRC). FIT is invariably used at a single faecal haemoglobin (f-Hb) concentration threshold. The aim of this observational study was to explore risk scoring models (RSMs) with f-Hb and other risk factors for CRC in symptomatic patients attending primary care, potentially speeding diagnosis and saving endoscopy resources. METHOD: Records of patients completing FIT were linked with The Scottish Cancer Registry and with other databases with symptoms, full blood count and demographic variables, and randomized into derivation and validation cohorts. Stepwise multivariable logistic regression created RSMs assessed in the validation cohort. RESULTS: Of 18 805 unique patients, 9374 and 9431 were in the derivation and validation cohorts, respectively: f-Hb, male sex, increasing age, iron deficiency anaemia and raised systemic immune inflammation index created the final RSM. A risk score threshold of ≥2.363, generating the same number of colonoscopies as a f-Hb threshold of ≥10 µg Hb/g gave improved sensitivity for CRC in both cohorts. A RSM which excluded f-Hb was used to investigate the effect of raising the f-Hb threshold from ≥10 to ≥20 µg Hb/g in those with a low risk score. This approach would have generated 234 fewer colonoscopies but missed four CRCs. CONCLUSION: The RSM conferred no significant benefit to patients with very low f-Hb and CRC. Alternative strategies combining FIT with other variables may be more appropriate for safety-netting of symptomatic patients. Further work to develop and investigate the value of RSM for significant bowel disease other than CRC may also be beneficial.


Asunto(s)
Neoplasias Colorrectales , Detección Precoz del Cáncer , Hemoglobinas , Sangre Oculta , Atención Primaria de Salud , Humanos , Masculino , Hemoglobinas/análisis , Femenino , Persona de Mediana Edad , Neoplasias Colorrectales/diagnóstico , Anciano , Medición de Riesgo , Detección Precoz del Cáncer/métodos , Factores de Riesgo , Colonoscopía/estadística & datos numéricos , Heces/química , Modelos Logísticos , Escocia , Sensibilidad y Especificidad , Inmunoquímica , Anemia Ferropénica/diagnóstico
2.
Knee Surg Sports Traumatol Arthrosc ; 32(5): 1317-1323, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38515265

RESUMEN

PURPOSE: Loose flexion gaps are associated with poor functional outcomes and instability in total knee arthroplasty (TKA). The effect of a trapezoidal flexion gap in a functionally aligned TKA remains unknown. The aim of this study was to investigate the effect of a larger lateral flexion gap in a robotic-assisted (RA), functionally aligned (FA) and cruciate-retaining (CR) TKA on clinical outcomes. METHODS: Data from 527 TKA in 478 patients from 2018 to 2020 were collected. All patients underwent an RA (MAKO, Stryker), FA and CR TKA. Gap measurements were collected intraoperatively. Patient-reported outcome measures (PROMs), pain Visual analogue score (VAS) and range of motion were collected postoperatively. Patients were also asked about the ease of stair ascent and descent and kneeling on a 5-point scale. The minimum follow-up was 2 years. Patients were stratified into three groups based on lateral flexion laxity. RESULTS: At 2 years postoperatively, the group with a looser gap (3-6 mm) had higher mean PROMs when compared with the group with a gap of 2-3 mm. There were no differences detected in any other outcomes at 2 years. A total of 70.9% of patients in the group with a 3-6 mm gap reported being able to walk down a flight of stairs 'easily', compared with 56.7% in the 2-3 mm group and 54% in the <2 mm group (p = 0.04). CONCLUSION: The study shows that a loose lateral flexion gap in functionally aligned CR TKA does not adversely affect outcomes in the short term. LEVEL OF EVIDENCE: Level III, retrospective cohort study.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Inestabilidad de la Articulación , Medición de Resultados Informados por el Paciente , Rango del Movimiento Articular , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Femenino , Masculino , Anciano , Inestabilidad de la Articulación/cirugía , Persona de Mediana Edad , Procedimientos Quirúrgicos Robotizados/métodos , Estudios Retrospectivos , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/fisiopatología
3.
Surg Technol Int ; 442024 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-38547432

