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Shalini L Kulasingam

Publications and source records attributed to Shalini L Kulasingam.

10 recordsLinked to original sources
PubMed2006

Cost-effectiveness analysis based on the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion Triage Study (ALTS).

BACKGROUND: The ALTS (atypical squamous cells of undetermined significance [ASCUS] and low-grade squamous intraepithelial lesion [LSIL] Triage Study) suggests that, for women diagnosed with ASCUS, human papillomavirus (HPV) DNA testing followed by referral to colposcopy of only those women with oncogenic HPV (i.e., HPV DNA testing) is as effective at detecting cervical intraepithelial neoplasia (CIN) 3 or cancer (CIN3+) as referring all women with ASCUS for immediate colposcopy. We conducted a cost-effectiveness analysis of the ALTS trial to determine whether HPV DNA testing is a cost-effective alternative to immediate colposcopy or conservative management with up to three cytology examinations. METHODS: Data from the ALTS trial were used in conjunction with medical care costs in a short-term decision model. The model compared the incremental costs per case of CIN3+ detected as measured by the incremental cost-effectiveness ratio (ICER) for the following management strategies for women with ASCUS: immediate colposcopy, HPV DNA testing, and conservative management with up to three cytology examinations. RESULTS: The least costly and least sensitive strategy was conservative management with one repeat cytology examination using a threshold of high-grade squamous intraepithelial lesion (HSIL) for referral to colposcopy. Compared with this strategy, triage to colposcopy based on a positive HPV DNA test result had an ICER of 3517 dollars per case of CIN3+ detected. Immediate colposcopy and conservative management with up to three repeat cytology visits detected fewer cases of CIN3+ and were more costly than HPV DNA testing. Immediate colposcopy became cost-effective at 20,370 dollars compared with HPV DNA testing only if colposcopy and biopsy were assumed to be 100% sensitive. CONCLUSIONS: HPV DNA testing is an economically viable strategy for triage of ASCUS cytology. The less than perfect sensitivity of colposcopy and biopsy needs to be accounted for in future clinical guidelines and policy analyses.

Adult↗
PubMed2006

Cost-effectiveness of extending cervical cancer screening intervals among women with prior normal pap tests.

OBJECTIVE: Annual cervical cancer screening in women with many prior normal Pap tests is common despite limited evidence on the cost-effectiveness of this strategy. We estimated the cost-effectiveness of screening women with 3 or more prior normal tests compared with screening those with no prior tests. METHODS: We used a validated cost-effectiveness model in conjunction with data on the prevalence of biopsy-proven cervical neoplasia in women enrolled in the Centers for Disease Control and Prevention National Breast and Cervical Cancer Early Detection Program. Women were grouped according to age at the final Program Pap test (aged < 30, 30-44, 45-59, and 60-65 years) and by screening history (0, 1, 2, and 3+ consecutive prior normal Program tests) to estimate cost per life-year and quality-adjusted life-year associated with annual, biennial, and triennial screening. RESULTS: For women aged 30-44 years with no prior tests, incremental cost-effectiveness ratios ranged from 20,533 US dollars for screening triennially (compared with no further screening) to 331,837 US dollars for screening annually (compared with biennially) per life-year saved. Among same-aged women with 3 or more prior normal Program tests, incremental cost-effectiveness ratios for the same measures ranged from 60,029 US dollars to 709,067 US dollars per life-year saved. Inclusion of the most conservative utility estimates resulted in incremental cost-effectiveness ratios in excess of 100,000 US dollars per quality-adjusted life-year saved associated with annual screening of same-aged women with 3 or more prior normal tests compared with biennial screening. CONCLUSION: As the number of prior normal Pap tests increases, the costs per life-year saved increase substantially. Resources should be prioritized for screening those never or rarely screened women. LEVEL OF EVIDENCE: II-2.

Adult↗
PubMed2005

FDG-PET for management of cervical and ovarian cancer.

