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Inherited multicentric osteolysis with carpal-tarsal localisation mimicking juvenile idiopathic arthritis.

UNLABELLED: Five patients with multicentric carpal-tarsal osteolysis are presented: a mother and her three children with an autosomal dominant mode of inheritance and one of the children with nephropathy, the fifth a sporadic case also with renal involvement. The main findings common to these five patients are symptoms and signs simulating arthritis of the wrists and/or ankles starting at a young age and mimicking juvenile idiopathic arthritis. Early signs of osteolysis and shortening of the carpus or tarsus are radiological characteristic. The disease may be associated with a peculiar face, but most importantly with nephropathy. The pathogenesis is still unknown. CONCLUSION: Recognition of this disease and differentiation from juvenile idiopathic arthritis is important to avoid unnecessary investigations and treatment. Follow-up of renal function is indicated.

Ankle↗

Severe hypoglycaemia, metabolic control and diabetes management in children with type 1 diabetes in the decade after the Diabetes Control and Complications Trial -- a large-scale multicentre study.

UNLABELLED: Hypoglycaemia is frequently the limiting factor in achieving optimal glycaemic control. Therefore, insulin therapy, the incidence of hypoglycaemia, and glycaemic control were investigated in 6309 unselected children with type 1 diabetes in a large-scale multicentre study. Using standardised computer-based documentation, the incidence of severe hypoglycaemia, HbA1( c) levels, insulin regimen, diabetes duration, and the number of patients attending a treatment centre were investigated for the age groups 0-<5 years ( n =782), 5-<7 years ( n =1053), and 7-<9 years ( n =4474). The average HbA1( c) level was 7.6% (no significant difference between age groups). Young children had more severe hypoglycaemic events (31.2/100 patient years) as compared to older children (19.7; 21.7/100 patient years, P <0.05) independent of the treatment regimen. Our data suggest that diabetes centres treating less than 50 patients per year have a higher incidence of hypoglycaemia in 0-<5-year-old children (43.0/100 patient years) as compared to larger centres (24.1/100 patient years; P <0.0001). Significant predictors of hypoglycaemia were younger age ( P <0.0001), longer diabetes duration ( P <0.0001), higher insulin dose/kg per day ( P <0.0001), injection regimen ( P <0.0005), and centre experience ( P <0.05). CONCLUSION: Despite modern treatment, young children have an elevated risk for developing severe hypoglycaemia compared to older children, especially when treated at smaller diabetes centres. The therapeutic goal of carefully regulating metabolic control without developing hypoglycaemia has still not been achieved. Further advances in diabetic treatment may result from giving more attention to hypoglycaemia in young children.

Age Factors↗

Multicentric infantile myofibromatosis: two perinatal cases.

Infantile myofibromatosis, the most common fibrous tumor of infancy, occurs in solitary, multiple, and generalized forms, with similar histology but different clinicopathologic and prognostic implications. This entity is a mesenchymal disorder characterized by the proliferation of fibrous tumors in the skin, muscles, viscera, bones, and subcutaneous tissues. Visceral lesions are associated with significant morbidity and mortality, generally within the first few months of life. They lead to failure to thrive, to infection, hemorrhage, or to the obstruction of vital organs. We describe two cases of multicentric myofibromatosis with significant in utero lesional growth, resulting in one fetal demise and one post-natal demise. To the best of our knowledge, this is the first report of a fetal death secondary to infantile myofibromatosis.

Fatal Outcome↗

Italian multicentre study on retinopathy of prematurity. The Italian ROP Study Group.

