Rare Presentation of Giant Cell Tumors of the Tendon Sheath: Bilateral Involvement of Tendoachilles.

Giant cell tumor of tendon sheath arises from the synovium of tendon sheaths, joints, or bursa, mostly affects adults between 30 and 50 years of age, and is slightly more common in females. It corresponds to a localized form of pigmented villonodular synovitis (PVNS). Typically occur in the hand where they represent the second most common type of soft tissue tumors after synovial ganglions. Bilateral giant cell tumor of tendon sheath of tendoachilles is a rare presentation. We report the case of a 22-years-old female presenting with pain in both ankles without any history of trauma. On clinical examination, tenderness on both tendoachilles and local indurations were observed. Ultrasonography showed focal thickening of Achilles tendon bilaterally, and Doppler demonstrated increased flow in peritendinous area. MRI findings showed that most of the tumor had intermediate signal intensity and portions of the tumor had low signal intensity. Fine needle aspiration cytology confirmed the diagnosis of giant cell tumor of tendon sheath. Excision biopsy was done with no recurrence on subsequent follow-up.

Association between Serum Vitamin D and Metabolic Syndrome in Women with Polycystic Ovary Syndrome.

Vitamin D deficiency (VDD) is common in women with and without polycystic ovary syndrome (PCOS) and may be associated with metabolic and endocrine disorders in PCOS. Aim of the study was to evaluate the association between serum vitamin D level and metabolic syndrome (MS) in PCOS. This cross-sectional study was conducted in PCOS clinic of infertility outpatient department of the department of Reproductive Endocrinology and Infertility at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2018 to June 2019. A total of 170 diagnosed patients with PCOS of aging 20 to 40 years were included in this study. Out of which 85 patients with PCOS MS and rest 85 patients without PCOS MS were considered as Group I and Group II respectively. Serum vitamin D was measured using a chemiluminescent microparticle immunoassay (CMIA). Almost two third (72.9%) populations had vitamin D moderate deficiency (10-20ng/ml) in Group I and 46(54.1%) in Group II. The mean vitamin D was 13.97±4.53ng/ml in Group I 16.02±6.62ng/ml in Group II. There were significant negative correlation found between vitamin D level with weight (r = -0.169; p=0.028), waist circumference (r = -0.208; p=0.007), Waist/Hip ratio (r = -0.205; p=0.007) and diastolic blood pressure (r = -0.187; p=0.014). In binary logistic regression analysis diastolic blood pressure (OR=1.04, 95% CI 0.89-1.29), fasting Glucose (OR=1.09, 95% CI 0.89 - 1.42), HDL (OR=1.11, 95% CI 1.05 - 1.17) and Vitamin D (OR=1.37, 95% CI 1.01 - 1.82) were significant risk factors of metabolic syndrome of the study patients. Vitamin D level was lower in PCOS subjects having MS and higher frequency of body weight, vitamin D deficiency was observed in them compared to the non-MS group. Waist: hip ratio, waist circumference and diastolic blood pressure were the negatively correlated with of vitamin D in the study subjects.

Clinical and Demographic Predictor of the Advanced Stage of Carcinoma Cervix in a Tertiary Level Hospital of Bangladesh.

Though cervical cancer is a preventable disease it is the most progressive and devastating diseases posing a threat of mortality for women of developing countries. Majority of the cases present to hospital at advanced stage when treatment is less feasible. Objective is to determine the factors associated with the advanced stage presentation to the hospital, socio-demographic factor, patterns of complications and histological types among patients with carcinoma cervix. This was an observational descriptive type of cross-sectional study carried out in the department of Obstetrics and Gynecology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from 15 January to 27 September 2017. Women who were newly confirmed to have cervical cancer by histology were enrolled. Stages IIB and above was considered as advanced disease. The patients were interviewed face to face by the researcher for the purpose of collection of data. Then the patients were examined by the researcher for certain sings and those would be recorded in the check-list. Histopathological report was noted in data collection sheet. In this study data analysis was done by SPSS version 22.0. Total 66 clinically and histologically confirmed advanced ca-cervixes were taken up during this study. Most common stage was stage III, 49(74.2%) out of 66 population. Majority of female were found 34(51.5%) in age group 51-60. More than half of population 54(81.8%) were living with their husband and 12(18.1%) were widow at the time of study. High level of illiteracy among women and their problematic health seeking behavior for gynecological symptoms are responsible for advanced diagnosis of cervical cancer.

