Family and group cognitive behavior therapy: Evaluation of treatment outcome and treatment specificity

This dissertation examined the efficacy of family cognitive behavior treatment (FCBT) and group cognitive behavior treatment (GBCT) for reducing anxiety disorders in children and adolescents using several approaches: clinical significant change, equivalence testing, and analyses of variance. It also examined treatment specificity in terms of targeting family/parents (in FCBT) and peers/group (in GCBT) contextual variables using two main approaches: analyses of variance and structural equation modeling (SEM). The sample consisted of 143 children and their parents who presented to the Child Anxiety and Phobia Program housed within the Child and Family Psychosocial Research Center at Florida International University. Diagnostic interviews and questionnaires were administered to assess youth anxiety. Questionnaires were administered to assess child and parent views of family/parents and peers/group contextual variables. In terms of clinical significant change, results indicated that 84.6% of youth in FCBT and 71.2% of youth in GBCT no longer met diagnostic criteria for their primary/targeted anxiety disorder. In addition, results from analyses of variance indicated that FCBT and GCBT were both efficacious in reducing anxiety disorders in youth across both child and parent ratings. Results using both analyses of variance and structural equation modeling also indicated that there was no meaningful treatment specificity between FCBT and GCBT in terms of either family/parents or peers/group contextual variables. That is, child social skills improved in GCBT in which these skills were targeted and in FCBT in which these skills were not targeted; parenting skills improved in FCBT in which these skills were targeted and in GCBT in which these skills were not targeted. Clinical implications and future research recommendations are discussed.

The influence of mandibular ridge anatomy on treatment outcome with conventional complete denture.

Visto que indicadores de prognóstico são uma ferramenta importante para a seleção de pacientes a serem tratados com prótese total, este estudo investigou a influência da forma e da resiliência do rebordo alveolar mandibular sobre a retenção e estabilidade de próteses totais convencionais. Noventa e três pacientes desdentados portadores de próteses totais superior e inferior compuseram a amostra. Os dados foram coletados quanto a forma e resiliência do rebordo mandibular. As próteses foram avaliadas para a retenção e estabilidade utilizando-se uma ferramenta objetiva e reproduzível. As associações entre as características clínicas do rebordo alveolar mandibular e retenção e estabilidade das próteses foram analisados por meio dos testes qui-quadrado e exato de Fisher (α = 0.05). Observou-se associação significativa entre a forma do rebordo e a estabilidade da prótese (p <0,05), enquanto que a resiliência foi associada significativamente com a retenção (p <0,001). Baseando-se nos resultados, a resiliência e forma do rebordo mandibular influenciaram, respectivamente, a retenção e estabilidade de próteses totais convencionais.

Correlation between pre-treatment quasispecies complexity and treatment outcome in chronic HCV genotype 3a

Pre-treatment HCV quasispecies complexity and diversity may predict response to interferon based anti-viral therapy. The objective of this study was to retrospectively (1) examine temporal changes in quasispecies prior to the start of therapy and (2) investigate extensively quasispecies evolution in a group of 10 chronically infected patients with genotype 3a, treated with pegylated alpha 2a-Interferon and ribavirin. The degree of sequence heterogeneity within the hypervariable region 1 was assessed by analyzing 20-30 individual clones in serial serum samples. Genetic parameters, including amino acid Shannon entropy, Hamming distance and genetic distance were calculated for each sample. Treatment outcome was divided into (1) sustained virological responders (SVR) and (2) treatment failure (TF).Our results indicate, (1) quasispecies complexity and diversity are lower in the SVR group, (2) quasispecies vary temporally and (3) genetic heterogeneity at baseline can be used to predict treatment outcome. We discuss the results from the perspective of replicative homeostasis. We discuss the results from the perspective of replicative homeostasis.

Quasispecies dynamics and treatment outcome during early hepatitis C infection in a cohort of HIV-infected men

Hepatitis C virus (HCV) is emerging as one of the leading causes of morbidity and mortality in individuals infected with HIV and has overtaken AIDS-defining illnesses as a cause of death in HIV patient populations who have access to highly active antiretroviral therapy. For many years, the clonal analysis was the reference method for investigating viral diversity. In this thesis, a next generation sequencing (NGS) approach was developed using 454 pyrosequencing and Illumina-based technology. A sequencing pipeline was developed using two different NGS approaches, nested PCR, and metagenomics. The pipeline was used to study the viral populations in the sera of HCV-infected patients from a unique cohort of 160 HIV-positive patients with early HCV infection. These pipelines resulted in an improved understanding of HCV quasispecies dynamics, especially regarding studying response to treatment. Low viral diversity at baseline correlated with sustained virological response (SVR) while high viral diversity at baseline was associated with treatment failure. The emergence of new viral strains following treatment failure was most commonly associated with emerging dominance of pre-existing minority variants rather than re-infection. In the new era of direct-acting antivirals, next generation sequencing technologies are the most promising tool for identifying minority variants present in the HCV quasispecies populations at baseline. In this cohort, several mutations conferring resistance were detected in genotype 1a treatment-naïve patients. Further research into the impact of baseline HCV variants on SVR rates should be carried out in this population. A clearer understanding of the properties of viral quasispecies would enable clinicians to make improved treatment choices for their patients.

