EBV-associated primary CNS lymphoma occurring after immunosuppression is a distinct immunobiological entity.

Primary central nervous system lymphoma (PCNSL) is confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. Rarely, PCNSL occurs in the context of immunosuppression (eg, posttransplant lymphoproliferative disorders or HIV [AIDS-related PCNSL]). These cases are poorly characterized, have dismal outcome, and are typically Epstein-Barr virus (EBV)-associated (ie, tissue-positive). We used targeted sequencing and digital multiplex gene expression to compare the genetic landscape and tumor microenvironment (TME) of 91 PCNSL tissues all with diffuse large B-cell lymphoma histology. Forty-seven were EBV tissue-negative: 45 EBV- HIV- PCNSL and 2 EBV- HIV+ PCNSL; and 44 were EBV tissue-positive: 23 EBV+ HIV+ PCNSL and 21 EBV+ HIV- PCNSL. As with prior studies, EBV- HIV- PCNSL had frequent MYD88, CD79B, and PIM1 mutations, and enrichment for the activated B-cell (ABC) cell-of-origin subtype. In contrast, these mutations were absent in all EBV tissue-positive cases and ABC frequency was low. Furthermore, copy number loss in HLA class I/II and antigen-presenting/processing genes were rarely observed, indicating retained antigen presentation. To counter this, EBV+ HIV- PCNSL had a tolerogenic TME with elevated macrophage and immune-checkpoint gene expression, whereas AIDS-related PCNSL had low CD4 gene counts. EBV-associated PCNSL in the immunosuppressed is immunobiologically distinct from EBV- HIV- PCNSL, and, despite expressing an immunogenic virus, retains the ability to present EBV antigens. Results provide a framework for targeted treatment.

Combined thoracic paravertebral and pectoral nerve blocks for breast surgery under sedation: a prospective observational case series.

Avoidance of general anaesthesia for breast surgery may be because of clinical reasons or patient choice. There is emerging evidence that the use of regional anaesthesia and the avoidance of volatile anaesthetics and opioid analgesia may have beneficial effects on oncological outcomes. We conducted a prospective observational case series of 16 breast cancer surgeries performed under thoracic paravertebral plus pectoral nerve block with propofol sedation to demonstrate feasibility of technique, patient acceptability and surgeon satisfaction. Fifteen out of 16 cases were successfully completed under sedation and regional anaesthesia, with one conversion to general anaesthesia. Eleven out of 16 cases required low-dose intra-operative opioid analgesia. Out of the 15 surgical procedures completed under regional anaesthesia with sedation, all patients experienced either no or minimal intra-operative pain, and all would choose this anaesthetic technique again. Surgeon-reported operating conditions were 'indistinguishable from general anaesthesia' in most cases, and surgeons were 'extremely satisfied' or 'satisfied' with the technique after every procedure. Combined thoracic paravertebral plus pectoral nerve block with intra-operative sedation is a feasible technique for breast surgery.

Screening whole spine magnetic resonance imaging in multiple myeloma.

BACKGROUND: Magnetic resonance imaging (MRI) is the most sensitive method for detecting focal spinal disease (FSD) in multiple myeloma (MM). It is unclear whether whole spine MRI (WS-MRI) should be employed as a screening test at diagnosis of MM. AIM: To determine the utility of screening WS-MRI at diagnosis of MM. METHODS: A retrospective analysis of data from January 2008 to January 2013 at the Townsville Hospital was performed. At this centre, WS-MRI is used routinely in all newly diagnosed MM. The findings of WS-MRI in patients with and without an agreed guideline indication for WS-MRI were compared. Clinical predictors of FSD were determined. RESULTS: Seventy-one patients were included in the analysis. Forty-four (62%) had an agreed indication for MRI; 33 (75%) of these had FSD. Within this group, 17 required urgent intervention and 13 had spinal plasmacytomas. Within a second group without a guideline indication, 4 of 27 (15%) were found to have FSD on MRI - none required urgent intervention and or had plasmacytomas. Three of eight smouldering myeloma patients were reclassified as symptomatic myeloma by documenting lytic lesions not identified on plain film. The strongest predictors of FSD were back pain (P < 0.001) and vertebral compression fracture (P = 0.003). CONCLUSION: WS-MRI in patients without a guideline indication did not detect any lesions that threatened the spinal cord. WS-MRI is essential in those with guideline indications. WS-MRI is of benefit to patients with smouldering myeloma where documentation of lesions not seen on plain film will result in treatment rather than observation.

Therapeutic feeding at a rural hospital in Zimbabwe.

