A review of the cost-effectiveness of genetic testing for germline variants in familial cancer.

BACKGROUND: Targeted germline testing is recommended for those with or at risk of breast, ovarian, or colorectal cancer. The affordability of genetic sequencing has improved over the past decade, therefore the cost-effectiveness of testing for these cancers is worthy of reassessment. OBJECTIVE: To systematically review economic evaluations on cost-effectiveness of germline testing in breast, ovarian, or colorectal cancer. METHODS: A search of PubMed and Embase databases for cost-effectiveness studies on germline testing in breast, ovarian, or colorectal cancer, published between 1999 and May 2022. Synthesis of methodology, cost-effectiveness, and reporting (CHEERS checklist) was performed. RESULTS: The incremental cost-effectiveness ratios (ICERs; in 2021-adjusted US$) for germline testing versus the standard care option in hereditary breast or ovarian cancer (HBOC) across target settings were as follows: (1) population-wide testing: 344-2.5 million/QALY; (2) women with high-risk: dominant = 78,118/QALY, 8,337-59,708/LYG; (3) existing breast or ovarian cancer: 3,012-72,566/QALY, 39,835/LYG; and (4) metastatic breast cancer: 158,630/QALY. Likewise, ICERs of germline testing for colorectal cancer across settings were: (1) population-wide testing: 132,200/QALY, 1.1 million/LYG; (2) people with high-risk: 32,322-76,750/QALY, dominant = 353/LYG; and (3) patients with existing colorectal cancer: dominant = 54,122/QALY, 98,790-6.3 million/LYG. Key areas of underreporting were the inclusion of a health economic analysis plan (100% of HBOC and colorectal studies), engagement of patients and stakeholders (95.4% of HBOC, 100% of colorectal studies) and measurement of outcomes (18.2% HBOC, 38.9% of colorectal studies). CONCLUSION: Germline testing for HBOC was likely to be cost-effective across most settings, except when used as a co-dependent technology with the PARP inhibitor, olaparib in metastatic breast cancer. In colorectal cancer studies, testing was cost-effective in those with high-risk, but inconclusive in other settings. Cost-effectiveness was sensitive to the prevalence of tested variants, cost of testing, uptake, and benefits of prophylactic measures. Policy advice on germline testing should emphasize the importance of these factors in their recommendations.

Breast, ovarian, prostate, and colorectal cancers are among the top causes of cancer related deaths. A substantial proportion of people with these cancers have inherited mutations. The identification of these gene abnormalities could provide people with opportunities to utilize preventive risk reduction surgeries or undertake frequent routine testing for these cancers. However, genetic testing requires healthcare resources and money. Previous reviews on the cost-effectiveness of genetic testing in familial cancers have concluded that targeted screening i.e., selective assessment of people at high-risk could justify the costs of testing. Our evaluation of economic studies in breast and ovarian cancer, however, suggests that genetic testing is cost-effective across a wide variety of situations starting from the screening of all healthy women above 30 years to the testing of women with existing breast or ovarian cancer. Testing in metastatic breast cancer to inform treatment with Olaparib, a drug known to selectively improve survival in people with genetic mutations, was the sole exception where testing was not cost-effective. Contrary to findings for breast or ovarian cancer, testing for colorectal cancer was cost-effective in people with high-risk i.e., family history but inconclusive in other situations. Evidence on the cost-effectiveness of testing in prostate cancer is lacking and as a result we were not able to provide advice in this cancer group.

Meta-analysis of health state utility values measured by EuroQol 5-dimensions (EQ5D) questionnaire in Chinese women with breast cancer.

