Revision knee arthroplasty: Can good outcomes be achieved at lower volumes?

BACKGROUND: The National Joint Registry (NJR) demonstrates a re-revision rate for primary knee arthroplasty of 14.2% at 7 years. The 2015 Getting it Right First Time (GIRFT) report highlighted that 58% of surgeons undertaking revision knee arthroplasty (RKA) performed fewer than five cases per year. It has been suggested that revision cases be centralised in specialist centres with a multidisciplinary team (MDT) approach. Such a hub and spoke or cluster models may still require revision surgery to be performed at relatively low volume units. METHODS: An analysis of RKA surgery performed in a four surgeon, lower volume revision knee unit over 10 years to December 2016 was undertaken. The effect of the introduction of a MDT was reviewed. The minimum follow up was two years. The primary outcome measure was re-revision. Hospital data as well as individual surgeon NJR reports were used to ensure all re-revisions were accounted for. Outcome scores were available for 68% of cases. RESULTS: There were 192 RKAs performed in 187 patients at a mean (stdev) of 6.3 (5.4) years from the index procedure. The mean age at surgery was 68.2 (10.9) years. Twenty nine (15.5%) patients had died at the time of final review. Twelve (6.3%) cases required a further revision procedure. The commonest complication was stiffness requiring MUA. The overall 7 year survivorship was 94.9% (95% CI 90.2-97.3). The mean Oxford score at 5.4 years was 30.4 (10.4). CONCLUSIONS: RKA can be reliably performed at lower volume centres with appropriate MDT systems in place.

Isoniazid-resistant disseminated Mycobacterium tuberculosis in a Jamaican infant with HIV/AIDS.

A case report of isoniazid-resistant disseminated tuberculosis in a young child perinatally co-infected with human immunodeficiency virus (HIV-1) and the challenges managing this child in a resource-constrained setting.

Paediatric and perinatal HIV/AIDS in Jamaica an international leadership initiative, 2002-2007.

BACKGROUND: Paediatric and Perinatal HIV/AIDS remain significant health challenges in the Caribbean where the HIV seroprevalence is second only to Sub-Saharan Africa. METHOD: We describe a collaborative approach to the prevention, treatment and care ofHIVin pregnant women, infants and children in Jamaica. A team of academic and government healthcare personnel collaborated to address the paediatric and perinatal HIV epidemic in Greater Kingston as a model for Jamaica (population 2.6 million, HIV seroprevalence 1.5%). A five-point plan was utilized and included leadership and training, preventing mother-to-child transmission (pMTCT), treatment and care of women, infants and children, outcomes-based research and local, regional and international outreach. RESULTS: A core group of paediatric/perinatal HIV professionals were trained, including paediatricians, obstetricians, public health practitioners, nurses, microbiologists, data managers, information technology personnel and students to serve Greater Kingston (birth cohort 20,000). During September 2002 to August 2007, over 69 793 pregnant women presented for antenatal care. During these five years, significant improvements occurred in uptake of voluntary counselling (40% to 91%) and HIV-testing (53% to 102%). Eight hundred and eighty-three women tested HIV-positive with seroprevalence rates of 1-2% each year The use of modified short course zidovudine or nevirapine in the first three years significantly reduced mother-to-child transmission (MTCT) of HIV from 29% to 6% (RR 0.27; 95%0 CI--0.10, 0.68). During 2005 to 2007 using maternal highly active antiretroviral therapy (HAART) with zidovudine and lamivudine with either nevirapine, nelfinavir or lopinavir/ritonavir and infant zidovudine and nevirapine, MTCT was further reduced to an estimated 1.6% in Greater Kingston and 4.75% islandwide. In five years, we evaluated 1570 children in four-weekly paediatric infectious diseases clinics in Kingston, St Andrew and St Catherine and in six rural outreach sites throughout Jamaica; 24% (377) had HIV/AIDS and 76% (1193) were HIV-exposed. Among the infected children, 79% (299 of 377) initiated HAART resulting in reduced HIV-attributable childhood morbidity and mortality islandwide. An outcomes-based research programme was successfully implemented. CONCLUSION: Working collaboratively, our mission of pMTCT of HIV and improving the quality of life for families living and affected by HIV/AIDS in Jamaica is being achieved.

Binding of vinblastine to recrystallized human alpha 1-acid glycoprotein.

