Adaptive Health Technology Assessment: A Scoping Review of Methods.

OBJECTIVES: Health technology assessment (HTA) is an established mechanism for explicit priority setting to support universal health coverage. However, full HTA requires significant time, data, and capacity for each intervention, which limits the number of decisions it can inform. Another approach systematically adapts full HTA methods by leveraging HTA evidence from other settings. We call this "adaptive" HTA (aHTA), although in settings where time is the main constraint, it is also called "rapid HTA." METHODS: The objectives of this scoping review were to identify and map existing aHTA methods, and to assess their triggers, strengths, and weaknesses. This was done by searching HTA agencies' and networks' websites, and the published literature. Findings have been narratively synthesized. RESULTS: This review identified 20 countries and 1 HTA network with aHTA methods in the Americas, Europe, Africa, and South-East Asia. These methods have been characterized into 5 types: rapid reviews, rapid cost-effectiveness analyses, rapid manufacturer submissions, transfers, and de facto HTA. Three characteristics "trigger" the use of aHTA instead of full HTA: urgency, certainty, and low budget impact. Sometimes, an iterative approach to selecting methods guides whether to do aHTA or full HTA. aHTA was found to be faster and more efficient, useful for decision makers, and to reduce duplication. Nevertheless, there is limited standardization, transparency, and measurement of uncertainty. CONCLUSIONS: aHTA is used in many settings. It has potential to improve the efficiency of any priority-setting system, but needs to be better formalized to improve uptake, particularly for nascent HTA systems.

A menace to fraternity: Early congenital syphilis - A rare case report.

Congenital syphilis (CS), once a forgotten disease, has now remerged. A 2-month-old male child presented with multiple discrete skin-colored papules over the trunk, back, bilateral lower limbs, and groin. He also had a deformity of bilateral lower limbs and a widening at the wrist. Radiological findings suggested syphilitic changes in long bones. Nontreponemal as well as treponemal tests were positive in the baby and both parents confirming the diagnosis of CS. The father had a history of multiple sex partners and untreated genital lesions in the past. The case emphasizes the importance of awareness regarding sexually transmitted infections and its timely treatment and judicious antenatal screening for the same.

Resource use, availability and cost in the provision of critical care in Tanzania: a systematic review.

OBJECTIVES: Critical care is essential in saving lives of critically ill patients, however, provision of critical care across lower resource settings can be costly, fragmented and heterogenous. Despite the urgent need to scale up the provision of critical care, little is known about its availability and cost. Here, we aim to systematically review and identify reported resource use, availability and costs for the provision of critical care and the nature of critical care provision in Tanzania. DESIGN: This is a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: Medline, Embase and Global Health databases were searched covering the period 2010 to 17 November 2020. ELIGIBILITY CRITERIA: We included studies that reported on forms of critical care offered, critical care services offered and/or costs and resources used in the provision of care in Tanzania published from 2010. DATA EXTRACTION AND SYNTHESIS: Quality assessment of the articles and data extraction was done by two independent researchers. The Reference Case for Estimating the Costs of Global Health Services and Interventions was used to assess quality of included studies. A narrative synthesis of extracted data was conducted. Costs were adjusted and reported in 2019 US$ and TZS using the World Bank GDP deflators. RESULTS: A total 31 studies were found to fulfil the inclusion and exclusion criteria. Critical care identified in Tanzania was categorised into: intensive care unit (ICU) delivered critical care and non-ICU critical care. The availability of ICU delivered critical care was limited to urban settings whereas non-ICU critical care was found in rural and urban settings. Paediatric critical care equipment was more scarce than equipment for adults. 15 studies reported on the costs of services related to critical care yet no study reported an average or unit cost of critical care. Costs of medication, equipment (eg, oxygen, personal protective equipment), services and human resources were identified as inputs to specific critical care services in Tanzania. CONCLUSION: There is limited evidence on the resource use, availability and costs of critical care in Tanzania. There is a strong need for further empirical research on critical care resources availability, utilisation and costs across specialties and hospitals of different level in low/middle-income countries like Tanzania to inform planning, priority setting and budgeting for critical care services. PROSPERO REGISTRATION NUMBER: CRD42020221923.

