Diagnostic Accuracy of 18F-Prostate Specific Membrane Antigen (PSMA) PET/CT Radiotracers in Staging and Restaging of Patients With High-Risk Prostate Cancer or Biochemical Recurrence: An Overview of Reviews.

The aim of this overview was to consolidate existing evidence syntheses and provide a comprehensive overview of the evidence for 18F-prostate specific membrane antigen (PSMA) PET/CT in the staging of high-risk prostate cancer and restaging after biochemical recurrence. An overview of reviews was performed and reported in line with the preferred reporting items for overview of reviews (PRIOR) statement and synthesis without meta-analysis (SWiM) reporting guidelines. A comprehensive database and grey literature search were conducted up to July 18, 2023. Systematic reviews were assessed using the risk of bias in systematic reviews (ROBIS) tool. The certainty of the evidence was assessed using grading of recommendations, assessment, development and evaluations (GRADE). 11 systematic reviews were identified; 10 were at high or unclear risk of bias. Evidence reported on a per-patient, per-lymph node, and per-lesion basis for sensitivity, specificity and overall accuracy was identified. There was a lack of data on dose, adverse events and evidence directly comparing 18F-PSMA PET/CT to other imaging modalities. Evidence with moderate to very low certainty indicated high sensitivity, specificity and accuracy of 18F-PSMA PET/CT in patients with high-risk prostate cancer and biochemical recurrence. There was considerably lower certainty evidence and greater variability in effect estimates for outcomes for the combined intermediate/high-risk cohort. While evidence gaps remain for some outcomes, and most systematic reviews were at high or unclear risk of bias, the current evidence base is broadly supportive of 18F-PSMA PET/CT imaging in the staging and restaging of patients with high-risk prostate cancer and biochemical recurrence.

Cost-effectiveness of metabolic surgery for the treatment of type 2 diabetes and obesity: a systematic review of economic evaluations.

AIM: To systematically identify and appraise the international literature on the cost-effectiveness of metabolic surgery for the treatment of comorbid type 2 diabetes (T2D) and obesity. METHODS: A systematic search was conducted in electronic databases and grey literature sources up to 20 January 2021. Economic evaluations in a T2D population or a subpopulation with T2D were eligible for inclusion. Screening, data extraction, critical appraisal of methodological quality (Consensus Health Economic Criteria list) and assessment of transferability (International Society for Pharmacoeconomics and Outcomes Research questionnaire) were undertaken in duplicate. The incremental cost-effectiveness ratio (ICER) was the main outcome. Costs were reported in 2020 Irish Euro. Cost-effectiveness was interpreted using willingness-to-pay (WTP) thresholds of €20,000 and €45,000/quality-adjusted life year (QALY). Due to heterogeneity arising from various sources, a narrative synthesis was undertaken. RESULTS: Thirty studies across seventeen jurisdictions met the inclusion criteria; 16 specifically in a T2D population and 14 in a subpopulation with T2D. Overall, metabolic surgery was found to be cost-effective or cost-saving. Where undertaken, the results were robust to sensitivity and scenario analyses. Of the 30 studies included, 15 were considered high quality. Identified limitations included limited long-term follow-up data and uncertainty regarding the utility associated with T2D remission. CONCLUSION: Published high-quality studies suggest metabolic surgery is a cost-effective or cost-saving intervention. As the prevalence of obesity and obesity-related diseases increases worldwide, significant investment and careful consideration of the resource requirements needed for metabolic surgery programmes will be necessary to ensure that service provision is adequate to meet demand.

Diagnostic accuracy of 18F Prostate Specific Membrane Antigen (PSMA) PET-CT radiotracers in staging and restaging of high-risk prostate cancer patients and patients with biochemical recurrence: protocol for an overview of reviews.

