Surveillance for brain metastases in patients receiving systemic therapy for advanced melanoma.

The objectives of this study were to determine the cumulative incidence and timing of new brain metastases over the course of systemic therapy for metastatic melanoma and to identify prognostic factors for brain metastases. Chemo-naive patients underwent computed tomography or MRI of the brain every 6 weeks. The cumulative incidence of confirmed brain metastases was calculated at 12-week intervals. Univariable and multivariable competing risk regression models were used to assess the association between the development of brain metastases and potential risk factors of interest. Cumulative incidence with competing risk and competing risk regression was used to assess the brain metastasis-free interval from the time of diagnosis of stage IV disease. The clinical characteristics of the 315 patients with brain metastases were compared with those of 370 brain metastasis-free patients. Among patients with brain metastases, a significantly higher proportion had stage M1b and M1c disease at diagnosis compared with stage M1a and a greater proportion had metastatic disease in three or more visceral sites. Significantly shorter brain metastasis-free intervals were found in these patients compared with patients with M1a disease and those with no visceral metastases. More than 80% of the 230 patients who developed brain metastases during systemic therapy had their brain metastases confirmed within 60 weeks from the onset of advanced melanoma. Imaging studies at 12-week intervals for 60 weeks after the diagnosis of advanced melanoma will detect brain metastases in most of the patients who will eventually develop them.

Risk of intracranial hemorrhage with anticoagulation therapy in melanoma patients with brain metastases.

Venous thromboembolism (VTE) is a frequent complication in melanoma patients with brain metastases (BM). The management of these patients is challenging because of the high risk of intracranial hemorrhage (ICH) and the limited data available on the safety of anticoagulation in this scenario. We reviewed the treatments and outcomes among melanoma patients with BM and VTE at our institution to determine the safety of anticoagulation in these patients. A retrospective chart review was performed to identify melanoma patients with BM who were diagnosed with VTE. The clinical characteristics of the BM and the VTE, the treatments given for VTE, subsequent ICH, and overall survival (OS) were determined. The characteristics and outcomes were compared between patients who received systemic anticoagulation and those who did not. A total of 74 evaluable melanoma patients with BM and VTE were identified. Fifty-seven (77%) patients received systemic anticoagulation. There was no significant difference in the number (P=0.40) or the maximum diameter (P=0.55) of brain metastasis between the patients who received anticoagulation and those who did not. Two (4%) patients who received anticoagulation developed ICH, which was not statistically different from the patients who did not receive anticoagulation (0%, P=1.00). There was a trend toward longer OS from VTE among patients who received systemic anticoagulation (median OS: 4.2 vs. 1.2 months, P=0.06). Anticoagulation for VTE did not significantly increase the risk of ICH or decrease OS in patients with melanoma BM. These data support the safety of systemic anticoagulation for VTE in these patients.

Comparison of two dosing schedules of palonosetron for the prevention of nausea and vomiting due to interleukin-2-based biochemotherapy.

BACKGROUND: Treatment of metastatic melanoma with interleukin-2-based biochemotherapy involves administration of a combination of moderately and highly emetogenic chemotherapies over 5 days. Corticosteroids for the prevention of biochemotherapy-induced nausea and vomiting (CINV) are contraindicated because they cause lysis of LAK cells produced in response to interleukin-2. Palonosetron is a long-acting, highly potent, second-generation serotonin receptor antagonist. The recommended dosing schedule of palonosetron for the control of CINV due to biochemotherapy is not known. METHODS: In a phase II design, treatment-naïve patients with metastatic melanoma undergoing the first cycle of biochemotherapy were randomized to receive palonosetron 0.25 mg intravenously for CINV prophylaxis on either days 1 and 4 (schedule 1) or days 1, 3, and 5 (schedule 2). All patients received dacarbazine on day 1, cisplatin, vinblastine, and interleukin-2 on days 1-4, and interferon alpha-2b on days 1-5. We evaluated and compared, by palonosetron dosing schedule, the pattern and the severity of CINV during the first 7 days of treatment and the duration of the 21-day cycle as well as the impact on daily function with the Functional Living Index-Emesis. RESULTS: Thirty patients (median age 53 years) were enrolled. Eighteen (60%) were men. A consistent trend of a better control of both nausea and vomiting favoring schedule 2 was observed during the first 7 days and throughout the cycle. Significantly more patients experienced nausea on any day during the first 7 days on schedule 1 (mean number of episodes 8.1 ± 1.5) than on schedule 2 (mean number of episodes 5.6 ± 2.3, p = 0.028). The impact on daily function was similar between the two groups. CONCLUSIONS: Both dosing schedules of palonosetron were tolerated well. Alternate day dosing of palonosetron was more effective in controlling CINV in this patient population.

Cirrhosis in Werner's syndrome: an unusual presentation of premature aging.

