Evaluation of Clinical Trials in Onco-haematology: A New Method Based on Risk Analysis and Multidisciplinarity.

BACKGROUND: European member states are increasingly vying with one another to recruit patients for clinical trials (CTs). The French national agency for medicines (ANSM) now receives an ever-growing number of CTs, extending response times. The aim of the new methodology presented herein is to reduce assessment times below the national mandatory timeframe of 60 days and to improve patient safety. MATERIALS AND METHODS: Based on an analysis of the criteria defining CTs, 4 key points were identified (safety, fragile population, loss of opportunity, design complexity) to build a criticality score which would determine evaluation type. This score also determines the resources needed (complete evaluation, multidisciplinary advice, ad hoc evaluation) and the timeframe required for appropriate analysis. All post-phase I CTs were analysed from the implementation of the new assessment method, on 01/02/2018 through to 31/12/2019. RESULTS: 447 CTs were analysed (63% industry and 37% academic sponsors). Based on a criticality scale, 27% of the CTs received a type A evaluation (complete), 37% a type B (multidisciplinary evaluation), 23% a type C evaluation (ad hoc evaluation) and 13% a type D evaluation (fast evaluation). From 2014 to 2017, 37% of the CTs were analysed within the mandatory timeframe, with a mean of 68 days, reaching a maximum of 102 days in 2017. Using this new assessment method, 92% of CTs respected the mandatory timeframe in 2019; the mean time in 2018-2019 was 34 days; Grounds for Non-Acceptance (GNA) were raised for 66% of the CTs (69% from academic sponsors and 65% from industrial firms). 3 CTs were refused. CONCLUSION: Here, we demonstrate the feasibility of risk analysis and multidisciplinarity method, which resulted in a dramatic improvement of assessment times.

Undocumented Border Crosser Deaths in Arizona: Expanding Intrastate Collaborative Efforts in Identification.

Undocumented Border Crosser (UBC) deaths in Arizona are a major issue faced by medicolegal authorities. Currently, the Maricopa County Office of the Medical Examiner (MCOME) is in possession of over two hundred unidentified individuals, more than half of whom are presumed to be UBCs. The primary goal of this study was to address the growing number of UBC deaths in Maricopa County in order to provide a more comprehensive picture of this important anthropological issue within the state of Arizona. Of the 107 total UBC cases evaluated for the study, the majority were male and age estimates for all individuals were between 15 to 60 years old. Modeled after the recording system established by the Pima County Office of the Medical Examiner, the biographic and geographic data for these cases were entered into a new UBC database at MCOME and later added to the online Map of Migrant Mortality.

Clinical application of an external fixator in the repair of bone fractures in 28 birds.

The repair of seven tibiotarsal fractures, three humeral fractures, three tarsometatarsal fractures, two femoral fractures and 13 radial and ulnar fractures with a tubular external fixator system was evaluated prospectively in 10 common pigeons (Columba livia), 11 psittacine birds, six birds of prey and one Bali starling (Leucopsar rothschildii). The fixations included type 1, type 2 and intramedullary tie-in methods, and the fractures healed in all but three cases. A comparison of the weight of different connecting bars showed that the external fixation system and polymethylmethacrylate are the lightest available systems and that there was no clinically relevant difference between them.

Effects of two diets on the haematology, plasma chemistry and intestinal flora of budgerigars (Melopsittacus undulatus).

Two groups of 22 budgerigars (Melopsittacus undulatus) were housed for 12 months under identical conditions. One group was fed a commercial seed mixture plus carrots and a mineral supplement, and the other group was fed a commercially formulated diet plus carrots. Samples of blood and faeces were collected initially and after three, six, nine and 12 months. There were no significant differences between the haematological values of the two groups. The group fed the seed mixture had significantly higher concentrations of glucose, albumin, triglycerides and uric acid, and higher activity of aspartate aminotransferase, but the values were within the published reference ranges for normal birds. There were no significant differences between the faecal samples from the two groups, except that the fungus Macrorhabdus ornithogaster was identified in 48.3 per cent of the samples from the group fed the commercially formulated diet but from only 3.4 per cent of the samples from the group fed the seed mixture.

Unilateral evisceration of an eye following cornea and lens perforation in a sulfur-crested cockatoo (Cacatua galerita).

A 24-year old male sulfur-crested Cockatoo (Cacatua galerita) was presented with a subacute perforation of the cornea without involvement of the lens. The bird was treated conservatively and the eye remained quiescent up to a second traumatic corneal perforation associated with a lens capsule rupture 15 months later. Due to the second perforating trauma of an already blind eye involving the lens, evisceration of the eye was performed. Two months after surgery the cosmetic result was excellent. Treatment options for perforating ocular traumas in captive birds are discussed in detail.

[Ferrets in veterinary practice]. / Frettchen in der Tierarztpraxis.

Ferrets (Mustela putorius furo) show up with increasing frequency in veterinary practice. Originally domesticated for hunting of rodents and rabbits, they became very popular pets which require legal permission though and the further fulfillment of various husbandry needs. Ferrets have to be maintained on a high protein diet which in practice is often done with commercial feline products. Physical examination is similar to dogs and cats whereas the frequent occurrence of non-specific symptoms require further diagnostic investigation including blood sampling, radiology, ultrasound or exploratory laparatomy. The preferred anaesthetic method is the direct face mask induction and maintenance using isoflurane without prämedication. Special attention of veterinarians has to be paid to canine distemper vaccination, the specialized reproduction physiology of the females (jills) which can develop, if unmated, a persistent oestrus with fatal consequences of hyperestrogenism, as well as the frequent occurrence of further endocrine disorders, congestive cardiomyopathy and gastrointestinal diseases.