A Rare Case of Polyorchidism: Sonographic and MR Evaluation of Four Testes.

Polyorchidism is a rare congenital anomaly reported about 200 cases in the world text. A number of theories have been planned concerning the making of polyorchidism, but the real explanation is still not acknowledged. Here we are going to present a case study of polyorchidism. A 70 years old gentleman complained with left supernumerary testes in the left hemiscrotum. His left hemiscrotum was painless with mass. Polyorchidism without malignancy or any other concomitant features were revealed by both ultrasound and MRI examinations. In most cases the ultrasonograph alone is diagnostic. In complicated cases of polyorchidism MRI may provide additional information.

Outcome of Operative Management of Lumbar Spinal Canal Stenosis at Mymensingh Medical College & Hospital.

Variety of conditions may be responsible for low back pain but lumber spinal canal stenosis is an important cause of low back pain. Lumber spinal canal stenosis usually presents with low backache with neurogenic claudication and shortness of walking distance in adult patient. Surgical management of lumbar spinal canal stenosis by decompression surgery is effective method. This prospective interventional study was performed in patient with clinical features like low back pain with radicular pain, neurogenic claudication, signs of root compression, positive MRI findings attending in department of Orthopaedic Surgery Mymensingh Medical College Hospital and Private Hospital from July 2016 to June 2019. Thirty patients were evaluated among those 20(66.6%) were 50 years and above. The mean age was 47.5±1.6 years. Male to female ratio was roughly 8:1. Almost all of the patients had low backache with radiation to the back of the thigh and leg with motor weakness (60%). About 66.6% of the patients had sensory deficit and 83.3% had neurogenic claudication. Majority (80.0%) of the patients at presentation had a suffering of 12 or >12 months. The mean duration of suffering was 14.7±5.1 months. About 55% of the patients were able to perform heel-walking and 36.0% tip-toe walking. Nearly 57% of the patients had sensory deficit along the distribution of 1st sacral nerve and 53.3% along the distribution of lumber 5 nerves. Diagnosis shows that 16.6% of patients had L4 lesion, 50% L5, 10.0% patients had L4 & L5 and 46.6% S1. Laminectomy was done in 26.6% of patients, laminectomy and disectomy in 33.3% and laminectomy, discectomy & foraminal decompression in 40.0% of patients. Twenty five (83.5%) of patients was free from symptoms. Eighty percent (80.0%) of patients shows minimal disability and 20.0% moderate disability on the basis of Oswestry Disability Index, while by MacNab criteria, most (80%) of patients was excellent, 10% good and another 10% fair. Repeated measure ANOVA statistics showed that mean Oswestry score decreased significantly from 54.5% at baseline to 22% at the end of 1 year (p<0.001).

Outcome of Bone Marrow Injection in Patient with Delayed Union and Non-Uninon of Long Bone Fracture.

Bone marrow is a source of osteoprogenitor cells which are the most important factor of bone formation and healing of fracture. The aim of the study is to evaluate the outcome of bone marrow injection in the management of delayed union and non-union. This prospective study was performed in the department of Orthopaedics, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from January 2017 to June 2019. In this study 21 patients with delayed union and non-union were treated by bone marrow injection. Bone marrow were aspirated from the anterior or posterior iliac crests then injected percutaneously into the fracture site. Full union was achieved in 15 cases, while failed in the others. No major complications were seen during or after the procedure. It is a safe, easy and a minimally invasive procedure compared to usual open bone graft especially for cases with high risk of anesthesia or risk of infection.

