Cost-effectiveness of approaches to cervical cancer screening in Malawi: comparison of frequencies, lesion treatment techniques, and risk-stratified approaches.

BACKGROUND: Recently-updated global guidelines for cervical cancer screening incorporated new technologies-most significantly, the inclusion of HPV DNA detection as a primary screening test-but leave many implementation decisions at countries' discretion. We sought to develop recommendations for Malawi as a test case since it has the second-highest cervical cancer burden globally and high HIV prevalence. We incorporated updated epidemiologic data, the full range of ablation methods recommended, and a more nuanced representation of how HIV status intersects with cervical cancer risk and exposure to screening to model outcomes of different approaches to screening. METHODS: Using a Markov model, we estimate the relative health outcomes and costs of different approaches to cervical cancer screening among Malawian women. The model was parameterized using published data, and focused on comparing "triage" approaches-i.e., lesion treatment (cryotherapy or thermocoagulation) at differing frequencies and varying by HIV status. Health outcomes were quality-adjusted life years (QALYs) and deaths averted. The model was built using TreeAge Pro software. RESULTS: Thermocoagulation was more cost-effective than cryotherapy at all screening frequencies. Screening women once per decade would avert substantially more deaths than screening only once per lifetime, at relatively little additional cost. Moreover, at this frequency, it would be advisable to ensure that all women who screen positive receive treatment (rather than investing in further increases in screening frequency): for a similar gain in QALYs, it would cost more than four times as much to implement once-per-5 years screening with only 50% of women treated versus once-per-decade screening with 100% of women treated. Stratified screening schedules by HIV status was found to be an optimal approach. CONCLUSIONS: These results add new evidence about cost-effective approaches to cervical cancer screening in low-income countries. At relatively infrequent screening intervals, if resources are limited, it would be more cost-effective to invest in scaling up thermocoagulation for treatment before increasing the recommended screening frequency. In Malawi or countries in a similar stage of the HIV epidemic, a stratified approach that prioritizes more frequent screening for women living with HIV may be more cost-effective than population-wide recommendations that are HIV status neutral.

A Non-Surgical and Cost-Effective Treatment Approach Employing Topical Imiquimod, 5-Fluorouracil, and Tretinoin for Primary Non-Melanoma Skin Cancers.

BACKGROUND: Minimally invasive alternative approaches to treat non-melanoma skin cancers remain limited and unproven. OBJECTIVE: We aim to assess the efficacy of varying combinations of anti-tumor agents—imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream—with brief cryotherapy in treating non-melanoma skin cancers. METHODS: This retrospective study included 690 cases of non-melanoma skin cancers in 480 patients who received a diagnosis of a basal cell carcinoma or squamous cell carcinoma during a ten-year period. During treatment period, patients applied 30 applications of one of three combinations (imiquimod/tretinoin, 5-fluorouracil/tretinoin, or imiquimod/5-fluorouracil/tretinoin) and had cryotherapy every 2 weeks. Each patient had a clinical examination at least three years post-treatment or documented treatment failure. Clearance was defined by a lack of persistence or recurrence for 3 years following the completion of treatment. The likelihood of lesion clearance was evaluated using multivariable logistic regression analysis. RESULTS: A total of 186 cases (97; basal cell carcinoma and 89; squamous cell carcinoma) in 133 patients [37% women and 63% men; median (interquartile range) age, 77 (69, 83) years] met the inclusion criteria. Multivariable logistic regression analysis adjusting for clinical and lesion variables demonstrated that, relative to the imiquimod/5-fluorouracil/tretinoin treatment approach, imiquimod/ tretinoin (odds ratio, 0.05; 95% confidence interval, 0.00-0.99) and 5-fluorouracil/tretinoin (0.02; 0.00–0.45) were associated with lower likelihoods of lesion clearance. Likewise, morpheaform basal cell carcinoma had a lower probability of clearance (0.05; 0.00–0.72). CONCLUSIONS: The combination of imiquimod/5-fluorouracil/tretinoin with cryotherapy had high clearance rates and was the most effective treatment regimen. J Drugs Dermatol. 2021;20(3):260-267. doi:10.36849/JDD.5427.

