Vitamin D status and associated genetic polymorphisms in a cohort of UK children with non-alcoholic fatty liver disease.

BACKGROUND: Vitamin D deficiency has been associated with non-alcoholic fatty liver disease (NAFLD). However, the role of polymorphisms determining vitamin D status remains unknown. OBJECTIVES: The objectives of this study were to determine in UK children with biopsy-proven NAFLD (i) their vitamin D status throughout a 12-month period and (ii) interactions between key vitamin D-related genetic variants (nicotinamide adenine dinucleotide synthase-1/dehydrocholesterol reductase-7, vitamin D receptor, group-specific component, CYP2R1) and disease severity. METHODS: In 103 paediatric patients with NAFLD, serum 25-hydroxyvitamin D (25OHD) levels and genotypes were determined contemporaneously to liver biopsy and examined in relation to NAFLD activity score and fibrosis stage. RESULTS: Only 19.2% of children had adequate vitamin D status; most had mean 25OHD levels considered deficient (<25 nmol·L-1 , 25.5%) or insufficient (<50 nmol·L-1 , 55.3%). Patients had significantly lower 25OHD levels in winter months (95% CI: 22.7-31.2 nmol·L-1 ) when compared with spring (30.5-42.1 nmol·L-1 ; P = 0.0089), summer (36.3-47.2 nmol·L-1 ; P < 0.0001) and autumn (34.2-47.5 nmol·L-1 ; P = 0.0003). Polymorphisms in the nicotinamide adenine dinucleotide synthase-1/dehydrocholesterol reductase-7 (rs3829251, rs12785878) and vitamin D receptor (rs2228570) genes were independently associated with increased steatosis; while a group-specific component variant (rs4588) was associated with increased inflammation in liver biopsies. CONCLUSIONS: Children with NAFLD in the UK have particularly low winter vitamin D status, with vitamin D insufficiency prevalent throughout the year. Polymorphisms in the vitamin D metabolic pathway are associated with histological severity of paediatric NAFLD.

Weight-adjusted dosing of tinzaparin in pregnancy.

BACKGROUND: Low molecular weight heparin (LMWH) is the preferred anticoagulant for the prevention and treatment of VTE in pregnancy. While dosing of LMWH based on weight alone is standard for most non-pregnant patients, there is no data on the utility of this approach in pregnancy. OBJECTIVES: To determine whether dosing of tinzaparin by current maternal weight, with adjustment for increasing weight, will achieve adequate levels of anticoagulation throughout pregnancy (target peak anti-Factor-Xa activity levels between 0.5-1.2IU/ml). PATIENTS/METHODS: Consecutive pregnant women with acute VTE or requiring high-risk thromboprophylaxis (recurrent VTE, on long-term anticoagulation) at a single centre were approached for enrollment. Subjects were weighed and prescribed tinzaparin 175IU/kg SC once daily and a peak anti-Factor-Xa level was determined. Re-dosing and monitoring was repeated monthly, and subjects were withdrawn from weight-based dosing if consecutive anti-Factor-Xa levels were outside the target range. Subsequent dosing of tinzaparin was titrated to achieve a level in the target range in these women. RESULTS: Thirteen subjects were recruited between January 2008 and May 2010, with one drop out lost to follow-up. Weight-based dosing failed to maintain therapeutic anticoagulation in 11 (92%) of women (95% CI 0.2% to 38.5%). The estimated dose requirement of tinzaparin per trimester increased from 14255IU in the first trimester to 16533IU in the second trimester to 17828IU in the third trimester (p<0.001). The estimated dose/kg required to maintain therapeutic anticoagulation increased across trimesters: 188.0IU/kg in the first trimester, 201.3IU/kg in the second trimester, and 208.6IU/kg in the third trimester (p=0.004). Treatment was well tolerated and no serious bleeding or recurrent thrombotic events occurred. CONCLUSIONS: Weight-based dosing of tinzaparin failed to achieve therapeutic anticoagulation in the vast majority of women, although clinical outcomes were good. Doses of tinzaparin in excess of the manufacturer's recommended weight-based dose were required to maintain therapeutic levels of anticoagulation.

A longitudinal study of pain in hospice and pre-hospice patients.

Pain continues to be a very formidable foe in the care of the hospice patient. The incidence among hospice admissions may range from 50 to 80 percent. With such a high initial incidence of pain, the rapidity with which pain can be controlled becomes a very high priority for the hospice effort. The assessment and management of pain in a home-based hospice program presents some unique problems--and opportunities, in that much of this work is done by hospice nurses on site, rather than by the physician, who might remain quite removed from the process. In the study described below, 250 consecutive admissions to either a hospice, or pre-hospice (bridge) program were assessed for pain on admission. Those with pain scores of 5 or greater (on a 1 to 10 scale) were followed daily for 15 days by phone to reassess pain and treatment effects. Of the 250 consecutive patients surveyed, 41 (16 percent) gave pain scores of 5 or greater. Mean pain scores for the 41 patients dropped to < 5 within 24 hours of admission.

Drugs in pregnancy. Anticoagulants.

Pregnancy is a period of heightened coagulability and enhanced risk for thrombotic complications. Thromboembolism is the leading cause of maternal mortality. Anticoagulants are very useful during pregnancy for the acute treatment of venous thromboembolism and for the prevention of recurrent venous thromboembolism. They may also be beneficial in patients with thrombophilias, particularly among women who have experienced adverse pregnancy outcomes such as recurrent pregnancy loss. Anticoagulation is essential but problematic in the management of pregnant women with mechanical heart valve prostheses. When utilizing these medications among pregnant women the potential benefits must be balanced against the possibility of maternal haemorrhagic complications, adverse effects on the pregnancy or toxic effects on the fetus. This chapter summarizes current knowledge about the anticoagulant agents, their potential toxicities and their therapeutic role in pregnant women with various indications for anticoagulant therapy.