Development of specific social skills training programmes for schizophrenia patients: results of a multicentre study.

OBJECTIVE: The efficacy of three newly developed cognitive social skills training programmes for residential, vocational and recreational functioning (experimental groups) were compared with a traditional social skills training programme (control group) referring to cognitive and social abilities, psychopathology and generalisation effects. METHOD: One hundred and five patients with a diagnosis of schizophrenia or schizoaffective disorder according to ICD-10 criteria were selected and assigned to the different treatment groups, using a matching procedure. The treatment phase lasted 6 months. A follow-up assessment was carried out after 1 year. RESULTS: Higher global therapy effects were obtained on almost all dependent variables in the experimental groups. Analyses of variance and covariance indicated higher symptom reduction for the experimental groups, but significantly greater improvements in some cognitive variables for the control group. Correlation analysis suggested associations between improvement of social behaviour with symptom reduction and improvements of cognitive skills. CONCLUSION: In view of these favourable effects, the developed cognitive social skills training programmes might facilitate the abilities of schizophrenia patients for their integration in the community.

[Effects of new cognitive-behavioral therapy programs for improvement of specific social skills of schizophrenics--a controlled study]. / Effekte neuer kognitiv-behavioraler Therapieprogramme zur Verbesserung spezifischer sozialer Fertigkeiten bei schizophren Erkrankten. Eine kontrollierte Studie.

Based on the Integrated Psychological Therapy (IPT) for schizophrenia patients, the Berne group developed three specific cognitive behaviour therapy programmes for treating residential, vocational, and recreational functioning. We added new cognitive-emotional methods to these programmes that were devised especially for schizophrenia patients, taking into consideration the criticism of traditional social skill training methods. In the present multicentre study, these new programmes (experimental group) were compared with a traditional social skills training programme (control group, IPT "Social Skills" subprogramme). Both the therapy and aftercare phase each lasted 12 weeks and the follow-up phase 1 year. Assessment instruments covered psychopathology, cognitive functioning, and social adjustment. Higher ratings of global treatment effects and significant reductions in symptoms were obtained in the experimental group. In view of the favourable results, these newly designed social skill training programmes may replace more conventional therapy approaches in the future.

Stability of bupivacaine hydrochloride and hydromorphone hydrochloride during simulated epidural coadministration.

Bupivacaine hydrochloride 625 and 1250 micrograms/mL and hydromorphone hydrochloride 20 and 100 micrograms/mL in 0.9% sodium chloride injection were stable and compatible for up to 72 hours under fluorescent light when stored in polyvinyl chloride containers at 24 degrees C.

Parenteral nutrition in gynecology.

Over a three-year period, 88 gynecology inpatients received 99 courses of parenteral nutrition. Indications included a variety of circumstances in patients with both benign and malignant conditions. Complications were infrequent and generally without significant sequelae. A correlation was noted between nutritional status and clinical outcome, indicating a need for continued monitoring of nutritional status during parenteral nutritional support.

[Determination of leukemic B-lymphoma cells with the monoclonal antibody anti-Y 29/55]. / Nachweis von leukämischen B-Lymphomzellen durch den monoklonalen Antikörper Anti-Y 29/55.

The monoclonal antibody anti-Y 29/55 recognizes a group specific antigen on sessile human B-lymphocytes which do not belong to the recirculating lymphocyte pool. The occurrence of this antigen in malignant NHL, with or without leukemic state, and in other leukemias has been studied. The antigen was expressed on cells of various histologic B-cell types but not on leukemic cells of ALL, T-lymphoma, AML or CML. It is concluded that in malignant B-lymphoma, B-CLL and HCL, cells appearing in blood carry a marker characteristic of virgin or activated sessile B-lymphocytes. Anti-Y 29/55 permits differentiation of such cells from normal recirculating B-cells and other leukemic cells including ALL, AML and CML. In follow-up studies this antibody may be helpful in detecting early leukemic output. B-lymphocytic leukemia may reflect a disproportion between binding sites on the lymphatic reticulum and the neoplastic cells bearing this antigen, which might be involved in binding of B-lymphocytes to the supporting lymphatic reticulum.

[The diagnostic value of T- and B-rosette formation and the unspecific acid esterase in the differential diagnosis of acute and chronic leukemia]. / Zur diagnostischen Bedeutung der T- und B-Rosetten-Bildung und der unspezifischen sauren Esterase in der Differentialdiagnose der akuten und chronischen Leukämien.

The diagnostic significance of acid non-specific alpha-naphthyl-acetate (ANAE) and of rosette formation of leukemic cells with sheep and mouse erythrocytes was studied in 8 patients with acute myeloic leukemia (AML), in 4 patients with acute lymphatic leukemia (ALL) and in 14 patients with chronic lymphatic leukemia (CLL). ANAE showed typical diffuse cytoplasmic activity in all cases of AML. The enzyme activity was granular in both of the lymphoid malignancies, T-ALL and B-CLL, allowing differentiation from AML but not between B- and T-leukemia cells. Rosette formation with mouse erythrocytes (ME) was diagnostic in all 14 cases of CLL and superior to labeling of surface immunoglobulin (8 of 14 cases positive). ME-rosette forming myeloblasts were detected in 2 of 4 evaluated cases of AML. Rosette formation with sheep erythrocytes (SE), including cytological evaluation of rosette-forming cells, was diagnostic in all cases of ALL (= T-ALL). In 6 of 9 patients with AML, however, rosette formation with SE was observed in a few cells, including myeloblasts with Auer rods. The occurrence of blasts in myeloic leukemia carrying lymphoid cell markers is discussed in the light of recent findings, according to which lymphoblastoid cells may arise in the course of myeloic leukemia requiring antileukemic treatment different from that of AML.