Core psychosocial issues for children and adolescents in the context of limb lengthening and reconstruction surgery treatment.

PURPOSE: Addressing the psychosocial needs of adolescents can improve surgical outcomes. The aim of this retrospective comparative study was to understand the core psychosocial factors that shaped the experiences of adolescents who underwent multiple limb lengthening/reconstruction surgeries (LLRS). METHODS: A novel 62-question survey was developed and administered to 31 patients from the study institution. Data was obtained using a self-report inventory assessing medical care, communication/connection to doctor, peer relations, physical space, self-esteem, counselling/clergy, physical/emotional support, school issues and concerns about future. This survey and demographic questions were administered to young adults (now aged 18 to 30 years) who underwent LLRS treatment between the ages of 11 to 20 years. RESULTS: Psychosocial needs were determined to be within the categories of body image/self-esteem, subjective perception of treatment, patient-physician relationship, role of parents, peer interactions, academic performance and hospital experience. Patients valued parental involvement while also wanting their surgeon to speak directly to them. They preferred to be in private rooms on the paediatric floor and to not socialize while in the hospital. They were indifferent to keeping up with friends, speaking to a counsellor and having their surgeon inquire about their emotions. They expressed concern about pain, carrying out activities and the financial impact of surgery. CONCLUSIONS: Adolescent LLRS patients value focused psychosocial support from their surgeon and caregivers. This perceived level of support influences their ability to cope with their condition. These findings helped us understand the psychological issues and preferences of adolescents who underwent LLRS and can assist orthopaedic surgeons in providing holistic care. LEVEL OF EVIDENCE: IV.

Tofogliflozin: a highly selective SGLT2 inhibitor for the treatment of type 2 diabetes.

Diabetes mellitus impacts a substantial number of people worldwide and despite numerous antidiabetic medications available, approximately half of the drugs do not attain their recommended target, glycated hemoglobin (HbA1c). Recently, the kidney and its role in glucose reabsorption through the sodium/glucose cotransporter 2 (SGLT2) has been the target for novel antidiabetic treatments. Pharmacologic inhibition of SGLT2 in patients with diabetes results in increased urinary glucose excretion and decreased blood glucose levels, decreasing HbA1c levels. Tofogliflozin is the most selective SGLT2 inhibitor, with HbA1c reductions ranging from -0.44% to -0.99% throughout clinical studies, and it is well tolerated with a low rate of drug-related adverse events. Tofogliflozin has demonstrated efficacy and safety as monotherapy or as add-on to various antidiabetic agents, and it is currently undergoing phase IV clinical studies in Japanese patients with diabetes on background insulin therapy. Tofogliflozin is currently approved in Japan for use in patients with type 2 diabetes at a dose of 20 mg orally once daily in the morning, either before or after breakfast.

Evaluating the role of HLA-DQ polymorphisms on immune response to bacterial superantigens using transgenic mice.

Bacterial superantigens bind directly to human leukocyte antigen (HLA) class II molecules and vigorously activate T cells expressing certain T-cell receptor variable region families. As interaction with HLA class II molecules is the primary step in this process, polymorphic variations in HLA class II can determine the extent of superantigen binding to HLA class II molecules, govern the magnitude of immune activation induced by given superantigens and determine the outcome of superantigen-mediated diseases. As direct assessment of the influence of HLA class II polymorphism in humans is impossible because of expression of more than one HLA class II alleles in a given individual and toxicity of superantigens, transgenic mice expressing HLA-DQ6 (HLA-DQA1*0103 and HLA-DQB1*0601) and HLA-DQ8 (HLA-DQA1*0301 and HLA-DQB1*0302) were used to achieve this goal. HLA-DQ6 and HLA-DQ8 elicited comparable in vitro and in vivo immune response to staphylococcal enterotoxins (SE) A, SEB, SEH and SEK, toxic shock syndrome toxin-1, streptococcal pyrogenic exotoxin (SPE) A and SPEC and streptococcal mitogenic exotoxin Z (SMEZ). However, each superantigen had a unique T-cell receptor activation profile. In vivo challenge with Streptococcus pyogenes, H305, capable of elaborating SPEA and SMEZ, yielded a similar clinical outcome in HLA-DQ6 and HLA-DQ8 transgenic mice. In conclusion, HLA-DQ6 and HLA-DQ8 elicited comparable response to certain bacterial superantigens. Our report highlights the advantages of HLA class II transgenic mice in such studies.