Role of healthcare cost accounting in pricing and reimbursement in low-income and middle-income countries: a scoping review.

OBJECTIVES: Progress towards universal health coverage (UHC) requires evidence-based policy including good quality cost data systems. Establishing these systems can be complex, resource-intensive and take time. This study synthesises evidence on the experiences of low-income and middle-income countries (LMICs) in the institutionalisation of cost data systems to derive lessons for the technical process of price-setting in the context of UHC. DESIGN: A scoping review and narrative synthesis of publicly available information. DATA SOURCES: PubMed, MEDLINE, EconLit, the Web of Science and grey literature searched from January 2000 to April 2021. ELIGIBILITY CRITERIA: English-language papers published since 2000 that identified and/or described development of and/or methods used to estimate or inform national tariffs for hospital reimbursement in LMICs. Papers were screened by two independent reviewers. DATA EXTRACTION AND SYNTHESIS: Extraction was performed by one reviewer and checked by the second reviewer on: the method and outputs of cost data collection; commentary on the use of cost data; description of the technical process of tariff setting; and strengths and challenges of the approach. Evidence was summarised using narrative review. RESULTS: Thirty of 484 papers identified were eligible. Fourteen papers reported on primary cost data collection; 18 papers explained how cost evidence informs tariff-setting. Experience was focused in Asia (n=22) with countries at different stages of developing cost systems. Experiences on cost accounting tend to showcase country costing experiences, methods and implementation. There is little documentation how data have been incorporated into decision making and price setting. Where cost information or cost systems have been used, there is improved transparency in decision making alongside increased efficiency. CONCLUSIONS: There are widely used and accepted methods for generating cost information. Countries need to build sustainable cost systems appropriate to their settings and budgets and adopt transparent processes and methodologies for translating costs into prices.

Association of Population Screening for Breast Cancer Risk With Use of Mammography Among Women in Medically Underserved Racial and Ethnic Minority Groups.

Importance: Black women bear a disproportionate burden of breast cancer mortality in the US, in part due to inequities in the use of mammography. Population screening for breast cancer risk in primary care is a promising strategy for mitigating breast cancer disparities, but it is unknown whether this strategy would be associated with increased mammography rates in underserved women of racial and ethnic minority groups. Objective: To examine whether providing individualized breast cancer risk estimates is associated with an increase in the rate of screening mammography. Design, Setting, and Participants: A cohort study was conducted in women receiving individualized risk estimates as part of routine primary health care at federally qualified health centers in medically underserved communities in Chicago, Illinois. The study was conducted from November 5, 2013, to December 19, 2014, with data acquisition completed on March 5, 2017; data analysis was performed from December 30, 2020, to February 2, 2021. A total of 347 women aged 25 to 69 years without a personal history of breast cancer presenting for an annual visit with their primary care clinician were enrolled. Exposures: Breast cancer risk estimates were obtained with validated risk assessment tools as a standard component of the clinic check-in process. One of 4 women at average risk and all women at high risk were invited to participate in the study. Main Outcomes and Measures: The primary outcome was the mammography rate during 18 months of usual care compared with the rate during 18 months after implementation of risk assessment. Results: Of the 347 women enrolled, 188 were age-eligible for mammography and were included in the analysis (mean [SD] age, 50.8 [7.04] years); 70 women (37.2%) were Hispanic, 114 (60.6%) were non-Hispanic African American, and 4 (2.1%) were from other racial and ethnic groups (4 non-Hispanic White women). Ninety-eight women (52.1%) had an average risk of developing breast cancer and 90 (47.9%) were at high risk. Overall, there was a nonsignificant increase in the mammography rate, from 38.8% during usual care to 48.9% following implementation of risk assessment (odds ratio, 1.37; 95% CI, 0.92-2.03). In preplanned subgroup analysis, the mammography rate among women at high risk was significantly higher after vs before risk assessment (51.1% vs 36.6%; odds ratio, 1.88; 95% CI, 1.10-3.23). Conclusions and Relevance: In this study, providing individualized breast cancer risk estimates as a component of primary health care in federally qualified health centers was associated with increased use of mammography among women of racial and ethnic minority groups who were at high risk. Implementation of this approach in underserved communities could promote equity in the use of mammography and reduce racial disparities in breast cancer mortality. This strategy warrants further investigation.