Preliminary clinical assessment of polyvinyl alcohol-tetrahydroxyborate hydrogels as potential topical formulations for local anesthesia of lacerations

The aim of this study was to assess a novel semisolid material as a potential topical drug delivery system for acute laceration. The objectives were to correlate physical characterization data using rheologic studies and to compare with clinical assessment of performance in an emergency department (ED).

An audit of first-aid treatment of pediatric burns patients and their clinical outcome

This study describes the first aid used and clinical outcomes of all patients who presented to the Royal Children's Hospital, Brisbane, Australia in 2005 with an acute burn injury. A retrospective audit was performed with the charts of 459 patients and information concerning burn injury, first-aid treatment, and clinical outcomes was collected. First aid was used on 86.1% of patients, with 8.7% receiving no first aid and unknown treatment in 5.2% of cases. A majority of patients had cold water as first aid (80.2%), however, only 12.1% applied the cold water for the recommended 20 minutes or longer. Recommended first aid (cold water for >or=20 minutes) was associated with significantly reduced reepithelialization time for children with contact injuries (P=.011). Superficial depth burns were significantly more likely to be associated with the use of recommended first aid (P=.03). Suboptimal treatment was more common for children younger than 3.5 years (P<.001) and for children with friction burns. This report is one of the few publications to relate first-aid treatment to clinical outcomes. Some positive clinical outcomes were associated with recommended first-aid use; however, wound outcomes were more strongly associated with burn depth and mechanism of injury. There is also a need for more public awareness of recommended first-aid treatment.

Superior outcome of women with stage I/II cutaneous melanoma: pooled analysis of four European Organisation for Research and Treatment of Cancer phase III trials.

PURPOSE: Several studies observed a female advantage in the prognosis of cutaneous melanoma, for which behavioral factors or an underlying biologic mechanism might be responsible. Using complete and reliable follow-up data from four phase III trials of the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group, we explored the female advantage across multiple end points and in relation to other important prognostic indicators. PATIENTS AND METHODS: Patients diagnosed with localized melanoma were included in EORTC adjuvant treatment trials 18832, 18871, 18952, and 18961 and randomly assigned during the period of 1984 to 2005. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for women compared with men, adjusted for age, Breslow thickness, body site, ulceration, performed lymph node dissection, and treatment. RESULTS: A total of 2,672 patients with stage I/II melanoma were included. Women had a highly consistent and independent advantage in overall survival (adjusted HR, 0.70; 95% CI, 0.59 to 0.83), disease-specific survival (adjusted HR, 0.74; 95% CI, 0.62 to 0.88), time to lymph node metastasis (adjusted HR, 0.70; 95% CI, 0.51 to 0.96), and time to distant metastasis (adjusted HR, 0.69; 95% CI, 0.59 to 0.81). Subgroup analysis showed that the female advantage was consistent across all prognostic subgroups (with the possible exception of head and neck melanomas) and in pre- and postmenopausal age groups. CONCLUSION: Women have a consistent and independent relative advantage in all aspects of the progression of localized melanoma of approximately 30%, most likely caused by an underlying biologic sex difference.

An EORTC phase I study of capecitabine (Xeloda) in combination with fixed doses of cyclophosphamide and epirubicin (cex) as primary treatment for large operable or locally advanced/inflammatory breast cancer.

In breast cancer, chemotherapy regimens that include infusional 5-fluorouracil (5-FU) lead to high response rates, but require central venous access and pumps. To avoid these inconveniences, we substituted infusional 5-FU with capecitabine. The main objective of this study was to determine the maximum tolerated dose (MTD) of capecitabine when given in combination with fixed doses of epirubicin and cyclophosphamide (100 and 600 mg/m(2) day 1 every (q) 3 weeks) as primary treatment for large operable or locally advanced/inflammatory breast cancer without distant metastasis. Capecitabine was escalated from 750 mg/m(2) twice a day (bid) to 1250 mg/m(2) bid from day 1 to day 14 in four dose levels. Dose escalation was permitted if 0/3 or 1/6 patients experienced dose-limiting toxicity (DLT). A total of 23 patients were included and 117 courses were administered. At dose level 4, 2 of 2 patients presented DLTs defining the MTD. A high rate of capecitabine treatment modification was required with capecitabine 1050 mg/m(2) bid (dose level 3). 19 patients achieved an objective response (83%). In conclusion, we believe that capecitabine 900 mg/m(2) bid (dose level 2) is the recommended dose in combination with epirubicin 100 mg/m(2) and cyclophosphamide 600 mg/m(2). The acceptable toxicity profile and encouraging activity of this regimen warrant further evaluation.

