Compelling Evidence Base Research Articles

Culling wildlife hosts to control disease: mountain hares, red grouse and louping ill virus

Summary 1. Culling wildlife hosts is often implemented as a management technique to control pathogen transmission from wildlife to domestic or other economically important animals. However, culling may have unexpected consequences, can be expensive and may have wider implications for biodiversity and ecosystem functioning. 2. We assess the evidence that culling mountain hares Lepus timidus is an effective and practical way to control louping ill virus in red grouse Lagopus lagopus scoticus. 3. Evidence from the available literature is limited, restricting our ability to reliably assess the effectiveness of culling mountain hares to control ticks, louping ill virus, or increase red grouse densities. Furthermore, the information required to assess the cost‐benefit of this management strategy is lacking. The population response of mountain hares to culling is not well understood and the possible effects on their conservation status and the upland ecosystem remain unexplored. 4. We conclude that there is no compelling evidence base to suggest culling mountain hares might increase red grouse densities. 5. Synthesis and applications. Widespread culling of wildlife is not necessarily effective in reducing disease or improving economic returns. The use of wildlife culls for disease control should be proposed only when: (i) the pathogen transmission cycle is fully understood with all host‐vector interactions considered; (ii) the response of wildlife populations to culling is known; and (iii) cost‐benefit analysis shows that increased revenue from reduced disease prevalence exceeds the cost of culling.

Acute ‘strokenomics’: efficacy and economic analyses of alteplase for acute ischemic stroke

Cerebrovascular disease is the leading cause of adult disability in Western countries and, as such, is associated with a considerable and increasing economic burden. Prevention of disability is preferable to a costly and prolonged period of rehabilitation; however, in this regard, we have only a limited number of acute treatments. Treatment of ischemic stroke with the tissue plasminogen activator alteplase has a considerable and compelling evidence base confirming its clinical efficacy. Good-quality trial data are complemented by years of ‘real-life’ clinical experience. There is limited pharmacoeconomic literature describing the use of alteplase in ischemic stroke, and published data are consistent and broadly supportive of its use in select patient populations. Delivery of stroke and other medical care can differ across countries; however, models based on American, Canadian and European data suggest that following initial monetary investment, net healthcare-associated costs for tissue plasminogen activator-treated patients are less than for untreated contemporaries. Potential savings are driven by reduced disability and associated long-term care costs. At present, robust economic data are only available for the period of 1-year following stroke. Continuing cost savings associated with reduced disability in the longer term make intuitive sense but are yet to be confirmed. A recurring theme in these economic analyses is of reducing healthcare costs associated with the increasing use of thrombolysis. In this regard, it is unfortunate that rates of tissue plasminogen activator utilization remain modest in most centers. This review will discuss the economics of alteplase in acute stroke, making particular reference to the current and projected economic burden of stroke, the evidence base for thrombolysis and published literature on the economics analyses of this therapy.

An update on papillary microcarcinoma

There is a worldwide increasing incidence of thyroid cancer, mostly due to the increased diagnosis of papillary microcarcinoma (PMC). This review examines its clinical significance and optimal treatment. It is unclear whether or not the increase in PMC is real, or is simply due to the increased detection and diagnosis. The increase has been attributed to the widespread availability of thyroid ultrasound, with increasing numbers of clinically insignificant thyroid nodules subject to fine needle aspiration biopsy and surgical excision. An additional explanation is simply an increase in the number of routine histologic sections taken from the thyroidectomy specimens over the years. There have been two recent large clinical series with long-term follow-up highlighting the excellent prognosis of PMC. Novel research into immunohistochemical markers and advanced imaging with fluorodeoxyglucose positron emission tomography aims to identify the markers of more aggressive PMC. Management of PMC remains controversial, from observation alone to total thyroidectomy/radioiodine ablation. PMC has been increasing rapidly over recent decades due to increased cervical ultrasound and increased detection in pathological specimens. There is no compelling evidence base for the management of PMC, with retrospective series highlighting the excellent prognosis.

Diabetes Prevention - From Physiology to Implementation

One of the major challenges today is the development of prevention programs for the clinical practice. Our aim was to develop a concept for a primary diabetes prevention program to be implemented in general health care. Lifestyle intervention addressing diet and exercise has reduced the diabetes risk by up to 58%. Early preventive pharmacological strategies have yielded a diabetes risk reduction of 25-30%. These findings offer a compelling evidence base, but delivery of intervention and care is essential. The challenge therefore is the management of prevention and intervention programs considering scientific aspects and practical requirements during implementation. The Diabetes Prevention Workgroup at the German Diabetes Association has developed a concept for a decentralized prevention program. Based on the results of the prevention studies, the intervention concept consists of a three-step program including identification of the individuals at high risk to develop type 2 diabetes (1), followed by general intervention based on individual choice (2) and maintained continuous intervention for motivation maintenance (3). Structured prevention programs will enable nationwide prevention of diabetes mellitus without consuming large resources. This process will be challenging and time consuming, requiring many partners but resulting in a profitable "health" investment.