Brachial Plexus Schwannoma: A Case Report with Emphasis on Imaging.

Brachial plexus tumors are rare. Schwannomas are benign nerve sheath tumors and only about 5% arise from brachial plexus. Diagnosis of these tumors are challenging for radiologists as well as clinicians as they are rare and the anatomy of the neck is complex. We report a case of a middle aged woman who was admitted in Mymensingh Medical College in Neurosurgery Department on 15th December 2017 with right supraclavicular swelling; based on the clinical findings was provisionally diagnosed as supraclavicular lymphadenopathy; Ultrasonography and Magnetic Resonance Imaging suggested schwannoma. Complete excision of the mass through supraclavicular approach showed the origin of it from the brachial plexus, which subsequently was confirmed to be a schwannoma with histopathology.

Giant Cell Tumour of the Talus: A Rare Case Report.

Giant-cell tumor constitutes 4-20% of all primary bone tumors in south East Asian population. They are benign locally aggressive bone tumour first described by cooper in 1818. These tumors occur predominantly in meta-epiphyseal region. Most often they are located around the knee joint. Although most of the tumors are diagnosed on plain radiograph alone, varying CT and MRI presentations of these tumors are essential to narrow down the differentials has an extended pre operative assessment.

Hepatic Hydatid Cyst: A Case Report.

Hepatic hydatid disease is a goonotic disease caused by Echinococcus granulosus and it is endemic in different parts of the world. This infection is an important public health problem. Although it is distributed throughout the world but common in the livestock grazing regions of the world such as in Central Europe, Africa, South America, Central Asia and China. Here we present the case "30 years old female" with the complaints of right upper abdominal pain for 3 months, nausea & occasional vomiting for 1 month and was admitted under general surgery ward at Mymensingh Medical College Hospital, Mymensingh, Bangladesh on 12th March 2018. Considering history, physical examination, serological investigations, imaging studies and exploratory laparotomy the diagnosis is hepatic hydatid cyst. Echinococcus granulosus produces cysts in almost every organs of the body most commonly in the liver. Man is the incidental intermediate host where definitive host is carnivores such as dogs. Hydatid cyst always starts as a fluid filled, cyst like structure (stage I), which may proceed to a stage II lesion if daughter cysts and/or matrix develop. In some instances, the stage II lesion becomes hypermature and due to starvation, dies to become a mummified, inert, calcified, stage III lesion. Ultrsound is the preferred firstline imaging but CECT give more precise information regarding the morphology of the cyst. Magnetic Resonance Imaging is particularly useful because of its multiplaner capabilities and more detail anatomical resolution.

Ultrasonographic Evaluation of Malignant Pediatric Abdominal Tumour with Histopathological Correlation.

Ultrasonography is a very useful diagnostic tool to evaluate pediatric abdominal mass. This cross sectional study was conducted among clinically suspected patients having malignant abdominal mass attending in the department of Radiology & Imaging, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from January 2008 to December 2009. Total 56 patients were included in this study. Patients were scanned by high resolution gray scale ultrasonography of the abdominal masses. After surgical procedure, biopsy specimen were collected in a container containing 10% formalin and sent for histopathological examination. Mean age of the patients group was 5.91 years with a standard deviation of ±3.21 years. All patients were within 2 to 13 years age. Out of all patients, male were 33(58.9%) and 23(41.1%) were female. Male and female ratio was 1.4:1. Ultrasonographic diagnosis as Wilm's tumour were 27(48.2%), hepatoblastoma 8(14.3%), lymphoma 7(12.5%), neuroblastoma 6(10.7%), suspected malignancy 6(10.7%) and lastly teratoma were 2(3.6%). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of ultrasonography in the evaluation of Wilm's tumour were 100.0%, 90.6%, 88.9%, 100.0% and 94.6% for neuroblastoma 83.3%, 98.0%, 83.3%, 98.0% and 96.4% for lymphoma 83.3%, 96.0%, 71.4%, 98.0% and 94.6% and for hepatoblastoma 100.0%, 100.0%, 100.0%, 100.0% and 100.0% respectively. It is a noninvasive and cost effective modality. Carefully performed ultrasonographic study would give reliable and accurate information needed in the diagnosis of abdominal malignancy in children.

