A comprehensive analysis of the pre- and postoperative responses to each of the 12 Oxford knee score questions one year following knee arthroplasty.

AIMS: To assess the pre- and postoperative responses to each of the 12 individual Oxford Knee Score (OKS) questions and percentages of those that were better, same or worse after primary knee arthroplasty (KA). METHODS: A single centre retrospective cohort study conducted over a 24-month period which included 3259 patients with completed OKS preoperatively and 1-year after KA. There were 1286 males and 1973 females, with an overall mean age of 70.0 (range 34-94). The mean scores for each question of the OKS were compared between baseline and 1-year. The percentage of patients who reported better, the same or worse postoperative symptoms for each question were calculated and represented on a heatmap. RESULTS: There were significant (p < 0.001) improvements in all 12 questions, all of which demonstrated moderate (Q2, Q7) or large effect sizes. Improvements in individual question responses varied. Symptoms of pain and limping demonstrated the greatest improvement, with 86% of patients enjoying a positive change in their symptoms. Despite this improvement 1067 (41.4%) continued to have mild to severe pain in their knee, and 442 (17.3%) patients limped often to all the time when walking postoperatively. Whereas other questions that did not improve to the same extent for example washing and drying only improved in 53% of patients but only 347 (13.5%) had moderate/extreme trouble or found it impossible to do this postoperatively. Preoperatively four questions (Q1, Q6, Q7, Q8) demonstrated floor effects, postoperatively all questions apart from question 7 (kneeling) demonstrated ceiling effects. CONCLUSION: The mean improvement and outcome at 1-year for each of the 12 questions varied according to the patient's preoperative response. As a clinical tool, the heatmap (improvement, same and worse) will enable communication to patients about their potential change in their knee specific symptoms according to their preoperative responses. LEVEL OF EVIDENCE: Retrospective study, Level III.

Posterior stabilised total knee arthroplasty is associated with improved post-operative knee specific function, health related quality of life and greater satisfaction when compared to cruciate retaining protheses.

PURPOSE: To assess whether there were differences in knee specific function, health related quality of life (HRQoL), and satisfaction between patients with a cruciate retaining (CR) or a posterior stabilised (PS) total knee arthroplasty (TKA) at 1 and 2 years postoperatively. METHODS: A retrospective review of TKA (CR and PS) patients from a prospectively collected arthroplasty database. Patient demographics, body mass index and ASA grade, Oxford knee score (OKS) and EuroQol 5-dimension (EQ-5D) 3-level, which was used to assess HRQoL, were collected preoperatively and 1 year and 2 years postoperatively. Regression was used to adjust for confounding factors. RESULTS: The sample included 3122 TKA, of which 1009 (32.3%) were CR and 2112 (67.7%) were PS. The PS group were more likely to be female (odd ratio (OR) 1.26, p = 0.003) and undergo resurfacing of the patella (OR 6.63, p < 0.001). There was a significantly greater improvement in the 1 year OKS in the PS group (mean difference (MD) 0.9, p = 0.016). The PS TKA was independently associated with a greater 1 year (MD 1.1, 95% CI 0.4 to 1.9, p = 0.001) and 2 years (MD 0.8, p = 0.037) post-operative improvements in OKS. PS TKA was also independently associated with a greater 1 year (MD 0.021, p = 0.024) and 2 years (MD 0.022, p = 0.025) post-operative and change in EQ-5D utility compared to the CR group. The PS group was more likely to be satisfied with their outcome at 1 year (OR 1.75, p < 0.001) and at 2 years (OR 1.38, p = 0.001) when adjusting for confounders. CONCLUSION: PS TKA was associated with a better knee specific function and HRQoL when compared to CR, but the clinical significance of this is not clear. However, the PS group was more likely to be satisfied with their outcome compared to the CR group.

Factors associated with a clinically significant improvement in health-related quality of life after total knee arthroplasty.