Icing oral mucositis: Oral cryotherapy in multiple myeloma patients undergoing autologous hematopoietic stem cell transplant.

Background Up to 70% of patients receiving hematopoietic stem cell transplant develop oral mucositis as a side effect of high-dose melphalan conditioning chemotherapy. Oral cryotherapy has been documented to be potentially effective in reducing oral mucositis. The aim of this study was to examine the effectiveness of the cryotherapy protocol implemented within the hematopoietic stem cell transplant program. Methods A retrospective chart review was conducted of adult multiple myeloma patients who received high-dose melphalan conditioning therapy for autologous hematopoietic stem cell transplant. Primary endpoints were incidence and severity of oral mucositis. Secondary endpoints included duration of oral mucositis, duration of hospital stay, parenteral narcotics use and total parenteral nutrition use. Results One hundred and forty patients were included in the study, 70 patients in both no cryotherapy and cryotherapy groups. Both oral mucositis incidence and severity were found to be significantly lower in the cryotherapy group. Fifty (71.4%) experienced mucositis post cryotherapy compared to 67 (95.7%) in the no cryotherapy group (p < 0.001). The median oral mucositis severity, assessed using the WHO oral toxicity scale from grade 0-4, experienced in the no group was 2.5 vs. 2 in the cryotherapy group (p = 0.03). Oral mucositis duration and use of parenteral narcotics were also significantly reduced. Duration of hospital stay and use of parenteral nutrition were similar between the two groups. Conclusion The cryotherapy protocol resulted in a significantly lower incidence and severity of oral mucositis. These results provide evidence for the continued use of oral cryotherapy, an inexpensive and generally well-tolerated practice.

A systematic review of cost-effective treatment of postoperative rotator cuff repairs.

OBJECTIVE: The Bundled Payments for Care Improvement initiative combines payment of multiple services for episodes of care into 1 bundle. Rotator cuff repair is a likely candidate for future inclusion. The objective of this study was to determine cost-effective, high-quality postoperative rehabilitation dosing and cryotherapy for patients undergoing rotator cuff repair based on systematic review of the literature. METHODS: Systematic review of level I and level II articles was performed in PubMed, Cochrane Databases, and PEDro. Conference references and bibliographies were also reviewed. For postoperative therapy, keywords included rotator cuff, rotator cuff repair, exercise therapy, exercise, unsupervised, self-care, postoperative period, physical therapy, and physiotherapy; for cryotherapy, keywords included rotator cuff repair, shoulder, cryotherapy, and ice. RESULTS: Five studies compared postoperative outcomes in participants assigned to supervised therapy vs. unsupervised therapy. Three found no difference between groups. One found improved outcomes in supervised therapy. Limitations included that therapies were not consistently defined and significant methodologic issues were present, decreasing the applicability and validity of the results. Five articles examined cryotherapy outcomes in the postoperative shoulder. Two studies showed improved patient outcomes with cryotherapy vs. no cryotherapy; 2 studies showed no decrease in joint space temperatures at 90 minutes but decrease in temperature at 4 to 23 hours postoperatively. One study indicated that an ice bag and Ace bandage might be as effective as continuous, compressive cryotherapy units using patient-reported outcomes. CONCLUSION: Further studies are needed to determine effective dosing of physical therapy after rotator cuff repair. Cryotherapy is favorable and cost-effective using simple methods for delivery.