UNLABELLED: The aim of this prospective multicentre study was to evaluate the influence of a number of perinatal factors on the development of ROP in high risk preterm infants with gestational age < or =30 weeks. All infants consecutively born in, or transferred to, one of the 14 participating centres from 1 January 1992 through 31 December 1993, who had a gestational age of 30 weeks or less and no congenital anomalies and survived to the age of 6 months, were included in the study. Of the 380 infants with mean +/- SD gestational age of 28.4 +/- 1.6 weeks (range 23-30 weeks) and birth weight of 1157 +/- 335 g (range 485-2480 g) that were eligible for the study, 82 (21.5%) developed ROP stage 1 or 2 and 57 (15%) ROP stage 3 or 3+. Step-wise logistic regression analysis showed that the following factors had a significant predictive value for the development of ROP stage 3 or 3+: gestational age (Odds Ratio (OR) = 0.6144 for each increment of 1 week of gestational age), birth weight (OR = 0.843 for each increment of 100 g of birth weight), prenatal steroids (OR 4.044 for lacking or incomplete prophylaxis), RDS (OR 2.294), oxygen dependency at 60 days (OR 2.085), necrotising enterocolitis (OR 2.597). CONCLUSION: This study confirms the role of prematurity, low birth weight and RDS in the pathogenesis of ROP, and emphasises the importance of prenatal steroid prophylaxis of RDS in very preterm infants. Furthermore, our data suggest that infants with oxygen dependency at 60 days or necrotising enterocolitis are at very high risk of developing ROP.

Gestational Age↗

Ureaplasma urealyticum colonization and bronchopulmonary dysplasia: a comparative prospective multicentre study.

UNLABELLED: To determine the role of tracheal colonization at birth with Ureaplasma urealyticum and other pathogenic bacteria with regard to the development of bronchopulmonary dysplasia (BPD), 97 premature infants with very low birth weight (< 1500 g) were followed prospectively over 30 days in a multicentre study. Of those infants, 35 were colonized with Ureaplasma urealyticum (group Ia), 22 with other pathogenic bacteria (group Ib) and 40 infants with sterile tracheal aspirates served as controls (group II). Colonization with Ureaplasma urealyticum or with pathogenic bacteria independently increased the risk of developing BPD as compared to the controls (OR 2.55; 95% CI [1.11, 5.87]). Among Ureaplasma urealyticum and bacterial colonized infants, duration of mechanical ventilation and oxygen requirement were significantly longer than among controls (P < 0.05); during the interval of 11 to 35 days of life, every additional day of ventilation significantly increased the risk of BPD (OR 1.22; CI [1.12, 1.32]). The rate of oxygen supplementation, which was similar in both groups during the first 2 weeks of life, was significantly higher among the colonized infants at day 21 (0.38+/-0.18 and 0.39+/-0.16 vs 0.31+/-0.13, P < 0.05) and at day 28 (0.38+/-0.21 and 0.34+/-0.15 vs 0.28+/-0.12, P < 0.05). For infants still ventilated at age of 28 days, Ureaplasma urealytricum and bacterial colonization were associated with a significant higher risk for BPD than for uncolonized controls (OR 5.53; [1.27, 24.02]. Association of Ureaplasma urealyticum and of bacterial colonization and BPD was not weakened after adjustments were made in a multivariate analysis for other significant risk factors. CONCLUSION: Ureaplasma urealyticum colonization is as an important risk factor in the development of bronchopulmonary dysplasia as bacterial colonization even after treatment with surfactant.

Bronchopulmonary Dysplasia↗

5-Fluorouracil plus interferon alpha-2a compared to 5-fluorouracil alone in the treatment of advanced colon carcinoma: a multicentric randomized study.