BACKGROUND: The aim was to identify independent preoperative factors associated with changes in health-related quality of life (HRQoL) following total knee arthroplasty (TKA), and whether these could be used as indicators for surgery. METHODS: A retrospective study of 3127 TKA patients was undertaken that included 1194 (38.2%) male and 1933 (61.8%) female patients, with a mean age of 70.5 years (standard deviation 9.0). Patient demographics, body mass index and ASA grade, Oxford Knee Score (OKS) and EuroQol 5-dimension (EQ-5D) 3-level, which was used to assess HRQoL, were collected preoperatively and 2 years postoperatively. RESULTS: When adjusting for confounding factors, obesity grade II (p = 0.002), ASA grade 3 (p = 0.002), and a better preoperative OKS (p < 0.001) or EQ-5D score (p < 0.001) were associated with a decreased improvement in the HRQoL at 2-years. A preoperative EQ-5D of < 0.8 (95.7% specific, AUC ≥ 67.0%) or an OKS of < 36 (97.1% specific, AUC ≥ 58.1%) was associated with a clinically significant improvement HRQoL. Patella resurfacing (n = 1454, 46.5%) was not independently associated with a clinical or statistically significant improvement in HRQoL. According to preoperative factors, no subgroup of patients benefited more from patella resurfacing according to improvement in their HRQoL. CONCLUSION: ASA grade 3, grade II obesity, a better preoperative EQ-5D or OKS were independently associated with a lesser improvement in HRQoL. The thresholds identified in the EQ-5D or OKS for a clinically significant improvement in HRQoL may be used as potential indicators for referral for TKA. Patella resurfacing was not independently associated with a clinically important improvement in HRQoL. LEVEL OF EVIDENCE: Retrospective diagnostic study, Level III.

The Oxford Knee Score is a reliable predictor of patients in a health state worse than death and awaiting total knee arthroplasty.

BACKGROUND: The health-related quality of life of patients awaiting a total knee arthroplasty (TKA) deteriorates with increasing time to surgery and identification of those with the worst quality of life may help to prioritize patients. The aims were to identify and validate independent variable(s) associated with a health state worse than death (WTD) in patients awaiting a TKA and whether these variables influenced patients-reported outcome measures. METHODS: A retrospective cohort of 5857 patients undergoing a primary TKA was identified from an established arthroplasty database. Patient demographics, body mass index (BMI), index of multiple deprivation, Oxford Knee Score (OKS), EuroQoL five dimension (EQ-5D) 3 level, and visual analogue scale (EQ-VAS) were collected preoperatively and one year postoperatively. An EQ-5D utility of less than zero was defined as WTD. A randomly selected subset of patients (n = 3076) was used to validate the variable that was most predictive of a state WTD and to assess the influence on patient-reported outcomes. RESULTS: There were 771 (13.2%) patients with a health state WTD. Increasing social deprivation (P = 0.050), worse preoperative OKS (P < 0.001), or EQ-VAS (P < 0.001) were independently associated with a health state WTD. The OKS was the most reliable predictor (area under curve 88.9%, 95% CI 87.8 to 90.1, P < 0.001) of a health state WTD. A threshold value of 16 or less, 80% sensitive and specific, was validated and confirmed to have a negative predictive value of 97.5%. Patients with an OKS of 16 or less had a significantly greater improvement in their OKS (difference 6.9, P < 0.001) and EQ-5D score (difference 0.257, P < 0.001). When adjusting for confounding factors, a health status WTD was not associated with worse postoperative OKS (difference -0.6, 95% CI -1.4 to 0.3, P = 0.177), EQ-5D (difference -0.016, 95% CI -0.036 to 0.003, P = 0.097) or patient satisfaction (difference -1.8, 95% CI -4.3 to 0.7, P = 0.162). CONCLUSION: A threshold score 16 or less in OKS was a reliable predictor of a health status WTD and was associated with a greater improvement in knee-specific and health-related quality of life following TKA.

Assessment of attitude and hesitancy toward vaccine against COVID-19 in a Pakistani population: A mix methods survey.

