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How best to treat agitation in patients with irreversible dementia?
Atypical antipsychotics modestly reduce agitation compared with placebo but have significant adverse effects (strength of recommendation [SOR]: A, systematic reviews of randomized controlled trials [RCTs]).
Haloperidol doesn’t reduce symptoms and has serious adverse effects (SOR: A, systematic reviews of RCTs).
Selective serotonin reuptake inhibitors (SSRIs) and melatonin—although well tolerated—don’t reduce agitation (SOR: B, extrapolated data from systematic reviews of RCTs).
Evidence summary
A meta-analysis by the Agency for Healthcare Research and Quality of 37 RCTs examined off-label use of atypical antipsychotics in a total of 5364 patients.1 Pooled results from 17 RCTs showed a statistically significant but clinically modest difference between atypical antipsychotics and placebo for agitation; the standard mean difference was 0.22 (95% confidence interval [CI], 0.09-0.35). Investigators found statistically significant but small effect sizes for aripiprazole, olanzapine, and risperidone.
Atypical antipsychotics are associated with serious adverse cerebrovascular events and extrapyramidal symptoms. A meta-analysis of 17 RCTs (N= 5106) demonstrated that patients who received antipsychotics had higher mortality than patients who received placebo (3.5% vs 2.3%).2
Haloperidol has significant adverse effects without significant results
A systematic review of 5 RCTs compared haloperidol with placebo over 3 to 16 weeks in 856 patients ages 72 to 81 years with dementia and agitation.3 When investigators pooled results from 3 RCTs (N=690) using an intention-to-treat analysis and 3 assessment tools, they found that haloperidol produced a statistically significant, but not clinically meaningful, standard mean difference in aggression.
Adverse effects included extrapyramidal symptoms (odds ratio [OR]=2.34; 95% CI, 1.25-4.38; number needed to harm [NNH]=6), somnolence (OR=4.20; 95% CI, 1.78-9.91; NNH=8), and fatigue (OR=5.39; 95% CI, 2.04-14.22; NNH=3). Most studies were underpowered, didn’t document randomization, and had dropout rates as high as 20%.
Antidepressants have no effect
A systematic review of 9 RCTs involving 692 patients with dementia compared antidepressants with placebo, other antidepressants, and antipsychotics using various neuropsychiatric symptom scales.4 Investigators performed meta-analyses for numerous outcomes but found none of clinical or statistical significance.
Pooled analysis of 2 RCTs that examined a total of 250 outpatients with Alzheimer’s disease found that sertraline and fluoxetine produced a statistically, but not clinically, significant difference in the Cohen Mansfield Agitation Inventory total score. One RCT (N=52) demonstrated that citalopram improved the Neurobehavioral Rating Scale total score after adjusting for baseline severity.
Investigators found no difference in withdrawal rates between SSRIs and placebo (relative risk=1.07; 95% CI, 0.55-2.11). All studies had multiple methodological limitations.
Melatonin has no adverse effects, but no benefit either
A systematic review that included 2 RCTs compared melatonin with placebo for agitation in 121 patients ages 77 to 79 years with dementia.5 Investigators prescribed melatonin for periods of 4 to 7 weeks and found reductions in agitation that were statistically significant, but not clinically meaningful. They reported no adverse events. The studies had a low risk of bias.
Recommendations
The American Psychiatric Association (APA) advocates evaluating and treating secondary causes of agitation and using environmental and behavioral measures to reduce agitation.6 The APA advocates using the lowest effective dosages of antipsychotics after considering adverse effect profiles and the risks of not treating.
The APA recommends benzodiazepines to treat prominent anxiety or infrequent agitation, preferably lorazepam and oxazepam rather than diazepam or clonazepam and suggests trazodone or SSRIs as alternative therapy for agitation in patients without psychosis or those who are intolerant to antipsychotics.6
1. Maglione M, Ruelaz Maher A, Hu J, et al. Off-label use of atypical antipsychotics: an update. Comparative Effectiveness Review Number 43. Executive Summary. Rockville, Md: Agency for Healthcare Research and Quality; 2011.
2. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo controlled trials. JAMA. 2005;295:1934-1943.
3. Lonergan E, Luxenberg J, Colford JM, et al. Haloperidol for agitation in dementia. Cochrane Database Syst Rev. 2002;(2):CD002852.
4. Seitz DP, Adunuri N, Gill SS, et al. Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst Rev. 2011;(2):CD008191.
5. Jansen SL, Forbes D, Duncan V, et al. Melatonin for the treatment of dementia. Cochrane Database Syst Rev. 2006;(1):CD003802.
6. American Psychiatric Association Work Group on Alzheimer’s Disease and Other Dementias. Practice guidelines for the treatment of patients with Alzheimer’s disease and other dementias. 2nd ed. Available at: http://psychiatryonline.org/
pdfaccess.ashx?ResourceID=243205&PDFSource=6. Accessed April 3, 2013.
Atypical antipsychotics modestly reduce agitation compared with placebo but have significant adverse effects (strength of recommendation [SOR]: A, systematic reviews of randomized controlled trials [RCTs]).
Haloperidol doesn’t reduce symptoms and has serious adverse effects (SOR: A, systematic reviews of RCTs).
Selective serotonin reuptake inhibitors (SSRIs) and melatonin—although well tolerated—don’t reduce agitation (SOR: B, extrapolated data from systematic reviews of RCTs).
Evidence summary
A meta-analysis by the Agency for Healthcare Research and Quality of 37 RCTs examined off-label use of atypical antipsychotics in a total of 5364 patients.1 Pooled results from 17 RCTs showed a statistically significant but clinically modest difference between atypical antipsychotics and placebo for agitation; the standard mean difference was 0.22 (95% confidence interval [CI], 0.09-0.35). Investigators found statistically significant but small effect sizes for aripiprazole, olanzapine, and risperidone.
Atypical antipsychotics are associated with serious adverse cerebrovascular events and extrapyramidal symptoms. A meta-analysis of 17 RCTs (N= 5106) demonstrated that patients who received antipsychotics had higher mortality than patients who received placebo (3.5% vs 2.3%).2
Haloperidol has significant adverse effects without significant results
A systematic review of 5 RCTs compared haloperidol with placebo over 3 to 16 weeks in 856 patients ages 72 to 81 years with dementia and agitation.3 When investigators pooled results from 3 RCTs (N=690) using an intention-to-treat analysis and 3 assessment tools, they found that haloperidol produced a statistically significant, but not clinically meaningful, standard mean difference in aggression.
Adverse effects included extrapyramidal symptoms (odds ratio [OR]=2.34; 95% CI, 1.25-4.38; number needed to harm [NNH]=6), somnolence (OR=4.20; 95% CI, 1.78-9.91; NNH=8), and fatigue (OR=5.39; 95% CI, 2.04-14.22; NNH=3). Most studies were underpowered, didn’t document randomization, and had dropout rates as high as 20%.
Antidepressants have no effect
A systematic review of 9 RCTs involving 692 patients with dementia compared antidepressants with placebo, other antidepressants, and antipsychotics using various neuropsychiatric symptom scales.4 Investigators performed meta-analyses for numerous outcomes but found none of clinical or statistical significance.
Pooled analysis of 2 RCTs that examined a total of 250 outpatients with Alzheimer’s disease found that sertraline and fluoxetine produced a statistically, but not clinically, significant difference in the Cohen Mansfield Agitation Inventory total score. One RCT (N=52) demonstrated that citalopram improved the Neurobehavioral Rating Scale total score after adjusting for baseline severity.
Investigators found no difference in withdrawal rates between SSRIs and placebo (relative risk=1.07; 95% CI, 0.55-2.11). All studies had multiple methodological limitations.