Resource availability, utilisation and cost in the provision of critical care in Tanzania: a protocol for a systematic review.

INTRODUCTION: Critical care is essential in saving lives of those that are critically ill, however, provision of critical care can be costly and heterogeneous across lower-resource settings. This paper describes the protocol for a systematic review of the literature that aims to identify the reported costs and resources available for the provision of critical care and the forms of critical care provision in Tanzania. METHODS AND ANALYSIS: The review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Three databases (MEDLINE, Embase and Global Health) will be searched to identify articles that report the forms of critical care, resources used in the provision of critical care in Tanzania, their availability and the associated costs. The search strategy will be developed from four key concepts; critical care provision, critical illness, resource use, Tanzania. The articles that fulfil the inclusion and exclusion criteria will be assessed for quality using the Reference Case for Estimating the Costs of Global Health Services and Interventions checklist. The extracted data will be summarised using descriptive statistics including frequencies, mean and median of the quantity and costs of resources used in the components of critical care services, depending on the data availability. This study will be carried out between February and November 2021. ETHICS AND DISSEMINATION: This study is a review of secondary data and ethical clearance was sought from and granted by the Tanzanian National Institute of Medical Research (reference: NIMR/HQ/R.8a/Vol. IX/3537) and London School of Hygiene and Tropical Medicine (ethics ref: 22866). We will publish the review in a peer-reviewed journal as an open access article in addition to presenting the findings at conferences and public scientific gatherings. PROSPERO REGISTRATION NUMBER: The protocol was registered with PROSPERO; registration number: CRD42020221923.

Agricultural land-uses consistently exacerbate infectious disease risks in Southeast Asia.

Agriculture has been implicated as a potential driver of human infectious diseases. However, the generality of disease-agriculture relationships has not been systematically assessed, hindering efforts to incorporate human health considerations into land-use and development policies. Here we perform a meta-analysis with 34 eligible studies and show that people who live or work in agricultural land in Southeast Asia are on average 1.74 (CI 1.47-2.07) times as likely to be infected with a pathogen than those unexposed. Effect sizes are greatest for exposure to oil palm, rubber, and non-poultry based livestock farming and for hookworm (OR 2.42, CI 1.56-3.75), malaria (OR 2.00, CI 1.46-2.73), scrub typhus (OR 2.37, CI 1.41-3.96) and spotted fever group diseases (OR 3.91, CI 2.61-5.85). In contrast, no change in infection risk is detected for faecal-oral route diseases. Although responses vary by land-use and disease types, results suggest that agricultural land-uses exacerbate many infectious diseases in Southeast Asia.

Phase I Study of Aurora A Kinase Inhibitor Alisertib (MLN8237) in Combination With Selective VEGFR Inhibitor Pazopanib for Therapy of Advanced Solid Tumors.

OBJECTIVES: Pazopanib is a multikinase angiogenesis inhibitor. Alisertib is a highly selective inhibitor of mitotic Aurora A kinase. There is preclinical evidence that mitosis-targeting agents exhibit antiangiogenic effects. Thus, the combination of these 2 agents may have a synergistic effect on tumor vasculature. The primary objective of this study is to determine the optimal tolerated dose (OTD) for alisertib and pazopanib. MATERIALS AND METHODS: This phase 1b study evaluated the OTD of alisertib twice a day, on days 1 to 7 with pazopanib, once a day, continuously in a 21-day cycle, both taken orally. Disease response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 every 2 cycles. OTD cohort was expanded to assure safety and perform pharmacokinetics analysis. RESULTS: A total of 27 patients received treatment. Seventy-seven percent of the patients had received at least 3 prior chemotherapy regimens. Dose-limiting toxicities occurred in dose level (DL) 2+ (grade 4 thrombocytopenia and grade 3 mucositis) and DL 3 (grade 3 liver transaminases elevation and grade 3 abdominal pain). The OTD was determined to be DL 2: alisertib 20 mg twice daily and pazopanib 600 mg daily. Pharmacokinetic analysis revealed that clearance of alisertib was reduced by ∼40% in the presence of pazopanib compared with clearance in the absence of pazopanib. Fourteen patients had stable disease and 2 patients had a partial response. CONCLUSIONS: The combination of alisertib with pazopanib demonstrates manageable safety and early clinical evidence of antitumor activity in patients with advanced malignancies (NCT01639911).

