- Email: [email protected]
Long-term outcome of Q fever endocarditis
Correspondence
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Goodman LB, Loregian A, Perkins GA, et al. A point mutation in a herpesvirus polymerase determines neuropathogenicity. PLoS Pathog 2007; 3: 1583–92. Skoldenberg B, Alestig K, Burman L, et al. Acyclovir versus vidarabine in herpes simplex encephalitis. Randomised multicentre study in consecutive Swedish patients. Lancet 1984; 324: 707–11. Gulliford MC, Chandrasekera CP, Cooper RA, Murphy RP. Acyclovir treatment of herpes simplex encephalitis: experience in a district hospital. Postgrad Med J 1987; 63: 1037–41. Kimberlin DW. Herpes simplex virus infections in neonates and early childhood. Semin Pediatr Infect Dis 2005; 16: 271–81.
An addition to the effect of treating co-infections on HIV-1 viral load After publication of our Review,1 we were informed of an omission by the authors of a study2 that met our systematic review’s inclusion criteria but was not identified by our search strategy. Using a crossover design, the investigators primarily assessed the effect of herpes simplex virus (HSV) 2 suppression on cervicovaginal HIV-1 shedding in women co-infected with HIV and HSV2. The effect on plasma HIV viral load was also measured, but as a secondary outcome. Dunne and colleagues2 reported that, among 67 women aged 18–49 years who had baseline CD4 cell counts of over 200 cells per μL, the mean plasma HIV viral load during aciclovir suppression (3·78 log10 copies per mL) was significantly lower than during placebo administration (4·26 log10 copies per mL; p<0·001). This reduction in HIV plasma viral load by 0·48 log10 copies per mL with acyclovir suppression among women co-infected with HIV and HSV is consistent with findings of other studies cited in our systematic review. We thank Dunne and colleagues for alerting us to their original and relevant work. www.thelancet.com/infection Vol 11 February 2011
We declare that we have no conflicts of interest.
Kayvon Modjarrad, Sten H Vermund [email protected] Department of Medicine (KM), Department of Pediatrics (SHV), and Institute for Global Health (KM, SHV), Vanderbilt University School of Medicine, Nashville, TN, USA 1
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Modjarrad K, Vermund SH. Effect of treating co-infections on HIV-1 viral load: a systematic review. Lancet Infect Dis 2010; 10: 455–63. Dunne EF, Whitehead S, Sternberg M, et al. Suppressive acyclovir therapy reduces HIV cervicovaginal shedding in HIV- and HSV-2-infected women, Chiang Rai, Thailand. J Acquir Immune Defic Syndr 2008; 49: 77–83.
Long-term outcome of Q fever endocarditis We read with interest Matthieu Million and colleagues’ study1 of the longterm outcome of Q fever endocarditis. In a survival analysis, eligible patients should not be excluded because of loss to follow-up or death from other causes, but should be analysed up to the time of events and then censored. However, figure 1 uses the word excluded at various timepoints after enrolment into the study. The mortality probabilities at different timepoints would be underestimated because they were calculated from only patients who survived up to those timepoints, and censored patients were ignored. Mortality probabilities should be based on the Kaplan-Meier estimators as described in the Methods. Because failure outcomes were identical in both groups, figures 4 and 5 present predicted plots from the fitted models rather than KaplanMeier plots (each drop on the line represents each failure outcome). If the fitted models were multivariable, presentation of the values that were selected for the other variables is required (eg, female sex, median age of 53 years). Furthermore, we would be interested to know how missing values were addressed; figure 5 was based on only 87 patients (rather than all 104 patients) and bias could arise in
multivariable models that were based on a subset of the data. The recommendations that optimum duration of treatment for native valves be 18 months were derived from the Cox model for serological relapse. The model analysed only patients who were living, and ignored those who died of Q-fever endocarditis and other causes; however, excluding these cases could cause selection bias. The total of six failure outcomes included in this analysis is very low. Additionally, the variable doxycycline treatment duration of less than 18 months is a time-dependent variable2,3 that can be directly included in the model only if follow-up time started at 18 months or later; however, in one report, first serological relapse occurred at 15 months. If the time at risk of serological relapse were different for each patient, and started after the patient had serological cure, this should be stated. Although treatment of less than 18 months is associated with failures, how many patients were treated for longer than 18 months is unclear, as is whether treatment for longer than 18 months is associated with any benefit. We declare that we have no conflicts of interest.
*Direk Limmathurotsakul, Ben Cooper, Sharon J Peacock, Bianca De Stavola [email protected] Department of Tropical Hygiene (DL), Mahidol-Oxford Tropical Medicine Research Unit (DL, BC, SJP), and Department of Microbiology and Immunology (SJP), Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand; Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK (BC); and Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK (BDS) 1
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Million M, Thuny F, Richet H, Raoult D. Long-term outcome of Q fever endocarditis: a 26-year personal survey. Lancet Infect Dis 2010; 10: 527–35. Fisher LD, Lin DY. Time-dependent covariates in the Cox proportional-hazards regression model. Annu Rev Public Health 1999; 20: 145–57. Beyersmann J, Wolkewitz M, Schumacher M. The impact of time-dependent bias in proportional hazards modelling. Stat Med 2008; 27: 6439–54.