BACKGROUND: To synthesise EQ5D health state utility values in Chinese women with breast cancer for parameterising a cost utility model. METHODS: Eligible studies had to report health state utility values measured by EQ-5D in Chinese women diagnosed with breast cancer. Risk of bias was assessed using the Newcastle Ottawa Scale (NOS). Data from single arm studies was pooled using meta-analysis of single proportions to provide overall point estimates and 95% confidence intervals for fixed and random effects models using the inverse variance and Der Simonian-Laird methods respectively. Heterogeneity was evaluated using the I2 statistic and sensitivity analysis and meta-regression were conducted. RESULTS: Five papers were included, when all studies were combined (n = 4,100) the mean utility (95% confidence interval) for random effects model was 0.83 (0.78, 0.89); for TNM 0-1 0.85 (0.75, 0.95); for TNM II 0.85 (0.78, 0.93); for TNM III 0.83 (0.77, 0.90) and for TNM IV 0.73 (0.63, 0.82).The utility of patients in State P (first year after primary breast cancer) 0.84 (0.80, 0.88); in State R (first year after recurrence) 0.73 (0.69, 0.76), in State S (second and following years after primary breast cancer or recurrence) 0.88 (0.83, 0.92); and in State M (metastatic disease) 0.78 (0.74, 0.82). Mean utility for duration since diagnosis 13 to 36 months was 0.88 (0.80, 0.96, I2 =95%); for 37 to 60 months 0.89 (0.82, 0.96, I2 =90%); for more than 60 months 0.86 (0.76, 0.96, I2 =90%). Mean utility for chemotherapy was 0.86 (0.79, 0.92, I2 =97%); for radiotherapy 0.83 (0.69, 0.96, I2 =97%); surgery 0.80 (0.69, 0.91, I2 =98%); concurrent chemo-radiation 0.70 (0.60, 0.81, I2 =86%) and endocrine therapy 0.90 (0.83, 0.97, I2 =91%). CONCLUSION: This study synthesises the evidence for health state utility values for Chinese women with breast cancer which is useful to inform cost utility models.

Cost of septic and aseptic revision total knee arthroplasty: a systematic review.

BACKGROUND: The increasing incidence of primary total knee arthroplasty (TKA) has led to an increase in both the incidence and the cost burden of revision TKA procedures. This study aimed to review the literature on the cost of revision TKA for septic and aseptic causes and to identify the major cost components contributing to the cost burden. METHODS: We searched MEDLINE (OvidSp), Embase, Web of Science, Cochrane Library, EconLit, and Google Scholar to identify relevant studies. Selection, data extraction and assessment of the risk of bias and cost transparency within the studies were conducted by two independent reviewers, after which the cost data were analysed narratively for 1- or 2-stage septic revision without re-revision; 2-stage septic revision with re-revision; and aseptic revision with and without re-revision, respectively. The major cost components identified in the respective studies were also reported. RESULTS: The direct medical cost from the healthcare provider perspective for high-income countries for 2-stage septic revision with re-revision ranged from US$66,629 to US$81,938, which can be about 2.5 times the cost of 1- or 2-stage septic revision without re-revision, (range: US$24,027 - US$38,109), which can be about double the cost of aseptic revision without re-revision (range: US$13,910 - US$29,213). The major cost components were the perioperative cost (33%), prosthesis cost (28%), and hospital ward stay cost (22%). CONCLUSIONS: Septic TKA revision with re-revision for periprosthetic joint infection (PJI) increases the cost burden of revision TKA by 4 times when compared to aseptic single-stage revision and by 2.5 times when compared to septic TKA revision that does not undergo re-revision. Cost reductions can be achieved by reducing the number of primary TKA that develop PJI, avoidance of re-revisions for PJI, and reduction in the length of stay after revision. TRIAL REGISTRATION: PROSPERO; CRD42020171988 .

Modelling a cost-effective vaccination strategy for the prevention of varicella and herpes zoster infection: A systematic review.

BACKGROUND: Varicella zoster virus (VZV) and its re-emergence as herpes zoster (HZ) is associated with significant morbidity and mortality. While studies show that VZV vaccination is effective in reducing VZV incidence, many decision makers have not added VZV to their vaccination schedule, largely due to uncertainty surrounding the effect of VZV vaccination on HZ incidence (exogenous boosting, EB), and the cost-effectiveness (CE) of vaccination. METHODS: A systematic review was conducted to identify the current published evidence of CE of VZV vaccination strategies where both VZV and HZ incidence were modelled. RESULTS: Six studies (one published in 2003 and five between 2010 and 2019), were identified with all conducting cost-utility analysis using a dynamic transmission modelling approach and assuming EB. All predicted that mass infant VZV vaccination would rapidly reduce VZV incidence, but HZ incidence would increase. Compared with no-vaccination, the CE of VZV vaccination strategies ranged from higher costs and poorer outcomes (dominated), towards CE (incremental cost-effectiveness ratios of between $7,000 to $61,000 USD), or lower cost and better outcomes (dominant). However, without EB, HZ incidence immediately dropped below pre-vaccination levels making VZV vaccination quickly CE and/or dominant to a no vaccination strategy. CONCLUSIONS: Current models are sensitive to assumptions of EB suggesting that future studies consider an agent-based modelling approach to address the individual nature of variables that determine the infectiousness of VZV.

