An audit of US FDA warning letters issued to sponsors, institutional review boards and investigators over a six-year period.

The present audit was carried out with the objective of evaluating warning letters (WLs) issued to trial sponsors, clinical investigators and institutional review boards (IRBs) by the United States Food and Drug Administration during a six-year period and compare it with two similar earlier audits. WLs were reviewed and classified as per stakeholders and further categorised as per predefined violation themes. The chi-square test was performed for trend analysis of WLs. A total of 62 WLs were issued to the three stakeholders. The maximum number of WLs were issued to the clinical investigators (36/62, 58.06%), followed by sponsors (19/62, 30.64%), and least to the IRBs (7/62, 11.29%). Among sponsors, lack of standard operating procedures for the monitoring, receipt, evaluation and reporting of post-marketing adverse drug events was the most common violation theme (8/19, 42.1%). Among clinical investigators, deviation from investigational plan was the most common violation theme (31/36, 86.11%.). For IRBs, inadequate documentation was the most common violation theme (6/7, 85.71%). We saw an overall reduction in the number of WLs issued to the stakeholders. Thus, we identified multiple areas on which each stakeholder should work for improvement.

Hypertensive disorders of pregnancy and maternal and foetal outcome: a case controlled study.

A case controlled prospective study of 250 cases of hypertension complicating pregnancy (study group) and 400 normal pregnant women (control group) was carried out to determine the effect of hypertension on maternal and foetal outcome. Pregnancy induced hypertension was present in 96% cases and chronic hypertension in 4% cases. Preterm delivery (28.8% versus 3%), labour induction rate (52.8% versus 3.25%), caesarean section rate (14.8% versus 3.5%), stillbirth rate (4.8% versus 0.25%) and overall perinatal mortality rate (14.8% versus 1%) were higher in study group compared to controls. In study group (40%) babies required special nursery care compared to controls (6.75%). From these results it can be concluded that maternal hypertension is associated with adverse pregnancy outcome.

Clinical, histopathologic & immunologic features of cutaneous lesions in acute meningococcaemia.

Fifty children with culture proven acute meningococcaemia were studied during the winter outbreak of the disease in 1986-87. Purpuric lesions were seen in 60 per cent, erythematous papules in 32 per cent, faint pink macules in 28 per cent, conjunctival petechiae in 10 per cent and herpes labialis in 20 per cent. Histopathology of skin lesions showed that the primary damage was to the dermal vessels, the extent of damage depending on the type of skin involvement. Diplococci in Gram's stained sections were seen frequently in purpuric as compared to the other skin lesions. They were located in degenerating neutrophils, endothelial cells, fibrin clots or freely in the vascular lumen. Electron microscopic study showed vascular changes accompanied by a perivascular phagocytic response. Both light and electronmicroscopy indicated the involvement of the coagulative mechanism in the pathogenesis of meningococcaemia. However, clinical parameters of clotting were often within normal limits. In the case of a child (who died eventually), a low platelet count and prolonged coagulation indices were observed. Sera from some of the children were tested for the presence of antibodies against meningococci by indirect immunofluorescence. Antibodies were detected in the sera and they may have a role in regulating the severity and course of the illness. The significance of immunoglobulin deposits in the skin lesions is not clear.