Background: Correct staging and risk stratification is essential in ensuring prostate cancer patients are offered the most appropriate treatment. Interest has been growing in the use of radiotracers targeting prostate specific membrane antigen (PSMA), including the use of 18F-PSMA PET-CT, as part of the primary staging or restaging of prostate cancer. Preliminary scoping identified a number of relevant systematic reviews and meta-analyses; however, individually, these each appear to look at only part of the picture. An overview of reviews aims to systematically identify, appraise and synthesise multiple systematic reviews, related to a relevant research question or questions. We present a protocol for an overview of reviews, which aims to collate existing evidence syntheses exploring the diagnostic accuracy of 18F-PSMA in staging and restaging of prostate cancer. It also aims to highlight evidence gaps in prostate cancer staging or restaging. Methods: This protocol is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for systematic review protocols (PRISMA-P). The search strategy will be designed in consultation with a librarian. Searches will be performed in Medline (EBSCO), Embase (Ovid), Google Scholar and the Cochrane Database for Systematic Reviews, supplemented by a targeted grey literature search, forward citation searching and searching reference lists of included reviews. No language or date restrictions will be applied to the eligibility criteria or the search strategy. Title & abstract and full text screening will be performed independently by two reviewers. Data will be extracted by one reviewer and checked in full by a second reviewer. Quality appraisal will be performed using the Risk of Bias in Systematic Reviews (ROBIS) tool independently by two reviewers, and results will be narratively synthesised. Conclusions: This overview of reviews may be of interest to healthcare professionals, academics and health policy decision-makers. Registration: OSF (September 7, 2023).

Effectiveness of rapid antigen testing for screening of asymptomatic individuals to limit the transmission of SARS-CoV-2: A rapid review.

Rapid antigen detection tests (RADTs) offer advantages over gold-standard reverse transcription polymerase chain reaction (RT-PCR) tests in that they are cheaper and provide faster results, thus enabling prompt isolation of positive SARS-CoV-2 cases and quarantine of close contacts. The aim of this study was to collate and synthesise empirical evidence on the effectiveness of rapid antigen testing for the screening (including serial testing) and surveillance of asymptomatic individuals to limit the transmission of SARS-CoV-2. A rapid review was undertaken in MEDLINE (EBSCO), EMBASE (OVID), Cochrane Library, Europe PMC and Google Scholar up until 19 July 2021, supplemented by a grey literature search. Of the identified 1222 records, 19 reports referring to 16 studies were included. Eight included studies examined the effectiveness of RADTs for population-level screening, four for pre-event screening and four for serial testing (schools, a prison, a university sports programme and in care homes). Overall, there is uncertainty regarding the effectiveness of rapid antigen testing for the screening of asymptomatic individuals to limit the transmission of SARS-CoV-2. This uncertainty is due to the inconsistent results, the relatively low number of studies identified, the predominantly observational and/or uncontrolled nature of the study designs used, and concerns regarding methodological quality. Given this uncertainty, more real-world research evidence in relevant settings, which is of good quality and timely, as well as economic evaluation, is required to inform public policy on the widespread use of RADTs in asymptomatic individuals.

The effectiveness of non-contact thermal screening as a means of identifying cases of Covid-19: a rapid review of the evidence.

The aim of this rapid review is to summarise the evidence on non-contact thermal screening as a method through which to identify cases and reduce the spread of coronavirus disease (Covid-19). The rapid review was conducted in accordance with Cochrane guidelines, with a systematic search of published peer-reviewed articles and non-peer-reviewed pre-prints undertaken from 1 January 2000 up to 7 October 2020. Eleven studies were included. One observational study and two mathematical modelling studies were conducted in the context of the Covid-19 pandemic; the remaining studies were conducted during the influenza A pandemic (H1N1) 2009 (n = 7) or middle east respiratory syndrome (n = 1) pandemics. One systematic review and three rapid reviews were identified and screened for relevant studies. Evidence on the effectiveness of thermal screening contained within this review was limited to points of entry (i.e., airports); thus the applicability to other community settings is uncertain. Thermal screening, implemented as part of a composite of screening measures (self-report of relevant symptoms, contact/travel history), was ineffective in identifying infectious individuals and limiting the spread of disease. Based on limited, low certainty evidence, non-contact thermal screening is ineffective in limiting the spread of Covid-19.

The HIQA's Health Technology Assessment of Breast Screening: Highlighting Some of the Challenges Posed by Evaluations of Screening Programs.

A review of the Health Information and Quality Authority's (HIQA) assessment of breast cancer surveillance cancer criticized how the results were presented and interpreted. The health technology assessment (HTA) investigated surveillance options for women aged less than 50 years who were at elevated risk of breast cancer. Surveillance strategies using digital mammography, magnetic resonance imaging, or a combination of the two modalities were modeled on the basis of diagnostic test accuracy. The HTA faced a number of issues, including the use of diagnostic test accuracy as a surrogate for long-term outcomes; modeling interventions that were not considered acceptable to clinicians; and extrapolating for screening intervals and age ranges not directly supported by available evidence. The evaluation of screening programs gives rise to challenges in terms of balancing an adequate exploration of the possible options while also being cognizant of what is appropriately supported by evidence. In this article, the authors of the HIQA report discuss the challenges posed by this particular HTA.

