Merkel Cell Carcinoma - Current Controversies and Future Directions.

Merkel cell carcinoma is a rare, aggressive neuroendocrine skin malignancy. Evidence for management comes from case series and single-arm trials. Optimal outcomes require assessment of the patient in a multidisciplinary team setting. Rapid diagnosis and staging are essential for locoregional control and may reduce metastasis. Sentinel lymph node biopsy (SLNB) adds prognostic information. FDG-positron emission tomography has high sensitivity and specificity and affects management in a quarter of cases. Surgical excision and radiotherapy provide good locoregional control even with positive margins. Wide surgical margins are needed if adjuvant radiotherapy is not used. It is uncertain whether adjuvant radiotherapy or elective surgery for uninvolved nodes or for patients selected by positive SLNB improves survival. Total doses of 50 Gy provide high levels of control for microscopic disease but at least 60 Gy should be given for macroscopic disease. Chemotherapy can be given safely with radiotherapy, but the benefit of adjuvant chemotherapy remains uncertain. Trials of adjuvant immune therapy are underway. Unresectable primaries might be controlled with radiotherapy alone or combination systemic therapy, radiotherapy and surgery. Metastatic disease often responds to chemotherapy, but the response duration can be short. Immunity is central to disease control. Immune checkpoint inhibitor treatment resulted in high response rates in chemotherapy-naive patients and lower rates in chemotherapy-refractory patients. Durable responses are observed.

Cost of dialysis therapies in rural and remote Australia - a micro-costing analysis.

BACKGROUND: Maintenance dialysis is a costly and resource intense activity. In Australia, inadequate health infrastructure and poor access to technically skilled staff can limit service provision in remote areas where many Aboriginal dialysis patients live. With most studies based on urban service provision, there is little evidence to guide service development. However permanent relocation to an urban area for treatment can have significant social and financial impacts that are poorly quantified. This study is part of a broader project to quantify the costs and benefits of dialysis service models in urban and remote locations in Australia's Northern Territory (NT). METHODS: We undertook a micro-costing analysis of dialysis service delivery costs in urban, rural and remote areas in the NT from the payer perspective. Recurrent maintenance costs (salaries, consumables, facility management and transportation) as well as capital costs were included. Missing and centralised costs were standardised; results were inflated to 2017 values and reported in Australian dollars. RESULTS: There was little difference between the average annual cost for urban and rural services with respective median costs of $85,919 versus $84,629. However remote service costs were higher ($120,172 - $124,492), driven by higher staff costs. The inclusion of capital costs did not add substantially to annual costs. Annual home haemodialysis costs ($42,927) were similar to other jurisdictions despite the significant differences in program delivery and payment of expenses not traditionally borne by governments. Annual peritoneal dialysis costs ($58,489) were both higher than home and in-centre haemodialysis by recent national dialysis cost studies. CONCLUSION: The cost drivers for staffed services were staffing models and patient attendance rates. Staff salaries and transport costs were significantly higher in remote models of care. Opportunities to reduce expenditure exist by encouraging community supported services and employing local staff. Despite the delivery challenges of home haemodialysis including high patient attrition, the program still provides a cost benefit compared to urban staffed services. The next component of this study will examine patient health service utilisation and costs by model of care to provide a more comprehensive analysis of the overall cost of providing services in each location.

Cross-sectional associations of albuminuria among Aboriginal and Torres Strait Islander adults: the eGFR Study.