Melatonin has no adverse effects, but no benefit either
A systematic review that included 2 RCTs compared melatonin with placebo for agitation in 121 patients ages 77 to 79 years with dementia.5 Investigators prescribed melatonin for periods of 4 to 7 weeks and found reductions in agitation that were statistically significant, but not clinically meaningful. They reported no adverse events. The studies had a low risk of bias.
Recommendations
The American Psychiatric Association (APA) advocates evaluating and treating secondary causes of agitation and using environmental and behavioral measures to reduce agitation.6 The APA advocates using the lowest effective dosages of antipsychotics after considering adverse effect profiles and the risks of not treating.
The APA recommends benzodiazepines to treat prominent anxiety or infrequent agitation, preferably lorazepam and oxazepam rather than diazepam or clonazepam and suggests trazodone or SSRIs as alternative therapy for agitation in patients without psychosis or those who are intolerant to antipsychotics.6
Atypical antipsychotics modestly reduce agitation compared with placebo but have significant adverse effects (strength of recommendation [SOR]: A, systematic reviews of randomized controlled trials [RCTs]).
Haloperidol doesn’t reduce symptoms and has serious adverse effects (SOR: A, systematic reviews of RCTs).
Selective serotonin reuptake inhibitors (SSRIs) and melatonin—although well tolerated—don’t reduce agitation (SOR: B, extrapolated data from systematic reviews of RCTs).
Evidence summary
A meta-analysis by the Agency for Healthcare Research and Quality of 37 RCTs examined off-label use of atypical antipsychotics in a total of 5364 patients.1 Pooled results from 17 RCTs showed a statistically significant but clinically modest difference between atypical antipsychotics and placebo for agitation; the standard mean difference was 0.22 (95% confidence interval [CI], 0.09-0.35). Investigators found statistically significant but small effect sizes for aripiprazole, olanzapine, and risperidone.
Atypical antipsychotics are associated with serious adverse cerebrovascular events and extrapyramidal symptoms. A meta-analysis of 17 RCTs (N= 5106) demonstrated that patients who received antipsychotics had higher mortality than patients who received placebo (3.5% vs 2.3%).2
Haloperidol has significant adverse effects without significant results
A systematic review of 5 RCTs compared haloperidol with placebo over 3 to 16 weeks in 856 patients ages 72 to 81 years with dementia and agitation.3 When investigators pooled results from 3 RCTs (N=690) using an intention-to-treat analysis and 3 assessment tools, they found that haloperidol produced a statistically significant, but not clinically meaningful, standard mean difference in aggression.
Adverse effects included extrapyramidal symptoms (odds ratio [OR]=2.34; 95% CI, 1.25-4.38; number needed to harm [NNH]=6), somnolence (OR=4.20; 95% CI, 1.78-9.91; NNH=8), and fatigue (OR=5.39; 95% CI, 2.04-14.22; NNH=3). Most studies were underpowered, didn’t document randomization, and had dropout rates as high as 20%.
Antidepressants have no effect
A systematic review of 9 RCTs involving 692 patients with dementia compared antidepressants with placebo, other antidepressants, and antipsychotics using various neuropsychiatric symptom scales.4 Investigators performed meta-analyses for numerous outcomes but found none of clinical or statistical significance.
Pooled analysis of 2 RCTs that examined a total of 250 outpatients with Alzheimer’s disease found that sertraline and fluoxetine produced a statistically, but not clinically, significant difference in the Cohen Mansfield Agitation Inventory total score. One RCT (N=52) demonstrated that citalopram improved the Neurobehavioral Rating Scale total score after adjusting for baseline severity.
Investigators found no difference in withdrawal rates between SSRIs and placebo (relative risk=1.07; 95% CI, 0.55-2.11). All studies had multiple methodological limitations.