RESUMEN

INTRODUCTION: Classical neutral mechanical alignment in total knee arthroplasty (TKA) has been a standard paradigm, while more recently, other alignment schemas, such as kinematic, individualized, and functional, have been explored. This study aimed to investigate the effect of three-dimensional (3D) computed tomography (CT)-based surgical robotics inputs on a classically trained surgeon's TKA component positions and alignment targets over time. MATERIALS AND METHODS: Data from 1,394 consecutive robotically-assisted TKAs by a single surgeon from 2016 to 2020 were analyzed. Metrics collected included pre-balance planned implant component positions, final planned implant component positions after soft tissue balancing, and constitutional alignment from CT scans. Joint line obliquity was plotted against the arithmetic hip-knee angle (aHKA) using coronal plane alignment of the knee (CPAK). Three categories of alignment strategy were defined: true mechanical alignment (tMA), adjusted mechanical alignment (aMA), and no mechanical alignment (noMA). RESULTS: A shift to overall varus component positioning was observed over the years. Joint line obliquity according to CPAK showed a wider spread in later years, and the distribution of tibial and femoral coronal alignment angles expanded over time. CONCLUSION: The study revealed a change in alignment targets and final positioning of components away from neutral biomechanical axes in a large volume of TKAs by a single, classically trained surgeon over five years of using a robotic arm-assisted TKA system with CT-based planning. The most dominant factor for this change was the use of 3D CT planning, allowing the surgeon to assess patient-specific anatomy and plan accordingly. Outcome data is needed to determine if this change in behavior and surgical technique was beneficial. In summary, using a CT scan-based robotically assisted technique led to a gradual and complete shift from tMA to predominantly a non-mechanically aligned philosophy in TKA.

4.
Eur J Public Health ; 33(2): 331-335, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36847663

RESUMEN

BACKGROUND: Colorectal cancer (CRC) screening using faecal tests reduces disease-specific mortality. To investigate mortality and its association with sex, rates in women and men, and in different age ranges, were examined, before and after screening began in Scotland. METHODS: From 1990-99, no structured screening existed. Three pilots ran from 2000 to 2007 and subsequent full roll-out completed in 2009. Crude mortality rates for 1990-2020 were calculated relative to Scottish population estimates, and age-sex standardized rates calculated for all, pre-screening (<50 years), screening (5-74 years) and post-screening (>74 years) age ranges. RESULTS: CRC mortality declined from 1990 to 2020, but not linearly, and differed between sexes. In women, 1990-99 showed a steady decline [average annual percentage change (AAPC): -2.1%, 95% confidence interval (CI): -2.8% to -1.4%], but a less marked decline after 2000 (AAPC: -0.7%, 95% CI: -0.9% to -0.4%). In men, no clear decline was seen from 1990 to 1999 (AAPC: -0.4%, 95% CI: -1.1% to 0.4%), but mortality declined from 2000 to 2020 (AAPC: -1.7%, 95% CI: -1.9% to -1.5%). This pattern was exaggerated in the screening age ranges. For 2000-20, the overall reduction in mortality was less in women and in the screening age range. In the post-screening age range, reductions were smaller, but an increase was seen in the pre-screening age range, greater in women. CONCLUSIONS: CRC mortality fell during 1990-2020, but the decline differed markedly between sexes, indicating a larger beneficial effect of screening on CRC mortality in men compared to women: use of different thresholds for the sexes might lead to equality.


Asunto(s)
Neoplasias Colorrectales , Detección Precoz del Cáncer , Masculino , Humanos , Femenino , Persona de Mediana Edad , Neoplasias Colorrectales/diagnóstico , Sangre Oculta , Escocia/epidemiología , Incidencia , Mortalidad
5.
Knee Surg Sports Traumatol Arthrosc ; 31(4): 1420-1426, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36116071