The cost-effectiveness of changes to the care pathway used to identify depression and provide treatment amongst people with diabetes in England: a model-based economic evaluation.

BACKGROUND: Diabetes is associated with premature death and a number of serious complications. The presence of comorbid depression makes these outcomes more likely and results in increased healthcare costs. The aim of this work was to assess the health economic outcomes associated with having both diabetes and depression, and assess the cost-effectiveness of potential policy changes to improve the care pathway: improved opportunistic screening for depression, collaborative care for depression treatment, and the combination of both. METHODS: A mathematical model of the care pathways experienced by people diagnosed with type-2 diabetes in England was developed. Both an NHS perspective and wider social benefits were considered. Evidence was taken from the published literature, identified via scoping and targeted searches. RESULTS: Compared with current practice, all three policies reduced both the time spent with depression and the number of diabetes-related complications experienced. The policies were associated with an improvement in quality of life, but with an increase in health care costs. In an incremental analysis, collaborative care dominated improved opportunistic screening. The incremental cost-effectiveness ratio (ICER) for collaborative care compared with current practice was £10,798 per QALY. Compared to collaborative care, the combined policy had an ICER of £68,017 per QALY. CONCLUSIONS: Policies targeted at identifying and treating depression early in patients with diabetes may lead to reductions in diabetes related complications and depression, which in turn increase life expectancy and improve health-related quality of life. Implementing collaborative care was cost-effective based on current national guidance in England.

Targeting Bone Marrow to Potentiate the Anti-Tumor Effect of Tyrosine Kinase Inhibitor in Preclinical Rat Model of Human Glioblastoma.

Antiangiogenic agents caused paradoxical increase in pro-growth and pro-angiogenic factors and caused tumor growth in glioblastoma (GBM). It is hypothesized that paradoxical increase in pro-angiogenic factors would mobilize Bone Marrow Derived Cells (BMDCs) to the treated tumor and cause refractory tumor growth. The purposes of the studies were to determine whether whole body irradiation (WBIR) or a CXCR4 antagonist (AMD3100) will potentiate the effect of vatalanib (a VEGFR2 tyrosine kinase inhibitor) and prevent the refractory growth of GBM. Human GBM were grown orthotopically in three groups of rats (control, pretreated with WBIR and AMD3100) and randomly selected for vehicle or vatalanib treatments for 2 weeks. Then all animals underwent Magnetic Resonance Imaging (MRI) followed by euthanasia and histochemical analysis. Tumor volume and different vascular parameters (plasma volume (vp), forward transfer constant (Ktrans), back flow constant (kep), extravascular extracellular space volume (ve) were determined from MRI. In control group, vatalanib treatment increased the tumor growth significantly compared to that of vehicle treatment but by preventing the mobilization of BMDCs and interaction of CXCR4-SDF-1 using WBIR and ADM3100, respectively, paradoxical growth of tumor was controlled. Pretreatment with WBIR or AMD3100 also decreased tumor cell migration, despite the fact that ADM3100 increased the accumulation of M1 and M2 macrophages in the tumors. Vatalanib also increased Ktrans and ve in control animals but both of the vascular parameters were decreased when the animals were pretreated with WBIR and AMD3100. In conclusion, depleting bone marrow cells or CXCR4 interaction can potentiate the effect of vatalanib.

What is the quality of economic evaluations of non-drug therapies? A systematic review and critical appraisal of economic evaluations of radiotherapy for cancer.