A feasibility study of breast cancer genetic risk assessment in a federally qualified health center.

BACKGROUND: The US Preventive Services Task Force (USPSTF) endorses routine screening for genetic risk of breast and/or ovarian cancer as a component of primary health care. Implementation of this recommendation may prove challenging, especially in clinics serving disadvantaged communities. METHODS: The authors tested the feasibility of implementing the USPSTF mandate at a federally qualified health center (FQHC) to identify women who were eligible for genetic counseling (GC). A 12-month usual-care phase was followed by a 12-month intervention phase, during which time cancer genetic risk assessment (CGRA) was systematically performed for all women aged 25 to 69 years who presented for an annual examination. Women who were eligible for GC were recruited to participate in the study. RESULTS: After initiating CGRA, 112 women who were eligible for GC consented to study participation, and 56% of them received a referral for GC from their primary care physician. A subgroup of 50 participants were seen by the same primary care physician during both the usual-care and intervention phases. None of these patients was referred for GC during usual care, compared with 64% after the initiation of CGRA (P < .001). Only 16% of referred participants attended a GC session. CONCLUSIONS: Implementing USPSTF recommendations for CGRA as a standard component of primary health care in FQHCs is feasible and improves referral of minority women for GC, but more work is needed to understand the beliefs and barriers that prevent many underserved women from accessing cancer genetic services.

A study of clinicopathological characteristics of thyroid carcinoma at a Tertiary Care Center.

CONTEXT: To share clinicopathological data of thyroid carcinoma from a high volume Tertiary Care Centre in East India. AIM: To share the epidemiology and clinicopathological presentation of thyroid cancer at a high volume Tertiary Care Center in East India. SETTINGS AND DESIGN: Retrospective observational study. SUBJECTS AND METHODS: Forty-two consecutive patients of thyroid neoplasm diagnosed by fine needle aspiration cytology (FNAC) and primarily underwent surgical treatment from July 2005 to June 2012 were included. Retrospective data analyses of patient's records were done. STATISTICAL ANALYSIS USED: The statistical analysis was performed using Epi Info version 3.5.3. RESULTS: Forty-two patients underwent surgery for thyroid neoplasm. Median age of diagnosis was 39 years. It was 6 times more common in females (female:male - 6:1). Papillary carcinoma consists of 63.15%, follicular carcinoma consists of 23.68%, and medullary carcinoma and anaplastic carcinoma each consist of 5.26% of malignant cases. Out of them, lymph node metastases were seen in 17 patients (44.73%). FNAC shows positive predictive value of 89.74%. CONCLUSIONS: In our study, differentiated thyroid cancers were found to be more common in younger age group. Cervical lymph node metastases occur in a large number of patients. Central compartment lymph node dissection with exploration of lateral neck and modified neck dissection whenever needed is helpful in all cases of thyroid carcinoma for proper pathological staging. FNAC is rapid and efficient procedure with high positive predictive value in diagnosing thyroid neoplastic lesions.

Correlation of tumor mutational burden and treatment outcomes in patients with colorectal cancer.

BACKGROUND: The Cancer Genome Atlas (TCGA) showed that 16% of colorectal cancers (CRCs) display DNA repair mechanisms and high tumor mutational burden (TMB). Although, there is accumulating evidence of greater benefit of immunotherapy in tumors with high-TMB, its impact on response to chemotherapy is unknown. METHODS: In this retrospective cohort study, we investigated the impact of TMB on progression-free survival (PFS) of CRC patients treated at tertiary care oncology clinics who had their tumors profiled by next-generation sequencing (NGS). Low TMB (TMB-L) and intermediate/high TMB (TMB-I/H) were defined as ≤5 mutations per base (MB) or ≥6 MB, respectively. RESULTS: Seventy-four CRC patients (61 colon and 13 rectal cancers) were identified from the database. In the TMB-L cohort, irinotecan-based chemotherapy treated patients had improved PFS compared to oxaliplatin-based chemotherapy treated patients (11.9 vs. 6.5 months, P<0.001). No difference in PFS was observed between the two treatment cohorts in TMB-I/H group. There was also no difference in time to recurrence in the TMB-L and TMB-I/H arms in patients treated with oxaliplatin-based therapy in perioperative setting. CONCLUSIONS: TMB-L may be a predictive biomarker in a subset of CRC patients treated with chemotherapy but these results need to confirmed in larger studies.