Immediate feedback during academic testing.

Performance on two multiple-choice testing procedures was examined during unit tests and a final examination. The Immediate Feedback Assessment Technique provided immediate response feedback in an answer-until-correct style of responding. The testing format which served as a point of comparison was the Scantron form. One format was completed by students in introductory psychology courses during unit tests whereas all students used the Scantron form on the final examination. Students tested with Immediate Feedback forms on the unit tests correctly answered more of the final examination questions which were repeated from earlier unit tests than did students tested with Scantron forms. Also, students tested with Immediate Feedback forms correctly answered more final examination questions previously answered incorrectly on the unit tests than did students tested previously with Scantron forms.

Clinical characteristics of neuroleptic-induced parkinsonism.

In order to characterize the clinical spectrum of neuroleptic-induced parkinsonism (NIP), we studied a population of consecutive psychiatric in-patients treated with neuroleptics for at least two weeks, who were diagnosed by their psychiatrist as having parkinsonism. Parkinsonism was confirmed by a movement disorders specialist who performed neurological assessment including the motor examination and the activities of daily living (ADL) sections of the Unified Parkinson's Disease Rating Scale (UPDRS), and the Hoehn and Yahr (H&Y) staging. Seventy-five patients (54 males), aged 46 +/- 13 years (range 21 to 73 years) were included in the analysis. The mean duration of neuroleptic therapy was 15 +/- 12 years, while 61% were treated for more than 10 years. Most of the patients (n = 66, 88%) were scored as H&Y stage 2.5 or less. Rest tremor was present in 44% of the patients, and usually persisted in action. Forty-one patients (61%) had symmetrical involvement. Parkinsonian signs were significantly more common and pronounced in the upper in comparison with the lower limbs (p = 0.0001). Gait disturbances were mild and freezing of gait was very rare (n = 2). Neither age nor duration of therapy or their interaction affected the total motor score or any of the motor sub-scores. In conclusion, NIP differs from PD for more bilateral involvement with relative symmetry, and by affecting upper limbs more often than the lower ones. NIP tends to be associated with the triad of bradykinesia, tremor and rigidity while PD tends to involve gait and posture more often. NIP develops unrelated to duration of neuroleptic treatment or age of the patient, suggesting an individual predisposition to blockage of the dopaminergic receptors.

Elderly cohort study subjects unable to return for follow-up have lower bone mass than those who can return.

Longitudinal studies of osteoporosis in older persons may underestimate bone loss because of a lack of follow-up measurements on subjects too frail to return. The authors addressed this possible bias as part of the population-based Framingham Study; in 1996-1997, they used quantitative ultrasound to assess the bone status of elderly subjects regardless of their ability to return to the clinic. Broadband ultrasound attenuation (BUA) and speed of sound of the calcaneus (heel) were measured in 433 subjects at the Framingham, Massachusetts, clinic and in 167 subjects at their homes or nursing homes. All ultrasound parameters were measured with intramachine coefficients of variation of <6.0%. The mean BUA for those subjects evaluated at the clinic was higher than for those measured at home (9.2% higher for men, p = 0.081; 8.6% higher for women, p = 0.034). After adjustment for age and weight, the differences in BUA were no longer significant. Among the elderly subjects participating in this longitudinal cohort study, those who were unable to return for follow-up were older, weighed less, and had a lower BUA than those who did return, suggesting that longitudinal studies of changes in bone mass with aging may underestimate the true population values.