The binding of vinblastine (VLB) to recrystallized human alpha 1-acid glycoprotein (alpha 1-AGP) dissolved in phosphate-buffered saline (pH 7.4) was determined at different drug concentrations using the technique of continuous ultrafiltration. Vinblastine was extremely highly bound (greater than 99.0%) at a drug concentration of 4.0 mumol X l-1, dropping to under 60% at 65.0 mumol X l-1. Binding was best described by a two-class model with higher- (9.4 microM-1) and lower- (0.1 microM-1) affinity sites but with a similar number of binding sites (1.5 as against 1.1 lower-affinity sites). These results strongly suggest that alpha 1-AGP would be a major binding protein for VLB in plasma.

Arteriovenous shunting of microspheres in patients with colorectal liver metastases: errors in assessment due to free pertechnetate, and the effect of angiotensin II.

In patients receiving locoregional therapy for liver metastases degradable microspheres are being increasingly used in an attempt to improve cytotoxic delivery to the tumour. However, counterproductive arteriovenous shunting through the liver following intrahepatic arterial injection can occur, leading to deposition in the lung. Measurement of the degree of shunting is important in the monitoring of this kind of therapy. In this study we describe the use of technetium-labelled microspheres of serum albumin (99Tcm MSA) to measure baseline shunting during hepatic arterial perfusion scintigraphy in five patients with liver metastases of colorectal origin, and assess the significance of the values obtained for relative lung uptake (RLU) which we define as: RLU = Activity in lung field/Activity in liver + lung fields X 100%. We found that shunting was less than 5% in all cases, zero shunting occurring in 14 of the 16 patients studied. The sources of error in this technique have been assessed, the most important being the presence of free pertechnetate in the injectate. The use of Boots 10 ml vials and glass syringes respectively to dispense and administer this radiopharmaceutical reduces this error to a small predictable level. In our small group of patients, we found no evidence to suggest that use of the vasoactive agent angiotensin II significantly increases baseline shunting in patients with colorectal liver tumour.

Predictive value for coeliac disease of antibodies to gliadin, endomysium, and jejunum in patients attending for jejunal biopsy.

OBJECTIVE: To investigate the extent to which the detection of antibodies to gliadin, endomysium, and jejunum predicts the eventual diagnosis of coeliac disease according to the revised ESPGAN diagnostic criteria in a group of patients in whom there is a high suspicion of coeliac disease. DESIGN: Clinical assessment and laboratory analysis of patients with suspected coeliac disease. SETTING: Gastroenterology department of teaching hospital. PATIENTS: 96 adults with suspected coeliac disease attending for jejunal biopsy. MAIN OUTCOME MEASURES: Diagnosis of coeliac disease with the revised criteria of the European Society of Paediatric Gastroenterology and Nutrition in patients with and without antibodies associated with coeliac disease. RESULTS: 28 patients had a clinical diagnosis of coeliac disease, seven of other gastrointestinal diseases, and 12 of miscellaneous diseases; 49 had no diagnosis. Gliadin IgA detected by ELISA was found in all patients with coeliac disease and none of those without, giving a sensitivity, specificity, positive and negative predictive values, and predictive efficiency of 100% for diagnosing coeliac disease within the group. Endomysial IgA was found in 25 (89%) patients with coeliac disease and jejunal IgA in 21 (75%); neither IgA was found in patients without coeliac disease. CONCLUSION: Detection of gliadin IgA by ELISA and to a lesser extent the endomysial IgA should allow better selection of patients for jejunal biopsy and thus make diagnosing coeliac disease simpler and more efficient.

Subungual melanoma: an important tip.

Acral lentiginous melanoma is rare, representing approximately 1% of malignant melanomas. Overall 5 year survival is disproportionately poor (25-51%) compared to other histological subtypes. This has been attributed to diagnostic delay resulting in more advanced presentation. Subungual presentation in the fingers is uncommon, reported in 1-13% of all acral lentiginous melanomas. We report a unique and diagnostically challenging case. Contrary to previously reported examples in the literature, the actual neoplastic pathology was detected in the less pigmented finger tip skin rather than the deeply pigmented nail bed germinal and sterile matrix that showed no evidence of malignancy. We therefore advocate that in cases where skin surrounding the nail is involved, this surrounding skin should also be biopsied, even if it is less pigmented than the primary lesion.

Natural killer cell cytotoxicity in patients with recurrent herpes infections: diagnostic utility of a flow cytometric assay.