Consensus for Nonmelanoma Skin Cancer Treatment, Part II: Squamous Cell Carcinoma, Including a Cost Analysis of Treatment Methods.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in the United States. Cutaneous squamous cell carcinoma has an estimated incidence of more than 700,000 new cases per year and a 5% risk of metastasis. OBJECTIVE: To provide clinicians with guidelines for the management of cSCC based on evidence from a comprehensive literature review and consensus among the authors. MATERIALS AND METHODS: The authors conducted an extensive review of the medical literature on treatment methods for cSCC, taking into consideration cure rates, recurrence and metastatic rates, aesthetic and functional outcomes, and cost effectiveness of the procedures. RESULTS: Surgical treatments provide the best outcomes for cSCC. Mohs micrographic surgery is a cost-effective procedure that affords the highest cure rate, maximal tissue preservation, and superior cosmetic outcomes. Nonsurgical methods may be used as a primary treatment for low-risk squamous cell carcinomas, but the cure rates are lower. CONCLUSION: The cure rate remains the most important consideration in choosing the treatment method, but additional factors, such as the patient's general medical condition, psychosocial circumstances, the location of the tumor and cost effectiveness of the therapy should be considered. Mohs micrographic surgery remains the preferred treatment for high-risk tumors and tumors located in cosmetically sensitive areas.

Comparative effectiveness of cryotherapy vs brachytherapy for localised prostate cancer.

UNLABELLED: Despite the increased popularity of emerging therapies for localised prostate cancer, such as cryotherapy and brachytherapy, outcomes data remains sparse beyond single-centre comparative studies. The present study identified that although less costly, cryotherapy was associated with more urinary and ED complications and a greater need for salvage ADT. Conversely, cryotherapy was associated with fewer bowel complications. Patients and providers alike should consider these population-based outcomes when discussing therapeutic options for localised prostate cancer. OBJECTIVE: To compare prostate cryotherapy vs brachytherapy outcomes and costs, as despite the greater popularity of these emerging therapies for localised prostate cancer, outcomes data remains sparse beyond single-centre comparative studies. PATIENTS AND METHODS: Observational study of 10 928 men who underwent primary cryotherapy (943 patients) or brachytherapy (9985) with ≥2 years of follow-up using USA Surveillance, Epidemiology, and End Results (SEER-) Medicare linked data. Weighted propensity score methods were used. RESULTS: Use of cryotherapy increased four-fold whereas brachytherapy utilization remained the same from 2001 to 2005 (P < 0.001). Men who underwent cryotherapy vs brachytherapy were older (P < 0.001), more likely to be Black (P < 0.001), less likely to live in areas of higher education (P < 0.001), less likely to live in areas with greater income (P < 0.001), and were more likely to live in urban vs rural areas (P = 0.007). In propensity score-weighted analyses, cryotherapy was associated with more urinary (41.4% vs 22.2%, P < 0.001) and erectile dysfunction (ED) complications (34.7% vs 21.0%, P < 0.001) while brachytherapy was associated with more bowel complications (19.0% vs 12.1%, P < 0.001). Cryotherapy was associated with greater use of salvage androgen deprivation therapy (ADT; 1.4 vs 0.5 per 100 person-years, P < 0.001), suggesting worse cancer control. Finally costs were significantly greater for brachytherapy vs cryotherapy ($16 887 vs $12 629 USA dollars, P < 0.001). CONCLUSIONS: Although less costly, cryotherapy was associated with more urinary and ED complications and greater need for salvage ADT. Conversely, cryotherapy was associated with fewer bowel complications. Patients and providers alike should consider these population-based outcomes when discussing therapeutic options for localised prostate cancer.

Efficacy, safety, acceptability and affordability of cryotherapy: a review of current literature.