Biochemical modulation is one of the most interesting fields in cancer chemotherapy. Interferon-alpha (IFNalpha) is a cytokine that is able to influence the pharmacodynamics of 5-fluorouracil (5FU) through a number of mechanisms. With the aim of confirming some data emerging from the literature, we initiated a multicentric randomized study comparing the combination of 5FU and IFNalpha-2a with 5FU alone in the treatment of advanced or metastatic colon cancer. A group of 205 colon cancer patients (104 in the 5FU arm and 101 in the 5FU + IFNapha-2a arm) were included in the final intention-to-treat analysis. Rectal cancers were not considered eligible. All patients had measurable disease, were aged 75 years or less, had a Karnofsky index of at least 60 and had good bone marrow, renal, liver and cardiac functions. No previous chemo-immunotherapy was allowed. The treatment was 750 mg/m2 5FU (4 h i.v. infusion) on days 1 5 and then i.v. bolus weekly, starting from day 12, with or without IFNalpha-2a given s.c. three times weekly (starting dose 3 x 10(6) IU rising to 9 x 10(6) IU, if tolerated). Patients were treated until progression or, if responsive, for a maximum of 48 weeks and then observed for a period of 2 years. The primary end-point of the study was objective clinical response (OR); secondary parameters were time to progression, overall survival, and time to death after progression. WHO criteria were used for both clinical response and toxicity measurements. Dose reduction was planned a priori in the event of significant toxicity due to 5FU, IFNalpha-2a or both. Association between primary and secondary end-points and treatment was studied by univariate and multivariate analysis. Altogether, 47 patients achieved a documented response. A 25% OR was observed in the combination arm while a 21% OR was seen in the 5FU arm; this difference is not statistically significant (P = 0.6). Patients with a small tumour burden (below 5 cm2) showed a higher probability of response in both arms. Patients in the experimental arm had a higher but not statistically significant cumulative progression-free probability. Median survival was 47.1 weeks overall, while it was 43.7 and 48.5 weeks in the control and experimental arms, respectively. The combination was clearly more toxic than 5FU alone, leukopenia being the most frequent side-effect in the experimental arm and nausea and vomiting in the control arm. In conclusion these results are quite disappointing and 5FU + IFNalpha-2a can not be considered a standard treatment for advanced colon cancer.

Aged↗

The multicentric epitheloid hemangioendothelioma of bone: a case example and review of the literature.

Epitheloid hemangioendothelioma of bone is a rare primary bone malignancy. Diagnosis can be difficult for physicians who are not experienced with bone neoplasms. We also had difficulties in diagnosis and treatment in one of our patients with a multicentric epitheloid hemangioendothelioma involving the pelvis, left femur, and left tibia. We recommend a complete skeletal survey with magnetic resonance imaging because it can reveal previously undetected lesions on conventional radiographs. We performed an extraarticular resection of the hip joint including the spina iliaca anterior inferior, resection of the femur, and amputation of the lower leg. The femur was replaced by a modular endoprosthesis. The patient is provided with an above-knee prosthesis and is able to walk even longer distances with a cane 2 years after surgery. In our opinion it is necessary to perform a wide resection of this tumour in order to treat a patient with curative intention. Palliative radiotherapy should only be used for a non-resectable tumour or in metastatic disease. Chemotherapy is not a treatment option.

Adult↗

[Quantitative thermotest - investigations of thermal and nociceptive afferents in neuropathy. Is a multicentric approach useful to investigate rare painful neuropathies?].

Disturbances of small afferent nerve fibres play an important role in painful neuropathies. Quantitative thermotest offers a possibility to quantify these disturbances that can not be detected by conventional electrophysiology. It is a psychophysical method to investigate thermal and nociceptive afferents by determining thermal thresholds. Former experiences have shown that quantitative thermotest can be a helpful tool not only in daily routine but also for research work concerning pathophysiological mechanisms of neuropathy. Therefore a multicentric approach to investigate rare painful neuropathies seems to be useful.

English Abstract↗

A double-blind, randomised, parallel group, multinational, multicentre study comparing a single dose of ondansetron 24 mg p.o. with placebo and metoclopramide 10 mg t.d.s. p.o. in the treatment of opioid-induced nausea and emesis in cancer patients.