OBJECTIVE: The purpose of this audit was to review treatment outcomes of participants in the Cooperazione e sviluppo/Cooperation and Development (CESVI), Therapeutic Feeding Programme (TFP) (i.e., death vs cure vs absconded) and to make recommendations for improving this and other similar programmes. DESIGN: This study was a retrospective chart review. The charts of all patients admitted to the TFP from 1 January 2005 to 31 December 2005 were analyzed. SETTING: The Salvation Army Howard Hospital is a district hospital in rural Zimbabwe. The hospital provides both inpatient and outpatient paediatric care. SUBJECTS: 132 consecutive children were enrolled in the TFP in 2005. INTERVENTION: The objectives of the TFP included identification of children with severe malnutrition; treating complications associated with severe malnutrition and prescribing appropriate dietary treatment. MAIN OUTCOME MEASURES: The main outcome of interest was whether TFP participants died, were cured, or absconded. We assessed factors that may be associated with these outcomes such as age, gender, comorbidities and length of stay. RESULTS: Female children and children with marasmus were more likely to abscond from the programme than male children and children with kwashiorkor (p = 0.041, 0.039 respectively). The majority of children who died while in the programme did so within the first week of their admission. The majority of children who were cured while in the programme achieved this goal after two weeks of hospitalization (p < 0.0001). CONCLUSION: Given the contextual factors in rural African settings that could potentially impede the healthy growth and development of children, this review has produced programmatic recommendations and suggestions for future research directions.

Regional differences in the provision of adult renal dialysis services in the UK.

BACKGROUND: Provision of renal dialysis varies between UK regions. AIM: To analyse these differences in provision and investigate their causes. DESIGN: Questionnaire-based survey. METHODS: A questionnaire was posted to all renal provider units and renal commissioning groups in the UK. Questions covered issues such as dialysis modalities and patient choice. Data were collected by telephone interview (or post in some cases) and analysed using SPSS. RESULTS: All renal provider units in the UK responded. A full range of modalities was provided by the majority of units. Clear variations in the level and quality of dialysis provision were seen between the UK regions. These included variation in choice of dialysis modality, provision of high-cost drugs, vascular access waiting times, number of support staff and availability of spare dialysis slots. DISCUSSION: The considerable variation between UK regions in the provision of adult renal dialysis services cannot be entirely explained by age or ethnic variation, and is in part due to limited bed space, dialysis machines and support staff, as well as changes in commissioning arrangements. To meet the requirements of the renal national service framework in most regions, changes to policy and funding will be required, such that the relatively new commissioning groups implement more appropriate funding structures in closer dialogue with their provider units.

Sudden cardiac death and the 'athlete's heart'.

OBJECTIVES: To review the current literature pertaining to the cardiovascular adaptations to exercise and the impact on the physical examination, the electrocardiogram, and the echocardiogram, and to distinguish those physiologic changes from pathologic conditions associated with sudden cardiac death in athletes. DATA SYNTHESIS: Specific cardiovascular adaptations occur in response to regular physical exercise. The extent of these changes depend on the type and duration of exercise as well as the gender of the athlete. These cardiac adaptations are morphologically different from those conditions associated with sudden cardiac death. In the athlete younger than 35 years, hypertrophic cardiomyopathy is the most common cardiac condition associated with sudden death. Right ventricular dysplasia, idiopathic left ventricular hypertrophy, coronary anomalies, premature atherosclerosis, and Marfan syndrome compose the majority of the remaining causes of sudden cardiac death in athletes. In the athlete older than 35 years, coronary atherosclerosis is the leading cause of sudden death followed by those conditions responsible for sudden death in the younger athlete. Despite this, regular exercise before or following a myocardial infarction provides a protective effect with respect to overall mortality, cardiovascular mortality, and fatal reinfarction rates. CONCLUSIONS: Cardiovascular adaptation to regular physical exercise leads to morphologic changes in the myocardium that influence the cardiac examination, the electrocardiogram, and the echocardiogram. Knowledge and recognition of those changes can allow the clinician to distinguish normal physiologic changes from cardiac abnormality. Proper detection of athletes at high risk for sudden cardiac death and abstention from vigorous physical activity in these athletes may prevent sudden death.

Comparison of three methods of respiratory care following upper abdominal surgery.

Incentive spirometry, as a method for preventing postoperative atelectasis, was compared with intermittent positive-pressure breathing (IPPB) and resistance breathing in 126 patients undergoing upper-abdominal surgery, most of whom had cholecystectomy. There was no statistically significant difference in the incidence of atelectasis among the three groups, who were matched for age, sex, smoking history, previous respiratory disease, and duration of surgery. There was a significantly higher incidence of atelectasis in patients over the age of 50 years (P = 0.004) than in younger subjects, where the incidence was not different among the three groups. Incentive spirometric therapy, as used in this study, offered no advantage over the other methods of treatment.