As a result of widespread screening and treatment programs, the incidence of cervical cancer has decreased by as much as 75% in the developed world. Commonly used treatment modalities for precancerous lesions include cone biopsy, the Loop Electrosurgical Excision Procedure (LEEP), laser ablation and cryotherapy. In recent years LEEP has replaced cryotherapy as a commonly provided outpatient procedure in many places; however increased awareness of the burden of cervical cancer in the developing world and increased awareness of long term consequences of LEEP ­ such as cervical insufficiency ­ have renewed interest in cryotherapy. We reviewed current literature addressing the technique, efficacy, safety and acceptability of cryotherapy, as well as special topics such as cost effectiveness, HIV, and low resource settings. Among studies we reviewed, cure rates ranged from 56.8-96.6% among prospective controlled trials and from 70-95.5% among observational studies. Cryotherapy has very low complication rates and serious complications requiring medical intervention or affecting future reproductive outcomes are extremely rare. Side effects including vaginal discharge and cramping are temporary, generally self-limited, and well tolerated after anticipatory patient counseling. When surveyed, women find cryotherapy highly acceptable. Compared to other treatment modalities, cryotherapy is very affordable and feasible to integrate into cervical cancer screening and treatment programs.

Costs of cervical cancer screening and treatment using visual inspection with acetic acid (VIA) and cryotherapy in Ghana: the importance of scale.

OBJECTIVES: To estimate the incremental costs of visual inspection with acetic acid (VIA) and cryotherapy at cervical cancer screening facilities in Ghana; to explore determinants of costs through modelling; and to estimate national scale-up and annual programme costs. METHODS: Resource-use data were collected at four out of six active VIA screening centres, and unit costs were ascertained to estimate the costs per woman of VIA and cryotherapy. Modelling and sensitivity analysis were used to explore the influence of observed differences between screening facilities on estimated costs and to calculate national costs. RESULTS: Incremental economic costs per woman screened with VIA ranged from 4.93 US$ to 14.75 US$, and costs of cryotherapy were between 47.26 US$ and 84.48 US$ at surveyed facilities. Under base case assumptions, our model estimated the costs of VIA to be 6.12 US$ per woman and those of cryotherapy to be 27.96 US$. Sensitivity analysis showed that the number of women screened per provider and treated per facility was the most important determinants of costs. National annual programme costs were estimated to be between 0.6 and 4.0 million US$ depending on assumed coverage and adopted screening strategy. CONCLUSION: When choosing between different cervical cancer prevention strategies, the feasibility of increasing uptake to achieve economies of scale should be a major concern.

Initial treatment costs of organ-confined prostate cancer: a general perspective.

With the increasing prevalence of prostate cancer and evolving methods for the definitive treatment of OCPCa, health economic analyses will be critically important, albeit difficult to carry out. Preliminary studies point to RPP as the most cost-effective treatment for OCPCa. The quickest postoperative recovery, in experienced hands, occurs in RARP and RPP, with ORPP having a slightly, but statistically in significant, shorter hospital stay. It should be stressed that initial treatment costs are not the only important factor in healthcare costs. Readmission for early and late complications and the loss of productivity resulting from variation in time to return to work, need also to be considered. Loss of productivity may also vary in cost between different institutions and countries depending upon the proportion of patients employed. Further large-scale multicentre studies are necessary to assess this.

[Referrals to dermatology: proportion of banal disorders]. / Demanda derivada a Dermatología: peso de la patología banal.

BACKGROUND AND OBJECTIVE: Skin diseases account for a large number of consultations in primary care. The objective of this study was to determine the characteristics and cost of referrals from primary care to a dermatology clinic. MATERIAL AND METHODS: Descriptive cross-sectional study of referrals from a primary care health center to a dermatology clinic. The dermatology clinic was situated in the same health center and was attended by a dermatologist from Complejo Hospitalario Universitario in Albacete, Spain. The study was performed on 10 days selected at random between April 21, 2009, and June 26, 2009. The data gathered included age, sex, use of cryotherapy, and diagnostic group. Patients were divided into 4 diagnostic groups: A) benign degenerative disease or trivial disorders whose treatment may not merit involvement of the national health service, B) diseases resolved with a single dermatology consultation at the health center, C) diseases requiring evaluation in hospital-based dermatology outpatients, and D) diseases referred for surgical treatment. RESULTS: Data were gathered on 257 patients with a mean age was 41.18 years and there was a slight female predominance. The majority of patients were in diagnostic group B (53.7%), followed by groups A (19.1%), C (19.1%), and D (8.2%). The total estimated cost of these 257 visits was €29 750.32, of which €5672.24 was for trivial disorders. CONCLUSIONS: The current high prevalence of trivial disorders in the caseload of dermatology clinics by trivial disorders makes it necessary to control referrals from primary care more strictly.