Cost-Effectiveness of a National Opportunistic Screening Program for Atrial Fibrillation in Ireland.

OBJECTIVES: To evaluate the cost-effectiveness of a national atrial fibrillation screening program in Ireland involving annual opportunistic pulse palpation of all those older than 65 years during general practitioner consultations, with an electrocardiogram being performed if an irregular pulse is detected. METHODS: A probabilistic Markov model was used to simulate costs and clinical outcomes in a hypothetical cohort of men and women with and without screening over the course of 25 years, using a societal perspective. RESULTS: Screening was associated with an incremental cost-effectiveness ratio of €23,004/quality-adjusted life-year compared with routine care. Nevertheless, if the relative risk of stroke and systematic embolism in screen-detected patients is more than 12% lower than that in patients with atrial fibrillation identified through routine practice, then screening would not be considered cost-effective at a willingness-to-pay threshold of €45,000/quality-adjusted life-year. An analysis comparing alternative combinations of start age and screening interval found that less frequent screening with a later start age may be more cost-effective than an annual screening from age 65 years. CONCLUSIONS: Annual opportunistic screening of men and women aged 65 years and older in primary care in Ireland is likely to be cost-effective using conventional willingness-to-pay thresholds, assuming that those detected through screening have a comparable stroke risk profile as those detected through routine practice. Raising the start age of screening or increasing the screening interval may improve the cost-effectiveness of a prospective screening program.

Systematic screening for the detection of atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF), the most common arrhythmia in clinical practice, is a leading cause of morbidity and mortality. Screening for AF in asymptomatic patients has been proposed as a way of reducing the burden of the disease by detecting people who would benefit from prophylactic anticoagulation therapy before the onset of symptoms. However, for screening to be an effective intervention, it must improve the detection of AF and provide benefit for those detected earlier as a result of screening. OBJECTIVES: This review aims to answer the following questions.Does systematic screening increase the detection of AF compared with routine practice? Which combination of screening population, strategy and test is most effective for detecting AF compared with routine practice? What safety issues and adverse events may be associated with individual screening programmes? How acceptable is the intervention to the target population? What costs are associated with systematic screening for AF? SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and EMBASE (Ovid) up to 11 November 2015. We searched other relevant research databases, trials registries and websites up to December 2015. We also searched reference lists of identified studies for potentially relevant studies, and we contacted corresponding authors for information about additional published or unpublished studies that may be relevant. We applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials comparing screening for AF with routine practice in people 40 years of age and older were eligible. Two review authors (PM and CT) independently selected trials for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors (PM and CT) independently assessed risk of bias and extracted data. We used odds ratios (ORs) and 95% confidence intervals (CIs) to present results for the primary outcome, which is a dichotomous variable. As we identified only one study for inclusion, we performed no meta-analysis. We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation Working Group) method to assess the quality of the evidence and GRADEPro to create a 'Summary of findings' table. MAIN RESULTS: One cluster-randomised controlled trial met the inclusion criteria for this review. This study compared systematic screening (by invitation to have an electrocardiogram (ECG)) and opportunistic screening (pulse palpation during a general practitioner (GP) consultation for any reason, followed by an ECG if pulse was irregular) versus routine practice (normal case finding on the basis of clinical presentation) in people 65 years of age or older.Results show that both systematic screening and opportunistic screening of people over 65 years of age are more effective than routine practice (OR 1.57, 95% CI 1.08 to 2.26; and OR 1.58, 95% CI 1.10 to 2.29, respectively; both moderate-quality evidence). We found no difference in the effectiveness of systematic screening and opportunistic screening (OR 0.99, 95% CI 0.72 to 1.37; low-quality evidence). A subgroup analysis found that systematic screening and opportunistic screening were more effective in men (OR 2.68, 95% CI 1.51 to 4.76; and OR 2.33, 95% CI 1.29 to 4.19, respectively) than in women (OR 0.98, 95% CI 0.59 to 1.62; and OR 1.2, 95% CI 0.74 to 1.93, respectively). No adverse events associated with screening were reported.The incremental cost per additional case detected by opportunistic screening was GBP 337, compared with GBP 1514 for systematic screening. All cost estimates were based on data from the single included trial, which was conducted in the UK between 2001 and 2003. AUTHORS' CONCLUSIONS: Evidence suggests that systematic screening and opportunistic screening for AF increase the rate of detection of new cases compared with routine practice. Although these approaches have comparable effects on the overall AF diagnosis rate, the cost of systematic screening is significantly greater than the cost of opportunistic screening from the perspective of the health service provider. Few studies have investigated effects of screening in other health systems and in younger age groups; therefore, caution needs to be exercised in relation to transferability of these results beyond the setting and population in which the included study was conducted.Additional research is needed to examine the effectiveness of alternative screening strategies and to investigate the effects of the intervention on risk of stroke for screened versus non-screened populations.