BACKGROUND: Breast, cervical and colorectal cancers are the three most frequent cancers in women, while lung, prostate and colorectal cancers are the most frequent in men. Much attention has been given to the economic evaluation of pharmaceuticals for treatment of cancer by the National Institute for Health and Care Excellence (NICE) in the UK and similar authorities internationally, while economic analysis developed for other types of anti-cancer interventions, including radiotherapy and surgery, are less common. OBJECTIVES: Our objective was to review methods used in published cost-effectiveness studies evaluating radiotherapy for breast, cervical, colorectal, head and neck and prostate cancer, and to compare the economic evaluation methods applied with those defined in the guidelines used by the NICE technology appraisal programme. METHODS: A systematic search of seven databases (MEDLINE, EMBASE, CDSR, NHSEED, HTA, DARE, EconLit) as well as research registers, the NICE website and conference proceedings was conducted in July 2012. Only economic evaluations of radiotherapy interventions in individuals diagnosed with cancer that included quality-adjusted life-years (QALYs) or life-years (LYs) were included. Included studies were appraised on the basis of satisfying essential, preferred and UK-specific methods requirements, building on the NICE Reference Case for economic evaluations and on other methods guidelines. RESULTS: A total of 29 studies satisfied the inclusion criteria (breast 14, colorectal 2, prostate 10, cervical 0, head and neck 3). Only two studies were conducted in the UK (13 in the USA). Among essential methods criteria, the main issue was that only three (10%) of the studies used clinical-effectiveness estimates identified through systematic review of the literature. Similarly, only eight (28%) studies sourced health-related quality-of-life data directly from patients with the condition of interest. Other essential criteria (e.g. clear description of comparators, patient group indication and appropriate time horizon) were generally fulfilled, while most of the UK-specific requirements were not met. CONCLUSION: Based on this review there is a dearth of up-to-date, robust evidence on the cost effectiveness of radiotherapy in cancer suitable to support decision making in the UK. Studies selected did not fully satisfy essential method standards currently recommended by NICE.

Color Doppler sonography and resistivity index in the differential diagnosis of hepatic neoplasm.

The purpose of this study was to determine the usefulness of color doppler sonography and resistivity index (RI) in differentiating liver tumors. The study was carried out in the Department of Radiology and Imaging, Mymensingh Medical College Hospital, and Institute of Nuclear Medicine and Allied Sciences (INMAS), Mymensingh, Bangladesh, during the period of July 2009 to June 2011. Total 50 consecutive cases were studied. Among them 27 were hepatocellular carcinomas, 19 were metastatic tumors, 03 were hemangiomas and 01 was hepatic adenoma. Doppler sonographic findings were then correlated, case by case, with final diagnosis- either pathologically by USG guided Fine-needle aspiration or by other imaging modalities (e.g., CT scan and RBC liver scan for hepatic hemangioma). The RI value of hepatocellular carcinoma was 0.69±0.096 and in metastatic tumors 0.73±0.079. The results showed no significant difference between the RI of hepatocellular carcinomas and metastatic liver tumors but it was significantly higher than benign lesions (p<0.05). RI of hemangiomas was 0.49±0.64 and in one hepatic adenoma was 0.65. When RI was <0.6 for benign liver tumors and ≥0.6 for malignant tumors we calculated a sensitivity of 89.14%, specificity of 66.7%, accuracy of 85.71% positive predictive value of 97.62% and negative predictive value of 28.57% in differentiating benign and malignant tumors. Thirty four of 46(73.9%) malignant lesions had intratumoral flow and 25% of benign lesions also showed intratumoral flow. The difference of intratumoral flow between malignant and benign lesions was significant (p<0.01). Two of 4 benign lesions (50%) had peritumoral vascularity where 6% of the malignant tumors showed peritumoral vascularity. In conclusion, combined studies of the type of intra-and peri-tumoral flow signals in CDFI and the parameter of RI would be more helpful in the differential diagnosis of benign and malignant liver tumors.