Poor outcomes with cryoplasty for lower extremity arterial occlusive disease.

OBJECTIVES: Cryoplasty has been proposed as a different therapy to address the problems of recurrent lesions. We reviewed our experience with cryoplasty to determine its outcome treating patients with lesions in native vessels and within stents. METHODS: A retrospective review of all patients undergoing cryotherapy between 2004 and 2008 was conducted. Patency was defined by at least one of the following criteria: flow through the vessel demonstrated by angiography or duplex ultrasonography, maintenance of an ankle-brachial index (ABI) greater than 0.10 above the preprocedural value, or maintenance of a palpable pedal pulse that was absent before the procedure in an asymptomatic patient. Patency, limb salvage, symptomatic improvement, and freedom from surgical bypass were determined with Kaplan-Meier survival analysis and compared by log-rank testing. Multivariate analysis was performed by Cox proportional-hazards regression. RESULTS: Eighty-eight cryoplasty procedures were performed in 71 patients, with 35 procedures for in-stent restenosis and 37 for native vessel disease. Sixteen of 88 procedures in grafts were excluded from analysis secondary to combined disease process and/or bypass graft stenosis. Lesions treated with cryoplasty had an average of 2.9 prior endovascular interventions. Eighty-five percent of the lesions were described as complex (multifocal, diffuse, or occlusion) and the mean lesion length was 15 +/- 10 cm. Initial cryoplasty technical success rate was 68% (25 of 37) for native vessels and 71% (25 of 35) for in-stent procedures. One year primary patency for the native vs stent group was 17% vs 28%, respectively (P = .18). The 1-year primary assisted patency for the native vs stent group was 28% vs 47%, respectively (P = .33). The 1-year secondary patency for the native vs stent group was 41% vs 57% (P = .42), respectively. Freedom from claudication at 1 year for the native vs stent group was 32% vs 21% (P = .80). Compared to balloon angioplasty, cryoplasty has an averaged up-cost of $1851.50 per procedure. CONCLUSION: Cryoplasty was used in patients with extensive disease and multiple prior interventions. Cryoplasty provided poor patency rates and poor relief from claudication at 1 year in this population. Overall, cryoplasty seems to be an expensive endovascular tool with marginal clinical improvement in our experience.

Systems-level barriers to treatment in a cervical cancer prevention program in Kenya: Several observational studies.

OBJECTIVE: To identify health systems-level barriers to treatment for women who screened positive for high-risk human papillomavirus (hrHPV) in a cervical cancer prevention program in Kenya. METHODS: In a trial of implementation strategies for hrHPV-based cervical cancer screening in western Kenya in 2018-2019, women underwent hrHPV testing offered through community health campaigns, and women who tested positive were referred to government health facilities for cryotherapy. The current analysis draws on treatment data from this trial, as well as two observational studies that were conducted: 1) periodic assessments of the treatment sites to ascertain availability of resources for treatment and 2) surveys with treatment providers to elicit their views on barriers to care. Bivariate analyses were performed for the site assessment data, and the provider survey data were analyzed descriptively. RESULTS: Seventeen site assessments were performed across three treatment sites. All three sites reported instances of supply stockouts, two sites reported treatment delays due to lack of supplies, and two sites reported treatment delays due to provider factors. Of the 16 providers surveyed, ten (67%) perceived lack of knowledge of HPV and cervical cancer as the main barrier in women's decision to get treated, and seven (47%) perceived financial barriers for transportation and childcare as the main barrier to accessing treatment. Eight (50%) endorsed that providing treatment free of cost was the greatest facilitator of treatment. CONCLUSION: Patient education and financial support to reach treatment are potential areas for intervention to increase rates of hrHPV+ women presenting for treatment. It is also essential to eliminate barriers that prevent treatment of women who present, including ensuring adequate supplies and staff for treatment.

