Estimating the economic impact of pneumococcal conjugate, Haemophilus influenzae type b and rotavirus vaccines in India: National and state-level analyses.

BACKGROUND: To support vaccine decision-making we estimated from the societal perspective the potential health impact and costs averted through immunization with three vaccines - Haemophilus influenzae type b (Hib), pneumococcal conjugate vaccine (PCV) and rotavirus vaccine (RVV). METHODS: Based on variability in disease burden, strength of health system and economic status, we selected four states in India: Bihar, New Delhi, Maharashtra and Tamil Nadu. We used secondary data sources to estimate the number of under-5 deaths averted from Hib, pneumococcus and rotavirus in each state and back-calculated the total cases averted. We synthesized available data to estimate the disease burden, treatment cost, caretaker productivity loss and vaccine coverage in each state. A Delphi Survey and roundtable among Indian experts was conducted to reach consensus on model inputs. RESULTS: By scaling up coverage of Hib, PCV and RVV, India could save over US$1 billion (uncertainty range: US$0.9-US$2.4 billion) in economic benefits and avert more than 90,000 needless child deaths each year. An estimated US$1 billion (US$0.9-US$2 billion) or 88% of the total amount of cost savings would be attributable to lost productivity due to premature pneumococcal death. Another US$112.8 million (US$105-297 million), or 10% of the total cost would be accounted by costs related to loss of productivity due to disability as a result of these diseases. Treatment costs of Hib, pneumococcal disease and rotavirus gastroenteritis, would account for US$8.4 million (US$4-12 million) or <1% of the total costs of these diseases. Finally, caretaker productivity loss from seeking care would represent US$1.5 million (US$ 1-4.9 million). Cost savings varied by vaccine, coverage scenarios and states. CONCLUSIONS: Hib, PCV and RVV vaccine introduction in India can result in immediate benefits to the government and households in terms of savings.

A Review of the Economic Evidence of Typhoid Fever and Typhoid Vaccines.

Typhoid places a substantial economic burden on low- and middle-income countries. We performed a literature review and critical overview of typhoid-related economic issues to inform vaccine introduction. We searched 4 literature databases, covering 2000-2017, to identify typhoid-related cost-of-illness (COI) studies, cost-of-delivery studies, cost-effectiveness analyses (CEAs), and demand forecast studies. Manual bibliographic searches of reviews revealed studies in the gray literature. Planned studies were identified in conference proceedings and through partner organization outreach. We identified 29 published, unpublished, and planned studies. Published COI studies revealed a substantial burden in Asia, with hospitalization costs alone ranging from $159 to $636 (in 2016 US$) in India, but there was less evidence for the burden in Africa. Cost-of-delivery studies are largely unpublished, but 1 study found that $671 000 in government investments would avert $60 000 in public treatment costs. CEA evidence was limited, but generally found targeted vaccination programs to be cost-effective. This review revealed insufficient economic evidence for vaccine introduction. Countries considering vaccine introduction should have access to relevant economic evidence to aid in decision-making and planning. Planned studies will fill many of the existing gaps in the literature.

Economic Impact of Meningococcal Outbreaks in Brazil and Colombia.

Background. The impact of meningitis outbreaks is substantial. We aim to calculate the costs of meningococcal outbreaks in Brazil and Colombia from the healthcare system perspective. Methods. A review of the literature was performed on costs associated with meningococcal outbreak in Latin America. Structured interviews capturing information about the use of resources, expenses allocated to treatment of infection, immunization campaigns, and response activities during the outbreak and disease surveillance pre- and postoutbreak were directed at local health authorities in Brazil and Colombia to foster a greater understanding of the economic impact of meningococcal outbreaks. All costs were expressed in 2014 US values. Results. The Vila Brandina outbreak in Brazil reported 3 cases that were associated with a total investigation and outbreak management cost of $34 425 ($11 475 per notified case), representing 2.7 more than the annual gross domestic product per capita in Brazil. In contrast, the outbreak in Cartagena de Indias in Colombia reported 6 cases at a cost of the disease response phase of $735 or 9.5% of the annual gross domestic product per capita ($123 per notified case). For the disease surveillance phase, the costs ranged from $3935 (in Cartagena de Indias) to $6667 (in Vila Brandina). Serogroups B and C were responsible for the majority of meningococcal outbreaks reported in Brazil and Colombia. Conclusions. Findings of this study underscore the importance of meningococcal disease in the region. Future research should focus on a more detailed investigation of costs of meningococcal outbreaks covering all phases of an outbreak.