Objective: The objective of this study was to assess the attitude and hesitancy toward vaccine against COVID-19 in a Pakistani Population. Materials and methods: A mix-method, prospective study was conducted and adults (aged ≥18 years) residing in Pakistan were invited to participate. The questionnaire was prepared, hosted in Google Forms and circulated through electronic platforms and was also available to be done in in-person. Data was compiled from 15th September to 30th November 2020. Results: The response rate was 80%. A total of 1003 participants were included in the final analysis. Of them, 75% completed survey questionnaire online, while remaining 25% responded in-person. The mean age of the participants was 29.62 ± 10.47 years. The majority of participants were females; 60.9% (n = 611). 57.02% (n = 572) of the participants were employed at the time of survey. Overall, 70.68% (n = 709) of the participants had previous experience of vaccines such as the flu vaccine Only 4.9% (n = 49) participants thought that they will be seriously ill from COVID-19 within six months and 39% (n = 392) participants were confident that they will get COVID-19. A total of 71.29% of the participants reported they would consider getting vaccinated once available. There was statistical association between gender and getting vaccinated (P < 0.001). Conclusion: This study demonstrated that majority of the participants showed positive attitude toward considering COVID-19 vaccine. However awareness with informed knowledge of efficacy, possible adverse effects and cost would be of added great value to increase the real response of Pakistani population toward COVID-19 vaccination.

Objetivo: El objetivo de este estudio fue evaluar la actitud y la renuencia hacia la vacuna frente a la COVID-19 en una población paquistaní. Materiales y métodos: Se realizó un estudio prospectivo de método mixto, invitándose a participar a personas adultas (edad ≥18 años) residentes en Paquistán. Se preparó el cuestionario, que se alojó en Google Forms y se hizo circular a través de plataformas electrónicas, pudiendo realizarse también de manera personal. Los datos se recopilaron desde el 15 de septiembre al 30 de noviembre de 2020. Resultados: La tasa de respuesta fue del 80%. El análisis final incluyó un total de 1.003 participantes, de los cuales el 75% completó el cuestionario-encuesta online, mientras que el 25% respondió en persona. La edad media de los participantes fue de 29,62 ± 10,47 años. La mayoría de los participantes eran mujeres: el 60,9% (n = 611). El 57,02% (n = 572) de los participantes tenía empleo en el momento de la encuesta. En general, el 70,68% (n = 709) de los participantes tenía experiencia previa sobre vacunas tales como la vacuna frente a la gripe. Solo el 4,9% (n = 49) de los participantes pensaba que padecerían la COVID-19 de forma grave en el plazo de seis meses, y el 39% (n = 392) de los participantes estaba seguro de que se contagiaría de dicha enfermedad. El 71,29% de los participantes reportó que consideraría recibir la vacuna una vez que se dispusiera de la misma. Existió una asociación estadística entre el sexo y el ser vacunado (P< 0,001). Conclusión: Este estudio demostró que la mayoría de los participantes mostró una actitud positiva hacia la consideración de la vacuna frente a la COVID-19. Sin embargo, la concienciación sobre el conocimiento informado de la vacuna, los posibles efectos adversos y el coste supondrían un gran valor añadido al incremento de la respuesta real de la población paquistaní hacia la vacuna frente a la COVID-19.

Prospect of microbial food borne diseases in Pakistan: a review / Perspectiva de doenças microbianas transmitidas por alimentos no Paquistão: uma revisão

Abstract Nowadays food borne illness is most common in people due to their epidemic nature. These diseases affect the human digestive system through bacteria, viruses and parasites. The agents of illness are transmitted in our body through various types of food items, water and uncooked. Pathogens show drastic changes in immunosuppressant people. This review gives general insights to harmful microbial life. Pakistan is a developed country and because of its improper food management, a lot of gastrointestinal problems are noted in many patients. Bacteria are most common agents to spread diarrhoea, villi infection, constipation and dysenteric disease in human and induce the rejection of organ transplant. Enhancement of their lifestyle, properly cooked food should be used and to overcome the outbreak of the diseases.