A systematic review of the clinical effectiveness of pioglitazone in the treatment of type 2 diabetes mellitus.

BACKGROUND: Pioglitazone is a member of a recently developed class of glucose-lowering agents, the thiazolidinediones, used in the treatment of type 2 diabetes mellitus. In the United States, it is approved for use both as monotherapy and in combination with metformin, a sulfonylurea, or insulin; in Europe, it is approved for use in combination with metformin or a sulfonylurea but not insulin. OBJECTIVE: This article presents a systematic review of the published literature on the effectiveness of pioglitazone in the treatment of type 2 diabetes, both as monotherapy and in combination with other antidiabetic agents. METHODS: The peer-reviewed English- and foreign-language literature was searched using MEDLINE, PubMED, EMBASE, Science Citation Index, the Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register, the UK National Health Service Centre for Reviews and Dissemination databases, and the Office of Health Economics Health Economic Evaluations Database. Searches were not limited to specific publication types, study designs, dates, or languages. The latest search was performed in March 2001. For a trial to be included in the review, at least 1 outcome measure had to involve the effects of pioglitazone on glycemic control or cardiovascular risk factors, or its side effects. Because of the heterogeneity of studies, no formal meta-analysis was performed. RESULTS: Eleven studies met the inclusion criteria, 6 involving pioglitazone monotherapy and 5 involving combination therapy. Full reports were available for only 6 of the 11 studies. No studies directly compared pioglitazone with other antidiabetic drugs. Both as monotherapy and in combination therapy, pioglitazone produced decreases in blood glucose levels (up to 95 mg/dL) and glycosylated hemoglobin (up to 2.6%). At doses of > or = 30 mg/d, pioglitazone was associated with reductions in triglyceride levels (-30-70 mg/dL) and increases in high-density lipoprotein cholesterol (HDL-C) levels (-4-5 mg/dL). Pioglitazone treatment was associated with significant weight gain (up to 4 kg over 16 weeks). Adverse effects included mild edema (in up to 11.7% of patients) and a clinically nonsignificant decrease in hemoglobin concentrations. Abnormal results on liver function testing were no more common in treated patients than in control groups. CONCLUSIONS: Pioglitazone has been shown to reduce blood glucose levels in patients with type 2 diabetes. Although the observed decreases in triglyceride levels and increases in HDL-C levels could be expected to lead to a reduction in cardiovascular risk, the effects of weight gain may counteract this benefit. The evidence suggests that the preferred role for pioglitazone may be as an adjunct to metformin or a sulfonylurea in patients whose condition is not well controlled with monotherapy and for whom a metformin-sulfonylurea combination is contraindicated. There is a need for large-scale, long-term studies comparing the effectiveness of combination therapy that includes pioglitazone with that of other combinations of antidiabetic drugs.

Treatments for spasticity and pain in multiple sclerosis: a systematic review.

OBJECTIVES: To identify the drug treatments currently available for the management of spasticity and pain in multiple sclerosis (MS), and to evaluate their clinical and cost-effectiveness. DATA SOURCES: Electronic bibliographic databases, National Research Register, MRC Clinical Trials Register and the US National Institutes of Health Clinical Trials Register. REVIEW METHODS: Systematic searches identified 15 interventions for the treatment of spasticity and 15 interventions for treatment of pain. The quality and outcomes of the studies were evaluated. Reviews of the treatment of spasticity and pain when due to other aetiologies were also sought. RESULTS: There is limited evidence of the effectiveness of four oral drugs for spasticity: baclofen, dantrolene, diazepam and tizanidine. Tizanidine appears to be no more effective than comparator drugs such as baclofen and has a slightly different side-effects profile. Despite claims that it causes less muscle weakness, there was very little evidence that tizanidine performed any better in this respect than other drugs, although it is more expensive. The findings of this review are consistent with reviews of the same treatments for spasticity derived from other aetiologies. There is good evidence that both botulinum toxin (BT) and intrathecal baclofen are effective in reducing spasticity, and both are associated with functional benefit. However, they are invasive, and substantially more expensive. None of the studies included in the review of pain were designed specifically to evaluate the alleviation of pain in patients with MS and there was no consistency regarding the use of validated outcome measures. It was suggested that, although expensive, the use of intrathecal baclofen may be associated with significant savings in hospitalisation costs in relation to bed-bound patients who are at risk of developing pressure sores, thus enhancing its cost-effectiveness. No studies of cost-effectiveness were identified in the review of pain. There is evidence, albeit limited, of the clinical effectiveness of baclofen, dantrolene, diazepam, tizanidine, intrathecal baclofen and BT and of the potential cost-effectiveness of intrathecal baclofen in the treatment of spasticity in MS. CONCLUSIONS: Many of the interventions identified are not licensed for the alleviation of pain or spasticity in MS and the lack of evidence relating to their effectiveness may also limit their widespread use. Indeed, forthcoming information relating to the use of cannabinoids in MS may result in there being better evidence of the effectiveness of new treatments than of any of the currently used drugs. It may therefore be of value to carry out double-blind randomised controlled trials of interventions used in current practice, where outcomes could include functional benefit and impact on quality of life. Further research into the development and validation of outcomes measures for pain and spasticity may also be useful, as perhaps would cost-utility studies.