[Economic impact of rotavirus vaccination in Panama]. / Impacto económico de la vacuna antirrotavirus en Panamá

INTRODUCTION: Rotavirus (RV) gastroenteritis (GE) causes a significant health and economic burden in Panama. The main objective of this study is to estimate the healthcare costs and the cost-effectiveness of vaccination in Panama from the societal perspective. METHODS: An economic model was constructed, using published epidemiological data, country-specific cost estimates, and vaccine efficacy data. The main outcome measures were disease burden, economic burden and the incremental cost-effectiveness ratio (US$/DALY and US$/life saved) of vaccination. RESULTS: In Panama, among children during the first five years of life, it is estimated that due to RV GE, 283 per 1,000 have a clinic visit, 24 per 1,000 are hospitalized, and 0.53 per 1,000 die. For every 1,000 children born, RV infection results in US$16,463 in total costs during their first five years of life. An estimated US$862,388 may be spent annually on treatment of outpatient and hospitalized cases in Panama. Vaccination would prevent 65% of the associated deaths, 68% of hospitalizations, 69% of outpatient visits and 65% of associated DALY (Disability Adjusted Life Years). From the societal perspective, RV vaccination produces a cost-effectiveness ratio of US$487 per DALY when the price of the vaccine is US$7.50 per dose. CONCLUSIONS: Vaccination can effectively reduce the disease burden and healthcare costs of RV GE in Panama.

Granulosa cell tumours of the ovary: demographics, survival and the management of advanced disease.

Ovarian granulosa cell tumours (OGCT) are rare, accounting for only 3%-5% of primary ovarian tumours. As a result of oestrogen production OGCTs tend to present with early stage disease, which has a good prognosis. For patients with advanced disease, surgery and radiotherapy have been the major modalities of treatment. More recently, platinum-based chemotherapy has been shown to have important activity in advanced disease. In this retrospective study, we have reviewed the results of 62 patients who were treated for adult OGCT at the Royal Marsden Hospital between 1969 and 1995, with particular emphasis on the management of advanced disease. The median age at primary diagnosis was 53 years (range 13-77). Sixty-one per cent of these patients had Stage I disease, 21% Stage II disease, 16% Stage III and 2% Stage IV. Stage I patients had a good prognosis with 5- and 10-year overall survival rates of 95% and 90%. Eleven Stage I patients received adjuvant pelvic radiotherapy, with no apparent benefit to recurrent rate or overall survival. Disease progression occurred in 40% of Stage I patients at a median interval of 76 months (range 12-240), and in 62% of the Stage II patients, at a median interval of 31 months (range 2-57). The median interval from progression of Stage I/II disease to death was 22 months (range 3-144). For patients with inoperable disease, radiotherapy produced a number of long-term remissions with an overall response rate of 50%. Platinum-based chemotherapy also appears active, with responses documented in four out of five patients treated with the PVB regimen (cisplatin, vinblastine, bleomycin) as first line therapy. There were no responses documented to non-platinum chemotherapy or to hormonal manipulation. The results from this study confirm the activity of platinum-containing chemotherapy regimens in OGCT and support the need for further trials to optimize the management of this rare tumour.

Randomized phase II trial of BCDT [carmustine (BCNU), cisplatin, dacarbazine (DTIC) and tamoxifen] with or without interferon alpha (IFN-alpha) and interleukin (IL-2) in patients with metastatic melanoma.

The purpose of this study was to evaluate in a randomized phase II trial the efficacy and toxicity of combination biochemotherapy compared with chemotherapy alone in patients with metastatic melanoma. Sixty-five patients with metastatic melanoma (ECOG performance status 0 or 1) were randomized to receive intravenous BCNU 100 mg m(-2) (day 1, alternate courses), cisplatin 25 mg m(-2) (days 1-3), DTIC 220 mg m(-2) (days 1-3) and oral tamoxifen 40 mg (BCDT regimen) with (n = 35) or without (n = 30) subcutaneous interleukin 2 (IL-2) 18 x 10(6) iu t.d.s. (day - 2), 9 x 10(6) iu b.d. (day - 1 and 0) and interferon 2 alpha (IFN-alpha) 9 MU (days 1-3). Evidence for immune activation was determined by flow cytometric analysis of peripheral blood lymphocytes. Treatment was repeated every 4 weeks up to six courses depending on response. The overall response rate of BCDT with IL-2/IFN-alpha was 23% [95% confidence interval (CI) 10-40%] with one complete response (CR) and seven partial responses (PR), and for BCDT alone 27% (95% CI 12-46%) with eight PRs; the median durations of response were 2.8 months and 2.5 months respectively. Sites of response were similar in both groups. There was no difference between the two groups in progression-free survival or overall survival (median survival 5 months for BCDT with IL-2/IFNalpha and 5.5 months for BCDT alone). Although 3 days of subcutaneous IL-2 resulted in significant lymphopenia, evidence of immune activation was indicated by a significant rise in the percentage of CD56- (NK cells) and CD3/HLA-DR-positive (activated T cells) subsets, without any change in the percentage of CD4 or CD4 T-cell subsets. Toxicity assessment revealed a significantly higher incidence of severe thrombocytopenia in patients treated with combination chemotherapy than with chemotherapy alone (37% vs 13%, P = 0.03) and a higher incidence of grade 3/4 flu-like symptoms (20% vs 10%) and fatigue (26% vs 13%). The addition of subcutaneous IL-2 and IFNalpha to BCDT chemotherapy in a randomized phase II trial resulted in immune activation but did not improve response rates in patients with metastatic melanoma, and indeed may increase some treatment-related toxicity.