OBJECTIVE: To describe the detailed associations of albuminuria among a contemporary cohort of Aboriginal and Torres Strait Islander people to inform strategies for chronic kidney disease prevention and management. METHODS: A cross-sectional analysis of Indigenous participants of the eGFR Study. MEASURES: Clinical, biochemical and anthropometric measures were collected (including body-circumferences, blood pressure (BP); triglycerides, HbA1c, liver function tests, creatinine; urine- microscopic-haem, albumin: creatinine ratio (ACR), prescriptions- angiotensin converting enzyme inhibitor or angiotensin receptor II antagonist (ACEI/ARB). Albuminuria and diabetes were defined by an ACR>3.0 mg/mmol, and HbA1c≥48 mmol/mol or prior history respectively. Waist: hip ratio (WHR), and estimated glomerular filtration rate (eGFR) were calculated. ACR was non-normally distributed; a logarithmic transformation was applied (in base 2), with each unit increase in log2-albuminuria representing a doubling of ACR. RESULTS: 591 participants were assessed (71% Aboriginal, 61.6% female, mean age 45.1 years, BMI 30.2 kg/m2 , WHR 0.94, eGFR 99.2 ml/min/1.73m2 ). The overall prevalence of albuminuria, diabetes, microscopic-haem and ACEI/ARB use was 41.5%, 41.5%, 17.8% and 34.7% respectively; 69.3% of adults with albuminuria and diabetes received an ACEI/ARB. Using multivariable linear regression modelling, the potentially modifiable factors independently associated with log2-albuminuria were microscopic-haem, diabetes, WHR, systolic BP, alkaline phosphatase (all positive) and eGFR (inverse). CONCLUSION: Albuminuria is associated with diabetes, central obesity and haematuria. High ACEI/ARB prescribing for adults with diabetes and albuminuria was observed. Further understanding of the links between fat deposition, haematuria and albuminuria is required.

Performance of formulas for estimating glomerular filtration rate in Indigenous Australians with and without Type 2 diabetes: the eGFR Study.

AIMS: It has been proposed that the Chronic Kidney Disease Epidemiology Collaboration formula estimates glomerular filtration rate more accurately than the Modification of Diet in Renal Disease formula. With the very high incidence of diabetes and end-stage kidney disease in Indigenous Australians, accurate estimation of glomerular filtration rate is vital in early detection of kidney disease. We aimed to assess the performance of the Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease and Cockcroft-Gault formulas in Indigenous Australians with and without diabetes. METHODS: Indigenous Australians with (n = 224) or without (n = 340) Type 2 diabetes had a reference glomerular filtration rate measure using plasma disappearance of iohexol (measured glomerular filtration rate) over 4 h. Serum creatinine was measured by an enzymatic method. Performance was assessed by bias (measured glomerular filtration rate - estimated glomerular filtration rate) and accuracy (percentage of estimated glomerular filtration rate within 30% of measured glomerular filtration rate). RESULTS: The median measured glomerular filtration rate (interquartile range) in participants with or without diabetes was 97 (68-119) and 108 (90-122) ml min(-1)  1.73 m(-2) , respectively. The Chronic Kidney Disease Epidemiology Collaboration formula had smaller bias and greater accuracy than the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall, for participants both with and without diabetes. However, for estimated glomerular filtration rate > 90 ml min(-1)  1.73 m(-2) , the Chronic Kidney Disease Epidemiology Collaboration formula had greater bias in participants with diabetes, underestimating measured glomerular filtration rate by 7.4 vs. 1.0 ml min(-1)  1.73 m(-2) in those without diabetes. The Chronic Kidney Disease Epidemiology Collaboration formula was less accurate across the whole range of estimated glomerular filtration rates in participants with vs. those without diabetes (87.1% vs. 93.3%). CONCLUSIONS: The Chronic Kidney Disease Epidemiology Collaboration formula outperforms the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall in Indigenous Australians with and without diabetes. However, the Chronic Kidney Disease Epidemiology Collaboration formula has greater bias in people with diabetes compared with those without diabetes, especially in those with normal renal function.

Multisite randomised controlled trial to evaluate polypropylene clips applied to the breech of lambs as an alternative to mulesing. I: effects on body weight, breech bare area measurements and scores, wrinkle scores and faecal and urine staining.

OBJECTIVE: To assess the effects of application of occlusive polypropylene clips to lambs on body weight, breech bare area measurements and scores, wrinkle scores, and faecal and urine stain scores. PROCEDURES: A randomised controlled trial using 32,028 lambs was conducted on 208 properties across Australia. Polypropylene clips were applied at lamb marking. At each site, 160 lambs were weighed, measured for breech bare area and scored for bare area, wrinkle, dag and urine staining, and skin type and thickness. Lambs were allocated to a control (no clips) or treatment (breech and tail clips) group. Lambs were assessed on days 14 (range 10-19) and 55 (range 34-129) after clip application for body weight, breech bare area measurements and scores. On day 55 the operators also scored wrinkling and urine staining. RESULTS: At an average of 55 days after treatment, treated ewe and wether lambs had 16% and 21% greater horizontal bare area measurements, and 31.7% and 32.7% higher bare area scores than control lambs, respectively. The ewes and wether lambs also had lower wrinkle (6.8% and 5.8%, respectively) and dag scores (12% and 12.3%, respectively) than controls. Treated ewes had lower urine stain scores (18.8%) than controls. However, body weight was slightly lower in clip-treated lambs compared with controls by 0.320 kg (1.2%) and 0.430 kg (1.6%) for ewes and wethers, respectively. CONCLUSION: Polypropylene clips applied to the breech and tail of lambs increased breech bare area and reduced dag, urine and wrinkle scores. Improvements in these measures of factors that predispose to blowfly strike suggest that the application of clips may reduce the risk of breech flystrike.