OBJECTIVE: To assess the diagnostic performance of Positron Emission Tomography using fluorodeoxyglucose (FDG-PET) in comparison to conventional imaging modalities in the assessment of patients with cervical and ovarian cancer. METHODS: Studies published between 1966 and 2003 were identified using an OVID search of the MEDLINE database. Inclusion criteria were use of a dedicated scanner, resolution specified, >/=12 human subjects, clinical follow-up >/=6 months or histopathology as reference standard, and sufficient data provided to construct a two-by-two table. Two reviewers independently abstracted data regarding sensitivity and specificity of PET. RESULTS: 25 studies (15 cervical cancer, 10 ovarian cancer) met inclusion criteria for full text review. For cervical cancer, pooled sensitivity and specificity of PET for aortic node metastasis are 0.84 (95% CI 0.68-0.94) and 0.95 (0.89-0.98). Pooled sensitivity and specificity for detection of pelvic node metastasis are: PET, 0.79 (0.65-0.90) and 0.99 (0.96-0.99); MRI, 0.72 (0.53-0.87) and 0.96 (0.92-0.98). Pooled sensitivity for CT is 0.47 (0.21-0.73) (pooled specificity not available). Pooled sensitivity and specificity of PET for recurrent cervical cancer with clinical suspicion are 0.96 (0.87-0.99) and 0.81 (0.58-0.94). For ovarian cancer, pooled sensitivity and specificity to detect recurrence with clinical suspicion are: PET, 0.90 (0.82-0.95) and 0.86 (0.67-0.96); conventional imaging, 0.68 (0.49-0.83) and 0.58 (0.33-0.80); CA-125, 0.81 (0.62-0.92) and 0.83 (0.58-0.96). When conventional imaging and CA-125 are negative, pooled sensitivity and specificity of PET are 0.54 (0.39-0.69) and 0.73 (0.56-0.87), respectively. When CA-125 is rising and conventional imaging is negative, the pooled sensitivity and specificity of PET are 0.96 (0.88-0.99) and 0.80 (0.44-0.97). CONCLUSIONS: There is good evidence that PET is useful for the pre-treatment detection of retroperitoneal nodal metastasis in cervical cancer. There is fair evidence that PET is useful for the detection of recurrent cervical cancer. PET is less useful for the detection of microscopic residual ovarian cancer but has fair sensitivity to detect recurrence in the setting of a rising CA-125 and negative conventional imaging studies. Available studies are limited by low numbers of patients and wide confidence intervals.

CA-125 Antigen↗
PubMed2004

Cigarette smoking, oncogenic human papillomavirus, Ki-67 antigen, and cervical intraepithelial neoplasia.

Although cigarette smoking has been identified as a cofactor for cervical neoplasia, it is not clear whether smoking exerts an early or late effect on the evolution of human papillomavirus (HPV)-related lesions. A case-control study of Washington State women who presented for routine gynecologic care from 1997 to 2001 was conducted. All women underwent cytologic testing and HPV DNA screening. Those with abnormal cytology findings or a positive oncogenic HPV test and a random sample of women negative on both tests were referred for colposcopically directed cervical biopsy with repeated testing. Among 461 women with oncogenic HPV were 181 controls with negative histology, 137 cases with histologically confirmed cervical intraepithelial neoplasia (CIN) grade 1 (CIN1), and 143 cases with histologically confirmed CIN grades 2-3 or higher (>/= CIN2-3). Smoking information was obtained by questionnaire. Immunohistochemistry testing for Ki-67 was performed on a subset of biopsy specimens (n = 139). Smoking 10 or more cigarettes per day was associated with >/= CIN2-3 (adjusted odds ratio = 2.6, 95% confidence interval: 1.3, 5.5) and CIN1 (adjusted odds ratio = 2.5, 95% confidence interval: 1.2, 5.3). Heavy smoking was positively associated with Ki-67 but not with repeated detection of oncogenic HPV. Since smoking was associated with both CIN1 and >/= CIN2-3, cigarette by-products may affect the early evolution of HPV-related lesions, possibly by increasing the rate of cell turnover.

Adult↗
PubMed2004

Lower observed versus expected (based on U.S. age and gender specific rates) survival in patients treated for near-fatal ventricular arrhythmias.

Implantable cardioverter defibrillators (ICDs) have improved survival for patients with ventricular fibrillation (VF) or sustained vertricular tachycardia (VT). However, the survival of these patients compared to the general population has not been assessed. Observed survival rates for patients randomized to either antiarrhythmic drug therapy (mainly amiodarone) arm or ICD arm were compared to expected rates, calculated using age and sex-specific survival rates derived from the 1989-1991 US population life tables and applied to the age and sex distribution of patients in each arm. Consistent with the results of the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, patients randomized to receive ICDs experienced significantly higher survival than those in the drug arm; however, both groups experienced significantly lower survival than expected using age and gender matched U.S. survival rates. Within arms, the difference between the observed and expected rates increased over 3 years of follow-up from 7.7% to 15.3% for the ICD arm, and from 14.6% to 26.4% for the drug arm. These results quantify the improvements in survival that can be expected for VF or VT patients using drug or ICD therapies and underscore the need for continued research into methods for further improving the overall level of health of these patients.