Nausea and emesis are common side effects of opioid drugs administered for pain relief in cancer patients. The aim of this study was to compare the anti-emetic efficacy and safety of ondansetron, placebo and metoclopramide in the treatment of opioid-induced nausea and emesis (OIE) in cancer patients. This was a multinational, multicentre, double-blind, parallel group study in which cancer patients who were receiving a full opioid agonist for cancer pain were randomised to receive one of oral ondansetron 24 mg once daily, metoclopramide 10 mg three times daily, or placebo. Study medication was started only if the patient experienced nausea and/or emesis following opioid administration. Efficacy and safety assessments were made over a study period of 24 h from the time of the first dose of anti-emetics/placebo. The study was terminated prematurely because of the difficulties in recruiting patients satisfying the stringent entry criteria. Ninety-two patients were included in the intent-to-treat population: 30 patients received placebo, 29 patients ondansetron and 33 patients metoclopramide. There was no statistically significant difference between the groups in the proportion achieving complete control of emesis (33% of patients on placebo, 48% on ondansetron and 52% on metoclopramide) or complete control of nausea (23% of patients on placebo, 17% on ondansetron and 36% on metoclopramide). Rescue anti-emetics were required in 8 of 33 patients on metoclopramide, 4 of 29 on ondansetron, and 3 of 30 on placebo. The incidence of adverse events was very low and similar in all treatment groups. Neither ondansetron 24 mg once daily nor metoclopromide 10 mg t.d.s. given orally was significantly more effective than placebo in the control of OIE in cancer patients.

Adult↗

Use of complementary and alternative therapies: a national multicentre study of oncology health professionals in Norway.

GOALS OF WORK: It is well documented that an increasing proportion of cancer patients today use complementary and alternative medicine, mostly alongside conventional therapies. This study investigates the use of complementary and alternative medicine among oncology health workers and the reported effects. PATIENTS AND METHODS: In June 2002, we conducted a national multicentre survey including 828 Norwegian oncologists, nurses, clerks and therapeutic radiographers. The response rate was 61.5%. MAIN RESULTS: We found that females were more often users of both complementary and alternative methods than males (39% versus 15% and 47% versus 17%) and that few oncologists had tried such treatments compared to nurses, therapeutic radiographers and clerks (20/12% versus 50/40%, 41/33%,and 31/50%). Interestingly, the majority of those who had tried unconventional methods reported some or very good effects. Acupuncture, homeopathy, aromatherapy and massage were the most popular therapies. Sub-group analyses including only oncologists showed that female physicians were more often users of both complementary and alternative methods compared to males (33% versus 12%, 25% versus 3%). Moreover, participants below the age of 35 years and Christians more often reported use. CONCLUSIONS: This survey demonstrates that significant proportion of oncology health workers in Norway have used non-proven therapies and that most have had a positive experience. Differences in use is highly dependent on gender, profession, age and religion.

Complementary Therapies↗

Surgical treatment of recurrent hepatocellular carcinoma based on the mode of recurrence: repeat hepatic resection or ablation are good choices for patients with recurrent multicentric cancer.

Hepatocellular carcinomas (HCC) often recur after curvative resection. Recurrence in the remnant liver originates from intrahepatic metastasis (IM) from the primary resected tumor, and/or from multicentric (MC) occurrence. In order to achieve better survival after intrahepatic recurrence in HCC patients, we have surgically treated patients according to the recurrence pattern. In this study, we investigated the advantage of repeat surgery for MC recurrent HCC. The subjects were 176 patients who had undergone primary macroscopically complete tumor removal for HCC at our department from 1984 to 1999. Differential diagnosis of IM and MC recurrence was done by pathological analysis. Twenty-nine of the 149 patients with recurrence (19.5%) underwent a total of 31 second and third operations. Of the 29 patients, 18 had MC (14 received repeat hepatectomy and 4, microwave tissue coagulation [MTC]), 7 had IM (4 had repeat hepatectomy and 3, MTC), and, in 4 patients, pathological investigation failed to determine the mode of recurrence. The 1-, 3-, and 5-year survival rates for MC patients after the repeat operations were 100%, 69.7%, and 58.1%, respectively, and the 1-, 3-, and 5-year survival rates for the IM patients were 57.1%, 14.3%, and 14.3%, respectively. Survival after the repeat operation was significantly better in the MC group than in the IM group (P = 0.0016). Moreover, there was no significant difference between survival in the MC group after a repeat operation and survival in control patients after an initial hepatectomy (P = 0.9282). These results indicated that patients with resectable or ablative recurrent MC HCC have almost the same survival benefit after repeat operations as patients who undergo initial curative resection of HCC.