Cisplatin and 5-fluorouracil for symptom control in advanced salivary adenoid cystic carcinoma.

Adenoid cystic carcinoma is a relatively rare tumour which arises in the parotid and submandibular salivary glands. Initial management is surgical, often with post-operative radiotherapy, but local relapse is common and distant metastasis not infrequent. Chemotherapy is generally reserved for cases where symptoms are not controlled by other means, since the tumour is slow growing and the response rate frequently disappointing. Cisplatin and 5-fluorouracil (5-FU) both show single agent activity in this disease but had not been previously investigated in combination. All patients referred for palliative chemotherapy of metastatic, symptomatic, histologically confirmed adenoid cystic carcinoma between November 1990 and February 1994 were considered for this study. The drugs were administered as follows: cisplatin 100 mg/m2 with appropriate pre- and post-hydration and 5-FU on a 4-day schedule of 1 g/m2/day. A total of 11 patients (7 male, 4 female) with median age 53 years (range 34-69) received 46 courses of chemotherapy (median four, range one to six). All patients had prior surgery and 8 had previously received radiotherapy. There were no objective responses of > 50% reduction in tumour size. 3 patients had a minor response and two progressed on treatment. The symptomatic response rate, however, was 64%, which compares favourably with other previously reported regimens. Toxicity was manageable. The median time to tumour progression was 9 months (range 0-38) and median survival was 12 months (range 1-65). This cisplatin/5-FU regimen would appear to produce a low rate of objective response but useful palliative benefits in advanced symptomatic adenoid cystic carcinoma. Prior series suggest that a higher objective response rate may be possible with a platinum/anthracycline/fluorouracil combination, and investigation of such a regimen is warranted.

Chemotherapy for symptom control in recurrent squamous cell carcinoma of the head and neck.

BACKGROUND: The role of chemotherapy in patients with recurrent squamous cell carcinomas of the head and neck (SCCHN) is unclear. The aim of this study was to assess the ability of combination chemotherapy to control symptoms in this setting. PATIENTS AND METHODS: Using a prospectively accrued database all patients referred for chemotherapy with symptomatic relapse following surgery were identified. Objective response was recorded using standard criteria and maximum symptom response was assessed retrospectively from case notes using a published scoring scale. RESULTS: A total of 57 (median age 56, range 37-85) patients were studied who had received mainly cisplatin/5-fluorouracil combinations. Thirty-seven had previously received radiotherapy. Fifty-two patients had evaluable disease; 18 (35%) had objective responses (14 PRs and 4 CRs). There were a total of 103 symptoms recorded with eight different individual symptoms. Forty-four (43%) symptoms improved on treatment, 52 (50%) were unchanged and 7 (7%) worsened. The number of patients with improvement in the most frequently recorded symptoms were as follows: pain 11/28 (39%), swelling 12/23 (52%) and dysphagia 6/18 (33%). Sixty-seven percent of patients with objective response also had an improvement in their symptoms but a significant proportion (33%) of non-responders had a symptomatic response. Lack of objective response was not correlated with worsening symptoms. Grade 3/4 toxicity was uncommon (6%-17%) and there were no toxic deaths. A majority of patients (82%) experienced either no change or an improvement in performance status. CONCLUSION: These results demonstrate that chemotherapy improves many of the symptoms associated with recurrent SCCHN, without deterioration in performance status. Symptomatic improvement is more likely if there is evidence of significant tumour shrinkage, but even non-responding patients can benefit.

The natural history and management of Merkel cell carcinoma of the skin: a review of 22 patients treated at the Royal Marsden Hospital.

Merkel cell carcinoma is a rare skin malignancy, which primarily affects the elderly. Currently, there is only limited data on the natural history of this condition and no consensus on its optimum management. We have reviewed the natural history and management of 22 patients with Merkel cell carcinoma, who were treated at the Royal Marsden Hospital between 1985 and 1994. The median age at diagnosis was 75 years (range 55-96), with the head and neck region being the most common site of disease (nine patients: 41%). Seventeen patients (77%) presented with skin disease, three (14%) with regional lymphadenopathy and two (9%) with metastatic disease. Of the Stage I patients, 41% developed local recurrence postoperatively at a median time to relapse of 12 months. Those with head and neck disease had the highest risk of local recurrence, which occurred in 62.5% of this group. Stage I patients also had a high risk of disease progression, with 53% developing regional lymphadenopathy or visceral metastases. The median survival for all disease stages was 47 months. The treatment of unresectable primary or recurrent disease with radiotherapy led to valuable long term control in four of nine patients treated. Six courses of chemotherapy were administered; one brief complete response was observed, occurring in a patient treated with cyclophosphamide, vincristine and doxorubicin. The data in this study confirms the predilection for the elderly and the aggressive nature of Merkel cell carcinoma, with only four of 17 Stage I patients remaining disease free. To clarify the role of adjuvant postoperative radiotherapy and to establish the appropriate use of chemotherapy in metastatic spread of this rare malignancy will require further studies with multicentre cooperation.