Using prediction intervals from random-effects meta-analyses in an economic model.

OBJECTIVES: When incorporating treatment effect estimates derived from a random-effect meta-analysis it is tempting to use the confidence bounds to determine the potential range of treatment effect. However, prediction intervals reflect the potential effect of a technology rather than the more narrowly defined average treatment effect. Using a case study of robot-assisted radical prostatectomy, this study investigates the impact on a cost-utility analysis of using clinical effectiveness derived from random-effects meta-analyses presented as confidence bounds and prediction intervals, respectively. METHODS: To determine the cost-utility of robot-assisted prostatectomy, an economic model was developed. The clinical effectiveness of robot-assisted surgery compared with open and conventional laparoscopic surgery was estimated using meta-analysis of peer-reviewed publications. Assuming treatment effect would vary across studies due to both sampling variability and differences between surgical teams, random-effects meta-analysis was used to pool effect estimates. RESULTS: Using the confidence bounds approach the mean and median ICER was €24,193 and €26,731/QALY (95%CI: €13,752 to €68,861/QALY), respectively. The prediction interval approach produced an equivalent mean and median ICER of €26,920 and €26,643/QALY (95%CI: -€135,244 to €239,166/QALY), respectively. Using prediction intervals, there is a probability of 0.042 that robot-assisted surgery will result in a net reduction in QALYs. CONCLUSIONS: Using prediction intervals rather than confidence bounds does not affect the point estimate of the treatment effect. In meta-analyses with significant heterogeneity, the use of prediction intervals will produce wider ranges of treatment effect, and hence result in greater uncertainty, but a better reflection of the effect of the technology.

Drug-drug interactions between antiretrovirals and drugs used in the management of neglected tropical diseases: important considerations in the WHO 2020 Roadmap and London Declaration on Neglected Tropical Diseases.

The group of infections known as the neglected tropical diseases (NTDs) collectively affect one billion people worldwide, equivalent to one-sixth of the world's population. The NTDs cause severe physical and emotional morbidity, and have a profound effect on cycles of poverty; it is estimated that NTDs account for 534 000 deaths per year. NTDs such as soil-transmitted helminth infections and the vector-borne protozoal infections leishmaniasis and trypanosomiasis occur predominantly in the most economically disadvantaged and marginalized communities. It is estimated that all low-income countries harbour at least five of the NTDs simultaneously. NTDs are neglected because they do not individually rank highly in terms of mortality data, and because they affect populations with little political voice. There is considerable geographic overlap between areas with high prevalence of NTDs and HIV, raising the possibility of complex polypharmacy and drug-drug interactions. Antiretrovirals pose a particularly high risk for potential drug-drug interactions, which may be pharmacokinetic or pharmacodynamic in nature and can result in raising or lowering plasma or tissue concentrations of co-prescribed drugs. Elevated drug concentrations may be associated with drug toxicity and lower drug concentrations may be associated with therapeutic failure. The aim of this paper is to review the currently available data on interactions between antiretrovirals and drugs used in the management of NTDs. It is intended to serve as a resource for policy makers and clinicians caring for these patients, and to support the recent WHO 2020 Roadmap and the 2012 London Declaration on NTDs.