BACKGROUND: Primary immune deficiencies of natural killer (NK) cells have been described in patients with a susceptibility to herpes infections. AIMS: To assess the diagnostic utility of measurement of NK cytotoxicity in patients with recurrent oral herpes infections. METHODS: A retrospective audit was carried out on results obtained over an 18-month period, from 28 NK cell cytotoxicity assays (24 patients; all with a history of recurrent oral herpes infections), and 24 control samples (three healthy donors). Percentage specific cytotoxicity (PSC) was determined by measurement of the percentage of K562 target cells lysed by NK cells after incubation, using the NK TEST. Comparison of PSC was made with reference ranges provided. RESULTS: No patient with absent NK/NKT cells or NK cell cytotoxicity was identified (95% CI 0 to 14.8%). Two patients had persistently low PSC. Two patients with reduced PSC showed PSC within the normal reference range on repeat testing. Patient and control samples were seen both above and below the reference ranges. A relationship was expected between NK cell percentage and PSC; however this correlation was not significant (r(s)=0.29, p=0.18, 95% CI -0.14 to 0.63). CONCLUSIONS: A deficiency of NK cell cytotoxicity has not been identified in this cohort. An apparent reduction in cytotoxicity may be due to normal interpersonal and intersample variability in NK cytotoxicity. Without reference ranges established from a large population of control samples to account for this, a reduction in PSC is difficult to define. Further studies are required to identify if a correlation exists between the percentage of NK cells and PSC.

Son preference in Vietnam.

This article assesses the strength of son preference in Vietnam, as reflected in fertility behavior. It formulates and estimates a proportional hazards model applied to birth intervals, and a contraceptive prevalence model, using household survey data from 2,636 ever-married women aged 15-49 with at least one living child who were interviewed for the Vietnam Living Standards Survey 1992-1993. Son preference is found to be strong by world standards, but nevertheless, it has a minor effect on fertility; in its absence, the total fertility rate would fall by roughly 10 percent from the current level of about 3.2 children per woman of reproductive age.

PIP: Vietnam has penalties for having children too soon or for having too many children. The penalties are not as severe as those in China and vary widely within the country. This study examines the impact of son preference on fertility behavior in Vietnam and establishes the existence of gender preferences. Hazard models are used to estimate the risk of having another child after the birth of a son and to determine whether families with a son are more likely to use contraceptives. Data are obtained from the Vietnam Living Standards Survey of 4800 households during 1992-93. The results of the application of four Cox proportional hazard models indicates that son preference is clear and strong for mothers who have 2-4 children. Women with 3 children are at greatest risk of having another child, if the children are all daughters, and at some risk, if the children are all sons. The risk is the least for women with one child of each gender. The desire for gender balance does not appear for women with two children. More maternal education reduces the risk of more births. If women's educational level increased from 6.6 to 8.0 years, the hazard rate would decline by about 9%. Risk of another birth is lowered by increased maternal age, higher expenditure per capita, and urban residence and residence in the Red River Delta. The contraceptive use rate is calculated to be 77% if there is no son preference, according to Arnold's methods. Families with at least one son are about 15% more likely than those with none to be using contraception. The likelihood of contraceptive use declines among breastfeeding women and increases among better educated women and among working women. The same increase in contraceptive use is achieved by 5 years of education and by women's employment. Contraceptive use is highest in the Red River Delta, a densely populated area. Contraceptive use is unaffected by age at first marriage, duration of marriage, gender of household head, expenditure per capita, cost of contraception, urban residence, and the age of the father. Estimates reveal that total fertility would be 10% lower, if son preference declined in importance, but this rate of decline is expected among countries experiencing demographic transition.

Using a mixture model to detect son preference in Vietnam.

Son preference is strong in Vietnam, according to attitudinal surveys and studies of contraceptive prevalence and birth hazards. These techniques assume a single model is valid for all families, but it is more plausible that son preference is found for some, but not all, families. Heterogeneous preferences may be addressed with a mixture model. This paper specifies and estimates a two-Weibull regression model, applied to the interval between the second and third births. The data come from the Vietnam Living Standards Survey of 1992-93. Applying information criteria, graphs, and martingale-based residuals, the two-Weibull model is found to fit better than a one-Weibull model. Roughly half of parents have son preference and, curiously, a propensity for fewer children. The other group has more children, no son preference, and is colourless in the sense that the birth interval is difficult to predict on the basis of the regressors used.

PIP: Attitudinal surveys consistently indicate that parents in Vietnam have a strong desire to bear at least one son before they terminate their childbearing. However, stated preferences for sons are believed to be unreliable as a guide to actual fertility behavior. Contraceptive prevalence models and proportional hazards model have therefore been used to get better insight into the existence or absence of son preference in Vietnam. These latter studies have also found son preference to be strong in Vietnam. A central problem, however, is that these techniques assume a single model is valid for all families. The authors explain that the propensity to have another child may actually depend upon different variables, or depend upon the same variables but in a different way, for different families. One way to address this problem of heterogenous preferences is to fit a mixture model. In the context of son preference, it is plausible that the population is naturally divided into those who prefer sons and those who do not. Such a scenario calls for a two-distribution mixture model. In this paper, a Weibull regression model is applied to the interval between the second and third child, using data from the Vietnam Living Standards Survey of 1992-93. A single Weibull regression model is first estimated, and then a mixture of two Weibull regression models, to explore whether this represents an improvement over the single model. The mixture model estimates that preference for a son is strong for about half of the parents surveyed and absent from the other half.