The clinical and cost-effectiveness of pulsatile machine perfusion versus cold storage of kidneys for transplantation retrieved from heart-beating and non-heart-beating donors.

OBJECTIVES: To evaluate the clinical and cost-effectiveness of machine perfusion (MP) compared to cold storage (CS), as a means of preserving kidneys prior to transplantation. Transplantation of kidneys from both heart-beating donors (HBDs) and non-heart-beating donors (NHBDs) is considered. Finally to review whether the use of MP can allow valid testing of kidney viability prior to transplantation. DATA SOURCES: Fifteen electronic bibliographic databases were searched. The reference lists of relevant articles and sponsor submissions were hand searched and various health service research-related resources were consulted via the Internet. REVIEW METHODS: A literature search was undertaken to identify relevant studies and a meta-analysis performed on the studies that had appropriate comparator groups and reported sufficient data. A structured review examined tests of viability of kidneys on MP. Economic modelling was used to determine the cost-effectiveness and cost-utility of MP. RESULTS: The meta-analysis suggested that the use of MP, as compared with CS, is associated with a relative risk of delayed graft function (DGF) of 0.804 (95% confidence limits 0.672 to 0.961). There was no evidence to suggest that this effect is different in kidneys taken from HBDs as opposed to NHBDs. Meta-analysis of 1-year graft survival data showed no significant effect, but the studies, even when aggregated, were severely underpowered with respect to the likely impact on graft survival. The size of effects demonstrated were in line with those predicted by an indirect model of graft survival based on the association of DGF with graft loss. The economic assessment indicated that it is unlikely that in the UK health setting complete cost recovery will be obtained from a reduction in the incidence of DGF. The probability that MP is cheaper and more effective than CS in the long term was estimated at around 80% for NHBD recipients and 50-60% for HBD recipients. Flow characteristics of the perfusate of kidneys undergoing MP may be an indicator of kidney viability, but data were inadequate to calculate the sensitivity and specificity of any test based on this. The concentration of alpha-glutathione-S-transferase (a marker of cell damage) in the perfusate may be the basis of a valid test. A threshold of 2800 micrograms/100 g gave a sensitivity of 93% and specificity of 33% (and hence a likelihood ratio of 1.41). CONCLUSIONS: The baseline analysis indicated that in the long-term MP would be expected to be cheaper and more effective than CS for both HBD and NHBD recipients. A definitive study of the clinical benefit of MP in order to establish its effect on DGF and longer term graft survival would be valuable, together with an economic evaluation of the benefits. While direct evidence relating to improvements in graft survival would be preferable, the small predicted improvement indicates that a very large sample size would be required. In addition to seeking direct evidence of the impact on DGF, research quantifying the impact of DGF on graft survival in this technology is required. Research is also needed to establish whether a valid test (or combination of tests) of kidney viability can be developed.

Risk adjustment and hospital cost-based resource allocation, with an application to El Salvador.

Ignorance about the costs, case loads and case mixes of different hospitals within the public health system constitutes an important obstacle to reforming health care spending in many developing countries. National (tertiary) hospitals generally receive significantly larger budgets, per patient, than lower-level (district) hospitals. One reason for these differential allocations is the widely held belief that national hospitals treat persons with more difficult illnesses and persons who are more severely ill than do other, non-national, hospitals. This belief is but a presumption and one that warrants investigation. This paper analyzes expenditures among public hospitals in El Salvador over a 12-year period to address this question. While controlling for patient morbidity, outputs and other characteristics, district hospitals are found to be substantially underfunded relative to national hospitals. Four policy options to redress this situation are examined.

Effect of control of hypertension on progressive renal failure.