Effect on the breech and tail characteristics of Merino lambs of varying the duration of application of occlusive plastic clips as an alternative to mulesing.

OBJECTIVE: The objective of the study was to determine the minimum duration of clip application required to increase the size of the perineal and tail bare areas and reduce breech wrinkle, dag or urine stain scores of Merino lambs. METHOD: The study was conducted on a single farm in western New South Wales using 491 unmulesed lambs of a plain body type (9-14 weeks of age; mean (±SD) bodyweight 26.9 ± 5.0 kg; 82% wrinkle score 1 or 2) randomly allocated into 10 groups. Groups 1-9 included 39-46 lambs treated with the clips, which were removed at 1-7, 10 or 14 days, respectively, after application. Group 10 comprised 53 lambs that were unclipped, unmulesed controls. Visual scores, bare area measurements and bodyweights were assessed before and at 28 and 60 days following clip application. RESULTS: Clips increased the size of the perineal and tail bare areas if left on the lambs for a minimum of 4-6 days. The increases in the size of the perineal and tail bare areas were similar to the results of previous studies. This indicates that the clips performed as expected, despite the current study being conducted on lambs with a plain body type. CONCLUSION: When used as an alternative to mulesing, clips should remain on lambs for a minimum of 4-6 days to effectively increase the size of the perineal and tail bare areas. Further research is required to determine the degree of protection against flystrike provided by the clip method.

Secondary amyloidosis in Indigenous Australians.

Secondary amyloidosis (AA) is an established consequence of many chronic inflammatory conditions. In the developed world, it is most often the result of rheumatological disease. However, the relative frequency of underlying causes may be different in indigenous populations. We present a case series of three remote-living, Indigenous Australians found to have pathologically confirmed amyloidosis and renal impairment at diagnosis. The presence of an underlying inflammatory condition was unclear in two cases. The remaining case had established bronchiectasis and suffered rapidly progressive renal impairment at a young age.

The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.

BACKGROUND: The international standard radiotherapy schedule for early breast cancer delivers 50 Gy in 25 fractions of 2.0 Gy over 5 weeks, but there is a long history of non-standard regimens delivering a lower total dose using fewer, larger fractions (hypofractionation). We aimed to test the benefits of radiotherapy schedules using fraction sizes larger than 2.0 Gy in terms of local-regional tumour control, normal tissue responses, quality of life, and economic consequences in women prescribed post-operative radiotherapy. METHODS: Between 1999 and 2001, 2215 women with early breast cancer (pT1-3a pN0-1 M0) at 23 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy over 5 weeks or 40 Gy in 15 fractions of 2.67 Gy over 3 weeks. Women were eligible for the trial if they were aged over 18 years, did not have an immediate reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 1105 women were assigned to the 50 Gy group and 1110 to the 40 Gy group. After a median follow up of 6.0 years (IQR 5.0-6.2) the rate of local-regional tumour relapse at 5 years was 2.2% (95% CI 1.3-3.1) in the 40 Gy group and 3.3% (95% CI 2.2 to 4.5) in the 50 Gy group, representing an absolute difference of -0.7% (95% CI -1.7% to 0.9%)--ie, the absolute difference in local-regional relapse could be up to 1.7% better and at most 1% worse after 40 Gy than after 50 Gy. Photographic and patient self-assessments indicated lower rates of late adverse effects after 40 Gy than after 50 Gy. INTERPRETATION: A radiation schedule delivering 40 Gy in 15 fractions seems to offer rates of local-regional tumour relapse and late adverse effects at least as favourable as the standard schedule of 50 Gy in 25 fractions.

