Paucity Of Good Quality Evidence Research Articles

Prion diseases motor and neuropsychiatric symptom cluster pharmacotherapy: structured scoping review

BackgroundPrion diseases are a group of rare, neurodegenerative conditions that are invariably fatal and cause a variety of symptoms, which can prove challenging to control. Through this paper, we aim...

International consensus on post-transplantation diabetes mellitus.

Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6-8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes.

The effect of a customised digital adherence tool on HIV treatment outcomes in young people living with HIV (YPLHIV) in Blantyre, Malawi: a protocol for a randomised controlled trial

BackgroundPeople living with HIV (PLHIV) have to take lifelong antiretroviral treatment, which is often challenging. Young people living with HIV (YPLHIV) have the lowest viral load suppression rates in Malawi and globally, mostly due to poor treatment adherence. This is a result of complex interactions of multiple factors unique to this demographic group. The use of digital health interventions, such as real-time medication monitor (RTMM)-based digital adherence tools (DATs), could improve ART adherence in YPLHIV and subsequently improve viral load suppression which in turn could lead to reduced HIV-associated morbidity and mortality.AimTo provide the evidence base for a digital adherence intervention to improve treatment outcomes in YPLHIV on ART.Objectives1. The primary objective is to determine the efficacy of a customised DAT compared to the standard of care in improving ART adherence in YPLHIV.2. The secondary objective is to determine the efficacy of the customised DAT compared to the standard of care in improving viral load suppression in YPLHIV.MethodologyThis will be a parallel open-label randomised control controlled two-arm trial in which non-adherent YPLHIV in selected ART facilities in Blantyre will be randomised in a 1:1 ratio to a customised DAT and standard care arms and followed up for 9 months. The primary outcome is the proportion adherent at 9 months (> = 95% by pill count), and the secondary outcome is the proportion with viral load suppressed at 9 months (< 200 copies/ml).DiscussionThere is a paucity of good quality evidence on effective digital health interventions to improve ART adherence and viral load suppression in YPLHIV globally and particularly in HIV high-burden settings like Malawi. This study will provide good-quality evidence on the effectiveness of a customised DAT in improving ART adherence and viral load suppression in this important demographic.Trial registrationThe trial has been registered in the Pan African Clinical Trials Registry number: PACTR202303867267716 on 23 March 2023 and can be accessed through the following URL: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25424. All items from the WHO Trial Registration Data Set are described in this manuscript.

Contemporary approaches for the management of aorto-iliac occlusive disease.

Aortoiliac occlusive disease (AIOD) secondary to peripheral arterial disease remains a challenging condition to manage due to anatomical complexities and comorbidities. Operative morbidity and mortality rates are high, and best-practice guidelines have traditionally been limited by a paucity of good quality evidence to aid decision-making. The advent of endovascular technology has enabled the clinician in providing a less invasive option in patients unsuitable for open surgery, but durability of endovascular approaches has remained questionable. However, emerging data on the contemporary management of aortoiliac occlusive disease is demonstrating comparable success rates between open and endovascular surgery. The purpose of this review is to provide an overview on the evolution of techniques, the contemporary management, limitations in the body of evidence and future treatment adjuncts aimed at improving success of intervention in aortoiliac occlusive disease.

A Qualitative Exploration of Consultant Anaesthetists Attitudes to, and Experiences of, Perioperative Medication Errors in Emergency and Elective Theatre Settings

In the UK, medication errors account for up to 20% of all reported adverse events in hospitalised patients. The potential for medication errors to occur during the peri-operative period is greater than in some other clinical settings and there is a paucity of good-quality evidence examining contributing factors.

Treatment of methicillin-resistant Staphylococcus aureus (MRSA): updated guidelines from the UK.

The UK guidelines for the treatment of infections caused by MRSA have been updated and are published in JAC-Antimicrobial Resistance. The update reviews new evidence published since the previous UK guidelines were published over 10 years ago. It includes evidence relating to antimicrobial agents that have been licensed since then for the treatment of Gram-positive bacterial infections including MRSA. It also considers the impact on treatment of the changing epidemiology of MRSA in the UK, especially relating to circulating community strains. A striking finding from the current literature review was the paucity of good quality evidence. The current guidelines therefore represent a hybrid of varying degrees of evidence and expert opinion. Where there was no new published evidence, we have retained some of the existing recommendations. We were unable to find strong evidence of the superior efficacy of newer agents compared with that of vancomycin.

Management of multiple trichoepithelioma: A review of pharmacological therapies.