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Goodman LB, Loregian A, Perkins GA, et al. A point mutation in a herpesvirus polymerase determines neuropathogenicity. PLoS Pathog 2007; 3: 1583–92. Skoldenberg B, Alestig K, Burman L, et al. Acyclovir versus vidarabine in herpes simplex encephalitis. Randomised multicentre study in consecutive Swedish patients. Lancet 1984; 324: 707–11. Gulliford MC, Chandrasekera CP, Cooper RA, Murphy RP. Acyclovir treatment of herpes simplex encephalitis: experience in a district hospital. Postgrad Med J 1987; 63: 1037–41. Kimberlin DW. Herpes simplex virus infections in neonates and early childhood. Semin Pediatr Infect Dis 2005; 16: 271–81.
An addition to the effect of treating co-infections on HIV-1 viral load After publication of our Review,1 we were informed of an omission by the authors of a study2 that met our systematic review’s inclusion criteria but was not identified by our search strategy. Using a crossover design, the investigators primarily assessed the effect of herpes simplex virus (HSV) 2 suppression on cervicovaginal HIV-1 shedding in women co-infected with HIV and HSV2. The effect on plasma HIV viral load was also measured, but as a secondary outcome. Dunne and colleagues2 reported that, among 67 women aged 18–49 years who had baseline CD4 cell counts of over 200 cells per μL, the mean plasma HIV viral load during aciclovir suppression (3·78 log10 copies per mL) was significantly lower than during placebo administration (4·26 log10 copies per mL; p<0·001). This reduction in HIV plasma viral load by 0·48 log10 copies per mL with acyclovir suppression among women co-infected with HIV and HSV is consistent with findings of other studies cited in our systematic review. We thank Dunne and colleagues for alerting us to their original and relevant work. www.thelancet.com/infection Vol 11 February 2011
We declare that we have no conflicts of interest.
Kayvon Modjarrad, Sten H Vermund [email protected] Department of Medicine (KM), Department of Pediatrics (SHV), and Institute for Global Health (KM, SHV), Vanderbilt University School of Medicine, Nashville, TN, USA 1
2
Modjarrad K, Vermund SH. Effect of treating co-infections on HIV-1 viral load: a systematic review. Lancet Infect Dis 2010; 10: 455–63. Dunne EF, Whitehead S, Sternberg M, et al. Suppressive acyclovir therapy reduces HIV cervicovaginal shedding in HIV- and HSV-2-infected women, Chiang Rai, Thailand. J Acquir Immune Defic Syndr 2008; 49: 77–83.
Long-term outcome of Q fever endocarditis We read with interest Matthieu Million and colleagues’ study1 of the longterm outcome of Q fever endocarditis. In a survival analysis, eligible patients should not be excluded because of loss to follow-up or death from other causes, but should be analysed up to the time of events and then censored. However, figure 1 uses the word excluded at various timepoints after enrolment into the study. The mortality probabilities at different timepoints would be underestimated because they were calculated from only patients who survived up to those timepoints, and censored patients were ignored. Mortality probabilities should be based on the Kaplan-Meier estimators as described in the Methods. Because failure outcomes were identical in both groups, figures 4 and 5 present predicted plots from the fitted models rather than KaplanMeier plots (each drop on the line represents each failure outcome). If the fitted models were multivariable, presentation of the values that were selected for the other variables is required (eg, female sex, median age of 53 years). Furthermore, we would be interested to know how missing values were addressed; figure 5 was based on only 87 patients (rather than all 104 patients) and bias could arise in
multivariable models that were based on a subset of the data. The recommendations that optimum duration of treatment for native valves be 18 months were derived from the Cox model for serological relapse. The model analysed only patients who were living, and ignored those who died of Q-fever endocarditis and other causes; however, excluding these cases could cause selection bias. The total of six failure outcomes included in this analysis is very low. Additionally, the variable doxycycline treatment duration of less than 18 months is a time-dependent variable2,3 that can be directly included in the model only if follow-up time started at 18 months or later; however, in one report, first serological relapse occurred at 15 months. If the time at risk of serological relapse were different for each patient, and started after the patient had serological cure, this should be stated. Although treatment of less than 18 months is associated with failures, how many patients were treated for longer than 18 months is unclear, as is whether treatment for longer than 18 months is associated with any benefit. We declare that we have no conflicts of interest.
*Direk Limmathurotsakul, Ben Cooper, Sharon J Peacock, Bianca De Stavola [email protected] Department of Tropical Hygiene (DL), Mahidol-Oxford Tropical Medicine Research Unit (DL, BC, SJP), and Department of Microbiology and Immunology (SJP), Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand; Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK (BC); and Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK (BDS) 1
2
3
Million M, Thuny F, Richet H, Raoult D. Long-term outcome of Q fever endocarditis: a 26-year personal survey. Lancet Infect Dis 2010; 10: 527–35. Fisher LD, Lin DY. Time-dependent covariates in the Cox proportional-hazards regression model. Annu Rev Public Health 1999; 20: 145–57. Beyersmann J, Wolkewitz M, Schumacher M. The impact of time-dependent bias in proportional hazards modelling. Stat Med 2008; 27: 6439–54.
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