The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.

BACKGROUND: The international standard radiotherapy schedule for breast cancer treatment delivers a high total dose in 25 small daily doses (fractions). However, a lower total dose delivered in fewer, larger fractions (hypofractionation) is hypothesised to be at least as safe and effective as the standard treatment. We tested two dose levels of a 13-fraction schedule against the standard regimen with the aim of measuring the sensitivity of normal and malignant tissues to fraction size. METHODS: Between 1998 and 2002, 2236 women with early breast cancer (pT1-3a pN0-1 M0) at 17 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy versus 41.6 Gy or 39 Gy in 13 fractions of 3.2 Gy or 3.0 Gy over 5 weeks. Women were eligible if they were aged over 18 years, did not have an immediate surgical reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 749 women were assigned to the 50 Gy group, 750 to the 41.6 Gy group, and 737 to the 39 Gy group. After a median follow up of 5.1 years (IQR 4.4-6.0) the rate of local-regional tumour relapse at 5 years was 3.6% (95% CI 2.2-5.1) after 50 Gy, 3.5% (95% CI 2.1-4.3) after 41.6 Gy, and 5.2% (95% CI 3.5-6.9) after 39 Gy. The estimated absolute differences in 5-year local-regional relapse rates compared with 50 Gy were 0.2% (95% CI -1.3% to 2.6%) after 41.6 Gy and 0.9% (95% CI -0.8% to 3.7%) after 39 Gy. Photographic and patient self-assessments suggested lower rates of late adverse effects after 39 Gy than with 50 Gy, with an HR for late change in breast appearance (photographic) of 0.69 (95% CI 0.52-0.91, p=0.01). From a planned meta-analysis with the pilot trial, the adjusted estimates of alpha/beta value for tumour control was 4.6 Gy (95% CI 1.1-8.1) and for late change in breast appearance (photographic) was 3.4 Gy (95% CI 2.3-4.5). INTERPRETATION: The data are consistent with the hypothesis that breast cancer and the dose-limiting normal tissues respond similarly to change in radiotherapy fraction size. 41.6 Gy in 13 fractions was similar to the control regimen of 50 Gy in 25 fractions in terms of local-regional tumour control and late normal tissue effects, a result consistent with the result of START Trial B. A lower total dose in a smaller number of fractions could offer similar rates of tumour control and normal tissue damage as the international standard fractionation schedule of 50 Gy in 25 fractions.

Can computerised tomography replace bone scintigraphy in detecting bone metastases from breast cancer? A prospective study.

BACKGROUND: The aim of this study was to determine whether bone scans (BS) can be avoided if pelvis was included in CT thorax and abdomen to detect bony metastases from breast cancer. MATERIALS AND METHODS: Results of 77 pairs of CT (thorax, abdomen, and pelvis) and BS in newly diagnosed patients with metastatic breast cancer (MBC) were compared prospectively for 12 months. Both scans were blindly assessed by experienced radiologists and discussed at multidisciplinary team meetings regarding the diagnosis of bone metastases. RESULTS: CT detected metastatic bone lesions in 43 (98%) of 44 patients with bone metastases. The remaining patient had a solitary, asymptomatic bony metastasis in shaft of femur. BS was positive in all patients with bone metastases. There were 11 cases of false positive findings on BS. CONCLUSION: Our findings suggest routine BS of patients presenting with MBC is not required if CT (thorax, abdomen, and pelvis) is performed.

Thrombotic microangiopathy from Australian brown snake (Pseudonaja) envenoming.