BACKGROUND: Werner's syndrome (WS) is an rare autosomal recessive, hereditary systemic disease with progeroid features, usually presenting in adolescence. It is associated with increased genetic instability and elevated risk of neoplasia. Clinical manifestations include sinall stature, scleroderma-like changes in the skin,juvenile cataracts, and premature aging. It has been reported mostly in ophthalmological, dermatological, and orthopedics literature. It is now being correctly acknowledged as a condition where a lack of Werner's protein (WRN protein) results in an overall decline of normal physiological functions of various organ systems. Cirrhosis is an extremely rare manifestation of Werner's syndrome and has been reported in <4% of patients. CASE REPORT: A case of cirrhosis in a patient with Werner's syndrome is described. A 25-year-old male presented with features of p remature senility and progressive abdominal distension with black tarry stools of over six months duration. His clinical presentation and work-up including a biopsy were consistent with cirrhosis. The work-up for other causes of chronic liver disease was negative. He was medically managed for portal hypertension. Despite maximal medical therapy, he (tied due to recurrent episodes of hematemesis. CONCLUSIONS: This case is not only the first documented case of Werner's from Pakistan, but describes an unusual presentation: cirrhosis, a very rare complication of WS. O verproduction of types I and III collagen and nonalcoholic steatohepatitis secondary to insulin resistance and dyslipidemia possibly contribute to cirrhosis in WS.

Womens' beliefs and practices regarding food restrictions during pregnancy and lactation: a hospital based study.

BACKGROUND: Maternal diet is an important determinant of outcomes of pregnancy. Malnutrition during pregnancy and its consequences maximally affect the health and long-term outcomes of the population. Low birth weight accounts for almost 30% of all births; with maternal malnutrition as a dominant risk factor. This study aims to investigate the existing beliefs and practices regarding food restrictions during pregnancy and lactation and also to assess whether there is any relationship with education level of the respondent and their beliefs and practices. METHODS: A cross-sectional survey was conducted at Community Health Center (CHC) of The Aga Khan University Hospital, Karachi from July-September 2000. Four hundred adult female respondents, who came to the outpatient services as a patient or as an attendant, were interviewed after taking verbal consent. A self administered pre-coded and pre-tested questionnaire was filled by the respondent. RESULTS: More than three fourths of respondents were literate. Twelve percent believed in restricting some food item during pregnancy and about 25% believed the same during lactation. No statistically significant association was found between belief about food restriction during pregnancy or during lactation and education level of the respondent. CONCLUSION: Undue food restrictions during pregnancy and lactation do exist in our culture. To assess the true picture we need to conduct larger studies in the community. The information obtained from the studies will help us in addressing these issues for improvement of nutritional knowledge and dietary practices and to avoid undue food restrictions.

Women s perception about food properties in a tertiary care hospital.

OBJECTIVE: To understand the existing food beliefs regarding hot, cold and badi (gas-producing) properties of different food items and also to assess whether there is any relationship with education of women and these beliefs. DESIGN: A cross-sectional study. PLACE AND DURATION OF STUDY: Community Health Center (CHC), The Aga Khan University Hospital, Karachi from July to September 2000. SUBJECTS AND METHODS: Four hundred adult female respondents, who came to CHC as a patient or as an attendant, were interviewed after taking verbal consent. A self-administered pre-coded and pre-tested questionnaire was filled by the respondent. Descriptive frequencies and cross tabulation were computed to assess the existing food beliefs. Chi-square test was used to assess the association between education level of women and belief regarding these food items. RESULTS: More than three-fourth of respondents were literate. The percentages of respondents saying that certain foods were hot, cold and badi were 71%, 55% and 80% respectively. Meat, either beef or mutton, fish, egg, chicken, was perceived as hot by majority of the respondents. Majority of vegetables was perceived as cold foods in our study. The other foods like rice, yogurt, banana, watermelon, milk and cold drink were also thought to be cold by many of the respondents. Cabbage, cauliflower, potato, rice, gram and mash pulses (chane and mash-ki-dal) were highly rated as badi foods. Level of education of women didn t show any statistically significant difference in keeping beliefs regarding hot, cold and badi properties of food items. CONCLUSION: A significant concept of different properties of food exists in our culture. We recommend future studies to explore scientific basis for classifying hot, cold or badi foods and also to look into its impact on health by their restriction based on their beliefs.

Women's beliefs regarding food restrictions during common childhood illnesses: a hospital based study.

BACKGROUND: Malnutrition continues to be a major problem in Pakistan. Inadequate nutrition contributes substantially to childhood death and disease. Restriction of diet during common childhood illnesses further compromises the nutritional status of the child. The present study aims to determine the beliefs and practices regarding food restrictions during common childhood illnesses. METHODS: A cross-sectional survey was conducted at Community Health Centre (CHC), of The Aga Khan University Hospital, Karachi to understand the beliefs and practices regarding food restrictions in common childhood illnesses. Four hundred adult females were interviewed from July-September 2000. A self-administered questionnaire was filled by the respondent. RESULTS: Major sources of information about restriction of various foods during different illnesses were relatives. Sixty five percent of the respondents believed that heavy food should be restricted during diarrhoea and oily food during jaundice. Sixty six percent of the respondents believed that cold food should be restricted during cold/cough and twenty three percent believed that oily food should be restricted during typhoid. CONCLUSION: Beliefs' regarding food restrictions during illnesses plays a very important role on the nutrition status. Surprisingly, medical doctors and other health care givers were also the source of information for advising food restrictions in certain childhood illnesses. Therefore there is a need for educating the physicians and other health care workers along with the mothers about food concepts and feeding practices during health and diseases. Protein energy malnutrition can be reduced to some extent if wrong dietary beliefs about child feeding practices in a community can be removed with health education programme.