One Health approach to cost-effective rabies control in India.

Over 20,000 rabies deaths occur annually in India, representing one-third of global human rabies. The Indian state of Tamil Nadu has pioneered a "One Health" committee to address the challenge of rabies in dogs and humans. Currently, rabies control in Tamil Nadu involves postexposure vaccination of humans after dog bites, whereas potential supplemental approaches include canine vaccination and sterilization. We developed a data-driven rabies transmission model fit to human rabies autopsy data and human rabies surveillance data from Tamil Nadu. Integrating local estimates for canine demography and costs, we predicted the impact of canine vaccination and sterilization on human health outcomes and evaluated cost-effectiveness according to the WHO criteria for India, which correspond to thresholds of $1,582 and $4,746 per disability-adjusted life-years (DALYs) for very cost-effective and cost-effective strategies, respectively. We found that highly feasible strategies focused on stray dogs, vaccinating as few as 7% of dogs annually, could very cost-effectively reduce human rabies deaths by 70% within 5 y, and a modest expansion to vaccinating 13% of stray dogs could cost-effectively reduce human rabies by almost 90%. Through integration over parameter uncertainty, we find that, for a cost-effectiveness threshold above $1,400 per DALY, canine interventions are at least 95% likely to be optimal. If owners are willing to bring dogs to central point campaigns at double the rate that campaign teams can capture strays, expanded annual targets become cost-effective. This case study of cost-effective canine interventions in Tamil Nadu may have applicability to other settings in India and beyond.

Periorbital hyperpigmentation: a study of its prevalence, common causative factors and its association with personal habits and other disorders.

BACKGROUND: Periorbital hyperpigmentation (POH) is one of the most commonly encountered conditions in routine dermatology practice. There are only few published studies about its prevalence, classification, and pathogenesis but none showing its association with habits, and other medical conditions in Indian patients. AIMS: To determine prevalence and type of POH, common causative factors, and its association with personal habits and other disorders within various age and sex groups. MATERIALS AND METHODS: Two hundred patients attending the dermatology OPD were included in study and were subjected to detailed history, careful clinical and Wood's lamp examination, eyelid stretch test and laboratory investigations. Clinical photographs of all patients were taken. RESULTS: POH was most prevalent in 16-25 years age group (47.50%) and in females (81%) of which majority were housewives (45.50%). Commonest form of POH was constitutional (51.50%) followed by post inflammatory (22.50%). Lower eyelids were involved in 72.50%. Grade 2 POH was seen in 58%. Wood's lamp examination showed POH to be dermal in 60.50%. Faulty habits were observed viz. lack of adequate sleep (40%), frequent cosmetic use (36.50%), frequent eye rubbing (32.50%), and lack of correction for errors of refraction like myopia in 12% patients. Strong association of POH with stress (71%), atopy (33%) and family history (63%) was noted. CONCLUSIONS: Periorbital hyperpigmentation is a multi-factorial entity. It is absolutely essential to classify the type of POH and determine underlying causative factors in order to direct appropriate measures for better and successful outcome in future.

A comparative study to evaluate efficacy, safety and cost-effectiveness between Whitfield's ointment + oral fluconazole versus topical 1% butenafine in tinea infections of skin.

