Costs and cost-effectiveness of different DOT strategies for the treatment of tuberculosis in Pakistan. Directly Observed Treatment

An economic study was conducted alongside a clinical trial at three sites in Pakistan to establish the costs and effectiveness of different strategies for implementing directly observed treatment (DOT) for tuberculosis. Patients were randomly allocated to one of three arms: DOTS with direct observation by health workers (at health centres or by community health workers); DOTS with direct observation by family members; and DOTS without direct observation. The clinical trial found no statistically significant difference in cure rate for the different arms. The economic study collected data on the full range of health service costs and patient costs of the different treatment arms. Data were also disaggregated by gender, rural and urban patients, by treatment site and by economic categories, to investigate the costs of the different strategies, their cost-effectiveness and the impact that they might have on patient compliance with treatment. The study found that direct observation by health centre-based health workers was the least cost-effective of the strategies tested (US dollars 310 per case cured). This is an interesting result, as this is the model recommended by the World Health Organization and International Union against Tuberculosis and Lung Disease. Attending health centres daily during the first 2 months generated high patient costs (direct and in terms of time lost), yet cure rates for this group fell below those of the non-observed group (58%, compared with 62%). One factor suggested by this study is that the high costs of attending may be deterring patients, and in particular, economically active patients who have most to lose from the time taken by direct observation. Without stronger evidence of benefits, it is hard to justify the costs to health services and patients that this type of direct observation imposes. The self-administered group came out as most cost-effective (164 dollars per case cured). The community health worker sub-group achieved the highest cure rates (67%), with a cost per case only slightly higher than the self-administered group (172 dollars per case cured). This approach should be investigated further, along with other approaches to improving patient compliance.     

Langerhans' cell histiocytosis with thyroid involvement masquerading as thyroid carcinoma

A 28-year-old woman was admitted to our Hospital with a chief complaint of progressive gingival swelling and loosening of teeth over about a year. According to past history, she had received total thyroidectomy 2 years previously due to thyromegaly. The thyroidectomy specimen was at first interpreted as 'poorly differentiated carcinoma of the thyroid'. One year ago, she began to be aware of gingival swelling and loosening of teeth. A gum biopsy was taken and the pathologic features were similar to her 'thyroid carcinoma'. Subsequent investigations, including immunohistochemical stain, showed the gum was heavily infiltrated with histiocyte-like Langerhans' cells which were positive for S-100 protein. Ultrastructural examination of the cells under electron microscope revealed many typical intra-cytoplasmic Birbeck granules. Langerhans' cell histiocytosis was diagnosed. Langerhans' cell histiocytosis with thyroid involvement is extremely rare and may run a relatively indolent course. Even on a retrospective examination, it may easily be confused with poorly differentiated carcinoma of the thyroid. We suspect that this error may have been made on other occasions and that the occurrence of this condition may be underreported.      

Echocardiographic findings in mild and severe forms of sickle cell anemia

M-mode echocardiographic findings were compared between sickle cell anemic and healthy children. Patients were composed of two groups; Group 1: mild group with no crises, no blood transfusions at the ages of 5.0 to 13.0, total of 12 children; Group 2: severe group, with frequent crises with requirement of blood transfusions at the ages of 3.0 to 13.0 years, total of 18 children. Control group was composed of 12 healthy children aged 5.0 to 13.0. When M-mode echocardiographic findings were compared, important findings were as follows: Mean left atrium dimension was increased both in the mild and severe groups (P < 0.001) compared with controls. This finding also supports the increase in the left ventricle end-diastolic dimension in both the severe and mild groups as compared with controls (P < 0.001). The increase in end-diastolic left ventricle dimension could be due to anemia present in the patients, but there was no difference between the two patient groups. Posterior left ventricle thickness and left ventricle mass was increased in both the mild and severe groups compared with controls (P < 0.001, P < 0.05), respectively. Left ventricular fractional shortening was more or less the same with controls. In spite of left ventricular volume load and dilatation, left ventricular contraction was good and systolic function was normal, and there was no correlation between the ECHO findings and hematological indices.     