Evaluation of the results of operative management of lumbar spinal canal stenosis.

Lumber spinal canal stenosis is an important cause of low back pain and it frequently presents with low backache with neurogenic claudication. Operative management of lumbar spinal canal stenosis by decompression surgery is an effective method. This prospective interventional (quasi experimental) study was performed in patient having history of characteristic clinical features like low backache with radicular pain, neurogenic claudication, signs of root compression, positive MRI findings attending in the department of Orthopaedic Surgery and Neurosurgery, Dhaka Medical College Hospital and NITOR. Dhaka, from July 2008 to June 2010. Thirty patients were evaluated among those 18(60%) were 50 years and above. Male to female ratio was roughly 9:1. About 87% of the patients had sensory deficit and 50% had neurogenic claudication. Majority (83.3%) of the patients at presentation had a suffering of 12 or >12 months. Diagnosis shows that 3.5% of patients had L4 lesion, 60% L5, 6.5% patients had L4 & L5 and 30% S1. Laminectomy was done in 43.3% of patients, laminectomy and disectomy in 30% and laminectomy, discectomy & foraminal decompression in 26.7% of patients. Relief of symptoms occurred in 25(83.5%) of patients. Over three-quarter (76.7%) of patients exhibited minimal disability and 23.3% moderate disability based on Oswestry Disability Index, while by MacNab criteria, most (80%) of patients was excellent, 10% good and another 10% fair. Repeated measure ANOVA statistics showed that mean Oswestry score decreased significantly from 54.5% at baseline to 22% at the end of 1 year (p<0.001).

Myosin Va is developmentally regulated and expressed in the human cerebellum from birth to old age

Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.

Glasgow outcome scale at hospital discharge as a prognostic index in patients with severe traumatic brain injury / Escala de resultados de Glasgow por ocasião da alta hospitalar como indicador prognóstico em pacientes com traumatismo cranioencefálico grave

OBJECTIVE: Evaluate the Glasgow outcome scale (GOS) at discharge (GOS-HD) as a prognostic indicator in patients with traumatic brain injury (TBI). METHOD: Retrospective data were collected of 45 patients, with Glasgow coma scale <8, age 25±10 years, 36 men, from medical records. Later, at home visit, two measures were scored: GOS-HD (according to information from family members) and GOS LATE (12 months after TBI). RESULTS: At discharge, the ERG showed: vegetative state (VS) in 2 (4%), severe disability (SD) in 27 (60%), moderate disability (MD) in 15 (33%) and good recovery (GR) in 1 (2%). After 12 months: death in 5 (11%), VS in 1 (2%), SD in 7 (16%), MD in 9 (20%) and GR in 23 (51%). Variables associated with poor outcome were: worse GOS-HD (p=0.03), neurosurgical procedures (p=0.008) and the kind of brain injury (p=0.009). CONCLUSION: The GOS-HD was indicator of prognosis in patients with severe TBI.

OBJETIVO: Avaliar a escala de resultados de Glasgow (ERG) à alta hospitalar (ERG-ALTA) como indicador prognóstico em pacientes com traumatismo cranioencefálico (TCE). MÉTODO: Dados retrospectivos de 45 pacientes (36 homens), com escala de coma de Glasgow <8, idade 25±10 anos, foram coletados do prontuário médico. Posteriormente, em visita domiciliar, foram pontuadas duas medidas: ERG-ALTA (de acordo com informações de familiares) e ERG TARDIA (após 12 meses do TCE). RESULTADOS: Por ocasião da alta hospitalar, a ERG evidenciou: estado vegetativo (EV) em 2 (4%); incapacidade grave (IG) em 27 (60%), incapacidade moderada (IM) em 15 (33%) e boa recuperação (BR) em 1 (2%). Após 12 meses: morte em 5 (11%), EV em 1 (2%), IG em 7 (16%), IM em 9 (20%) e BR em 23 (51%). Variáveis associadas com má evolução foram: pior ERG-ALTA (p=0,03); procedimentos neurocirúrgicos (p=0,008) e o tipo de lesão cerebral (p=0,009). CONCLUSÃO: A ERG-ALTA foi indicador adequado de prognóstico tardio em pacientes com TCE grave.