Development of a new mouse brain tumor model using implantable micro-cannulas.

The objective of this study was to develop a brain tumor model in a mouse where gene therapy could be delivered either directly into a pre-established tumor bed or prophylacticly prior to tumor delivery (protective treatment). Micro-cannulas were constructed from metal tubing, implanted into the right frontal lobe of mice, and then secured in place in the skull with cement. Experiments evaluating the usefulness, reproducibility and morbidity of the system were performed. It was found that tumor cells could reproducibly be delivered into the right frontal lobe of the mice. Two tumors could be precisely delivered into the same area following injections at different times. Repeat injections were performed without a stereotaxic frame and without the need for repeat intracerebral needle tracts. There were no noticeable side effects of maintaining the cannulas in place for long periods of time. In summary, this system is useful for studying the effects of various treatment strategies on established brain tumors in a mouse model which more closely simulates the clinical situation. It obviates the need for time consuming stereotaxic procedures or repeat invasive intracerebral injections.

Diagnosis and carrier detection of chronic granulomatous disease in five families by flow cytometry.

BACKGROUND: The application of flow cytometric assays, for determination of phagocyte respiratory burst (ROB) activity, to the investigation of chronic granulomatous disease (CGD) may lead to improved laboratory detection of patients and carriers and indicate the nature of the molecular defect. To evaluate the diagnostic capability of flow cytometry an investigation of 5 CGD families was undertaken. METHODS: Phorbol myristate acetate (PMA)-induced neutrophil ROB was determined using dihydrorhodamine 123 (DHR) and flow cytometric analysis in 26 members of 5 CGD families (2: X-CGD; 3: autosomal recessive CGD). RESULTS: Neutrophils from X-CGD patients displayed absence of reactivity. Female carriers demonstrated dual fluorescence peaks of high and low intensity indicative of normal and abnormal populations, respectively. Normal ROB activity was observed in a boy whose X-CGD was successfully treated by bone marrow transplantion. Reduced ROB activity was observed in 3 patients with autosomal-recessive CGD compared with their parents and siblings. The patterns of flow cytometric reactivity correlated with the different molecular defects identified. Absence of the p22phox membrane component of the NADPH oxidase complex resulted in a significantly reduced level of respiratory burst activity which was comparable to that observed in X-CGD, whereas reduced but detectable levels of respiratory burst activity were observed in a patient with diminished levels of p22phox and in a patient with deficiency of the cytosolic p47phox component. CONCLUSIONS: The DHR flow cytometric assay offers a sensitive diagnostic screening test for CGD and furthermore may provide an indication of the likely underlying molecular defect.

Isoniazid-resistant disseminated Mycobacterium tuberculosis in a Jamaican infant with HIV/AIDS / Mycobacterium tuberculosis diseminada resistente a isoniacida en infantes jamaicanos con VIH/SIDA

A case report of isoniazid-resistant disseminated tuberculosis in a young child perinatally co-infected with human immunodeficiency virus (HIV-1) and the challenges managing this child in a resource-constrained setting.

Un reporte de caso de tuberculosis diseminada resistente a isoniacida en un niño co-infectado perinatalmente con el virus humana de la inmunodeficiencia (VIH-1) y los desafíos para tratar a este niño en un contexto con recursos restringidos.

Paediatric and perinatal HIV/AIDS in Jamaica: an international leadership initiative, 2002-2007 / VIH/SIDA pediátrico y perinatal en Jamaica: iniciativa de liderazgo internacional, 2002-2007