Extracorporeal life support in paediatrics

Extracorporeal membrane oxygenation (ECMO) is a life support technique based on modifications of heart-lung bypass technology. It is used to support severe but potentially reversible pulmonary or cardiopulmonary failure. There is increasing use of the technique for neonates and a return of interest in its use for adults. The number of non-neonatal paediatric patients receiving pulmonary support with ECMO worldwide is, however, small, and survival rates average less than 50%. Initial experience in 15 patients aged 3 months to 5 years with a high survival and low morbidity is reported.     

Muscular sufficiency, serum protein, enzymes and bioenergetic studies (31-phosphorus magnetic resonance spectroscopy) in chronic malnutrition

Muscle sufficiency was significantly lower in 1336 children with chronic malnutrition of moderate to severe degree. Eighteen children with a chronic moderate degree of malnutrition and 8 well-nourished, age-matched controls were selected for biochemical and 31-phosphorus magnetic resonance spectroscopy (31 -P MRS) studies. The results showed that: (a) serum total protein, albumin, iron, calcium and inorganic phosphate were similar in both groups; (b) serum enzyme levels were significantly increased in the malnourished group; (c) 31-P MRS showed significantly higher means for total ATP, β-ATP, a-ATP and inorganic phosphate for the malnourished compared to the control group. In chronic malnutrition, proteins are maintained by degradation in muscle resulting in release of amino acids and enzymes. 31-P MRS studies showing increases in total ATP, β-ATP and inorganic phosphate and a decrease in phosphocreatine suggest that ATP is maintained at the cost of phosphocreatine.     

Pathological complications of non-survivors of newborn extracorporeal membrane oxygenation

The pathology was reviewed of the early deaths identified from the first 50 neonates treated with extracorporeal membrane oxygenation (ECMO) during its introduction to the UK. Fifteen neonates died during or shortly after ECMO between August 1989 and June 1992. Data on 12 are presented (three did not have a postmortem examination). The clinical diagnoses at referral for ECMO were as follows: persistent pulmonary hypertension of the newborn (six infants), primary congenital pneumonia (one infant), community acquired pneumonia (two infants), birth asphyxia (one infant), respiratory distress syndrome (one infant), and meconium aspiration syndrome (one infant). In our group, at necropsy, five had significant haemorrhage (three intracranial, one pulmonary, one pericardial and intraventricular). Three of five infants with evidence of haemorrhage also had signs of sepsis. Six infants had evidence at necropsy of systemic sepsis, five showed evidence of severe anoxic brain injury, and four infants had cerebellar haemorrhages. Three infants had evidence of myocardial ischaemia. It is difficult to discriminate between the relative influence of the primary diagnosis, the mode of treatment, and the severity of presentation in the genesis of this pathology. It is likely that the extent and severity of some of the findings represent a pathological progression that would have been interrupted by the death of the patient, had ECMO not been instituted.     

Twins with moyamoya disease

Moyamoya disease is a progressive disease which involves the internal carotid arteries and its branches bilaterally. The disease is reported both in adults and in children. Moyamoya disease is frequently seen in Japanese patients having certain human leucocyte antigen (HLA) haplotypes including HLA-Aw24, Bw46 and Bw54. Twin cases are rarely reported in the literature. We hereby present the first Turkish monozygotic twins with moyamoya disease whose HLA haplotypes are A2, A9, B21, Bw22, Bw4, Bw6, Cw3, and DR2, DR4, DRw52, DRw53, Dq7. The patients with advanced disease were given nifedipine and intravenous immunoglobulin (400mg/kg/d for 5 days). During the 11 months of follow-up, the patients were attack free.     

The biology of bone grafting

Many approaches are used to repair skeletal defects in reconstructive orthopaedic surgery, and bone grafting is involved in virtually every procedure. The type of bone graft used depends on the clinical scenario and the anticipated final outcome. Autogenous cancellous bone graft, with its osteogenic, osteoinductive, and osteoconductive properties, remains the standard for grafting. However, the high incidence of morbidity during autogenous graft harvest may make the acquisition of grafts from other sources desirable. The clinical applications for each type of bone graft are dictated by the structure and biochemical properties of the graft. An elegant cellular and molecular cascade follows bone transplantation. Bone graft incorporation within the host, whether autogenous or allogeneic, depends on many factors: type of graft (autogenous versus allogeneic, vascular versus nonvascular), site of transplant, quality of transplanted bone and host bone, host bed preparation, preservation techniques, systemic and local disease, and mechanical properties of the graft.