Aged↗
PubMed2003

Risk of cervical cancer associated with extending the interval between cervical-cancer screenings.

BACKGROUND: Although contemporary guidelines suggest that the intervals between Papanicolaou tests can be extended to three years among low-risk women with previous negative tests, the excess risk of cervical cancer associated with less frequent than annual screening is uncertain. METHODS: We determined the prevalence of biopsy-proven cervical neoplasia among 938,576 women younger than 65 years of age, stratified according to the number of previous consecutive negative Papanicolaou tests. Using a Markov model that estimates the rate at which dysplasia will progress to cancer, we estimated the risk of cancer within three years after one or more negative Papanicolaou tests, as well as the number of additional Papanicolaou tests and colposcopic examinations that would be required to avert one case of cancer given a particular interval between screenings. RESULTS: Among 31,728 women 30 to 64 years of age who had had three or more consecutive negative tests, the prevalence of biopsy-proven cervical intraepithelial neoplasia of grade 2 was 0.028 percent and the prevalence of grade 3 neoplasia was 0.019 percent; none of the women had invasive cervical cancer. According to our model, the estimated risk of cancer with annual Papanicolaou tests for three years was 2 in 100,000 among women 30 to 44 years of age, 1 in 100,000 among women 45 to 59 years of age, and 1 in 100,000 among women 60 to 64 years of age; these risks would be 5 in 100,000, 2 in 100,000, and 1 in 100,000, respectively, if screening were performed once three years after the last negative test. To avert one additional case of cancer by screening 100,000 women annually for three years rather than once three years after the last negative test, an average of 69,665 additional Papanicolaou tests and 3861 colposcopic examinations would be needed in women 30 to 44 years of age and an average of 209,324 additional Papanicolaou tests and 11,502 colposcopic examinations in women 45 to 59 years of age. CONCLUSIONS: As compared with annual screening for three years, screening performed once three years after the last negative test in women 30 to 64 years of age who have had three or more consecutive negative Papanicolaou tests is associated with an average excess risk of cervical cancer of approximately 3 in 100,000.

Adolescent↗
PubMed2003

Potential health and economic impact of adding a human papillomavirus vaccine to screening programs.

CONTEXT: Recently published results suggest that effective vaccines against cervical cancer-associated human papillomavirus (HPV) may become available within the next decade. OBJECTIVE: To examine the potential health and economic effects of an HPV vaccine in a setting of existing screening. DESIGN, SETTING, AND POPULATION: A Markov model was used to estimate the lifetime (age 12-85 years) costs and life expectancy of a hypothetical cohort of women screened for cervical cancer in the United States. Three strategies were compared: (1) vaccination only; (2) conventional cytological screening only; and (3) vaccination followed by screening. Two of the strategies incorporated a vaccine targeted against a defined proportion of high-risk (oncogenic) HPV types. Screening intervals of 1, 2, 3, and 5 years and starting ages for screening of 18, 22, 24, 26, and 30 years were chosen for 2 of the strategies (conventional cytological screening only and vaccination followed by screening). MAIN OUTCOME MEASURES: Incremental cost per life-year gained. RESULTS: Vaccination only or adding vaccination to screening conducted every 3 and 5 years was not cost-effective. However, at more frequent screening intervals, strategies combining vaccination and screening were preferred. Vaccination plus biennial screening delayed until age 24 years had the most attractive cost-effectiveness ratio (44 889 dollars) compared with screening only beginning at age 18 years and conducted every 3 years. However, the strategy of vaccination with annual screening beginning at age 18 years had the largest overall reduction in cancer incidence and mortality at a cost of 236 250 dollars per life-year gained compared with vaccination and annual screening beginning at age 22 years. The cost-effectiveness of vaccination plus delayed screening was highly sensitive to age of vaccination, duration of vaccine efficacy, and cost of vaccination. CONCLUSIONS: Vaccination for HPV in combination with screening can be a cost-effective health intervention, but it depends on maintaining effectiveness during the ages of peak oncogenic HPV incidence. Identifying the optimal age for vaccination should be a top research priority.

Adolescent↗
PubMed2002

Evaluation of human papillomavirus testing in primary screening for cervical abnormalities: comparison of sensitivity, specificity, and frequency of referral.