RESUMEN

PURPOSE: Total knee arthroplasty with functional alignment uses pre-resection balancing to determine component position within the soft tissue envelope to achieve balance and restoration of native joint obliquity. The purpose of this study was to assess the balance achievable with a mechanical axis alignment and kinematic axis alignment plan, and the subsequent balance achievable after adjustment of the component position to functional alignment. METHODS: A prospective cohort of 300 knees undergoing cruciate retaining total knee arthroplasty were included in this study. Of these, 130 were initially planned with mechanical alignment (MA) and 170 with kinematic alignment (KA). Maximal stressed virtual gaps were collected using an optical tracking software system. The gaps were measured medially and laterally in flexion and extension. Following assessment of balance, implant position was adjusted to balance the soft tissues in functional alignment (FA) and the maximal gaps reassessed. Gaps were considered to be balanced when within 2 mm of equality. Incidence of balance within each cohort was compared to independent samples proportions test. RESULTS: Functional alignment obtained significantly better balance in extension, medially and overall than both MA and KA alignment without soft tissue release (p < 0.001). Overall balance was observed in 97% of FA knees, 73% of KA knees and in 55% of MA knees. The difference between KA and MA was also significant (p = 0.002). Whilst there was no difference observed in balanced achieved or limb alignment when FA was planned with either MA or KA, the joint line obliquity was maintained with an initial KA plan. CONCLUSION: Functional alignment more consistently achieves a balanced total knee arthroplasty than either mechanical alignment or kinematic alignment prior to undertaking soft tissue release. Utilising an individualised KA plan allows FA to best achieve the stated goals of maintaining joint line plane and obliquity. LEVEL OF EVIDENCE: Level III: retrospective cohort study.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Humanos , Articulación de la Rodilla/cirugía , Fenómenos Biomecánicos , Estudios Retrospectivos , Estudios Prospectivos , Osteoartritis de la Rodilla/cirugía
6.
J Arthroplasty ; 38(6S): S238-S245, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36933677

RESUMEN

BACKGROUND: Ideal goals for alignment and balance in total knee arthroplasty (TKA) remain controversial. We aimed to compare initial alignment and balance using mechanical alignment (MA) and kinematic alignment (KA) techniques and to analyze the percentage of knees that could achieve balance using limited adjustments to component position. METHODS: Prospective data on 331 primary robotic TKAs (115 MAs and 216 KAs) were analyzed. Medial and lateral virtual gaps were recorded in both flexion and extension. A computer algorithm was used to calculate potential (theoretical) implant alignment solutions to achieve balance within 1 millimeter (mm) without soft tissue release given an alignment philosophy (MA or KA), angular boundaries (±1, ±2, or ±3°), and gap targets (equal gaps or lateral laxity allowed). The percentage of knees that could theoretically achieve balance was compared. RESULTS: Less than 5% of TKAs were initially balanced. Limited adjustments to component position increased the percentage of TKAs that could be balanced in a graduated manner, with no difference between MA and KA start points: adjustments of ±1 (10% versus 6%, P = .17), ±2 (42% versus 39%, P = .61), or of ±3 (54% versus 51%, P = .66). A higher percentage of TKAs could be balanced when a greater range for lateral gap laxity was allowed. Balancing from KA resulted in increased joint line obliquity in the final implant alignment. CONCLUSION: A high percentage of TKAs can be balanced without soft tissue release using minor adjustments to component position. Surgeons should consider the relationship between alignment and balance goals when optimizing component positioning in TKA.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Procedimientos Quirúrgicos Robotizados , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Articulación de la Rodilla/cirugía , Estudios Prospectivos , Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Rango del Movimiento Articular , Fenómenos Biomecánicos
7.
J Arthroplasty ; 38(7 Suppl 2): S239-S244, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37061140