Aged↗

Predeposit autologous donation in spinal surgery: a multicentre study.

BACKGROUND: Allogeneic blood transfusions (ABT) are often necessary in elective spine surgery because of perioperative blood loss. Preoperative autologous blood donation (PABD) has emerged as the principal means to avoid or reduce the need for ABT. Consequently, a multicentre study was conducted to determine the yield and efficacy of PABD in spine surgery and the possible role of recombinant human erythropoietin (EPO) in facilitating PABD. METHODS: We retrospectively reviewed the hospital charts and blood bank records from all consecutive spine surgery patients who were referred for PABD. Data were obtained from two A-category hospital blood banks and one general hospital. Although we collected data from 1994, the analytic study period was from the last quarter of 1995 to December 2003. Fifty-four (7%) out of 763 patients referred for PABD were rejected, and medical records were available for 680 patients who were grouped into spinal fusion (556; 82%) and scoliosis surgery (124;18%). EPO was administered to 120 patients (17.6%). From 1999 to 2003, PABD steadily increased from 60 to 209 patients per year. RESULTS: Overall, 92% of the patients were able to complete PABD, 71% were transfused, and almost 80% avoided ABT. PABD was more effective in fusions (86%) than in scoliosis (47%). Blood wastage was 38%, ranging from 18% for scoliosis to 42% for fusions. EPO allowed the results in the anaemic patients to be improved. CONCLUSIONS: Therefore, despite the limitations of this retrospective study, we feel that PABD is an excellent alternative to ABT in spine surgery. However, the effectiveness of PABD may be enhanced if associated with other blood-saving techniques.

Adult↗

Synchronous multicentric thymona: report of a case.

We report a case of multiple thymoma with different histological subtypes, not associated with myasthenia gravis. We describe the histological findings, especially the results of immunohistochemical staining, which support the possibility of multicentric thymoma. The validity of extended thymectomy is also discussed.

Adult↗

Multicentric occurrence of esophageal cancer after gastrectomy: a preliminary report.

The effect of gastrectomy on the subsequent development of esophageal cancer was investigated, focusing on its multicentric occurrence. We retrospectively evaluated 28 patients who underwent subtotal esophagectomy for intrathoracic esophageal cancer between 1985 and 1999. They were divided into two groups according to whether or not they had previously undergone a gastrectomy: group 1, comprising 7 patients who had undergone gastrectomy and group 2, comprising 21 patients who had not. Clinical profiles of the patients were obtained from the medical records and the whole resected esophagus was histopathologically examined. The interval between gastrectomy and esophagectomy in group 1 was significantly shorter in the patients who had undergone gastrectomy for gastric cancer than in those who had undergone gastrectomy for a peptic ulcer, and also in the patients for whom anastomosis had been performed by Billroth I compared with Billroth II. The patients in group 1 were significantly younger than those in group 2. The multiple occurrence of esophageal cancer was found in 4 of 5 patients (80%) in group 1, and in 2 of 18 patients (11%) in group 2, with significantly higher frequency being seen in group 1. More than two coexisting cancer lesions apart from the primary tumor were detected in all four patients. Histological examination of all the coexisting cancer lesions showed well-differentiated squamous cell carcinoma confined within the superficial mucosal layer. No significant differences were noted in the location of the coexisting lesions between the oral and anal side of the primary tumors. Squamous dysplasia was randomly observed, especially around the cancer lesions. These findings suggest that gastrectomy precipitated subsequent chronic gastroesophageal reflux which in turn induced the development of squamous dysplasia and carcinoma at multiple locations in the esophagus.

Aged↗

An open-label, multicentre clinical trial to determine the levodopa dose-sparing capacity of pramipexole in patients with idiopathic Parkinson's disease.