Resumo Hoje em dia, as doenças transmitidas por alimentos são mais comuns em pessoas devido à sua natureza epidêmica. Essas doenças afetam o sistema digestivo humano por meio de bactérias, vírus e parasitas. Os agentes das doenças são transmitidos em nosso corpo por meio de diversos tipos de alimentos, água e crus. Os patógenos mostram mudanças drásticas em pessoas imunossupressoras. Esta revisão fornece uma visão geral da vida microbiana prejudicial. O Paquistão é um país desenvolvido e, devido ao seu manejo alimentar inadequado, muitos problemas gastrointestinais são observados em muitos pacientes. As bactérias são os agentes mais comuns para espalhar diarreia, infecção de vilosidades, obstipação e doença disentérica em humanos e induzem a rejeição de transplantes de órgãos. Melhoria de seu estilo de vida, alimentos devidamente cozidos devem ser utilizados e para superar o aparecimento de doenças.

Prospect of microbial food borne diseases in Pakistan: a review / Perspectiva de doenças microbianas transmitidas por alimentos no Paquistão: uma revisão

Abstract Nowadays food borne illness is most common in people due to their epidemic nature. These diseases affect the human digestive system through bacteria, viruses and parasites. The agents of illness are transmitted in our body through various types of food items, water and uncooked. Pathogens show drastic changes in immunosuppressant people. This review gives general insights to harmful microbial life. Pakistan is a developed country and because of its improper food management, a lot of gastrointestinal problems are noted in many patients. Bacteria are most common agents to spread diarrhoea, villi infection, constipation and dysenteric disease in human and induce the rejection of organ transplant. Enhancement of their lifestyle, properly cooked food should be used and to overcome the outbreak of the diseases.

Resumo Hoje em dia, as doenças transmitidas por alimentos são mais comuns em pessoas devido à sua natureza epidêmica. Essas doenças afetam o sistema digestivo humano por meio de bactérias, vírus e parasitas. Os agentes das doenças são transmitidos em nosso corpo por meio de diversos tipos de alimentos, água e crus. Os patógenos mostram mudanças drásticas em pessoas imunossupressoras. Esta revisão fornece uma visão geral da vida microbiana prejudicial. O Paquistão é um país desenvolvido e, devido ao seu manejo alimentar inadequado, muitos problemas gastrointestinais são observados em muitos pacientes. As bactérias são os agentes mais comuns para espalhar diarreia, infecção de vilosidades, obstipação e doença disentérica em humanos e induzem a rejeição de transplantes de órgãos. Melhoria de seu estilo de vida, alimentos devidamente cozidos devem ser utilizados e para superar o aparecimento de doenças.

Prospect of microbial food borne diseases in Pakistan: a review.

Nowadays food borne illness is most common in people due to their epidemic nature. These diseases affect the human digestive system through bacteria, viruses and parasites. The agents of illness are transmitted in our body through various types of food items, water and uncooked. Pathogens show drastic changes in immunosuppressant people. This review gives general insights to harmful microbial life. Pakistan is a developed country and because of its improper food management, a lot of gastrointestinal problems are noted in many patients. Bacteria are most common agents to spread diarrhoea, villi infection, constipation and dysenteric disease in human and induce the rejection of organ transplant. Enhancement of their lifestyle, properly cooked food should be used and to overcome the outbreak of the diseases.

There is no clinically important difference in the Oxford knee scores between one and two years after total knee arthroplasty: The one-year score could be used as the benchmark timepoint to assess outcome.