Experimental study for evaluation of a low-cost spray cryotherapy system.

OBJECTIVE: To evaluate the feasibility and applicability of a low-cost cryotherapy system. METHODS: Experimental study with 25kg Landrace pigs submitted to a longitudinal cervico-thoraco-abdominal incision for exposure of the trachea, thorax and abdomen. The tissues were frozen by continuous spray application at different periods of time (5, 10 and 15 seconds). Spray cryotherapy was performed using a fluorinated gas (tetrafluorethane) delivered at - 47°C temperature (DermaFreeze®, Emdutos; ANVISA registration 80409950001; price R$ 394,00). via an adapted, disposable 1.8mm cholangiography catheter (Olympus; price R$ 280,00). The specimens were resected for histopathological analysis. RESULTS: Thirty samples were obtained from ten different organs and divided according to spray cryotherapy application time. System activation for 5, 10 or 15 seconds led to consumption of 14g, 27g and 40g of gas respectively (average gas consumption, 2.7g/s using a 1.8mm catheter). The system comprising a spray tube and catheter proved user-friendly and effective, with constant gas dispersion and adequate tissue freezing. In spite of effective freezing, microscopy failed to reveal tissue changes. This may have reflected methodological constraints precluding evaluation at tissue damage peak time (48 hours). CONCLUSION: The low-cost spray cryotherapy system proved feasible and safe.

Anatomic, Visual, and Financial Outcomes for Traditional and Nontraditional Primary Pneumatic Retinopexy for Retinal Detachment.

PURPOSE: To determine factors predictive of anatomic, visual, and financial outcomes after traditional and nontraditional primary pneumatic retinopexy (PR) for rhegmatogenous retinal detachment (RD). DESIGN: Retrospective interventional case series and cost comparison. METHODS: Participants: Total of 178 eyes (156 patients) with PR-repaired primary RD by a single surgeon at a clinical practice from January 2001 to December 2013 and followed for ≥1 year. The cohort had 2 subgroups: traditional (TPR) and nontraditional (NTPR) PR. MAIN OUTCOME MEASURES: Characteristics associated with best-corrected visual acuity (BCVA) and anatomic outcomes. Cost analysis and potential cost savings comparing PR to scleral buckle and vitrectomy. RESULTS: One hundred thirty-one of 178 eyes (73.5%) were successfully treated at 1 year (postoperative year 1): 72.8% (75/103) in TPR and 74.6% (56/75) in NTPR. Macula-off detachment (-0.44 logMAR, P < .001) and clock hours of RD (-0.84 logMAR, P < .001) correlated with improved BCVA; pseudophakia (0.26 logMAR, P = .002) and inferior retinal tears (0.62 logMAR, P = .009) correlated with worsening BCVA. Pseudophakia (-0.15, P = .03), inferior quadrant RD (-0.27, P < .001), and proliferative vitreoretinopathy (-0.68, P < .001) correlated with anatomic failure. Total average cost for TPR and NTPR was $1248.37 ± $882.11 and $1471.91 ± $942.84, respectively (P = .10). PR had a potential cost savings of 62% and 60.8% when compared to scleral buckle and vitrectomy, respectively. CONCLUSIONS: PR results in successful anatomic and visual outcomes in both TPR and NTPR repair of primary RD. Preoperative pseudophakia is associated with worse visual outcomes and less anatomic success. The cost of primary PR and subsequent procedures to achieve final anatomic success was not significantly different between TPR and NTPR, and supports the possible cost-effectiveness of expanded indications for PR.

CryoPlasty therapy of the superficial femoral and popliteal arteries: a reappraisal after 44 months' experience.