RESUMEN

BACKGROUND: Functional alignment (FA) strives to balance the knee soft-tissue envelope during total knee arthroplasty (TKA) using implant alignment adjustments rather than soft-tissue releases. There is a debate on how best to achieve FA. We compared minimum two-year outcomes between FA with a mechanical alignment plan [FA(m)] and FA with a kinematic alignment plan [FA(k)]. The null hypothesis was that there would be no difference in outcomes between FA(m) and FA(k). METHODS: Prospective data was collected from 300 consecutive robotic-assisted FA TKAs [135 FA(m) and 165 FA(k)]. Patient reported outcomes were obtained preoperatively and 2 years postoperatively. The coronal plane alignment of the knee classification was used to classify knee alignment phenotypes. RESULTS: Overall limb alignment was equivalent between groups. Final implant alignment was different between FA(m) and FA(k) groups, with FA(k) TKAs having higher tibial varus (P < .01), higher femoral valgus (P < .01), and higher joint line obliquity (P < .01). Patients reported higher Forgotten Joint Score-12 scores with FA(k) TKAs (79.4 versus 71.6, P = .018) and greater range of motion (125 versus 121°; P = .003). Patients who had constitutional varus reported the greatest improvement with FA(k) technique (Forgotten Joint Score at minimum 2 years of 89 versus 65; P < .001). CONCLUSION: Utilizing an individualized alignment plan [FA(k)] led to a final implant position with greater joint line obliquity, yet the same overall limb alignment. This was associated with improved outcomes at 2 years post-TKA in patients who had constitutional varus. Three-dimensional component position and joint line obliquity affect the outcomes following TKA independently of coronal limb alignment.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Fracturas Óseas , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Estudios Prospectivos , Articulación de la Rodilla/cirugía , Rodilla/cirugía , Fenómenos Biomecánicos , Fracturas Óseas/cirugía , Osteoartritis de la Rodilla/cirugía , Estudios Retrospectivos
8.
Lancet Oncol ; 23(5): 587-600, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35397210

RESUMEN

BACKGROUND: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries. METHODS: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies. FINDINGS: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75-84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I2=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28-4·7) and 7·0% (1·2-13·0). INTERPRETATION: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control. FUNDING: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network.


Asunto(s)
Neoplasias Ováricas , Neoplasias del Recto , Anciano de 80 o más Años , Benchmarking , Canadá , Estudios Transversales , Femenino , Hospitales , Humanos , Pronóstico , Factores de Riesgo , Medicina Estatal , Victoria
9.
Clin Chem Lab Med ; 60(10): 1496-1505, 2022 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-35848100

RESUMEN

Currently, women are disadvantaged compared to men in colorectal cancer (CRC) screening, particularly in programmes that use faecal immunochemical tests for haemoglobin (FIT) followed by colonoscopy. Although there is no single cause for all the known disadvantages, many can be attributed to the ubiquitous finding that women have lower faecal haemoglobin concentrations (f-Hb) than men; there are many plausible reasons for this. Generally, a single f-Hb threshold is used in CRC screening programmes, leading to lower positivity for women than men, which causes poorer outcomes for women, including lower CRC detection rate, higher interval cancer (IC) proportion, and higher CRC mortality. Many of the now widely advocated risk scoring strategies do include factors taking account of sex, but these have not been extensively piloted or introduced. Using different f-Hb thresholds for the sexes seems advantageous, but there are difficulties, including deciding which characteristic should be selected to achieve equivalency, for example, positivity, IC proportions, or specificity. Moreover, additional colonoscopy resources, often constrained, would be required. Governments and their agencies should be encouraged to prioritise the allocation of resources to put simple strategies into practice, such as different f-Hb thresholds to create equal positivity in both sexes.


Asunto(s)
Neoplasias Colorrectales , Detección Precoz del Cáncer , Colonoscopía , Heces , Femenino , Hemoglobinas , Humanos , Masculino , Tamizaje Masivo , Sangre Oculta
10.
Gut ; 70(1): 106-113, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32234803

RESUMEN

OBJECTIVE: Faecal immunochemical tests (FIT) are replacing guaiac faecal occult blood tests (FOBT) in colorectal cancer (CRC) screening. Data from the first year of FIT screening were compared with those from FOBT screening and assumptions based on a pilot evaluation of FIT. DESIGN: Data on uptake, positivity, positive predictive value (PPV) for CRC and higher-risk adenoma from participants in the first year of the FIT-based Scottish Bowel Screening Programme (n=919 665), with a threshold of 80 µg Hb/g faeces, were compared with those from the penultimate year of the FOBT-based programme (n=862 165) and those from the FIT evaluation (n=66 225). RESULTS: Overall, uptake of FIT was 63.9% compared with 56.4% for FOBT. Positivity was 3.1% and 2.2% with FIT and FOBT; increases were seen in both sexes, and across age range and deprivation. More CRC and adenomas were detected by FIT, but the PPV for CRC was less (5.2% with FIT and 6.4% with FOBT). However, for higher-risk adenoma, PPV was greater with FIT (24.3% with FIT and 19.3% with FOBT). In the previous FIT evaluation, uptake was 58.5% with FIT compared with 54.0% with FOBT; positivity was 2.5% with FIT and 2.0% with FOBT. CONCLUSION: Transition to FIT from FOBT produced higher uptake and positivity with lower PPV for CRC and higher PPV for adenoma. The FIT pilot evaluation underestimated uptake and positivity. Introducing FIT at the same threshold as the evaluation caused a 67.2% increase in colonoscopy demand instead of a predicted 10%.