Effectiveness of systematic screening for the detection of atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a leading cause of morbidity and mortality. Screening for AF in asymptomatic patients has been proposed as a way of reducing the burden of the disease by detecting people who would benefit from prophylactic anticoagulation therapy prior to the onset of symptoms. However, for screening to be an effective intervention it must improve the detection of AF and provide benefit for those who are detected earlier as a result of screening. OBJECTIVES: The primary objective of this review was to examine whether screening programmes increase the detection of new cases of AF compared to routine practice. The secondary objectives were to identify which combination of screening strategy and patient population is most effective, as well as assessing any safety issues associated with screening, its acceptability within the target population and the costs involved. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE (Ovid) and EMBASE (Ovid) up to March 2012. Other relevant research databases, trials registries and websites were searched up to June 2012. Reference lists of identified studies were also searched for potentially relevant studies and we contacted corresponding authors for information about additional published or unpublished studies that may be relevant. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials, controlled before and after studies and interrupted time series studies comparing screening for AF with routine practice in people aged 40 years and over were eligible. Two authors (PM, CT or MF) independently selected the trials for inclusion. DATA COLLECTION AND ANALYSIS: Assessment of risk of bias and data extraction were performed independently by two authors (PM, CT). Odds ratios (OR) and 95% confidence intervals (CI) were used to present the results for the primary outcome, which is a dichotomous variable. Since only one included study was identified, no meta-analysis was performed. MAIN RESULTS: One cluster randomised controlled trial met the inclusion criteria for this review. This study compared systematic screening (by invitation to have an electrocardiogram (ECG)) and opportunistic screening (pulse palpation during a general practitioner (GP) consultation for any reason followed by an ECG if pulse was irregular) to routine practice (normal case finding on the basis of clinical presentation) in people aged 65 years or older. The risk of bias in the included study was judged to be low.Both systematic and opportunistic screening of people over the age of 65 years are more effective than routine practice (OR 1.57, 95% CI 1.08 to 2.26 and OR 1.58, 95% CI 1.10 to 2.29, respectively). The number needed to screen in order to detect one additional case compared to routine practice was 172 (95% CI 94 to 927) for systematic screening and 167 (95% CI 92 to 806) for opportunistic screening. Both systematic and opportunistic screening were more effective in men (OR 2.68, 95% CI 1.51 to 4.76 and OR 2.33, 95% CI 1.29 to 4.19, respectively) than in women (OR 0.98, 95% CI 0.59 to 1.62 and OR 1.2, 95% CI 0.74 to 1.93, respectively). No data on the effectiveness of screening in different ethnic or socioeconomic groups were available. There were insufficient data to compare the effectiveness of screening programmes in different healthcare settings.Systematic screening was associated with a better overall uptake rate than opportunistic screening (53% versus 46%) except in the ≥ 75 years age group where uptake rates were similar (43% versus 42%). In both screening programmes men were more likely to participate than women (57% versus 50% in systematic screening, 49% versus 41% in opportunistic screening) and younger people (65 to 74 years) were more likely to participate than people aged 75 years and over (61% versus 43% systematic, 49% versus 42% opportunistic). No adverse events associated with screening were reported.The incremental cost per additional case detected by opportunistic screening was GBP 337, compared to GBP 1514 for systematic screening. All cost estimates were based on data from the single included trial, which was conducted in the UK between 2001 and 2003. AUTHORS' CONCLUSIONS: Systematic and opportunistic screening for AF increase the rate of detection of new cases compared with routine practice. While both approaches have a comparable effect on the overall AF diagnosis rate, the cost of systematic screening is significantly more than that of opportunistic screening from the perspective of the health service provider. The lack of studies investigating the effect of screening in other health systems and younger age groups means that caution needs to be exercised in relation to the transferability of these results beyond the setting and population in which the included study was conducted.Additional research is needed to examine the effectiveness of alternative screening strategies and to investigate the effect of the intervention on the risk of stroke for screened versus non-screened populations.

Robot-assisted hysterectomy compared to open and laparoscopic approaches: systematic review and meta-analysis.

PURPOSE: To review the safety and effectiveness of robot-assisted hysterectomy compared to traditional open and conventional laparoscopic surgery, differentiating radical, simple total with node staging, and simple total hysterectomy. METHODS: Medline, Embase, the Cochrane library, and the Journal of Robotic Surgery were searched for controlled trials and observational studies with historic or concurrent controls. Data were pooled using random effects meta-analysis. RESULTS: Compared to open surgery, robot-assisted radical hysterectomy is associated with reduced hospital stay and blood transfusions. For simple total hysterectomy with node staging, robot-assisted surgery is associated with reduced hospital stay, complications, and blood transfusions compared to open surgery. Compared to conventional laparoscopic surgery, robot-assisted simple total hysterectomy with node staging is associated with complications and conversions. CONCLUSIONS: Compared to open surgery, robot-assisted hysterectomy offers benefits for reduced length of hospital stay and blood transfusions. The best evidence of improved outcomes is for simple total hysterectomy with node staging. Study quality was poor.

Robot-assisted radical prostatectomy compared with open and laparoscopic approaches: a systematic review and meta-analysis.