OBJECTIVES: Long-term patency remains a significant hurdle in the minimally invasive treatment of arteriosclerosis in the superficial femoral (SFA) and popliteal arteries. CryoPlasty therapy (PolarCath, Boston Scientific Corp, Natick, Mass) is a novel approach designed to significantly reduce injury, elastic recoil, neointimal hyperplasia, and constrictive remodeling. The technique combines the dilatation forces of percutaneous transluminal angioplasty (PTA) with cold thermal energy applied to the plaque and vessel wall. We previously reported a technical success rate of 96% and a 12-month freedom from restenosis rate of 82.2%. However, a review of the original cohort supplemented by experience with a further 47 lesions has demonstrated less desirable results. METHODS: From December 2003 through July 2007, 92 lesions in 64 consecutive patients were treated and followed up for a median of 16 months with statistically significant follow-up at 24 months. RESULTS: The immediate technical success rate was 88%. Nine stents were immediately required after unsuccessful CryoPlasty (9.8%) five of which were as a result of a dissection. No unanticipated adverse events occurred, specifically, no thrombus, acute occlusions, distal embolizations, aneurysms, or groin complications. Vascular calcification was responsible for technical failure in six of the 11 immediately unsuccessful procedures. Freedom from restenosis for successfully treated lesions was 57% and 49% at 12 and 24 months, respectively. CryoPlasty of heavily calcified lesions, vein graft lesions, and in-stent stenosis faired poorly. Excluding these lesions from analysis would have resulted in an immediate success of 94% (81 of 86) and freedom from restenosis of 61% and 52% at 12 and 24 months, respectively. However, on an intention-to-treat basis, freedom from restenosis was 47% and 38% at 12 and 24 months, and CryoPlasty added approximately $1700 to the cost of each procedure. CONCLUSION: Analysis of this expanded, longer-term data suggests that our earlier, smaller study provided an overly optimistic appraisal of the benefits of CryoPlasty. It is possible that a larger analysis might have identified a subset of patients or lesions that would benefit from CryoPlasty, but considering the additional cost, we no longer use this technique in our practice.

Pharmacoeconomic analysis of the treatment of multiple actinic keratoses.

Actinic keratosis (AK) is common and lesions may progress to squamous cell carcinoma. The choice of therapy depends mainly on 2 factors: the efficacy of therapeutic options and the number of lesions present. Cryotherapy alone is suitable for treating a few lesions, whereas topical medications, photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), or either in combination with cryotherapy are appropriate for treating multiple (>15) lesions. When combinations are necessary, the total cost to treat multiple AKs to 100% clearance becomes important. This report provides a simple pharmacoeconomic analysis of 4 FDA-cleared therapies (imiquimod, diclofenac, 5-fluorouacil [5-FU], and ALA PDT) for AK given in combination with cryotherapy. This analysis assumes standard costs of procedures and office visits (based on April 2007 reimbursement data) and 2 treatment courses (medications: imiquimod, diclofenac, 5-FU) or sessions (ALA PDT) of each modality followed by cryotherapy to 100% clearance. The total cost of each combination is $725.17 for ALA PDT, $845.07 for diclofenac, $942.13 for 5-FU, and $1,473.39 for imiquimod. When phase III trial efficacies of the 4 modalities are considered, the actual cost of using imiquimod or diclofenac increases because additional treatments may be required. Among these 4 FDA-cleared therapies for multiple AK lesions, ALA PDT is the least expensive treatment and imiquimod is the most expensive treatment under the stated assumptions.

Costs and cost-effectiveness of LEEP versus cryotherapy for treating cervical dysplasia among HIV-positive women in Johannesburg, South Africa.