Asunto(s)
Adenoma/diagnóstico , Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer , Anciano , Heces , Femenino , Guayaco , Humanos , Inmunoquímica , Indicadores y Reactivos , Masculino , Persona de Mediana Edad , Sangre Oculta , Valor Predictivo de las Pruebas
11.
Prev Med ; 151: 106606, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34217418

RESUMEN

Screening is an important component of cancer control internationally. In Scotland, the National Health Service Scotland provides screening programmes for cervical, bowel and breast cancers. The COVID-19 pandemic resulted in the suspension of these programmes in March 2020. We describe the integrated approach to managing the impact of the pandemic on cancer screening programmes in Scotland throughout 2020. We outline the policy context and decision-making process leading to suspension, and the criteria and framework informing the subsequent, staggered, restart in subsequent months. The decision to suspend screening services in order to protect screening invitees and staff, and manage NHS capacity, was made after review of numbers of screening participants likely to be affected, and the potential number of delayed cancer diagnoses. Restart principles and a detailed route map plan were developed for each programme, seeking to ensure broad consistency of approach across the programmes and nationally. Early data indicates bowel, breast and cervical screening participation has increased since restart. Primary care has had to adapt to new infection prevention control measures for delivery of cervical screening. Cancer charities provided cancer intelligence and policy briefs to national bodies and Scottish Government, as well as supporting the public, patients and screening invitees through information and awareness campaigns. Emerging from the pandemic, there is recognition of the need and the opportunity to transform and renew both cancer and screening services in Scotland, and in particular to address long-standing workforce capacity problems through innovation and investment, and to continue to prioritise addressing health inequalities.


Asunto(s)
COVID-19 , Neoplasias del Cuello Uterino , Detección Precoz del Cáncer , Femenino , Humanos , Pandemias , SARS-CoV-2 , Escocia , Medicina Estatal , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control
12.
Biochem Biophys Res Commun ; 523(1): 208-213, 2020 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-31848046

RESUMEN

Activating mutations in the membrane-proximal region of the colony-stimulating factor 3 receptor (CSF3R) are a hallmark of chronic neutrophilic leukemia (CNL) with the T618I mutation being most common. The mechanisms underlying constitutive activation of the T618I CSF3R and its signal propagation are poorly understood. Ligand-independent activation of the T618I CSF3R has previously been attributed to loss of receptor O-glycosylation and increased receptor dimerization. Here, we show that the T618I CSF3R is indeed glycosylated but undergoes enhanced spontaneous internalization and degradation that results in a marked decrease in its surface expression. Inhibition of the proteasome dramatically increases expression of the O-glycosylated T618I CSF3R. We also demonstrate that the O-glycosylated wild-type CSF3R is tyrosine phosphorylated in response to ligand but constitutively phosphorylated in cells expressing T618I CSF3R. Constitutive tyrosine phosphorylation of the O-glycosylated T618I receptor form correlated with activation of JAK2 and both the mutant receptor and JAK2 were found to be constitutively ubiquitinated. These observations provide novel insights into the mechanisms of oncogenic signaling by T618I CSF3R mutations in CNL.