BACKGROUND: Australian brown snake (genus Pseudonaja) envenoming causes a venom-induced consumptive coagulopathy (VICC). A proportion of cases go on to develop thrombotic microangiopathy characterized by thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and acute renal failure (ARF). AIM: The aim of the study was to define better the natural history and empirical treatments for thrombotic microangiopathy in brown snake envenoming. METHODS: A review of brown snake bites recruited to the Australian Snakebite Project (ASP), a national multicentre study of snake envenoming was undertaken. Serial data are recorded on clinical effects and laboratory results, including measurement of venom concentrations. We describe cases of thrombotic microangiopathy and compare these to cases without thrombotic microangiopathy. RESULTS: From 32 cases of brown snake envenoming with severe VICC, four (13%) developed thrombotic microangiopathy, we also included two cases of thrombotic microangiopathy from prior to ASP. All six developed severe thrombocytopenia (<20 x 10(-9)/L), worst 3 days after the bite and resolving over a week, MAHA with fragmented red blood cells on the blood film and five developed anuric ARF requiring dialysis and lasting 2-8 weeks. All six received antivenom, which was delayed compared with other brown snake-envenoming cases. Four were treated with plasmapheresis. The severity and recovery of the thrombocytopenia, anaemia and renal function were similar with and without plasmapheresis. The median length of stay for MAHA cases was 14 days (interquartile range (IQR) 12-14) compared to 1.8 days (IQR 1.3-2) for all other cases. CONCLUSION: Thrombotic microangiopathy resulting from brown snake bite appears to have a good prognosis and management should focus on early antivenom therapy and supportive care including dialysis. The role of plasmapheresis is yet to be defined.

High dose chemotherapy and autologous stem cell transplantation as adjuvant therapy for primary breast cancer patients with four or more lymph nodes involved: long-term results of an international randomised trial.

BACKGROUND: The purpose of this study was to assess whether a short course of anthracycline containing chemotherapy followed by high dose therapy with autologous stem-cell support improves disease-free and overall survival as compared with conventional, anthracycline containing chemotherapy, in patients with primary breast cancer and four or more histologically involved lymph nodes. PATIENTS AND METHODS: Two hundred and eighty one patients entered into a randomised clinical trial were allocated to receive standard, conventional treatment (5-fluorouracil, epirubicin and cyclophosphamide-FEC for six cycles) or FEC for three cycles followed by high dose therapy consisting of cyclophosphamide, thiotepa and carboplatin and stem cell rescue (HDT). To be eligible, patients had to be free of overt metastatic disease and be < or =60 years of age. Analyses were according to intention to treat. RESULTS: At a median follow up of 68 months, 118 patients have experienced a relapse or death from breast cancer (62 in the FEC followed by HDT arm and 56 in the conventional FEC arm) and a total of 100 patients have died (54 in the FEC followed by HDT arm and 46 in the conventional FEC arm). No significant difference was observed in relapse-free survival [hazard ratio 1.06, 95% CI 0.74-1.52, p = 0.76] or overall survival [hazard ratio 1.18, 95% CI 0.80-1.75, p = 0.40]. Five patients died from treatment related causes, three as a consequence of HDT and two in the conventional FEC arm. CONCLUSIONS: At the present time, no benefit has been observed from replacing three cycles of conventional chemotherapy with the HDT regimen described here. Patients should continue to receive conventional chemotherapy as adjuvant therapy for breast cancer.

Weight gain during adjuvant and neoadjuvant chemotherapy for breast cancer: an audit of 100 women receiving FEC or CMF chemotherapy.

Weight gain is reported as a common finding in patients treated for breast cancer but its aetiology appears to be complex. The aim of this study was to investigate the incidence and degree of weight gain during chemotherapy and to examine possible contributory factors. Data were collected on 100 women treated with CMF or FEC chemotherapy. The mean change in weight was +3.68 kg (P<0.001). 64% of patients gained more than 2 kg in weight, 31% maintained a stable weight (within + or - 2 kg) and 5 patients lost more than 2 kg. Approximately 1/3 of patients (33) gained more than 5 kg and 6 patients gained more than 10 kg in weight. The majority of patients (85%) received steroids as antiemetics but no effect of steroid dose was seen on the level of weight change. No significant differences in weight gain were seen in patients receiving tamoxifen (37%) compared with those not taking it. Similarly, menopausal status did not appear to be a significant factor influencing weight gain. In summary, a high incidence of weight gain was found. The literature on weight gain in breast cancer and possible interventions to avoid weight gain are discussed.

In vitro effects of isoprinosine and a dipeptide methyl ester on Echinococcus multilocularis protoscoleces.