Cellular immune responses of preterm infants after vaccination with whole-cell or acellular pertussis vaccines.

Based on studies reporting specific antibody titers, it is recommended to vaccinate preterm infants against Bordetella pertussis according to their chronological age. However, as specific T-cell responses also are involved in the protection against B. pertussis, we have determined whether highly preterm infants (<31 weeks) are able to mount these immune responses during vaccination. Forty-eight premature infants were vaccinated at 2, 3, and 4 months of their chronological age with an acellular (Pa; n = 24) or a whole-cell (Pw; n = 24) tetravalent diphtheria-tetanus-pertussis-polio vaccine, and blood samples were collected at 2, 3, and 6 months of age. Most of the Pa- and Pw-vaccinated infants developed at 3 or 6 months of age a gamma interferon (IFN-gamma) response to the B. pertussis antigens, accompanied by an interleukin-5 (IL-5) and IL-13 secretion for the Pa-vaccinated infants. No association was found between a very low infant birth weight, the occurrence of severe infections, and corticosteroid treatment or the administration of gammaglobulins with a low level of antigen-induced IFN-gamma secretion. We conclude that like full-term infants, most preterm infants are able to mount a specific cellular immune response to the administration of the first doses of an acellular or a whole-cell pertussis vaccine.

Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes:results of the MRC AML15 trial

Two hundred eighty-five patients, median age 42, with PML-RARa-positive acute promyelocytic leukaemia were randomised to Ara-C-containing 'Medical Research Council (MRC) Chemotherapy'+ATRA (All-trans-retinoic acid) or anthracycline+ATRA (modified 'Spanish') therapy. MRC treatment comprised four courses with ATRA in courses 1-2. Spanish treatment comprised four anthracycline-based courses with ATRA in courses 1-3. In course 3 patients were randomised to gemtuzumab ozogamicin (GO) or not. The Spanish arm received 24-month maintenance. Patients were sequentially molecularly monitored. Quality of life was assessed at baseline, 3, 6, 9, 12, 24 months. Remission rates were similar in both arms (93%): cumulative incidence of haematological relapse (CIHR) was 6% at 5 years; 5 patients relapsed molecularly. Survival post relapse was 80%. There were more deaths in remission in the MRC arm (4% vs 10%: P=0.2). The overall 5-year relapse-free and overall survival was similar between arms (81% vs 82% and 84% vs 83%, respectively). More supportive care and hospitalisation (81.8 vs 63 days, P10 × 10(9)/l) was not prognostic overall, or within treatment arms. Both approaches deliver similar results with minor differences in quality of life. MRC treatment required more hospitalisation. This suggests that additional chemotherapy, Ara-C in particular, is not required.

A Non-Inferiority Randomized Controlled Trial Comparing the Clinical Effectiveness of Anesthesia Obtained by Application of a Novel Topical Anesthetic Putty With the Infiltration of Lidocaine for the Treatment of Lacerations in the Emergency Department

We test the hypothesis that anesthesia, measured as pain scores, induced by a novel topical anesthetic putty is non-inferior (margin=1.3) to that provided by conventional lidocaine infiltration for the repair of lacerations.

Immune haemolytic anaemia following T cell-depleted allogeneic bone marrow transplantation for chronic myeloid leukaemia:association with leukaemic relapse and treatment with donor lymphocyte infusions

Immune haemolytic anaemia (IHA) is a recognised complication after allogeneic stem cell transplantation (SCT) and occurs more frequently if marrow cells have been subjected to T cell depletion (TCD). Among 58 consecutive patients who underwent TCD-allogeneic SCT from volunteer unrelated donors for the treatment of CML at the Hammersmith Hospital during a 3-year period (1 March 1996 to 28 February 1999) we identified nine cases of IHA. All patients had a strongly positive direct and indirect antiglobulin test and in eight patients the serological findings were typical of warm-type haemolysis often with antibody specificities within the Rh system. All nine cases had clinically significant haemolysis and were treated initially with prednisolone and immunoglobulin. The onset of IHA coincided with the occurrence of leukaemic relapse in six cases, and the presence of host haemopoiesis confirmed by lineage-specific chimerism in all four cases studied. Five patients received donor lymphocyte infusions (DLI); in three molecular remission and the restoration of full donor chimerism coincided with resolution of haemolysis. We conclude that in the context of leukaemic relapse, DLI is an effective therapy for IHA following allografts involving TCD.