Asunto(s)
Leucemia Neutrofílica Crónica/genética , Oncogenes/genética , Receptores del Factor Estimulante de Colonias/metabolismo , Transducción de Señal/genética , Animales , Células Cultivadas , Glicosilación , Leucemia Neutrofílica Crónica/metabolismo , Leucemia Neutrofílica Crónica/patología , Ratones , Mutación , Fosforilación , Receptores del Factor Estimulante de Colonias/genética
13.
Clin Chem Lab Med ; 58(12): 2073-2080, 2020 11 26.
Artículo en Inglés | MEDLINE | ID: mdl-32324157

RESUMEN

Objectives Faecal immunochemical tests for haemoglobin (FIT) are becoming widely used in colorectal cancer (CRC) screening and assessment of symptomatic patients. Faecal haemoglobin concentration (f-Hb) thresholds are used to guide subsequent investigation. We established the distributions of f-Hb in a large screening population by sex, age, deprivation and geography. Methods Single estimates of f-Hb were documented for all individuals participating in the first 18 months of the Scottish Bowel Screening Programme (SBoSP). The distributions of f-Hb were generated for all participants, all men and women, and men and women by age quintile and deprivation quintile. Distributions were also generated by geographical region for all participants, men and women, and by deprivation. Comparisons of f-Hb distributions with those found in a pilot evaluation of FIT and three other countries were performed. Results f-Hb was documented for 887,248 screening participants, 422,385 men and 464,863 women. f-Hb varied by sex, age, deprivation quintile and geographical region. The f-Hb distributions by sex and age differed between the SBoSP and the pilot evaluation and the three other countries. Conclusions f-Hb is higher in men than in women and increases with age and deprivation in both sexes. f-Hb also varies by geographical region, independently of deprivation, and by country. The f-Hb distribution estimated by pilot evaluation may not represent the population distribution. Decision limits have advantages over reference intervals. Use of partitioned f-Hb thresholds for further investigation, based on the data generated, has advantages and disadvantages, as do risk scores based on a spectrum of influencing variables.


Asunto(s)
Neoplasias Colorrectales/diagnóstico , Heces/química , Hemoglobinas/análisis , Factores de Edad , Anciano , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Sangre Oculta , Escocia , Factores Sexuales
14.
J Gambl Stud ; 36(4): 1045-1063, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31177372

RESUMEN

Previous research has demonstrated that gambling cues (e.g., flashing lights on poker-machines) can trigger an urge to gamble in poker-machine gamblers. However, the psychological mechanisms that promote the urge to gamble remain poorly understood. The present study explored whether reward responsiveness predicted urge to gamble and positive affect, and whether cue-reactive rationality, volitional control and imagery mediated these relationships. Ninety-three (45% male and 55% female) Australian regular poker-machine gamblers aged between 18 and 77 participated in an online cue-reactivity experiment. Participants initially completed the Problem Gambling Severity Index and Reward Responsiveness scale. Subsequently, at three time points (i.e., baseline, directly after a neutral cue and directly after a gambling cue) participants completed the rationality, volitional control and imagery subscales of the Phenomenology of Consciousness Inventory and two visual analogue scales that measured urge to gamble and positive affect. Analyses indicated that gambling cues triggered statistically significant increases in both urge to gamble and positive affect and these variables were statistically significantly positively correlated with reward responsiveness. Furthermore, only cue-reactive imagery mediated the relationships between reward responsiveness and the two outcome variables (i.e., cue-reactive urge to gamble and positive affect). These findings highlight the potential importance of targeting reward responsiveness and cue-reactive mental imagery in the context of exposure therapies for poker-machine problem gamblers.


Asunto(s)
Afecto , Señales (Psicología) , Juego de Azar/psicología , Recompensa , Adolescente , Adulto , Anciano , Conducta Adictiva/psicología , Condicionamiento Psicológico , Estado de Conciencia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
15.
Clin Psychol Psychother ; 27(3): 408-447, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32112606

RESUMEN

Early maladaptive schemas (EMSs) have been hypothesized to be associated with interpersonal problems. Furthermore, a stronger contention is that EMSs impact negatively on, or cause, interpersonal problems. The aims of this meta-analysis were (a) to assess the strength of the association between EMSs and interpersonal problems, (b) clarify which EMSs are most strongly associated with interpersonal problems, (c) examine any possible moderators on the relationship between EMSs and interpersonal problems, and (d) examine whether any empirical evidence exists supporting a causal relationship between EMSs and interpersonal problems. A comprehensive systematic literature search and meta-analysis were conducted using the PRISMA guidelines for systematic reviews. A total of 49 empirical studies were reviewed investigating EMSs and interpersonal problems. EMSs were found to have a moderate positive association with interpersonal problems with different EMSs having small to moderate effect sizes. To date, there has been limited evidence supporting a causal effect of EMSs on interpersonal problems. Possible limitations and avenues for future research were discussed.