What is the clinical effectiveness and cost-effectiveness of using drugs in treating obese patients in primary care? A systematic review.

BACKGROUND: Obesity [defined as a body mass index (BMI) ≥ 30 kg/m(2)] represents a considerable public health problem and is associated with a significant range of comorbidities and an increased mortality risk. The primary aim of the management of obesity is to achieve weight reduction in the interests of health. For obese patients who cannot achieve or maintain a healthy weight by non-pharmacological means, drug therapy is recommended in combination with non-pharmacological interventions such as dietary modifications and exercise. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of three pharmacological interventions in obese patients. DATA SOURCES: Clinical effectiveness data used in the meta-analysis were sourced from articles identified in a systematic review of the literature. Data used to inform transitions to obesity-related comorbidities were derived from the General Practice Research Database (GPRD). The results of the meta-analysis and GPRD analyses informed the economic model supplemented by data from the Health Survey for England and other UK-specific data sourced from the literature. REVIEW METHODS: A systematic literature review was conducted of the clinical effectiveness and cost-effectiveness of orlistat, sibutramine and rimonabant within their licensed indications for the treatment of obese patients. Electronic bibliographic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched in January 2009, and the reference lists of relevant articles were checked. Studies were included if they compared orlistat, sibutramine or rimonabant with lifestyle and/or exercise advice (standard care), placebo or metformin. RESULTS: Overall, 94 studies involving 24,808 individuals were included in the clinical meta-analysis. Eighty-three trials included data on weight change, 41 included data on BMI change and 45 and 36 studies reported on 5% and 10% body weight loss, respectively. Overall, the results show that the active drug interventions are all effective at reducing weight and BMI compared with placebo. In the case of sibutramine, the higher dose (15 mg) resulted in a greater reduction than the lower dose (10 mg). Generally, the data quality of the trials included was low with poor reporting of standard errors and standard deviations. Results from the BMI risk models derived from the GPRD showed consistent increases in risk with increasing BMI. Adjustments for key confounders, such as age, sex and smoking status, were found to be statistically significant at the 5% level, in all risk models. Applying linear models to estimate BMI trajectories, for the diabetic cohort, an average increase in BMI of 0.040 per year for both men and women was observed. The non-diabetic cohort model showed an increase in BMI of 0.175 per year for women and 0.145 per year for men. The results of the cost-effectiveness analyses suggest that sibutramine 15 mg dominates the other three active interventions and the net benefit analyses show that sibutramine 15 mg is the most cost-effective alternative for thresholds > £2000 per quality-adjusted life-year (QALY). However, both sibutramine and rimonabant have been withdrawn because of safety concerns relating to potential treatment-induced fatal adverse events. If the proportion of patients who experienced a fatal adverse event was > 1.8% (1.5%, 1.0%) for sibutramine 15 mg (sibutramine 10 mg, rimonabant) the treatment would not be considered cost-effective when using a threshold of £20,000 per QALY. LIMITATIONS: The clinical review did not include all possible lifestyle comparators, with the inclusion limited to only those trials included one of the active drug interventions. We also excluded all studies not reported in English. Although the clinical review included data from 94 studies, the quality of data was generally low, particularly in terms of the reporting of standard deviation. There was also inconsistency between the results of the mixed-treatment comparison (MTC) and the pair-wise analyses. CONCLUSION: The MTC of anti-obesity treatments shows that all the active treatments are effective at reducing weight and BMI. The economic results show that, compared with placebo, the treatments are all cost-effective when using a threshold of £20,000 per QALY, and, within the limitations of the data available, sibutramine 15 mg dominates the other three interventions. This work has highlighted many areas of methodological research that could be explored, including assessing inconsistencies within a network to determine differences between the results of pair-wise and MTC analyses; the use of meta-regression methods to look for effect modifiers; exploring the effect of local publication bias; and the use of joint models to analyse the repeated measures of BMI and the time-to-event processes simultaneously. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The cost-effectiveness of etanercept in patients with severe ankylosing spondylitis in the UK.