An unusual cause of spinal cord injury: case report and discussion.

Traumatic spinal cord injury is a devastating condition that alters every aspect of the victim's life. Motor vehicle accidents cause about half of the cases, whereas others are the result of falls, recreational and sporting accidents, or acts of violence. We report a case of a C3 spinal fracture with a resultant Brown Sequard syndrome, which occurred in a unique manner and could have easily been prevented. There is a need for the medical community to play a more active role in educating the public to prevent accidents that lead to these catastrophic injuries.

Metastatic nonresectable fibrolamellar hepatoma: prognostic features and natural history.

Fibrolamellar hepatoma has a clinical course distinct from that of typical histologic hepatocellular carcinoma. The clinical behavior and prognostic features of nonresectable metastatic fibrolamellar hepatoma have not previously been fully addressed and are the focus of this report. Retrospective chart review of all patients (n = 17) with nonresectable metastatic fibrolamellar hepatoma referred to the Johns Hopkins Oncology Center from 1985 through 1990 was carried out. All patients had hepatic parenchymal involvement and regional node metastases at the time of referral. Metastases were limited to regional nodes in four patients. The remaining patients had lung metastases (n = 4), peritoneal metastases (n = 5), or both (n = 4). To assess the impact of the fibrolamellar variant, characteristic-matched control patients with typical histologic hepatocellular carcinoma were obtained from the Radiation Therapy Oncology Group database. Actuarial median survival from treatment was 14 months in the patients with fibrolamellar hepatoma and 7.7 months in the patients with hepatocellular carcinoma (p < 0.001). Karnofsky performance status and hepatic tumor volume at time of referral were important prognostic features. Multimodality treatment included radiation therapy and radiolabelled antibody, cisplatin-based chemotherapy, or both; results are discussed. Thirteen patients died, nine of liver failure, three of metastatic disease, and one of sepsis. Fibrolamellar histologic type, liver function tests, tumor volume, and patient performance status were significant predictors of survival. The cause of death in fibrolamellar hepatoma differs considerably from that observed in typical histologic hepatocellular carcinoma in the United States. The techniques of treatment of this uncommon disease were modeled after advances in the multimodality treatment of hepatocellular carcinoma and are discussed. Median survival was 14 months in patients with metastatic nonresectable fibrolamellar hepatoma.

Submucosal hemorrhage of the esophagus associated with endoscopy in a patient with cervical osteophytes.

Submucosal hemorrhage of the esophagus is an uncommon complication of endoscopy. It has a characteristic appearance and is most likely to occur in patients with cervical osteophytes. It is important to recognize the lesion so that unnecessary biopsies are not taken and other investigations are limited.

Dose escalation with 3D conformal treatment: five year outcomes, treatment optimization, and future directions.