A protoscoleces/vesicles in vitro maintenance test with assessment of viability by eosin exclusion was used to evaluate the quantitative and qualitative activities of isoprinosine, its active component inosine and the dipeptide methylester L-Phe-Phe-OMe on isolated protoscoleces of Echinococcus multilocularis for 24 and 48 h. Isoprinosine and inosine showed dose- and time-dependent activity, the latter displaying a more rapid effect than the former. A high activity was shown with L-Phe-Phe-OMe, when compared to praziquantel. Ultrastructural alterations were much more striking with L-Phe-Phe-OMe, with an effect similar to that of praziquantel, whereas the chemotherapeutic activity of inosine and isoprinosine appeared to be directed against a metabolic target, with a lethal effect not immediately visible at the ultrastructural level. Thus, the previously reported in vivo activities of these drugs result largely from a direct effect on the parasite.

Echinococcus multilocularis alkaline phosphatase as a marker for metacestode damage induced by in vitro drug treatment with albendazole sulfoxide and albendazole sulfone.

Alveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapeworm Echinococcus multilocularis. The disease affects the human liver and occasionally other organs and is fatal if treatment is unsuccessful. The present chemotherapy of AE is based on the administration of benzimidazole carbamate derivatives, such as mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some cases, parasitostatic rather than parasiticidal, and the recurrence rate is rather high. Therefore, chemotherapy usually involves the lifelong uptake of massive doses of albendazole and new treatment options are urgently needed. In order to avoid costly and time-consuming animal experimentation, a first step in searching for novel parasiticidal compounds could be the in vitro drug screening of novel compounds by employing metacestode cultivation. However, presently used techniques (e.g., transmission electron microscopy) for determination of parasite viability involve costly equipment and time-consuming preparation of rather large amounts of parasite material. We therefore searched for a parasite marker which can be easily traced and the presence or absence of which is indicative of parasite viability. In this study we show that the increase of E. multilocularis alkaline phosphatase activity in culture supernatants during in vitro drug treatment with albendazole derivatives correlates with the progressive degeneration and destruction of the metacestode tissue. The inexpensive and rapid assay presented here will serve as an ideal tool for performing first-round in vitro tests on the efficacy of a large number of antiparasitic compounds.

Use of Percoll for the infection of cells in vitro with Cryptosporidium parvum oocysts.

A method for the infection of non-adherent THP-1 cells and adherent MDBK cells with Cryptosporidium parvum oocysts using isotonic Percoll solutions was developed. Excystation was maximal after 2 h, but toxicity increased with the oocyst/cell ratio and the incubation time. The infection rates did not increase with the oocyst/cell ratio and both cell types were equally parasitized.

Electroconvulsive therapy is associated with superior symptomatic and functional change in depressed patients after psychiatric hospitalization.

BACKGROUND: Major depressive episode is associated with quality of life (QOL) deficits, and QOL improves following remission of depression. We conducted an observational study of the relationship between depressive symptoms and QOL for 1 year after psychiatric hospitalization, and compared QOL in patients who received ECT against those who did not. METHODS: We examined 88 patients with major depressive disorder (53.4+/-15.4 years old; 69 women) upon admission, with repeated measurements at discharge, 1, 3, 6, and 12 months after discharge. Depression severity was measured with the Beck Depression Inventory. QOL measurements encompassed ADLs, IADLs, performance in major roles, and satisfaction with relationships. Treatment for depression was at the discretion of the respective physicians. RESULTS: Depression severity dropped dramatically by discharge, and changed little thereafter. QOL measures showed improvement at the first month, with additional improvement at the third month. Improvement in QOL was closely tied to improvement in depression severity. ECT during the index hospitalization was associated with greater improvement in depressive symptoms and in most measures of QOL. LIMITATIONS: The results of this study may not apply to the treatment of outpatients, and the large number of statistical comparisons may have resulted in some spurious associations. CONCLUSIONS: Inpatient treatment of depression is followed by improvement in QOL. Novel findings in this study include evidence that maximum improvement in QOL does not occur until an average of 3 months after discharge, and that ECT-treated patients had superior outcomes.

Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations.

The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production of tumor necrosis factor (TNF) family members appears to be important in many cases. BAFF, a new member of the TNF family, binds to B cells and costimulates their growth in vitro. Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti-DNA autoantibodies, and immunoglobulin deposition in the kidneys. This phenotype is reminiscent of certain human autoimmune disorders and suggests that dysregulation of BAFF expression may be a critical element in the chain of events leading to autoimmunity.