Ninety-three patients with idiopathic Parkinson's disease (PD) entered a 12 week open-label, baseline controlled, multicentre study. The study was designed to determine the levodopa sparing effect of pramipexole as add-on treatment in PD while maintaining an optimal clinical improvement in motor performance. The overall reduction in adjusted levodopa dose was the primary endpoint. Unified Parkinson's Disease Rating Scale (UPDRS) subscores as well as motor fluctuations, frequency and severity of dyskinesia (assessed by patient diaries) were secondary endpoints. Pramipexole permitted a median reduction of adjusted levodopa by 40% while maintaining or improving the UPDRS scores in 61 patients (per protocol [PP] analysis). The intent-to-treat (ITT) analysis (90 patients) similarly revealed a median reduction of 40%. An anticipated short-term levodopa dose reduction as substantiated by 95% confidence interval calculations lies within a range of 35% to 50%. If unadjusted levodopa doses were considered, a median reduction of 42% (PP) or 43% (ITT) was achieved. 47% patients (ITT) had a levodopa dose reduction (adjusted) of more than 40% while maintaining or improving their level of efficacy, and 72.2% had a reduction of at least 20%. Motor fluctuations improved compared to baseline according to patient diaries and UPDRS part IV. These findings suggest that pramipexole can markedly reduce the daily levodopa dosage without deterioration of motor response and support that this new selective D2/D3 receptor agonist also improves later levodopa-associated motor complications.

Aged↗

Multicentre prospective study of perinatal depression in Japan: incidence and correlates of antenatal and postnatal depression.

A multicentre study on the epidemiology of perinatal depression was conducted among Japanese women expecting the first baby (N = 290). The incidence rate of the onset of the DSM-III-R Major Depressive Episode during pregnancy (antenatal depression) and within 3 months after delivery (postnatal depression) were 5.6% and 5.0%, respectively. Women with antenatal depression were characterised by young age and negative attitude towards the current pregnancy, whereas women with postnatal depression were characterised by poor accommodation, dissatisfaction with sex of the newborn baby and with the emotional undermining. Antenatal depression was a major risk factor for postnatal depression.

Adult↗

Multicentric synchronous osteosarcoma: a case report with autopsy findings.

We report a typical case of multicentric synchronous osteosarcoma. An 8-year-old girl was referred to us. At diagnosis she had a dominant bone lesion in the left proximal tibia and other lesions in the pelvis, thoracic spine, right femoral shaft, and left lower limb, without any lung lesions. We administered high doses of cisplatin and doxorubicin hydrochloride, but they were not effective. A pulmonary metastatic lesion was first detected by chest X-ray 4 months after the diagnosis, and she died of pulmonary insufficiency within 1 year after the first presentation.

Antineoplastic Combined Chemotherapy Protocols↗

Deciding whether interventions for antisocial behaviour work: principles of outcome assessment, and practice in a multicentre trial.

Factors influencing the reported effectiveness of interventions for antisocial behaviour are reviewed, with illustrative findings from a multicentre controlled trial of parenting groups. The merits and validity of different types of measuring instrument are discussed and it is concluded that it is desirable to have more than one informant (parent, teacher, observer) and at least one instrument with objective criteria, for example a semi-structured interview or direct observation. In the illustrative trial, the effect size was larger with semi-structured interviews than questionnaires, for conduct problems compared to hyperactivity symptoms, and for trial completers compared to the total sample it was intended to treat. The discrepancy between the encouraging results of trials conducted in university centres and the disappointing findings of those carried out in 'real life' clinics is discussed. The trial discussed here was conducted in health service clinics by regular staff but still reported good effect sizes. Measuring likely mediators and moderators so mechanisms of change can be investigated is discussed. In the trial, change was mediated through acquisition of parenting skills but not through maternal depression or criticism directed at the child, even though these were reduced by the intervention. This suggests that programmes that impart skills are more likely to be effective than those that offer counselling only.

Attention Deficit and Disruptive Behavior Disorder↗