Prevention of type 2 diabetes: what challenges do we have to address?

The worldwide epidemic of type 2 diabetes mellitus is a major challenge for medical care and health-care systems. Type 2 diabetes is a complex metabolic disease developing in genetically susceptible individuals as a result of environmental and lifestyle risk factors. These risk factors are well known: obesity, central adiposity, physical inactivity and an unhealthy diet. To prevent the personal and socioeconomic burden of diabetes, the effort to prevent the disease needs to be started before the its onset and should address all susceptibility factors. Four recent studies have shown that prevention of type 2 diabetes is possible and that reinforced lifestyle intervention/modification can significantly reduce the onset of the disease. The studies showed repeatedly that diabetes was prevented from developing in about 60% of those with an increased diabetes risk compared to a control group. Early pharmacological preventive strategies have yielded a 25–30% risk reduction. These studies have convincingly demonstrated that the primary aim in prevention of type 2 diabetes is the stabilization of glucose tolerance due to improvement of insulin resistance. Based on the results of the studies, the intervention protocol focused on achieving five core goals. With respect to the worldwide burden of diabetes, these studies offer a compelling evidence base for the translation of the research findings into community-based prevention strategies on a national scale. The workgroup “Diabetes Prevention” at the German Diabetes Association together with the German Diabetes Foundation have developed a concept for a National Diabetes Prevention Programme. To achieve this, a large number of partners are necessary. For the implementation of such a programme at the population level, the intervention is primarily based on reinforced behaviour modification (lifestyle and physical activity). In addition, the pharmacoprevention of type 2 diabetes will be of increasing importance.

An Increasingly Common Challenge: Management of the Complete Responder With Multi-Focal Metastatic Colorectal Cancer

K.A. is a 61-year-old woman diagnosed with a nonobstructing, moderately differentiated adenocarcinoma of the ascending colon in the spring of 2003. At diagnosis, she had palpable left supraclavicular adenopathy that was biopsied and found to be consistent with metastasis of colonic primary tumor. Contrast-enhanced computed tomography (CT) scan of the chest, abdomen, and pelvis revealed wall thickening of the ascending colon as well as diffuse adenopathy in hilar, gastrohepatic, retroperitoneal, para-aortic, mesenteric, and iliac regions. Pretreatment fluorodeoxyglucose positron emission tomography (FDG PET) scan revealed diffuse uptake in these multiple nodal stations but no evidence of pulmonary or hepatic involvement. The patient was a widowed administrator for a nursery school program and had no notable past medical history and an unremarkable family history. When the patient presented for medical oncology opinion in June 2003, she had intermittent, mild, crampy abdominal pain, no melena or bright red blood per rectum, and was able to tolerate a low residue diet. She had experienced an 8-lb unintentional weight loss but denied fevers, chills, or sweats. She was informed that treatment options for stage IV colon cancer are palliative rather than curative, with median survival estimated at 20 months based on recent clinical trials. The FOLFOX6 regimen, consisting of biweekly fluorouracil, leucovorin, and oxaliplatin, was recommended. With initiation of treatment, her abdominal cramping improved, and the left supraclavicular lymph node was no longer palpable after three cycles. Treatment was administered for five cycles, and first interval restaging CT scan indicated dramatic response. Treatment was continued for five more cycles, and the second restaging revealed persistence of the colonic primary and stable adenopathy (Fig 1B). The patient was able to continue work during treatment and experienced transient neutropenia, fatigue, nausea, and mild neuropathy. Although she tolerated therapy well, because comparison of her first and second interval CT scans suggested that her response to FOLFOX had reached a plateau, she was referred to a colorectal surgeon for consultation regarding the possibility of resection of the primary tumor. To further evaluate the extent of residual tumor, PET scan was obtained and revealed persistent uptake in the ileocecal region (standardized uptake value 4.0) primary, but no evidence of increased uptake in areas corresponding to the multifocal adenopathy appreciated on the pretreatment PET scan. In January 2004, the patient opted for surgery despite both the surgeon and the oncologist’s caution that there is no compelling evidence base to suggest that resection of the primary tumor in this circumstance provides survival advantage. At exploratory laparotomy, stricture of the ascending colon was appreciated, and an extended right hemicolectomy with resection of mesentery and regional lymph nodes was performed. Gross pathologic examination revealed an ulcerated firm lesion in the proximal ascending colon that, under microscopic examination, consisted of transmural fibrosis and inflammation associated with surface ulceration. Sixteen regional lymph nodes were recovered, and all 16 were negative for metastasis. No residual viable tumor was identified in the entire resection specimen (Figs 2C and 2D). Thus, this patient with pathologically confirmed distant disease has a surgically confirmed complete response to 10 cycles of FOLFOX therapy. JOURNAL OF CLINICAL ONCOLOGY COMMENTS AND CONTROVERSIES VOLUME 23 NUMBER 9 MARCH 2