Trichoepithelioma is a rare benign adnexal neoplasm that can occur in various forms including solitary, multiple, familial or nonfamilial. Multiple facial trichoepithelioma can be associated with significant psychosocial burden. Conventional treatment modalities such as surgical excision and ablative laser have variable results and can be associated with unacceptable complications and tumour regrowth. Pharmacological interventions such as topical and systemic agents are potentially effective but clinical data are limited and treatments are poorly standardised. We review the available evidence to determine the role of pharmacological therapies in the management of multiple trichoepithelioma. Demographic and clinical data were retrospectively collected from the available English literature. Majority of cases treated with pharmacological therapies (93.75%) had a positive treatment outcome, achieving partial lesion response. Adverse effects associated with pharmacological therapies were generally well tolerated and did not interrupt treatment. There are limitations as to how our results can be interpreted owing to the paucity of good quality evidence, spectrum of disease severity, and diversity of study designs utilised in the included articles. Nonetheless, the results of our study indicate that while most pharmacological interventions for multiple trichoepithelioma produce a partial response, they can be employed as effective suppressive therapies, either alone or in conjunction with conventional treatments. The current evidence for pharmacological therapies remains largely anecdotal justifying the need for further clinical studies in this area.

Trimodality treatment in malignant pleural mesothelioma - Ordeal or real deal?

Management of MPM is complex and controversial as there is a paucity of good quality evidence. We report the toxicity and outcomes in patients who received trimodality treatment for non-metastatic MPM at our institution. We reviewed the electronic medical records of surgically managed MPM patients at our institution in the last decade. Dosimetric parameters of target volume and organs at risk were documented by the treatment planning workstation. SPSS was used for statistical analysis. Between January 2008 and October 2018, 21 patients underwent surgery for MPM - all but 2 patients underwent extra-pleural pneumonectomy (EPP); epithelioid MPM was the most common histology. All patients, except 2, received neoadjuvant Pemetrexed/platinum doublet chemotherapy. Fourteen patients received adjuvant hemithoracic RT; ten patients were treated with a conformal technique at our institute and dosimetric data was available for analysis. Average time to start RT after surgery was 51 days (range 32-82 days). All patients were treated with a conformal technique using IMRT/VMAT to a dose of 45Gy in 25 fractions. Mean overall RT duration was 35 days (range 30-42 days). Grade I/II Pneumonitis was seen in 4 patients. One patient developed grade III acute lung toxicity unrelated to RT. At a median follow up of 25 months, 8 patients had died, of whom six died due to the disease and two died in the immediate post op period. Two-year DFS and OS were 58% and 73%, respectively. In spite of the extensive surgery and complex hemithoracic RT, we demonstrated excellent dosimetry, toxicity profile and favorable outcomes in non-metastatic MPM.

Anti-epileptic Drug (AED) Use in Subarachnoid Hemorrhage (SAH) and Intracranial Hemorrhage (ICH).

Aneurysmal subarachnoid hemorrhage (aSAH) and spontaneous intracranial hemorrhage (ICH) are frequently associated with epileptic complications. The use of anti-epileptic drugs (AEDs) for seizure prophylaxis, however, is controversial. In patients with aSAH, nonconvulsive status epilepticus has been associated with poor outcome. Effect of other forms of less severe epileptiform activity on clinical outcome remains unclear. Evidence on efficacy of AEDs in reducing seizure incidence is also mixed. However, increasing number of studies suggest that AEDs may have significant adverse effects on outcome, especially with phenytoin. Similarly, in patients with ICH, the impact of seizures that do not progress to status epilepticus on clinical outcome is controversial, and whether prophylactic AED use has independent effects on outcome remains ambiguous. Currently, there are no large scale randomized control trials investigating the efficacy and safety of AED prophylaxis in patients with hemorrhagic stroke. There are also no trials comparing the efficacy and safety of the different AEDs. Survey based studies have found a wide range of prescribing patterns across treatment centers and clinicians for seizure prophylaxis in patients with hemorrhagic stroke. The lack of clear guidelines and recommendations also highlights the paucity of good quality evidence in this area. In conclusion, a well-designed randomized, double blinded, and appropriately powered trial is needed to evaluate the incidence as well as clinical outcomes in patients with aSAH and ICH who received AED prophylaxis versus controls. The results will be extremely valuable in providing evidence to establish management guidelines for patients with hemorrhagic stroke.

