Therapeutic aims of drugs offering only progression-free survival are misunderstood by patients, and oncologists may be overly optimistic about likely benefits.

PURPOSE: The use of novel and often expensive drugs offering limited survival benefit in advanced disease is controversial. Treatment recommendations are influenced by patient characteristics and trial data showing overall response rates (ORR), progression-free survival (PFS) and overall survival (OS). PFS is frequently the primary outcome in licencing studies. PATIENTS AND METHODS: As part of a longitudinal study Assessing the 'VALue' to patients of PROgression Free Survival (AVALPROFS), oncologists completed checklists at baseline following consultations with patients. Questions probed perceived clinical benefits of the drugs to populations in general. Patients completed study-specific interview schedules at baseline, 6 weeks into treatment, and at withdrawal due to toxicity or progression. Patients also completed tumour- and treatment-specific quality of life questionnaires monthly for their time in the study. Only baseline results are reported here. RESULTS: Thirty-two UK oncologists discussed management options with 90 patients with heterogeneous advanced cancers. Oncologists' estimates of medical benefit in general from treatment varied between 10 and 80 %. They expected 46/90 (51 %) of their patients to derive some clinical benefit from the prescribed treatment but were either unsure or expected none for 44/90 (49 %). Predictions of life expectancy were variable but 62 % (56/90) of patients were expected to survive longer with treatment. A majority of patients 51/90 (57 %) had 'no idea' or were 'unclear' what PFS meant and 45/90 (50 %) thought extension of life was the primary therapeutic aim of treatment. CONCLUSION: Discussions between doctors and patients with metastatic disease about future management plans and likely therapeutic gains are challenging. Factors influencing decisions about putative benefits of novel drugs are often applied inconsistently can be overly optimistic and may even contradict published data.

Effects of deep and superficial heating in the management of frozen shoulder.

OBJECTIVES: To determine whether the addition of deep or superficial heating to stretching produces better clinical outcomes than stretching alone in the management of frozen shoulder. DESIGN: A single-blinded, randomized controlled study. SUBJECTS: Thirty subjects suffering from the stiffness phase of frozen shoulder. METHODS: Subjects were randomly allocated to receive: (i) deep heating plus stretching; (ii) superficial heating plus stretching; or (iii) stretching alone. Both heating groups received the respective treatments 3 times per week for 4 weeks. All groups received a standard set of shoulder stretching exercises. The American Shoulder and Elbow Surgeons assessment form was recorded at the baseline, sessions 6 and 12, and at the 4-week follow-up session. RESULTS: A significant improvement was seen in all groups in all outcome measures except for that of shoulder flexion range. The improvement in the shoulder score index and in the range of motion was significantly better in the deep heating group than in the superficial heating group. CONCLUSION: The addition of deep heating to stretching exercises produced a greater improvement in pain relief, and resulted in better performance in the activities of daily living and in range of motion than did superficial heating.

Effect of periconceptional undernutrition and gender on hypothalamic-pituitary-adrenal axis function in young adult sheep.

Glucocorticoids are proposed to act as intermediary factors that transcribe the developmental programming sequelae of maternal nutrient restriction (NR). Periconceptional under-nutrition of sheep markedly activates fetal hypothalamic-pituitary-adrenal (HPA) axis activity leading to preterm birth, while transient undernutrition during late gestation in sheep programs adult HPA axis function. To date, no study has examined resting or stimulated HPA axis function in young adult offspring following a periconceptional nutritional challenge. In the present study, 20 ewes were either periconceptionally undernourished (50% metabolisable energy requirements from days 1 to 30 gestation; NR, n = 8) or fed to control levels (100% requirement; controls, n = 12) to term (147 days gestation). Ewes were blood sampled remotely at 2 and 30 days using automated blood sampling equipment. Thereafter, offspring (controls, n = 6/6 males/females; NR, n = 4/4 males/females) were reared to 1 year of age and on separate days received either an i.v. corticotrophin-releasing hormone (CRH; 0.5 microg/kg) and vasopressin (AVP; 0.1 microg/kg) challenge or a synthetic ACTH i.v. bolus (Synacthen; 1.25 microg/kg), and blood samples were taken (manually and remotely) at appropriate intervals for measurement of plasma ACTH and cortisol accordingly. Resting plasma cortisol, assessed remotely, was similar in ewes during undernutrition (control 18.3 +/- 1.4 vs NR 23.4 +/- 1.9 nmol/l) and in offspring at 4 months of age (control male 17.6 +/- 2.9; control female 17.2 +/- 0.4, NR male 16.5 +/- 3.1, NR female 21.7 +/- 4.0 nmol/l). At 12 months of age, however, resting plasma cortisol was significantly increased in NR females (control male 28.0 +/- 1.5, control female 32.9 +/- 9, NR male 32 +/- 7, NR female 53 +/- 10 nmol/l, F 5.7, P = 0.02) despite no difference in plasma ACTH concentration. There was an interaction between nutritional group and gender for both the pituitary and adrenal responses to CRH and AVP, i.e. for controls, females exhibited increased plasma ACTH or cortisol relative to males but for NR this trend was either not present or reversed. The adrenocortical response to synthetic ACTH was gender-dependent only, being greater in female offspring. Combined CRH and AVP provoked a transient hypertension and marked bradycardia in all animals, irrespective of dietary group or gender and could be effectively reproduced by an AVP bolus alone. In conclusion, the present study has shown that periconceptional undernutrition of sheep has only a minor influence on HPA axis function in their young adult offspring when considered alongside the effect of gender per se.