BACKGROUND: Paediatric and Perinatal HIV/AIDS remain significant health challenges in the Caribbean where the HIV seroprevalence is second only to Sub-Saharan Africa. METHOD: We describe a collaborative approach to the prevention, treatment and care of HIV in pregnant women, infants and children in Jamaica. A team of academic and government healthcare personnel collaborated to address the paediatric and perinatal HIV epidemic in Greater Kingston as a model for Jamaica (population 2.6 million, HIV seroprevalence 1.5%). A five-point plan was utilized and included leadership and training, preventing mother-to-child transmission (pMTCT), treatment and care of women, infants and children, outcomes-based research and local, regional and international outreach. RESULTS: A core group of paediatric/perinatal HIV professionals were trained, including paediatricians, obstetricians, public health practitioners, nurses, microbiologists, data managers, information technology personnel and students to serve Greater Kingston (birth cohort 20 000). During September 2002 to August 2007, over 69 793 pregnant women presented for antenatal care. During these five years, significant improvements occurred in uptake of voluntary counselling (40% to 91%) and HIV-testing (53% to 102%). Eight hundred and eighty-three women tested HIV-positive with seroprevalence rates of 1-2% each year. The use of modified short course zidovudine or nevirapine in the first three years significantly reduced mother-to-child transmission (MTCT) of HIV from 29% to 6% (RR 0.27; 95% CI - 0.10, 0.68). During 2005 to 2007 using maternal highly active antiretroviral therapy (HAART) with zidovudine and lamivudine with either nevirapine, nelfinavir or lopinavir/ritonavir and infant zidovudine and nevirapine, MTCT was further reduced to an estimated 1.6% in Greater Kingston and 4.75% islandwide. In five years, we evaluated 1570 children in four-weekly paediatric infectious diseases clinics in Kingston, St Andrew and St Catherine and in six rural outreach sites throughout Jamaica; 24% (377) had HIV/AIDS and 76% (1193) were HIV-exposed. Among the infected children, 79% (299 of 377) initiated HAART, resulting in reduced HIV-attributable childhood morbidity and mortality islandwide. An outcomes-based research programme was successfully implemented. CONCLUSION: Working collaboratively, our mission of pMTCT of HIV and improving the quality of life for families living and affected by HIV/AIDS in Jamaica is being achieved.

ANTECEDENTES: El VIH/SIDA pediátrico y el perinatal continúan siendo retos significativos para la salud en el Caribe, donde la seroprevalencia de VIH ocupa el segundo lugar tras el África Subsahariana. MÉTODO: Se describe un enfoque colaborativo para tratamiento, prevención y cuidado de embarazadas, bebés y niños en Jamaica. Un equipo de personal académico y gubernamental vinculados a la salud, colaboraron para abordar la epidemia de VIH pediátrico y perinatal en Greater Kingston, como modelo para Jamaica (población de 2.6 millones, 1.5% seroprevalencia VIH). Se utilizó un plan de cinco puntos que incluyó liderazgo y entrenamiento, prevención de la transmisión madre a hijo (PTMAH), tratamiento y cuidado de mujeres, bebés y niños, investigaciones basadas en resultados, y outreach local, regional e internacional. RESULTADOS: Un grupo básico de profesionales del VIH pediátrico/perinatal, que incluía pediatras, obstetras, trabajadores de la salud, enfermeras, microbiólogos, administradores de datos, así como personal y estudiantes de la tecnología de la información, fue entrenado para servir en Greater Kingston (cohorte de nacimiento 20 000). De septiembre de 2002 hasta Agosto de 2007, más de 69 793 embarazadas se presentaron para recibir atención prenatal. Durante estos cinco años, tuvieron lugar mejoras significativos en cuanto a la recepción de asesoramiento (40% to 91%) y pruebas (53% to 102%) de VIH voluntarios. Ochocientos ochenta y tres mujeres resultaron VIH positivas en las pruebas, con tasas de seroprevalencia de 1-2% cada año. El uso de un ciclo corto modificado de zidovudina o nevirapina en los primeros tres años, redujo la transmisión madre a hijo (TMAH) de VIH significativamente de 29% a 6% (RR 0.27; 95% CI - 0.10, 0.68). Durante el 2005 hasta 2007, usando terapia antiretroviral altamente activa (TARAA) materna, con zidovudina y lamivudina con nevirapina, nelfinavir o lopinavir/ritonavir y nevirapina y zidovudina para niños, la TMAH se redujo a un estimado de 1.6 % en Greater Kingston y a .75% a lo largo de la isla. En cinco años, evaluamos 1570 niños en cuatro clínicas infecciosas pediátricas semanales en Kingston, Saint Andrew y Saint Catherine, así como en seis otros lugares destinados al servicio comunitario (outreach) por toda Jamaica; 24% (377) tenían VIH/SIDA y 76% (1193) estaba expuestos al VIH. Entre los niños infectados, 79% (299 de 377) iniciaron el TARAA, lo que trajo como resultado una reducción de la mortalidad y la morbilidad infantil atribuible al VIH, en todo el país. Se implementó exitosamente un programa de investigación basado en resultados. CONCLUSIÓN: Trabajando en colaboración, estamos logrando nuestra misión de prevenir la TMAH del VIH, y mejorar la calidad de vida de las familias que viven afectadas por el VIH/SIDA en Jamaica.