CONTEXT: Human papillomavirus (HPV) DNA testing of women having Papanicolaou (Pap) smears showing atypical squamous cells of undetermined significance (ASCUS) has clinical usefulness. Whether HPV DNA testing alone is useful in primary screening remains to be determined. OBJECTIVE: To determine the accuracy of HPV DNA testing for detecting cervical intraepithelial neoplasia (CIN) grade 3 or cancer (the criterion standard). DESIGN, SETTING, AND PARTICIPANTS: Between December 1997 and October 2000, 4075 women who attended Planned Parenthood clinics in Washington State were screened simultaneously using thin-layer Pap and HPV DNA testing by a polymerase chain reaction (PCR)-based method and by a liquid-based RNA-DNA hybridization capture with signal amplification assay (signal amplification). Women who were positive for high-risk HPV types, or had Pap results of ASCUS or higher, were considered to have positive screening test results and were referred for colposcopy and biopsy. Additionally, a random sample of women with negative screening test results was referred for colposcopy. Based on individual and combined thin-layer Pap, HPV PCR, and HPV signal amplification test results from the screening and the colposcopy visits, 7 colposcopy triage strategies were defined and evaluated. MAIN OUTCOME MEASURE: Sensitivity and specificity for detecting cervical lesions graded CIN 3 or higher for each of the 7 triage strategies. RESULTS: The estimated prevalence of CIN 3 or higher was 3.2%. The sensitivity (95% confidence interval) of thin-layer Pap (with a result of > or = ASCUS) for identifying women with CIN 3 or higher was only 61.3% (48.5%-70.9%) compared with 88.2% (78.9%-93.8%) for HPV testing by PCR and 90.8% (83.1%-95.8%) by signal amplification. Differences in specificities were also observed: 82.4% (81.8%-83.1%) for thin-layer Pap (with a result of > or = ASCUS), 78.8% (77.9%-79.7%) for PCR, and 72.6% (69.4%-75.0%) for signal amplification. Compared with referral for colposcopy of all women with ASCUS or higher, signal amplification testing of women with ASCUS and referral of those with a positive result was about as sensitive (61.3% vs 60.3%, respectively) and significantly more specific (82.4% vs 88.9%, respectively). The strategy requiring repeat positive PCR tests on 2 visits had a sensitivity of 84.2% (75.3%-91.0%) and a specificity of 86.2% (85.1%-87.3%). All tests were more specific and less sensitive in older (> or = 30 years) vs younger women. CONCLUSIONS: Testing for HPV has higher sensitivity but lower specificity than thin-layer Pap screening. In some settings, particularly where screening intervals are long or haphazard, screening for HPV DNA may be a reasonable alternative to cytology-based screening of reproductive-age women.

Adult↗
PubMedDate not supplied

When should functional neuroimaging techniques be used in the diagnosis and management of Alzheimer's dementia? A decision analysis.

BACKGROUND: Functional neuroimaging, including positron emission tomography (PET), has been proposed for use in diagnosing Alzheimer's disease-related dementia (AD). OBJECTIVE: The objective of this study was identify the circumstances under which PET scanning for the diagnosis of AD maximizes health outcomes. METHODS: A Markov-model-based decision analysis was conducted using estimates derived from the literature on AD epidemiology, the accuracy of PET, and donepezil treatment efficacy. The target population for the analysis was assumed to be US men and women who either have mild AD or are asymptomatic but at an elevated risk of developing AD owing to disease in a first-degree relative (parent or sibling). The time horizon was the patient lifetime. We compared treatment 1) based on an American Academy of Neurology (AAN) clinical evaluation either alone; 2) in combination with PET scanning; or 3) empirically based on a family history. Outcomes measures were life expectancy, quality-adjusted life-years (QALYs), and (severe) dementia-free life expectancy (SDFLE). RESULTS: For both patient populations, treating all patients based on an AAN evaluation without further testing using PET resulted in the greatest gains in life expectancy, QALYs, and SDFLEs. PET-based testing was the second preferred strategy compared to no intervention. The rankings of the strategies were sensitive to severity of treatment complications: analyses of hypothetical treatments with the potential for severe complications indicated that testing was preferred if the treatment was effective but had moderate complications. CONCLUSIONS: These results suggest that current treatments, which are relatively benign and may slow progression of disease, should be offered to patients who are identified as having AD based solely on an AAN clinical evaluation. A clinical evaluation that includes functional neuroimaging based testing will be warranted, however, when new treatments that are effective at slowing disease progression but have the potential for moderate to severe complications become available.

Aged↗