PURPOSE: To report the 5-year outcomes of dose escalation with 3D conformal treatment (3DCRT) of prostate cancer. METHODS AND MATERIALS: Two hundred thirty-two consecutive patients were treated with 3DCRT alone between 6/89 and 10/92 with ICRU reporting point dose that increased from 63 to 79 Gy. The median follow-up was 60 months, and any patient free of clinical or biochemical evidence of disease was termed bNED. Biochemical failure was defined as prostate-specific antigen (PSA) rising on two consecutive recordings and exceeding 1.5 ng/ml. Morbidity was reported by the Radiation Therapy Oncology Group (RTOG) scale, the Late Effects Normal Tissue (LENT) scale, and a Fox Chase modification of the latter (FC-LENT). All patients were treated with a four-field technique with a 1 cm clinical target volume (CTV) to planning target volume (PTV) margin to the prostate or prostate boost; the CTV and gross tumor volume (GTV) were the same. Actuarial rates of outcome were calculated by Kaplan-Meier and cumulative incidence methods and compared using the log rank and Gray's test statistic, respectively. Cox regression models were used to establish prognostic factors predictive of the various measures of outcome. Five-year Kaplan-Meier bNED rates were utilized by dose group to estimate logit response models for bNED and late morbidity. RESULTS: PSA <10 ng/ml: No dose response was demonstrated using estimated bNED rates or by analysis of PSA nadir vs. dose. PSA 10-19.9 ng/ml: A bNED dose response was demonstrated (p = 0.02) using the log rank test. The logit response model showed 5-year bNED rates of 35% at 70 Gy and 75% at 76 Gy (p = 0.0049) and illustrated the relative ineffectiveness of conventional dose treatment. PSA 20+ ng/ml: A bNED dose response was demonstrated (p = 0.02) using the log rank test. The logit response model indicated a 5-year bNED rate of 10% at 70 Gy and 32% at 76 Gy (p = 0.10). Morbidity: Dose response was demonstrated for FC-LENT grade 2 and grade 3,4 GI morbidity and for LENT grade 2 GU sequelae. RTOG grade 3,4 GI morbidity at 5 years was <1%. Factors associated with bNED, cause-specific survival, and metastasis were studied using Cox multivariate analysis. Pretreatment PSA (p = 0.0001), Gleason score 7-10 (p = 0.0001), and dose (p = 0.017) were significantly predictive of bNED. For each 1 Gy increase in dose, the hazard of bNED failure decreased by 8%. Palpation stage was associated with cause-specific survival (p = 0.002) and distant metastasis (p = 0.0004). Gleason score was also predictive of distant metastasis (p = 0.02). CONCLUSIONS: A dose response was observed for patients with pretreatment PSA >10 ng/ml based on 5-year bNED results. No dose response was observed for patients with pretreatment PSA < 10 ng/ml. Dose response was observed for FC-LENT grade 2 and grade 3,4 GI sequelae and for LENT grade 2 GU sequelae. Optimization of treatment was made possible by the results in this report. The improvement in 5-year bNED rates for patients with PSA levels > 10 ng/ml strongly suggests that clinical trials employing radiation should investigate the use of 3DCRT and prostate doses of 76-80 Gy.

Population nutrient intake approaches dietary recommendations: 1991 to 1995 Framingham Nutrition Studies.

OBJECTIVE: To estimate population nutrient intake levels and to assess adherence to current dietary recommendations for health promotion and disease prevention. DESIGN: Cross-sectional analysis of nutrient intake estimated from 3-day food records. Median macronutrient and micronutrient intake levels for men, women, and the total population are reported along with the proportions of men and women who achieved intakes compatible with nutrient goals defined by published guidelines. SETTING: Adult participants (2,520: 1,375 women and 1,145 men) in the Framingham Offspring-Spouse Study surveyed between 1991 and 1995. STATISTICAL ANALYSES: chi 2 Analyses were used to test for gender differences in the proportions of persons who had intakes that met nutrient guidelines. RESULTS: Population intake levels of certain key nutrients, including total and saturated fat, appear to be approaching recommended levels. High proportions of the Framingham population (70% or more) met current recommendations for intakes of protein, polyunsaturated and monounsaturated fat, cholesterol, alcohol, vitamins C and B-12, and folacin. About half or fewer met guidelines for carbohydrate; total and saturated fat; fiber; beta carotene; vitamins A, E, and B-6; calcium; and sodium. Important gender differences in the proportion of those meeting nutrient guidelines were observed for 12 of the 18 nutrients examined, including carbohydrate; total, saturated, and monounsaturated fat; cholesterol; fiber; sodium; calcium; and several vitamins. CONCLUSIONS: Although progress has been made toward achieving population adherence to preventive nutrition recommendations, large proportions of adults fall short of guidelines for some key nutrients. Differences in adherence rates between men and women suggest areas for gender-specific, targeted nutrition messages and behavioral interventions.