Medline and Embase were searched for studies comparing robot-assisted radical prostatectomy with open prostatectomy and conventional laparoscopic prostatectomy. Random effects meta-analysis was used to calculate a pooled estimate of effect. The 95% prediction intervals are also reported. One randomized study and 50 observational studies were identified. The results show that compared with open surgery, robot-assisted surgery is associated with fewer positive surgical margins for pT2 tumors (relative risk 0.63, 95% confidence interval 0.49-0.81, P < 0.001) and improved outcomes for sexual function at 12 months (relative risk 1.60, 95% confidence interval 1.33-1.93, P = <0.001), and, to a lesser extent, urinary function at 12 months (relative risk 1.06, 95% confidence interval 1.02-1.11, P < 0.01). Compared with conventional laparoscopic prostatectomy, robot-assisted surgery is associated with a slight increase in urinary function at 12 months (relative risk 1.09, 95% confidence interval 1.02 to 1.17, P = 0.013). The overall methodological quality of the included studies was low, with high levels of heterogeneity. The use of prediction intervals as an aid to decision making in regard to the introduction of this technology is examined. Clinically significant improvements in positive surgical margins rates for pT2 tumors and sexual function at 12 months associated with robot-assisted surgery in comparison with open surgery should be interpreted with caution given the limitations of the evidence. Differences between robot-assisted and conventional laparoscopic surgery are minimal.

The cost-effectiveness of cotrimoxazole prophylaxis in HIV-infected children in Zambia.

OBJECTIVE: To assess the cost-effectiveness of cotrimoxazole prophylaxis in HIV-infected children in Zambia, as implementation at the local health centre level has yet to be undertaken in many resource-limited countries despite recommendations in recent updated World Health Organization (WHO) guidelines. DESIGN: A probabilistic decision analytical model of HIV/AIDS progression in children based on the CD4 cell percentage (CD4%) was populated with data from the placebo-controlled Children with HIV Antibiotic Prophylaxis trial that had reported a 43% reduction in mortality with cotrimoxazole prophylaxis in HIV-infected children aged 1-14 years. METHODS: Unit costs (US$ in 2006) were measured at University Teaching Hospital, Lusaka. Cost-effectiveness expressed as cost per life-year saved, cost per quality adjusted life-year (QALY) saved, cost per disability adjusted life-year (DALY) averted was calculated across a number of different scenarios at tertiary and primary healthcare centres. RESULTS: : Cotrimoxazole prophylaxis was associated with incremental cost-effectiveness ratios (ICERs) of US$72 per life-year saved, US$94 per QALY saved and US$53 per DALY averted, i.e. substantially less than a cost-effectiveness threshold of US$1019 per outcome (gross domestic product per capita, Zambia 2006). ICERs of US$5 or less per outcome demonstrate that cotrimoxazole prophylaxis is even more cost-effective at the local healthcare level. The intervention remained cost-effective in all sensitivity analyses including routine haematological and CD4% monitoring, varying starting age, AIDS status, cotrimoxazole formulation, efficacy duration and discount rates. CONCLUSION: Cotrimoxazole prophylaxis in HIV-infected children is an inexpensive low technology intervention that is highly cost-effective in Zambia, strongly supporting the adoption of WHO guidelines into essential healthcare packages in low-income countries.

Pricing and reimbursement of drugs in Ireland.

Expenditure on healthcare in Ireland, which is mainly derived from taxation, has increased considerably in recent years to an estimated 9.2 billion euro in 2003. Pharmaceuticals account for approximately 10% of total healthcare expenditure. Approximately one-third of patients receive their medications free of charge whilst the remaining two-thirds are subject to a co-payment threshold of 78 euro per month, i.e. 936 euro per year. The price of medications in Ireland is linked to those of five other member states where the price to the wholesaler of any medication will not exceed the lesser of the currency-adjusted wholesale price in the United Kingdom or the average of wholesale prices in Denmark, France, Germany, The Netherlands and the United Kingdom. A price freeze at the introduction price has been in existence since 1993. Despite the price freeze, expenditure on medicines on the community drugs scheme has increased from 201 million euro in 1993 to 898 million euro in 2002. The two main factors contributing to the increased expenditure on medicines include "product mix", the prescribing of new and more expensive medication, and "volume effect" comprising growth in the number of prescription items. Changing demographics and the extension of the General Medical Services (GMS) Scheme to provide free medicines for all those over the age of 70 years have also contributed. Prior to reimbursement under the community drugs schemes, a medicine must be included in the GMS code book or positive list. A demonstration of cost-effectiveness is not a pre-requisite for reimbursement.