Hydralazine vs nifedipine for acute hypertensive emergency in pregnancy: a randomized controlled trial

There is a paucity of good quality evidence regarding the best therapeutic option for acute control of blood pressure during acute hypertensive emergency of pregnancy. We sought to compare the efficacy of intravenously administered hydralazine and oral nifedipine for acute blood pressure control in acute hypertensive emergency of pregnancy. In this double-blind, randomized, controlled trial, pregnant women (≥24 weeks period of gestation) with sustained increase in systolic blood pressure of ≥160 mm Hg or diastolic blood pressure of ≥110 mm Hg were randomized to receive intravenous hydralazine injection in doses of 5, 10, 10, and 10 mg and a placebo tablet or oral nifedipine (10 mg tablet up to 4 doses) and intravenous saline injection every 20 minutes until the target blood pressure of 150 mm Hg systolic and ≤100 mm Hg diastolic was achieved. Crossover treatment was administered if the initial treatment failed. The primary outcome of the study was time necessary to achieve target blood pressure. The secondary outcomes were the number of dosages required, adverse maternal and neonatal effects, and perinatal outcome. From December 2014 through September 2015, we enrolled 60 patients. The median time to achieve target blood pressure was 40 minutes in both groups (intravenous hydralazine and oral nifedipine) (interquartile interval 5 and 40 minutes, respectively, P = .809). The median dose requirement in both groups was 2 (intravenous hydralazine and oral nifedipine) (interquartile range 1 and 2 doses, respectively, P = .625). Intravenous hydralazine was associated with statistically significantly higher occurrence of vomiting (9/30 vs 2/30, respectively, P = .042). No serious adverse maternal or perinatal side effects were witnessed in either group. Both intravenous hydralazine and oral nifedipine are equally effective in lowering of blood pressure in acute hypertensive emergency of pregnancy.

BET 1: Lidocaine with propofol to reduce pain on injection

A short review was carried out to see if mixing lidocaine with propofol is a safe and effective method in reducing the commonly reported pain at the injection site. Four...

Review on history and current practices of cancer multidisciplinary care

Cancer care can be complex with increased specialization within disciplines and more-sophisticated treatment techniques. Multidisciplinary care (MDC) is an integrated team approach to bring together a group of health professionals with appropriate skills to consider patient's treatment and care options. MDC are now conducted worldwide and is recommended as best practice for the management of patients with cancer. There is increasing evidence that MDC improves quality of care, treatment outcomes of patient with cancer and. other clinical outcomes, but concerns are raised over the paucity of good-quality evidence on their overall impact. In this review, we described available evidence on the impact of cancer MDC, and also reviewed focused on cancer MDC strategy depending on countries.

Traditional medicine use and the anaesthetist

This review considers traditional medicine, with an emphasis on traditional African medicine and its influence on perioperative care. Western and Eastern herbal remedies are widely used. The paucity of good quality evidence concerning these medicinal products has led to only some of the effects of these medicines being known. The wide range of preparatory methods and lack of regulation has resulted in patient exposure to unknown side-effects. The nature of the use of African traditional medicine is even less known, and probably disclosed to the Western health practitioner even less. This review aims to raise awareness of African traditional medicine healthcare practice and its implications in a perioperative population.