Melatonin has no adverse effects, but no benefit either
A systematic review that included 2 RCTs compared melatonin with placebo for agitation in 121 patients ages 77 to 79 years with dementia.5 Investigators prescribed melatonin for periods of 4 to 7 weeks and found reductions in agitation that were statistically significant, but not clinically meaningful. They reported no adverse events. The studies had a low risk of bias.
Recommendations
The American Psychiatric Association (APA) advocates evaluating and treating secondary causes of agitation and using environmental and behavioral measures to reduce agitation.6 The APA advocates using the lowest effective dosages of antipsychotics after considering adverse effect profiles and the risks of not treating.
The APA recommends benzodiazepines to treat prominent anxiety or infrequent agitation, preferably lorazepam and oxazepam rather than diazepam or clonazepam and suggests trazodone or SSRIs as alternative therapy for agitation in patients without psychosis or those who are intolerant to antipsychotics.6
1. Maglione M, Ruelaz Maher A, Hu J, et al. Off-label use of atypical antipsychotics: an update. Comparative Effectiveness Review Number 43. Executive Summary. Rockville, Md: Agency for Healthcare Research and Quality; 2011.
2. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo controlled trials. JAMA. 2005;295:1934-1943.
3. Lonergan E, Luxenberg J, Colford JM, et al. Haloperidol for agitation in dementia. Cochrane Database Syst Rev. 2002;(2):CD002852.
4. Seitz DP, Adunuri N, Gill SS, et al. Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst Rev. 2011;(2):CD008191.
5. Jansen SL, Forbes D, Duncan V, et al. Melatonin for the treatment of dementia. Cochrane Database Syst Rev. 2006;(1):CD003802.
6. American Psychiatric Association Work Group on Alzheimer’s Disease and Other Dementias. Practice guidelines for the treatment of patients with Alzheimer’s disease and other dementias. 2nd ed. Available at: http://psychiatryonline.org/
pdfaccess.ashx?ResourceID=243205&PDFSource=6. Accessed April 3, 2013.
1. Maglione M, Ruelaz Maher A, Hu J, et al. Off-label use of atypical antipsychotics: an update. Comparative Effectiveness Review Number 43. Executive Summary. Rockville, Md: Agency for Healthcare Research and Quality; 2011.
2. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo controlled trials. JAMA. 2005;295:1934-1943.
3. Lonergan E, Luxenberg J, Colford JM, et al. Haloperidol for agitation in dementia. Cochrane Database Syst Rev. 2002;(2):CD002852.
4. Seitz DP, Adunuri N, Gill SS, et al. Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst Rev. 2011;(2):CD008191.
5. Jansen SL, Forbes D, Duncan V, et al. Melatonin for the treatment of dementia. Cochrane Database Syst Rev. 2006;(1):CD003802.
6. American Psychiatric Association Work Group on Alzheimer’s Disease and Other Dementias. Practice guidelines for the treatment of patients with Alzheimer’s disease and other dementias. 2nd ed. Available at: http://psychiatryonline.org/
pdfaccess.ashx?ResourceID=243205&PDFSource=6. Accessed April 3, 2013.
Evidence-based answers from the Family Physicians Inquiries Network
Does anal cancer screening reduce morbidity and mortality in men who have sex with men?
IT’S UNCLEAR whether anal cancer screening benefits men who have sex with men because high-quality studies on this subject are lacking. In the absence of high-quality data, anal pap smears aren’t recommended for routine screening of men who have sex with men (strength of recommendation: C, expert opinion).
Evidence summary
The National Cancer Institute reports an annual anal cancer incidence of 1.6 per 100,000 and as of November of last year, expected that 5820 men and women would receive the diagnosis in 2011.1 The 5-year survival rate is 64.9%. For men who have sex with men, the incidence ranges from 35 to 100 per 100,000, with a higher incidence in HIV-positive men.2
Men who have sex with men also have a higher prevalence of human papillomavirus (HPV) than the general population.3,4 HPV is the most common cause of anal squamous intraepithelial lesions. In theory, screening for anal cancer may reduce morbidity and mortality by identifying and treating anal cancer precursors, much as screening has done for cervical cancer.