This study assesses the direct effect of different degrees of blood pressure control on the progression of chronic renal failure (CRF) in 18 patients with nephropathies of varying etiology (Glomerular filtration rate [GFR]: 14.99 +/- 5.94 ml/min/1.73 m2). The study involves three consecutive phases; Phase 1 consisted of a retrospective analysis of blood pressure and biochemical data: mean diastolic blood pressure (MDBP) was 89.9 +/- 7.9 mmHg and the mean rate of decline in renal function was -68.9 1/mol of creatinine/month. Phase 2 consisted of a 6 months prospective period of frequent (monthly) follow-up and optimization of blood pressure control when MDBP was reduced to 83.9 +/- 6.5 mmHg (p < 0.001 cf phase 1) and the rate of decline in renal function fell to -25.2 1/mol/month (p < 0.05 cf phase 1). Phase 3 consisted of another 6-month period when further reduction of MDBP 77.1 +/- 6.6 mmHg (p < 0.01 cf phase 2) was brought about by the addition of the calcium antagonist nifedipine (10 mg thrice/daily). This was not associated with further improvement in the rate of decline of renal function as in this phase the rate of decline was -53.2 1/mol/month. This study confirms that frequent follow-ups with improved blood pressure control slow the rate of decline in renal function. Further reduction of diastolic blood pressure to below 80-85 mmHg could not be shown to confer additional benefit.

The SF36 as an outcome measure of services for end stage renal failure.

OBJECTIVE: To evaluate the use of the short form 36 (SF36) as a measure of health related quality of life of patients with end stage renal failure, document the results, and investigate factors, including mode of treatment, which may influence it. DESIGN: Cross sectional survey of patients with end stage renal failure, with the standard United Kingdom version of the SF36 supplemented by specific questions for end stage renal failure. SETTING: A teaching hospital renal unit. SUBJECTS AND METHODS: 660 patients treated at the Sheffield Kidney Institute by haemodialysis, peritoneal dialysis, and transplantation. Internal consistency, percentage of maximal or minimal responses, SF36 scores, effect sizes, correlations between independent predictor variables and individual dimension scores of the SF36. Multiple regression analysis of the SF36 scores for the physical functioning, vitality, and mental health dimensions against treatment, age, risk (comorbidity) score, and other independent variables. RESULTS: A high response rate was achieved. Internal consistency was good. There were no floor or ceiling effects other than for the two "role" dimensions. Overall health related quality of life was poor compared with the general population. Having a functioning transplant was a significant predictor of higher score in the three dimensions (physical functioning, vitality, and mental health) for which multiple regression models were constructed. Age, sex, comorbidity, duration of treatment, level of social and emotional support, household numbers, and hospital dialysis were also (variably) significant predictors. CONCLUSIONS: The SF36 is a practical and consistent questionnaire in this context, and there is evidence to support its construct validity. Overall the health related quality of life of these patients is poor, although transplantation is associated with higher scores independently of the effect of age and comorbidity. Age, comorbidity, and sex are also predictive of the scores attained in the three dimensions studied. Further studies are required to ascertain whether altering those predictor variables which are under the influence of professional carers is associated with changes in health related quality of life, and thus confirm the value of this outcome as a measure of quality of care.

Clinical reasoning case studies as teaching tools.

OBJECTIVE: Students are taught how to apply clinical reasoning methods through a variety of teaching methods, including the use of case studies. Various types of case studies have been described in the literature: paper cases, videotape cases, simulated client cases, and real client cases. This study examined the effectiveness of a new type of paper case study--the clinical reasoning case study--in teaching the clinical reasoning process to occupational therapy students. METHOD: Four seniors in an undergraduate occupational therapy program completed intervention plans in response to both traditional medical model and clinical reasoning paper case studies. Qualitative methods were used to analyze intervention plans and videotaped discussion about this learning experience. RESULTS: Themes discovered in the data sources suggest that compared with traditional case studies, the clinical reasoning case studies increased the quality of participants' intervention plans, participants' confidence levels about their plans, and participants' understanding of the clinical reasoning process. Participants also reported preferring clinical reasoning case studies over traditional paper case studies. CONCLUSION: The clinical reasoning case studies are effective teaching tools because they provide students with a holistic picture of the client and his or her occupational therapy treatment. In addition, these case studies model the clinical reasoning process by organizing client information according to the types of clinical reasoning that would be used to gather that information. Occupational therapy educators may find this type of paper case study useful in introducing students to the intervention planning process.

Non-formal nutrition/education for rural development in Latin America.

Innovative health and nutrition messages arising from and by rural groups in developing countries, can contribute to their improved nutritional status.