Achilles and Patellar Tendinopathy Loading Programmes

Achilles and patellar tendinopathy are overuse injuries that are common among athletes. Isolated eccentric muscle training has become the dominant conservative management strategy for Achilles and patellar tendinopathy but, in some cases, up to 45 % of patients may not respond. Eccentric-concentric progressing to eccentric (Silbernagel combined) and eccentric-concentric isotonic (heavy-slow resistance; HSR) loading have also been investigated. In order for clinicians to make informed decisions, they need to be aware of the loading options and comparative evidence. The mechanisms of loading also need to be elucidated in order to focus treatment to patient deficits and refine loading programmes in future studies. The objectives of this review are to evaluate the evidence in studies that compare two or more loading programmes in Achilles and patellar tendinopathy, and to review the non-clinical outcomes (potential mechanisms), such as improved imaging outcomes, associated with clinical outcomes. Comprehensive searching (MEDLINE, EMBASE, CINAHL, Current Contents and SPORTDiscus(™)) identified 403 studies. Two authors independently reviewed studies for inclusion and quality. The final yield included 32 studies; ten compared loading programmes and 28 investigated at least one potential mechanism (six studies compared loading programmes and investigated potential mechanisms). This review has identified limited (Achilles) and conflicting (patellar) evidence that clinical outcomes are superior with eccentric loading compared with other loading programmes, questioning the currently entrenched clinical approach to these injuries. There is equivalent evidence for Silbernagel combined (Achilles) and greater evidence for HSR loading (patellar). The only potential mechanism that was consistently associated with improved clinical outcomes in both Achilles and patellar tendon rehabilitation was improved neuromuscular performance (e.g. torque, work, endurance), and Silbernagel-combined (Achilles) HSR loading (patellar) had an equivalent or higher level of evidence than isolated eccentric loading. In the Achilles tendon, a majority of studies did not find an association between improved imaging (e.g. reduced anteroposterior diameter, proportion of tendons with Doppler signal) and clinical outcomes, including all high-quality studies. In contrast, HSR loading in the patellar tendon was associated with reduced Doppler area and anteroposterior diameter, as well as greater evidence of collagen turnover, and this was not seen following eccentric loading. HSR seems more likely to lead to tendon adaptation and warrants further investigation. Improved jump performance was associated with Achilles but not patellar tendon clinical outcomes. The mechanisms associated with clinical benefit may vary between loading interventions and tendons. There is little clinical or mechanistic evidence for isolating the eccentric component, although it should be made clear that there is a paucity of good quality evidence and several potential mechanisms have not been investigated, such as neural adaptation and central nervous system changes (e.g. cortical reorganization). Clinicians should consider eccentric-concentric loading alongside or instead of eccentric loading in Achilles and patellar tendinopathy. Good-quality studies comparing loading programmes and evaluating clinical and mechanistic outcomes are needed in both Achilles and patellar tendinopathy rehabilitation.

Understanding the effectiveness of school-based interventions to prevent suicide: a realist review.

Schools appear an obvious place to deliver suicide prevention interventions for children and adolescents. The complexity of suicide interventions lead to a paucity of good quality evidence. An alternate approach of information gathering is needed to identify and collate evidence from existing interventions. We completed a realist review of school-based suicide interventions. This is a novel method of understanding complex interventions that uses an iterative approach. In this review, we attempt to clarify and lay out what type of suicide intervention programme might be useful in schools, based on the local needs and context. It is possible to develop and implement an evidence-based suicide intervention in schools by understanding the different processes that can contribute to success or failure of these interventions in a real-world setting.

Surgical management for upper urinary tract transitional cell carcinoma (UUT‐TCC): a systematic review

Surgical management of upper urinary tract transitional cell carcinoma (UUT-TCC) has significantly changed over the past two decades. Data for several new surgical techniques, including nephron-sparing surgery (NSS), is emerging. The study systematically reviewed the literature comparing (randomised and observational studies) surgical and oncological outcomes for various surgical techniques MEDLINE, EMBASE, Cochrane Library, CINAHL, British Nursing Index, AMED, LILACS, Web of Science, Scopus, Biosis, TRIP, Biomed Central, Dissertation Abstracts, ISI proceedings, and PubMed were searched to identify suitable studies. Data were extracted from each identified paper independently by two reviewers (B.R. and B.S.) and cross checked by a senior member of the team. The data analysis was performed using the Cochrane software Review manager version 5. Comparable data from each study was combined in a meta-analysis where possible. For dichotomous data, odds ratios with 95% confidence intervals (CIs) were estimated based on the fixed-effects model and according to an intention-to-treat analysis. If the data available were deemed not suitable for a meta-analysis it was described in a narrative fashion. One randomised control trial (RCT) and 19 observational studies comparing open nephroureterectomy (ONU) and laparoscopic NU (LNU) were identified. The RCT reported the LNU group to have statistically significantly less blood loss (104 vs 430 mL, P < 0.001) and mean time to discharge (2.30 vs 3.65 days, P < 0.001) than the ONU group. At a median follow-up of 44 months, the overall 5-year cancer-specific survival (CSS; 89.9 vs 79.8%) and 5-year metastasis-free survival rates (77.4 vs 72.5%) for the ONU were better than for LNU, respectively, although not statistically significant. A meta-analysis of the observational studies favoured LNU group for lower urinary recurrence (P < 0.001) and distant metastasis. The meta-analyses for local recurrence for the two groups were comparable. One retrospective study comparing ONU with a percutaneous approach for grade 2 disease reported no significant differences in CSS rates (53.8 vs 53.3 months). Three retrospective studies compared NSS and radical NU, and reported no significant differences in overall CSS and recurrence-free survival between the two approaches. Five retrospective studies compared various techniques of en bloc excision of the lower ureter. No technique was reported to be better (operative and oncological) than any other. This review concludes that there is a paucity of good quality evidence for the various surgical approaches for UUT-TCC. The techniques have been assessed and reported in many retrospective single-centre studies favouring LNU for better perioperative outcomes and comparable oncological safety. The reported observational studies data is further supported by one RCT.