Asunto(s)
Adaptación Psicológica , Relaciones Interpersonales , Desarrollo de la Personalidad , Adulto , Causalidad , Niño , Correlación de Datos , Humanos , Solución de Problemas , Habilidades Sociales
16.
J Gambl Stud ; 33(2): 617-632, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27619216

RESUMEN

In Australia, poker-machine gamblers represent a disproportionate number of problem gamblers. To cultivate a greater understanding of the psychological mechanisms involved in poker-machine gambling, a repeated measures cue-reactivity protocol was administered. A community sample of 38 poker-machine gamblers was assessed for problem-gambling severity and trait mindfulness. Participants were also assessed regarding altered state of awareness (ASA) and urge to gamble at baseline, following a neutral cue, and following a gambling cue. Results indicated that: (a) urge to gamble significantly increased from neutral cue to gambling cue, while controlling for baseline urge; (b) cue-reactive ASA did not significantly mediate the relationship between problem-gambling severity and cue-reactive urge (from neutral cue to gambling cue); (c) trait mindfulness was significantly negatively associated with both problem-gambling severity and cue-reactive urge (i.e., from neutral cue to gambling cue, while controlling for baseline urge); and (d) trait mindfulness did not significantly moderate the effect of problem-gambling severity on cue-reactive urge (from neutral cue to gambling cue). This is the first study to demonstrate a negative association between trait mindfulness and cue-reactive urge to gamble in a population of poker-machine gamblers. Thus, this association merits further evaluation both in relation to poker-machine gambling and other gambling modalities.


Asunto(s)
Concienciación , Conducta Adictiva/psicología , Juego de Azar/psicología , Atención Plena , Personalidad , Adulto , Australia , Señales (Psicología) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
17.
J Gambl Stud ; 33(3): 807-823, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27804002

RESUMEN

Poker-machine gamblers have been demonstrated to report increases in the urge to gamble following exposure to salient gambling cues. However, the processes which contribute to this urge to gamble remain to be understood. The present study aimed to investigate whether changes in the conscious experience of visual imagery, rationality and volitional control (over one's thoughts, images and attention) predicted changes in the urge to gamble following exposure to a gambling cue. Thirty-one regular poker-machine gamblers who reported at least low levels of problem gambling on the Problem Gambling Severity Index (PGSI), were recruited to complete an online cue-reactivity experiment. Participants completed the PGSI, the visual imagery, rationality and volitional control subscales of the Phenomenology of Consciousness Inventory (PCI), and a visual analogue scale (VAS) assessing urge to gamble. Participants completed the PCI subscales and VAS at baseline, following a neutral video cue and following a gambling video cue. Urge to gamble was found to significantly increase from neutral cue to gambling cue (while controlling for baseline urge) and this increase was predicted by PGSI score. After accounting for the effects of problem-gambling severity, cue-reactive visual imagery, rationality and volitional control significantly improved the prediction of cue-reactive urge to gamble. The small sample size and limited participant characteristic data restricts the generalizability of the findings. Nevertheless, this is the first study to demonstrate that changes in the subjective experience of visual imagery, volitional control and rationality predict changes in the urge to gamble from neutral to gambling cue. The results suggest that visual imagery, rationality and volitional control may play an important role in the experience of the urge to gamble in poker-machine gamblers.


Asunto(s)
Conducta Adictiva/psicología , Estado de Conciencia , Señales (Psicología) , Juego de Azar/psicología , Autoeficacia , Adulto , Femenino , Humanos , Masculino , Asunción de Riesgos
18.
J Gambl Stud ; 32(2): 661-74, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26026986

RESUMEN

In order to enhance our understanding of the nature of poker-machine problem-gambling, a community sample of 37 poker-machine gamblers (M age = 32 years, M PGSI = 5; PGSI = Problem Gambling Severity Index) were assessed for urge to gamble (responses on a visual analogue scale) and altered state of consciousness (assessed by the Altered State of Awareness dimension of the Phenomenology of Consciousness Inventory) at baseline, after a neutral cue, and after a gambling cue. It was found that (a) problem-gambling severity (PGSI score) predicted increase in urge (from neutral cue to gambling cue, controlling for baseline; sr (2) = .19, p = .006) and increase in altered state of consciousness (from neutral cue to gambling cue, controlling for baseline; sr (2) = .57, p < .001), and (b) increase in altered state of consciousness (from neutral cue to gambling cue) mediated the relationship between problem-gambling severity and increase in urge (from neutral cue to gambling cue; κ(2) = .40, 99 % CI [.08, .71]). These findings suggest that cue-reactive altered state of consciousness is an important component of cue-reactive urge in poker-machine problem-gamblers.


