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US expert panel reaffirms benefit of perinatal zidovudine
THE LANCET
SCIENCE AND MEDICINE
US expert panel reaffirms benefit of perinatal zidovudine and female genital-tract tumours the predominant derivative and than the offspring of untreated mice. zidovudine triphosphate is less than The effect on lung and liver was eval1% of the drug. In murine cells, the uated as “moderate”. The female triphosphate is the predominant form. Mice excrete zidovudine genital cancers were more unusual, largely unchanged and similar to some of but human beings the tumours seen in excrete mainly the daughters of mice glucuronide. In addigiven diethylstilbestion, mice generate trol during pregnancy. much more of the Anderson and highly toxic 3' amino Poirier’s results derivative than do differ from results human beings (Jeanobtained previously Pierre Sommadossi, by Glaxo-Wellcome. Birmingham, USA). These showed that Consequently, the although zidovudine Continue with zidovudine panel agreed that the given early in pregcancer risk for children exposed to nancy was embryotoxic in rats, when zidovudine perinatally remains given later, at dose rates designed to hypothetical while the reduction of yield peak concentrations up to three risk of HIV-1 infection has been well times the human dose rates, the main proven (see Lancet Nov 30, p 1503). side-effect was anaemia. TransThe panel suggested continued placental carcinogenicity was not seen. monitoring of the involved children. So far, no tumours have been Anderson concurred with the panel’s found in children whose mothers view, saying, “whatever cancer risk received perinatal zidovudine, and there is, it is certainly not as great as the predictive value of the mouse the risk of HIV. Zidovudine treatmodel is uncertain owing to the many ment is still the way to go”. differences in human and murine zidovudine metabolism. In human cells, zidovudine monophosphate is Paul M Rowe Science Photo Library
n Jan 14 a panel of experts met at the US National Institutes of Health, Bethesda, to consider the implications of the findings from a study in which zidovudine administered to pregnant mice induced lung, liver, skin, and genital-tract cancers in their offspring. The panel said that HIV-1-positive pregnant women should be informed of these results before deciding whether to use zidovudine to decrease the risk of vertical viral transmission. But the panel also concluded that the overall risk–benefit calculation had not changed. They said the recommendation that HIV-1-positive women take zidovudine during pregnancy should remain in place. Lucy Anderson (Frederick, USA) and Miriam Poirier (Bethesda, USA) of the US National Cancer Institute gave mice in the second half of gestation doses of zidovudine such that the total accumulated dose per kg was similar to the total dose some women receive during pregnancy. The individual daily doses given to the mice were, however, substantially higher than those given to women. The offspring had a significantly higher incidence of liver, lung, skin,
O
Many patients in US hospitals die in pain wanted treatment that focused on any patients who die in hospital comfort, 10% of these patients are in severe physical and received care contrary to this emotional pain during the final days preference. One in four patients was of their life, report US researchers. on a ventilator, four in ten had a Information about the last days of feeding tube, and one in ten under3357 seriously ill and elderly patients went a resuscitation attempt. was gathered by reviewing medical In an interview, records and interlead author of the viewing the patients’ study, Joanne Lynn surrogate decision(George Washington makers. Of these University Medical patients, more than Center, Washington, half died in hospital DC) said the and the surrogates findings show that reported that 55% the US health-care of these patients system has a long were conscious durway to go to improve ing their last 3 days. its care of people 80% of these con- Pain-relief and comfort needed near death. It was scious patients were particularly worrisome, she said, reported to have fatigue; 40% severe that two-thirds of families had the pain; more than 50% severe dyspimpression that the patients suffered noea; and 25% severe confusion “intolerable” symptoms at the end. (Ann Intern Med 1997; 126: 97–106). “If you want a reason for why Anxiety and depression were the public is looking to suicide, there common and 17% of family members you go.” reported that patients felt “alone and isolated in the last days of life”. Although 59% of patients had Michael McCarthy Photofusion
M
258
Single-shot treatment for acute otitis media?