Dasatinib, high-dose imatinib and nilotinib for the treatment of imatinib-resistant chronic myeloid leukaemia: a systematic review and economic evaluation.

The present report was commissioned as a supplement to an existing technology assessment report produced by the Peninsula Technology Assessment Group (PenTAG), which evaluated the clinical effectiveness and cost-effectiveness of dasatinib and nilotinib in patients who are either resistant or intolerant to standard-dose imatinib. This report evaluates the clinical effectiveness and cost-effectiveness of dasatinib, nilotinib and high-dose imatinib within their licensed indications for the treatment of people with chronic myeloid leukaemia (CML) who are resistant to standard-dose imatinib. Bibliographic databases were searched from inception to January 2011, including The Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), and MEDLINE In-Process & Other Non-Indexed Citations. Bibliographies of related papers were screened, key conferences were searched, and experts were contacted to identify additional published and unpublished references. This report includes systematic reviews of clinical effectiveness and cost-effectiveness studies, an independent appraisal of information submitted by drug manufacturers to the National Institute for Health and Clinical Excellence (NICE), an independent appraisal of the PenTAG economic evaluation, and new economic analyses adapting the PenTAG economic model. Standard systematic procedures involving two reviewers to maintain impartiality and transparency, and to minimise bias, were conducted. Eleven studies met the inclusion criteria. Four of these studies included new data published since the PenTAG report; all of these were in chronic-phase CML. No relevant studies on the clinical effectiveness of nilotinib were found. The clinical effectiveness studies on dasatinib [one arm of a randomised controlled trial (RCT)] and high-dose imatinib (one arm of a RCT and three single-arm cohort studies) had major methodological limitations. These limitations precluded a comparison of the different arms within the RCT. Data from the studies are summarised in this report, but caution in interpretation is required. One economic evaluation was identified that compared dasatinib with high-dose imatinib in patients with chronic-phase CML who were CML resistant to standard-dose imatinib. Two industry submissions and the PenTAG economic evaluation were critiqued and differences in the assumptions and results were identified. The PenTAG economic model was adapted and new analyses conducted for the interventions dasatinib, nilotinib and high-dose imatinib and the comparators interferon alfa, standard-dose imatinib, stem cell transplantation and hydroxycarbamide. The results suggest that the three interventions, dasatinib, nilotinib and high-dose imatinib, have similar costs and cost-effectiveness compared with hydroxycarbamide, with a cost-effectiveness of around £30,000 per quality-adjusted life-year gained. However, it is not possible to derive firm conclusions about the relative cost-effectiveness of the three interventions owing to great uncertainty around data inputs. Uncertainty was explored using deterministic sensitivity analyses, threshold analyses and probabilistic sensitivity analyses. The paucity of good-quality evidence should be considered when interpreting this report. This review has identified very limited new information on clinical effectiveness of the interventions over that already shown in the PenTAG report. Limitations in the data exist; however, the results of single-arm studies suggest that the interventions can lead to improvements in haematological and cytogenetic responses in people with imatinib-resistant CML. The economic analyses do not highlight any one of the interventions as being the most cost-effective; however, the analysis results are highly uncertain owing to lack of agreement on appropriate assumptions. Recommendations for future research made by PenTAG, for a good-quality RCT comparing the three treatments remain.

Cancer Multidisciplinary Team Meetings: Evidence, Challenges, and the Role of Clinical Decision Support Technology

Multidisciplinary team (MDT) model in cancer care was introduced and endorsed to ensure that care delivery is consistent with the best available evidence. Over the last few years, regular MDT meetings have become a standard practice in oncology and gained the status of the key decision-making forum for patient management. Despite the fact that cancer MDT meetings are well accepted by clinicians, concerns are raised over the paucity of good-quality evidence on their overall impact. There are also concerns over lack of the appropriate support for this important but overburdened decision-making platform. The growing acceptance by clinical community of the health information technology in recent years has created new opportunities and possibilities of using advanced clinical decision support (CDS) systems to realise full potential of cancer MDT meetings. In this paper, we present targeted summary of the available evidence on the impact of cancer MDT meetings, discuss the reported challenges, and explore the role that a CDS technology could play in addressing some of these challenges.