Asunto(s)
Conducta Adictiva/psicología , Estado de Conciencia , Señales (Psicología) , Juego de Azar/psicología , Adulto , Femenino , Humanos , Masculino , Asunción de Riesgos
19.
Behav Cogn Psychother ; 43(6): 744-58, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25362937

RESUMEN

BACKGROUND: Patients with anxiety disorder diagnoses commonly have more than one anxiety diagnosis. While cognitive-behavioural interventions have proven efficacy in treating single anxiety disorder diagnoses, there has been little investigation of their efficacy in treating co-occurring anxiety disorders. AIMS: To evaluate the efficacy of a transdiagnostic cognitive-behavioural intervention for treating co-occurring anxiety disorders. METHOD: An A-B single case study design (N = 6) was used to evaluate the efficacy of a 12 to 13-session modular transdiagnostic cognitive-behavioural intervention for treating co-occurring anxiety disorders across patients with at least two of the following diagnoses: GAD, Social Phobia, Panic Disorder and/or OCD. RESULTS: Five of the six participants completed treatment. At posttreatment assessment the five treatment completers achieved diagnostic and symptomatic change, with three participants being diagnosis free. All participants who completed treatment no longer met criteria for any DSM-IV-TR Axis-I diagnosis at the 3-month follow-up assessment, and demonstrated reliable and clinically-significant improvements in symptoms. Across the participants, statistically significant improvements from pre to postintervention were found on measures of anxiety, depression and general well-being, and all improvements were maintained at 3-month follow-up. CONCLUSIONS: Results suggest that transdiagnostic cognitive behavioural interventions can be of benefit to patients with co-occurring anxiety disorders.


Asunto(s)
Trastornos de Ansiedad/terapia , Terapia Cognitivo-Conductual/métodos , Adulto , Trastornos de Ansiedad/psicología , Estudios de Casos y Controles , Comorbilidad , Femenino , Humanos , Masculino , Autoinforme , Resultado del Tratamiento
20.
Int Orthop ; 38(7): 1375-8, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24599486

RESUMEN

PURPOSE: Total knee arthroplasty (TKA) prosthesis designs are constantly evolving to obtain greater functional performance. The aim of this study is to compare the functional outcomes between the newer single radius (SR) Triathlon prosthesis with its multiradius (MR) predecessor the Duracon. METHOD: We analysed 1,012 primary TKA procedures which used either the Triathlon SR prosthesis or the Duracon MR prosthesis (338 Triathlon, 674 Duracon). Patients were assessed using the Knee Society score (KSS), range of movement measurements, pain and walking assessments at time points pre-operatively, one year and two years postoperatively. RESULTS: Both groups were similar pre-operatively in terms of age, gender and body mass index (BMI). At one year postoperatively the Triathlon group had a significantly better flexion (P = 0.005) and KSS (function score P = 0.037, knee score P = 0.000). At two years postoperatively the Triathlons had maintained a significantly better KSS (function score P = 0.046, knee score P = 0.000) and also knee flexion (P = 0.02). Pain assessments at two years were significantly better in the Triathlon group (P = 0.002) with 66.3 % of patients experiencing no pain at that point compared to 54.4 % with Duracon knees. CONCLUSION: This data supports the proposition that the use of Triathlon TKA results in improved outcomes for patients when compared to the Duracon TKA.


Asunto(s)
Artritis/cirugía , Artroplastia de Reemplazo de Rodilla/instrumentación , Articulación de la Rodilla/cirugía , Prótesis de la Rodilla , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Rango del Movimiento Articular , Resultado del Tratamiento
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