OBJECTIVES: To examine the costs and benefits associated with long-term etanercept (ETN) treatment in patients with severe ankylosing spondylitis (AS) in the UK in accordance with the BSR guidelines. METHODS: A mathematical model was constructed to estimate the costs and benefits associated with ETN plus non-steroidal anti-inflammatory drugs (NSAIDs) compared with NSAIDs alone. Individual patient data from Phase III RCTs was used to inform the proportion and magnitude of initial response to treatment and changes in health-related quality of life. A retrospective costing exercise on patients attending a UK secondary care rheumatology unit was used to inform disease costs. Published evidence on long-term disease progression was extrapolated over a 25-yr horizon. Uncertainty was examined using probabilistic sensitivity analyses. RESULTS: Over a 25-yr horizon, ETN plus NSAIDs gave 1.58 more QALYs at an additional cost of 35,978 pounds when compared with NSAID treatment alone. This equates to a central estimate of 22,700 pounds per QALY. The incremental cost per QALYs using shorter time periods were 27,600 pounds, 23,600 pounds and 22,600 pounds at 2, 5 and 15 yrs, respectively. Using a 25-yr horizon, 93% of results from the probabilistic analyses fall below a threshold of 25,000 pounds per QALY. CONCLUSIONS: This study demonstrates the potential cost-effectiveness of ETN plus NSAIDs compared with NSAIDs alone in patients with severe AS treated according to the BSR guidelines in the UK.

Estimating the cost and health status consequences of treatment with TNF antagonists in patients with psoriatic arthritis.

OBJECTIVES: Tumour necrosis factor (TNF) has been shown to improve the outcomes in patients with psoriatic arthritis (PsA). We estimate the long-term impact on health status of prescribing the TNF antagonist etanercept, and evaluate the cost-effectiveness in a health economic model. METHODS: The relationship between disability (Health Assessment Questionnaire) and health state utility was explored to estimate the quality-adjusted life years (QALYs) gained from the TNF antagonist etanercept. A model was then used to compare sequences of treatments for PsA after failure of two conventional disease modifying anti-rheumatic drugs (DMARDs). One arm commences on etanercept therapy and this is compared with a strategy commencing with combination therapy of methotrexate and ciclosporin and another commencing with leflunomide. Individual patient data from Phase III etanercept trials is used to populate the model supported by published evidence from extensive literature searches. By incorporating a life table specific for a PsA population, and using a number of evidence- and expert opinion-based assumptions for disease progression, the model was extended beyond the trial duration to a 10-yr time horizon. Cost offsets were produced by avoiding surgery through delayed progression; drug and monitoring costs were also modelled. RESULTS: Over the 10 yrs, modelled etanercept treatment gave 0.82 more QALYs when compared with combination therapy with methotrexate and ciclosporin, and 0.65 more QALYs in comparison with leflunomide. This equates to a central estimate for the cost per QALY of pound28 189 and pound28 189 for ciclosporin and leflunomide, respectively. Sensitivity analyses demonstrated this could vary by as much as +/-28%. CONCLUSIONS: With limited data currently available, the potential cost-effectiveness of etanercept in DMARD failures for adults with PsA appears encouraging. The result for other TNF antagonists will depend on how their relative efficacy and drug price compares with etanercept. A number of limitations are described and priorities for further research suggested.