AIMS AND OBJECTIVES: The aim of this study is to compare the efficacy, safety and cost-effectiveness of topical Whitfield's ointment plus oral fluconazole with topical 1% butenafine in tinea infections of the skin. MATERIALS AND METHODS: Patients were randomly allocated to the two treatment groups and advised to apply either agent topically twice-a-day for 4 weeks on the lesions and fluconazole (150 mg) was administered once a week for 4 weeks in the study group applying Whitfield's ointment. Patients were followed-up at an interval of 10 days for clinical score and global evaluation response was assessed at baseline and during each follow-up. RESULTS: Out of 120 patients enrolled in the study 103 completed the study. Patients treated with Whitfield's ointment and oral fluconazole reduced mean sign and symptom score from 8.81 ± 0.82 to 0.18 ± 0.59 while butenafine treated patients reduced it from 8.88 ± 0.53 to 0.31 ± 0.67 at the end of the treatment. Nearly, 98% patients were completely cleared of the lesion on the 3(rd) follow-up with both treatments. CONCLUSION: Whitfield's ointment with oral fluconazole is as efficacious, safe and cost-effective as compared with 1% butenafine in tinea infections of the skin.

A comparative randomized open label study to evaluate efficacy, safety and cost effectiveness between topical 2% sertaconazole and topical 1% butenafine in tinea infections of skin.

BACKGROUND: Dermatophytoses are the superficial fungal infections of skin, hair, and nail. Butenafine is a benzylamine group of antifungal that inhibits the biosynthesis of ergosterol by blocking squalene epoxidase. Sertaconazole is a newer imidazole antifungal which inhibits the biosynthesis of ergosterol by inhibiting 14-α lanosterol demethylase. The study was done to compare a newer antifungal with a relatively older one. AIM: To compare the efficacy, safety and cost effectiveness of topical 2% sertaconazole cream and 1% butenafine in tinea infections of skin. MATERIALS AND METHODS: Patients were randomly allocated to two treatment groups. They were advised to apply the drug topically twice a day for one month on the lesions. They were followed up at an interval of 10 days. Clinical score and Global Evaluation Response were assessed at baseline and during each follow up. RESULTS: A total 125 patients were recruited, out of them 111 completed the whole study. Median Sign and Symptom Score of tinea on the baseline was 9 [5,9] that was reduced to 0 [0,4] by 2% sertaconazole while it was 9 [6,9] in the butenafine group on the baseline that was reduced to 0 [0,6] at the end of the treatment. 98% and 90% of the patients got complete clearance of the lesions with butenafine and sertaconazole, respectively. Treatment with butenafine was more cost effective as compared to sertaconazole. CONCLUSION: 1% butenafine is more efficacious, cost effective, and equally safe as compared to 2% sertaconazole in the tinea infections of skin.

Comparative efficacy and safety of topical permethrin, topical ivermectin, and oral ivermectin in patients of uncomplicated scabies.

BACKGROUND: Ivermectin has opened a new era in the management of scabies as orally effective drug. However, topical route has been little explored for ivermectin. AIMS: To compare the efficacy and safety of topical permethrin, oral ivermectin, and topical ivermectin in the treatment of uncomplicated scabies. METHODS: This was an open-label, randomized, comparative, parallel clinical trial conducted in 315 patients, randomly allocated to 3 groups. First group received permethrin 5% cream as single application, second group received tablet ivermectin 200 mcg/kg as single dose, and third group received ivermectin 1% lotion as single application. All the patients received anti-histaminic for pruritus. The patients were followed up at intervals of 1, 2, 3, and 4 weeks. If there were no signs of cure, the same intervention was repeated at each follow up. Primary efficacy variable was clinical cure of lesions. Statistical analysis was done by chi square test and one way ANOVA test using SPSS version 12. RESULTS: At the end of first week, cure rate was 74.8% in permethrin group, 30% in oral ivermectin group, and 69.3% in topical ivermectin group (P < 0.05). At the end of second week, cure rate was 99% in permethrin group, 63% in oral ivermectin group, and 100% in topical ivermectin group (P < 0.05). At the end of third week, 100% cure rate was observed in permethrin and topical ivermectin group while 99% in oral ivermectin group (P = 0.367). No serious adverse events were observed. CONCLUSIONS: Permethrin and topical ivermectin were equally effective against scabies while oral ivermectin was significantly less effective up to 2 weeks. Topical ivermectin can be used as an alternative to permethrin.