BACKGROUND: Cervical cancer incidence is significant in countries, such as South Africa, with high burdens of both HIV and human papillomavirus (HPV). Cervical cancer is largely preventable if dysplasia is diagnosed and treated early, but there is debate regarding the best approaches for screening and treatment, especially for low-resource settings. Currently South Africa provides Pap smears followed by colposcopic biopsy and LEEP if needed in its public health facilities. We estimated the costs and cost-effectiveness of two approaches for treating cervical intraepithelial neoplasia grade 2 or higher (CIN2+) among HIV-infected women, most of whom were taking antiretroviral treatment, at a public HIV treatment facility in Johannesburg, South Africa. METHODS: Method effectiveness was derived from an intention-to-treat analysis of data gathered in a clinical trial completed previously at the study facility. In the trial, women who were diagnosed with CIN2+ and eligible for cryotherapy were randomized to cryotherapy or LEEP. If women were CIN2+ at six months as determined via Pap smear and colposcopic biopsy, all women-regardless of their original treatment assignment-received LEEP. "Cure" was then defined as the absence of disease at 12 months based on Pap smear and colposcopic biopsy. Health service costs were estimated using micro-costing between June 2013 and April 2014. Capital costs were annualized using a discount rate of 3%. Two different service volume scenarios were considered, and results from an as-treated analysis were considered in sensitivity analysis. RESULTS: In total, 166 women with CIN2+ were enrolled (86 had LEEP; 80 had cryotherapy). At 12 months, cumulative loss to follow-up was 12.8% (11/86) for the LEEP group and 13.8% (11/80) for cryotherapy. Based on the unadjusted intention-to-treat analysis conducted for this economic evaluation, there was no significant difference in efficacy. At 12 months, 83.8% (95% CI 73.8-91.1) of women with CIN2+ at baseline and randomized to cryotherapy were free of CIN2+ disease. In contrast, 76.7% (95% CI 66.4-85.2) of women assigned to LEEP were free from disease. On average, women initially treated with cryotherapy were less costly per patient randomized at US$ 118.00 (113.91-122.10), and per case "cured" at US$ 140.90 (136.01-145.79). Women in the LEEP group cost US$ 162.56 (157.90-167.22) per patient randomized and US$ 205.59 (199.70-211.49) per case cured. In the as-treated analysis, which was based on trial data, LEEP was more efficacious than cryotherapy; however, the difference was not significant. Cryotherapy remained more cost-effective than LEEP in all sensitivity and scenario analyses. CONCLUSIONS: For this cost-effectiveness analysis, using an intention-to-treat approach and taking into consideration uncertainty in the clinical and cost outcomes, a strategy involving cryotherapy plus LEEP if needed at six months was dominant to LEEP plus LEEP again at six months if needed for retreatment. However, compared to other studies comparing LEEP and cryotherapy, the efficacy results were low in both treatment groups-possibly due to the HIV-positivity of the participants. Further research is needed, but at present choosing the "right" treatment option may be less important than ensuring access to treatment and providing careful monitoring of treatment outcomes.

Prevention of 5-fluorouracil-related stomatitis by oral cryotherapy: a randomized controlled study.

Stomatitis is a common adverse effect of intravenously infused 5-fluorouracil (5FU). Although there are encouraging studies about the preventive role of oral cryotherapy in stomatitis induced by intravenous administration of 5FU, this simple and cost-effective method is not part of clinical practice. This prospective randomized study investigates whether oral cryotherapy alleviates 5FU-induced stomatitis. Thirty six patients, included in the cryotherapy group, were instructed to hold ice cubes in their oral cavity, shortly before, during and shortly after the infusion of 5FU. Both mean physician and patient-graded stomatitis of our cryotherapy group were compared with those of a control group (40 patients) and were found significantly reduced for all three chemotherapy cycles. The percentage of patients who were free from oral toxicity was significantly higher in the cryotherapy group in all three chemotherapy cycles, as judged both by patients and physicians. The results of this study encourage the use of cryotherapy in patients receiving 5FU in alleviating stomatitis by using a side-effect-free, easy to perform and inexpensive measure, which does not interfere with the efficacy of antineoplastic agents.