Small studies suggest that screening may be effective
One study has demonstrated that anal pap smears are potentially effective as a screening tool for detecting anal intraepithelial neoplasia.5 The study was limited by small sample size and failure to address patient-centered outcomes, however. It included only 395 subjects, most of whom (54%) were HIV positive. Additional studies evaluated 265 HIV-positive men and 658 men, of whom 407 were HIV positive, with similar findings.6,7
But a larger study shows no impact
The largest study to date, which included 5083 HIV-positive patients (contributing 13,411 patient-years), didn’t demonstrate a decrease in invasive anal carcinoma during the screening period.8 The difference in HPV prevalence between HIV-positive and HIV-negative men who have sex with men (96% vs 58.9%; P<.001) limits the ability to generalize the conclusions of this study to all men who have sex with men.9
Recommendations
No consensus guidelines exist on screening for anal cancer in men who have sex with men, regardless of HIV status.
The New York State Department of Health recommends baseline cytology and annual anal cancer screening for all HIV-positive men who have sex with men.
Based on the high prevalence of HPV in the HIV-positive population, some experts suggest anal cancer screening for HIV-positive men who have sex with men.10
1. National Cancer Institute. SEER stat fact sheets: anal cancer. November 10, 2011. Available at: http://seer.cancer.gov/statfacts/html/anus.html. Accessed February 24, 2012.
2. Altekruse SF, Kosary CL, Krapcho M, et al. eds. SEER cancer statistics review, 1975-2007. Available at: http://seer.cancer.gov/csr/1975_2007. Accessed February 24, 2012.
3. Chin-Hong PV, Vittinghoff E, Cranston RD, et al. Age-specific prevalence of anal human papillomavirus infection in HIV-negative sexually active men who have sex with men: the EXPLORE Study. J Infect Dis. 2004;190:2070-2076.
4. Chin-Hong PV, Berry JM, Cheng SC, et al. Comparison of patient- and clinician-collected anal cytology samples to screen for human papillomavirus-associated anal intraepithelial neoplasia in men who have sex with men. Ann Intern Med. 2008;149:300-306.
5. Nathan M, Singh N, Garrett N, et al. Performance of anal cytology in a clinical setting when measured against histology and high-resolution anoscopy findings. AIDS. 2010;24:373-379.
6. Scott H, Khoury J, Moore BA, et al. Routine anal cytology screening for anal squamous intraepithelial lesions in an urban HIV clinic. Sex Transm Dis. 2008;35:197-202.
7. Palefsky JM, Holly EA, Hogeboom CJ, et al. Anal cytology as a screening tool for anal squamous intraepithelial lesions. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;14:415-422.
8. Mathews C, Caperna J, Cachay ER, et al. Early impact and performance characteristics of an established anal dysplasia screening program: program evaluation considerations. Open AIDS J. 2007;1:11-20.
9. Gao L, Zhou F, Li X, et al. Anal HPV infection in HIV-positive men who have sex with men from China. PLoS ONE. 2010;5:e15256.-
10. Silverberg MJ, Chao C, Leyden WA, et al. HIV infection and the risk of cancers with and without a known infectious cause. AIDS. 2009;23:2337-2345.
IT’S UNCLEAR whether anal cancer screening benefits men who have sex with men because high-quality studies on this subject are lacking. In the absence of high-quality data, anal pap smears aren’t recommended for routine screening of men who have sex with men (strength of recommendation: C, expert opinion).