A
trial of 596 children aged 3 months to 3 years with acute otitis media has shown that a single intramuscular injection of ceftriaxone was as effective as 10 days of oral trimethoprim-sulfamethoxazole (TMP-SMZ). At day 14, 80·2% of the ceftriaxone group and 82·1% of the TMP-SMZ group were cured. In Pediatrics (1997; 99: 23–28), the researchers claim that the injectable treatment increases compliance, decreases cost, and reduces opportunities for resistant organisms. They also acknowledge that defining the disease and the spontaneous resolution rate in other trials made results difficult to interpret. Peter Marshall, (Reading, UK) was uncertain whether parents would put their child through the trauma of an injection for a selflimiting illness. He also noted that because of its potentially harmful side-effects, SMZ is not recommended for routine use in the UK. Pete Moore
Vol 349 • January 25, 1997
SCIENCE AND MEDICINE
US expert panel reaffirms benefit of perinatal zidovudine and female genital-tract tumours the predominant derivative and than the offspring of untreated mice. zidovudine triphosphate is less than The effect on lung and liver was eval1% of the drug. In murine cells, the uated as “moderate”. The female triphosphate is the predominant form. Mice excrete zidovudine genital cancers were more unusual, largely unchanged and similar to some of but human beings the tumours seen in excrete mainly the daughters of mice glucuronide. In addigiven diethylstilbestion, mice generate trol during pregnancy. much more of the Anderson and highly toxic 3' amino Poirier’s results derivative than do differ from results human beings (Jeanobtained previously Pierre Sommadossi, by Glaxo-Wellcome. Birmingham, USA). These showed that Consequently, the although zidovudine Continue with zidovudine panel agreed that the given early in pregcancer risk for children exposed to nancy was embryotoxic in rats, when zidovudine perinatally remains given later, at dose rates designed to hypothetical while the reduction of yield peak concentrations up to three risk of HIV-1 infection has been well times the human dose rates, the main proven (see Lancet Nov 30, p 1503). side-effect was anaemia. TransThe panel suggested continued placental carcinogenicity was not seen. monitoring of the involved children. So far, no tumours have been Anderson concurred with the panel’s found in children whose mothers view, saying, “whatever cancer risk received perinatal zidovudine, and there is, it is certainly not as great as the predictive value of the mouse the risk of HIV. Zidovudine treatmodel is uncertain owing to the many ment is still the way to go”. differences in human and murine zidovudine metabolism. In human cells, zidovudine monophosphate is Paul M Rowe Science Photo Library
n Jan 14 a panel of experts met at the US National Institutes of Health, Bethesda, to consider the implications of the findings from a study in which zidovudine administered to pregnant mice induced lung, liver, skin, and genital-tract cancers in their offspring. The panel said that HIV-1-positive pregnant women should be informed of these results before deciding whether to use zidovudine to decrease the risk of vertical viral transmission. But the panel also concluded that the overall risk–benefit calculation had not changed. They said the recommendation that HIV-1-positive women take zidovudine during pregnancy should remain in place. Lucy Anderson (Frederick, USA) and Miriam Poirier (Bethesda, USA) of the US National Cancer Institute gave mice in the second half of gestation doses of zidovudine such that the total accumulated dose per kg was similar to the total dose some women receive during pregnancy. The individual daily doses given to the mice were, however, substantially higher than those given to women. The offspring had a significantly higher incidence of liver, lung, skin,
O
Many patients in US hospitals die in pain wanted treatment that focused on any patients who die in hospital comfort, 10% of these patients are in severe physical and received care contrary to this emotional pain during the final days preference. One in four patients was of their life, report US researchers. on a ventilator, four in ten had a Information about the last days of feeding tube, and one in ten under3357 seriously ill and elderly patients went a resuscitation attempt. was gathered by reviewing medical In an interview, records and interlead author of the viewing the patients’ study, Joanne Lynn surrogate decision(George Washington makers. Of these University Medical patients, more than Center, Washington, half died in hospital DC) said the and the surrogates findings show that reported that 55% the US health-care of these patients system has a long were conscious durway to go to improve ing their last 3 days. its care of people 80% of these con- Pain-relief and comfort needed near death. It was scious patients were particularly worrisome, she said, reported to have fatigue; 40% severe that two-thirds of families had the pain; more than 50% severe dyspimpression that the patients suffered noea; and 25% severe confusion “intolerable” symptoms at the end. (Ann Intern Med 1997; 126: 97–106). “If you want a reason for why Anxiety and depression were the public is looking to suicide, there common and 17% of family members you go.” reported that patients felt “alone and isolated in the last days of life”. Although 59% of patients had Michael McCarthy Photofusion
M
258
Single-shot treatment for acute otitis media?
A
trial of 596 children aged 3 months to 3 years with acute otitis media has shown that a single intramuscular injection of ceftriaxone was as effective as 10 days of oral trimethoprim-sulfamethoxazole (TMP-SMZ). At day 14, 80·2% of the ceftriaxone group and 82·1% of the TMP-SMZ group were cured. In Pediatrics (1997; 99: 23–28), the researchers claim that the injectable treatment increases compliance, decreases cost, and reduces opportunities for resistant organisms. They also acknowledge that defining the disease and the spontaneous resolution rate in other trials made results difficult to interpret. Peter Marshall, (Reading, UK) was uncertain whether parents would put their child through the trauma of an injection for a selflimiting illness. He also noted that because of its potentially harmful side-effects, SMZ is not recommended for routine use in the UK. Pete Moore
Vol 349 • January 25, 1997