BACKGROUND: The aim was to assess the whether there was a clinically important change in the Oxford knee score (OKS) between one and two years after total knee arthroplasty (TKA), and to identify predictors associated with a clinically important change. METHODS: A retrospective cohort study was undertaken using an established arthroplasty database of 5857 primary TKA. Patient demographics, body mass index, social deprivation, OKS and EuroQoL five-domain (EQ-5D) score were collected preoperatively and at one and two years postoperatively. A clinically important change in the OKS was defined as ≥5 points. RESULTS: There was a 0.2 point increase in the OKS between one and two years, which was statistically significant (95% confidence interval (CI) 0.1 to 0.4, p < .0001), but not clinically important. A better preoperative OKS (p < .001) and in contrast a worse one year OKS (p < .001) were independently associated with a greater improvement from one to two years. There were 1006 (17.3%) patients that had a clinically important improvement in the OKS between one and two years. Receiver operating characteristic curve analysis showed that a one year OKS of less than 35 was a reliable predictor of a clinically important improvement between one and two years (area under the curve 0.77, 95% CI 0.76 to 0.78, p < .001). CONCLUSION: There was not a clinically important change in the OKS from one to two years after TKA when assessed as a group. However, individual patients with a one year OKS of less than 35 may demonstrate a clinically important improvement at two years. LEVEL OF EVIDENCE: Retrospective diagnostic study, Level III.

Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress.

It has become increasingly clear that oncogenes not only provide aberrant growth signals to cells but also cause DNA damage at replication forks (replication stress), which activate the ataxia telangiectasia mutated (ATM)/p53-dependent tumor barrier. Here we studied underlying mechanisms of oncogene-induced replication stress in cells overexpressing the oncogene Cyclin E. Cyclin E overexpression is associated with increased firing of replication origins, impaired replication fork progression and DNA damage that activates RAD51-mediated recombination. By inhibiting replication initiation factors, we show that Cyclin E-induced replication slowing and DNA damage is a consequence of excessive origin firing. A significant amount of Cyclin E-induced replication slowing is due to interference between replication and transcription, which also underlies the activation of homologous recombination. Our data suggest that Cyclin E-induced replication stress is caused by deregulation of replication initiation and increased interference between replication and transcription, which results in impaired replication fork progression and DNA damage triggering the tumor barrier or cancer-promoting mutations.

Effects of anti-GLUT antibodies on glucose transport into human erythrocyte ghosts.

We have studied the effects of anti-GLUT1 antibodies on the uptake of glucose into erythrocytes. Glucose transport into human erythrocyte ghosts was measured directly using 3H-2-deoxy-glucose, or indirectly by monitoring associated volume changes using light scattering. The uptake of glucose was significantly inhibited in ghosts resealed in solutions containing specific antibodies against GLUT1. Such an effect was not observed when an antibody against the oestrogen receptor, lacking specificity towards GLUT1, was employed instead. The antibodies were also without effect on the efflux of preloaded glucose from erythrocyte ghosts. The demonstration that anti-GLUT antibodies can inhibit glucose uptake is support for the hypothesis that they exaggerate the cytoplasmic barrier to glucose uptake created by endofacial segments of GLUT1.

Effects of high pressure on glucose transport in the human erythrocyte.

The effects of raised hydraulic pressure on D-glucose exit from human red cells at 25 degrees C were determined using light scattering measurements in a sealed pressurized spectrofluorimeter cuvette. The reduction in the rates of glucose exit with raised pressure provides an index of the activation volume, deltaV++ (delta ln k/deltaP)(T) = -deltaV++/RT. Raised pressure decreased the rate constant of glucose exit from 0.077 +/- 0.003 s(-1) to 0.050 +/- 0.002 s(-1) (n = 5, P < 0.003). The Ki for glucose binding to the external site was 2.7 +/- 0.4 mm (0.1 MPa) and was reduced to 1.45 +/- 0.15 mm (40 MPa), (P < 0.01, Student's t test). Maltose had a biphasic effect on deltaV++. At [maltose] <250 microM, deltaV++ of glucose exit increased above that with [maltose = 0 mM], at >1 mm maltose, deltaV++ was reduced below that with [maltose = 0 mM]. Pentobarbital (2 mM) decreased the deltaV++ of net glucose exit into glucose-free solution from 30 +/- 5 ml mol(-1) (control) to 2 +/- 0.5 ml mol(-1) (P < 0.01). Raised pressure had a negligible effect on L-sorbose exit. These findings suggest that stable hydrated and liganded forms of GLUT with lower affinity towards glucose permit higher glucose mobilities across the transporter and are modelled equally well with one-alternating or a two-fixed-site kinetic models.