Evidence summary
The National Cancer Institute reports an annual anal cancer incidence of 1.6 per 100,000 and as of November of last year, expected that 5820 men and women would receive the diagnosis in 2011.1 The 5-year survival rate is 64.9%. For men who have sex with men, the incidence ranges from 35 to 100 per 100,000, with a higher incidence in HIV-positive men.2
Men who have sex with men also have a higher prevalence of human papillomavirus (HPV) than the general population.3,4 HPV is the most common cause of anal squamous intraepithelial lesions. In theory, screening for anal cancer may reduce morbidity and mortality by identifying and treating anal cancer precursors, much as screening has done for cervical cancer.
Small studies suggest that screening may be effective
One study has demonstrated that anal pap smears are potentially effective as a screening tool for detecting anal intraepithelial neoplasia.5 The study was limited by small sample size and failure to address patient-centered outcomes, however. It included only 395 subjects, most of whom (54%) were HIV positive. Additional studies evaluated 265 HIV-positive men and 658 men, of whom 407 were HIV positive, with similar findings.6,7
But a larger study shows no impact
The largest study to date, which included 5083 HIV-positive patients (contributing 13,411 patient-years), didn’t demonstrate a decrease in invasive anal carcinoma during the screening period.8 The difference in HPV prevalence between HIV-positive and HIV-negative men who have sex with men (96% vs 58.9%; P<.001) limits the ability to generalize the conclusions of this study to all men who have sex with men.9
Recommendations
No consensus guidelines exist on screening for anal cancer in men who have sex with men, regardless of HIV status.
The New York State Department of Health recommends baseline cytology and annual anal cancer screening for all HIV-positive men who have sex with men.
Based on the high prevalence of HPV in the HIV-positive population, some experts suggest anal cancer screening for HIV-positive men who have sex with men.10
IT’S UNCLEAR whether anal cancer screening benefits men who have sex with men because high-quality studies on this subject are lacking. In the absence of high-quality data, anal pap smears aren’t recommended for routine screening of men who have sex with men (strength of recommendation: C, expert opinion).
Evidence summary
The National Cancer Institute reports an annual anal cancer incidence of 1.6 per 100,000 and as of November of last year, expected that 5820 men and women would receive the diagnosis in 2011.1 The 5-year survival rate is 64.9%. For men who have sex with men, the incidence ranges from 35 to 100 per 100,000, with a higher incidence in HIV-positive men.2
Men who have sex with men also have a higher prevalence of human papillomavirus (HPV) than the general population.3,4 HPV is the most common cause of anal squamous intraepithelial lesions. In theory, screening for anal cancer may reduce morbidity and mortality by identifying and treating anal cancer precursors, much as screening has done for cervical cancer.
Small studies suggest that screening may be effective
One study has demonstrated that anal pap smears are potentially effective as a screening tool for detecting anal intraepithelial neoplasia.5 The study was limited by small sample size and failure to address patient-centered outcomes, however. It included only 395 subjects, most of whom (54%) were HIV positive. Additional studies evaluated 265 HIV-positive men and 658 men, of whom 407 were HIV positive, with similar findings.6,7
But a larger study shows no impact
The largest study to date, which included 5083 HIV-positive patients (contributing 13,411 patient-years), didn’t demonstrate a decrease in invasive anal carcinoma during the screening period.8 The difference in HPV prevalence between HIV-positive and HIV-negative men who have sex with men (96% vs 58.9%; P<.001) limits the ability to generalize the conclusions of this study to all men who have sex with men.9
Recommendations
No consensus guidelines exist on screening for anal cancer in men who have sex with men, regardless of HIV status.
The New York State Department of Health recommends baseline cytology and annual anal cancer screening for all HIV-positive men who have sex with men.
Based on the high prevalence of HPV in the HIV-positive population, some experts suggest anal cancer screening for HIV-positive men who have sex with men.10
1. National Cancer Institute. SEER stat fact sheets: anal cancer. November 10, 2011. Available at: http://seer.cancer.gov/statfacts/html/anus.html. Accessed February 24, 2012.