Optimization of conformal radiation treatment of prostate cancer: report of a dose escalation study.

PURPOSE: The development of conformal radiation technique including improved patient immobilization has allowed us to test the value of dose escalation in optimizing the radiation treatment of prostate cancer. METHODS AND MATERIALS: Outcome is reported for 233 consecutive patients treated with conformal technique between March 1989 and October 1992. Dose was escalated from 68 Gy to 79 Gy. Patient status is reported at 3 years follow-up, which is available in all alive patients. Pretreatment and serial posttreatment prostate specific antigen (PSA) values are available for all patients. Biochemical freedom of disease (bNED) defines failure as PSA > 1.5 ngm/ml and rising on two consecutive measures. Dose response for bNED control of cancer and late morbidity are represented by logit response models fitted to the data. Kaplan-Meier methods, the log rank test, and Cox Regression models are also used. RESULTS: No dose response is observed for bNED survival for patients with pretreatment PSA <10 ngm/ml comparing patients treated above or below 71.5 Gy or on multivariate analysis. Dose response is observed for bNED survival for pretreatment PSA groups of 10-19.9 ngm/ml and 20+ ngm/ml. The dose associated with 50% bNED survival at 3 years is 64 Gy and 76 Gy, respectively. The slope of the dose responses are 13 and 9%, respectively. Dose response is demonstrated for Grade 2 gastrointestinal (GI), Grade 2 genitourinary (GU), and Grade 3,4 combined GI and GU late morbidity. The slopes of the morbidity responses are steeper than for cancer control (19 to 21%). CONCLUSIONS: Patients with pretreatment PSA < 10 ngm/ml do not benefit from dose escalation, and the serious late morbidity of conformal radiation at 70 Gy is < 3%. Patients with PSA values 10-19.9 ngm/ml and 20+ ngm/ml benefit from dose escalation beyond 70 Gy. Treatment beyond 75 Gy results in > 10% serious morbidity unless special precautions are taken to protect the rectal mucosa. All levels of severity of radiation morbidity show a dose response and combined with the dose response for bNED survival these data allow the optimization of treatment.

A pilot study of protracted low dose cisplatin and etoposide with concurrent thoracic radiotherapy in unresectable stage III nonsmall cell lung cancer.

PURPOSE: A Phase II study to evaluate the response rate and toxicity of daily protracted cisplatin and etoposide with concurrent chest irradiation in patients with locally advanced, unresectable nonsmall cell lung cancer (NSCLC). METHODS AND MATERIALS: Twenty-one patients with histologically confirmed locally advanced inoperable NSCLC (Stage IIIA or IIIB) were entered on study. Radiotherapy consisted of 50.4 Gy in 1.8 Gy fractions followed by a 10 Gy boost in 2 Gy fractions. Chemotherapy included the following: Cisplatin was given at 5 mg/m2 i.v. Monday-Friday before RT weeks 1-6. Etoposide was given at 25 mg/m2 i.v. M-F weeks 1, 2, 5, and 6, with 50 mg/m2 p.o. daily on the same weekends. Because of severe myelosuppression in the first two patients, etoposide only was subsequently changed to 20 mg/m2 i.v. M-F weeks 1, 2, 5, and 6. RESULTS: Twenty patients were eligible and evaluable. The overall response rate was 65% (95% confidence interval 41-85%). The median progression-free survival was 43 weeks. The median overall survival was 50.2 weeks with a 1-year survival rate of 45%. Five patients (25%) developed severe radiation pneumonitis, leading to early closure of the study. CONCLUSIONS: Combining daily protracted cisplatin and etoposide with concurrent thoracic irradiation in patients with locally advanced unresectable NSCLC yields a high overall response rate and a median survival that is at least comparable to other combined modality trials. However, future studies using protracted radiosensitizing chemotherapy should be approached cautiously in light of the high incidence of severe radiation pneumonitis encountered in this trial.