Cost-effectiveness of screening high-risk HIV-positive men who have sex with men (MSM) and HIV-positive women for anal cancer.

Anal cancer is uncommon and predominantly a disease of the elderly. The human papillomavirus (HPV) has been implicated as a causal agent, and HPV infection is usually transmitted sexually. Individuals who are human immunodeficiency virus (HIV)-positive are particularly vulnerable to HPV infections, and increasing numbers from this population present with anal cancer. To estimate the cost-effectiveness of screening for anal cancer in the high-risk HIV-positive population [in particular, men who have sex with men (MSM), who have been identified as being at greater risk of the disease] by developing a model that incorporates the national screening guidelines criteria. A comprehensive literature search was undertaken in January 2006 (updated in November 2006). The following electronic bibliographic databases were searched: Applied Social Sciences Index and Abstracts (ASSIA), BIOSIS previews (Biological Abstracts), British Nursing Index (BNI), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, NHS Database of Abstracts of Reviews of Effects (DARE), NHS Health Technology Assessment (HTA) Database, PsycINFO, Science Citation Index (SCI), and Social Sciences Citation Index (SSCI). Published literature identified by the search strategy was assessed by four reviewers. Papers that met the inclusion criteria contained the following: data on population incidence, effectiveness of screening, health outcomes or screening and/or treatment costs; defined suitable screening technologies; prospectively evaluated tests to detect anal cancer. Foreign-language papers were excluded. Searches identified 2102 potential papers; 1403 were rejected at title and a further 493 at abstract. From 206 papers retrieved, 81 met the inclusion criteria. A further treatment paper was added, giving a total of 82 papers included. Data from included studies were extracted into data extraction forms by the clinical effectiveness reviewer. To analyse the cost-effectiveness of screening, two decision-analytical models were developed and populated. The reference case cost-effectiveness model for MSM found that screening for anal cancer is very unlikely to be cost-effective. The negative aspects of screening included utility decrements associated with false-positive results and with treatment for high-grade anal intraepithelial neoplasia (HG-AIN). Sensitivity analyses showed that removing these utility decrements improved the cost-effectiveness of screening. However, combined with higher regression rates from low-grade anal intraepithelial neoplasia (LG-AIN), the lowest expected incremental cost-effectiveness ratio remained at over 44,000 pounds per quality-adjusted life-year (QALY) gained. Probabilistic sensitivity analysis showed that no screening retained over 50% probability of cost-effectiveness to a QALY value of 50,000 pounds. The screening model for HIV-positive women showed an even lower likelihood of cost-effectiveness, with the most favourable sensitivity analyses reporting an incremental cost per QALY of 88,000 pounds. Limited knowledge is available about the epidemiology and natural history of anal cancer, along with a paucity of good-quality evidence concerning the effectiveness of screening. Many of the criteria for assessing the need for a screening programme were not met and the cost-effectiveness analyses showed little likelihood that screening any of the identified high-risk groups would generate health improvements at a reasonable cost. Further studies could assess whether the screening model has underestimated the impact of anal cancer, the results of which may justify an evaluative study of the effects of treatment for HG-AIN.

Current and future management of treatment failure in low- and middle-income countries

Access to second-line therapy in low- and middle-income countries has been limited to date. The WHO predicts that between 500 000 and 800 000 HIV-infected people on first-line combination antiretroviral therapy will require switch to second-line therapy by 2010. This paper aims to describe and review access to second-line therapy in low- and middle-income countries at present and examine future possibilities. The majority of HIV-infected patients failing first-line combination antiretroviral therapy is identified by way of routine monitoring of clinical and immunological status as a surrogate for virological monitoring. Evidence suggests that immunological and clinical monitoring lack both sensitivity and specificity for virological failure. Consequently, at treatment failure, patients have often selected a degree of resistance within the nucleoside/nucleotide reverse transcriptase inhibitor class that questions the efficacy of using nucleoside/nucleotide reverse transcriptase inhibitors in a second-line regimen. There is a paucity of good-quality evidence on which to base guidelines and policy. Optimally, a second-line regimen would be simple, potent, tolerable and lend itself to provision according to the successful 'public health' approach. Provision of second-line therapy to HIV-infected individuals failing first-line therapy is a major challenge to the ongoing success of access to HIV care programmes in low- and middle-income countries. The optimal second-line combination antiretroviral therapies are unknown. Research trials to help define best practice are in advanced stages of development and implementation.