2. Altekruse SF, Kosary CL, Krapcho M, et al. eds. SEER cancer statistics review, 1975-2007. Available at: http://seer.cancer.gov/csr/1975_2007. Accessed February 24, 2012.
3. Chin-Hong PV, Vittinghoff E, Cranston RD, et al. Age-specific prevalence of anal human papillomavirus infection in HIV-negative sexually active men who have sex with men: the EXPLORE Study. J Infect Dis. 2004;190:2070-2076.
4. Chin-Hong PV, Berry JM, Cheng SC, et al. Comparison of patient- and clinician-collected anal cytology samples to screen for human papillomavirus-associated anal intraepithelial neoplasia in men who have sex with men. Ann Intern Med. 2008;149:300-306.
5. Nathan M, Singh N, Garrett N, et al. Performance of anal cytology in a clinical setting when measured against histology and high-resolution anoscopy findings. AIDS. 2010;24:373-379.
6. Scott H, Khoury J, Moore BA, et al. Routine anal cytology screening for anal squamous intraepithelial lesions in an urban HIV clinic. Sex Transm Dis. 2008;35:197-202.
7. Palefsky JM, Holly EA, Hogeboom CJ, et al. Anal cytology as a screening tool for anal squamous intraepithelial lesions. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;14:415-422.
8. Mathews C, Caperna J, Cachay ER, et al. Early impact and performance characteristics of an established anal dysplasia screening program: program evaluation considerations. Open AIDS J. 2007;1:11-20.
9. Gao L, Zhou F, Li X, et al. Anal HPV infection in HIV-positive men who have sex with men from China. PLoS ONE. 2010;5:e15256.-
10. Silverberg MJ, Chao C, Leyden WA, et al. HIV infection and the risk of cancers with and without a known infectious cause. AIDS. 2009;23:2337-2345.
1. National Cancer Institute. SEER stat fact sheets: anal cancer. November 10, 2011. Available at: http://seer.cancer.gov/statfacts/html/anus.html. Accessed February 24, 2012.
2. Altekruse SF, Kosary CL, Krapcho M, et al. eds. SEER cancer statistics review, 1975-2007. Available at: http://seer.cancer.gov/csr/1975_2007. Accessed February 24, 2012.
3. Chin-Hong PV, Vittinghoff E, Cranston RD, et al. Age-specific prevalence of anal human papillomavirus infection in HIV-negative sexually active men who have sex with men: the EXPLORE Study. J Infect Dis. 2004;190:2070-2076.
4. Chin-Hong PV, Berry JM, Cheng SC, et al. Comparison of patient- and clinician-collected anal cytology samples to screen for human papillomavirus-associated anal intraepithelial neoplasia in men who have sex with men. Ann Intern Med. 2008;149:300-306.
5. Nathan M, Singh N, Garrett N, et al. Performance of anal cytology in a clinical setting when measured against histology and high-resolution anoscopy findings. AIDS. 2010;24:373-379.
6. Scott H, Khoury J, Moore BA, et al. Routine anal cytology screening for anal squamous intraepithelial lesions in an urban HIV clinic. Sex Transm Dis. 2008;35:197-202.
7. Palefsky JM, Holly EA, Hogeboom CJ, et al. Anal cytology as a screening tool for anal squamous intraepithelial lesions. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;14:415-422.
8. Mathews C, Caperna J, Cachay ER, et al. Early impact and performance characteristics of an established anal dysplasia screening program: program evaluation considerations. Open AIDS J. 2007;1:11-20.
9. Gao L, Zhou F, Li X, et al. Anal HPV infection in HIV-positive men who have sex with men from China. PLoS ONE. 2010;5:e15256.-
10. Silverberg MJ, Chao C, Leyden WA, et al. HIV infection and the risk of cancers with and without a known infectious cause. AIDS. 2009;23:2337-2345.
Evidence-based answers from the Family Physicians Inquiries Network