Examining evidence based resistance plus balance training in community-dwelling older adults with complex health care needs: Trial protocol for the Muscling Up Against Disability project.

Progressive resistance plus balance training (PRBT) has been demonstrated as effective in reducing later life physical disability, falls risk and poor health, even among those with complex health care needs. However, few studies have examined the influence of PRBT on health service utilisation, cognitive wellbeing and training modality acceptance or undertaken a cost benefit analysis. This project will investigate the broad scope benefits of PRBT participation among community-dwelling older Australians receiving Government supported aged care packages for their complex health care needs. Using a modified stepped-wedge design, 248 community-dwelling adults 65 years and older with some level of government support aged care have been randomised into the study. Those randomised to exercise undertake six months of twice weekly machine-based, moderate to high intensity, supervised PRBT, followed by a six month unsupervised, unsupported follow-up. Controls spend six months undertaking usual activities, before entering the PRBT and follow-up phases. Data are collected at baseline and after each of the six month phases. Measures include level of and change in health and care needs, body composition, muscle capacity, falls, sleep, quality of life, nutritional and mental health status. In addition, acceptance and engagement is determined through telephone and focus group interviews complementing a multi-model health cost benefit evaluation. It is hypothesised this study will demonstrate the feasibility and efficacy of PRBT in improving primary and secondary health outcomes for older adults with aged care needs, and will support the value of this modality of exercise as an integral evidence-based service model of care.

What carers and family said about music therapy on behaviours of older people with dementia in residential aged care.

AIM: This study sought to evaluate the effectiveness of group music therapy (MT) intervention on behaviours of older people with dementia. METHOD: Reported here are qualitative data from five, semi-structured focus groups; two comprising a total of seven family members and three comprising a total of 23 staff members. RESULTS: A number of core themes emerged: temporality, effect and policy with a number of subthemes. The MT effect is tempered by the temporality of (i) the older person's dementia state, (ii) the session and (iii) the psychosomatic effect on the older person. Music therapy is perceived to (i) evoke memories and facilitate reminiscence, (ii) act as a diversion (has an instrumental value) and it is contentious to discount the (iii) dichotomy between music and therapist in terms of the overall effect. Finally, policymakers need to know that MT is (i) highly prized and more, not less, MT is recommended. CONCLUSION: Findings from this study illustrate that the timing of the MT session has consequences for the workflow in the residential aged care facility; MT has a psychosomatic effect and participants here evaluate this as temporal. Care providers and family members acknowledge the instrumental value of MT and its helping with cognition and exercise. They have mixed views about the effects of the music and the effect on the older person by the therapist but most definitely want policymakers to ensure more, not less, planned and better funded MT is part of ongoing care in the residential aged care context. Areas for future research and policy are also highlighted. IMPLICATIONS FOR PRACTICE: These views on group MT in residential aged care can initiate critical reflection on current practices and systems. Research is needed exploring the timing and scheduling of MT sessions at different times in the day for older person with dementia exhibiting negative behaviours.

Best practice in the management of primary nocturnal enuresis in children: a systematic review.

OBJECTIVE: Nocturnal enuresis is the involuntary loss of urine at night in a child of an age and physical health where they would be expected to be dry. The prevalence of this condition in Australia has been estimated at 18.9% in children 5 to 12 years of age, with up to 19% of boys and 16% of girls aged 5 years wetting the bed at least once per month. Up to the age of 13 years bedwetting is more common in boys and more common in girls after this age. Nocturnal enuresis has a spontaneous cure rate of approximately 14% however up to 3% of children remain enuretic as adults. Although this condition is pathologically benign, it can have serious social and psychological repercussions for the sufferer including affects on self esteem, school success, parental disapproval and even sexual activity in later life. Despite the volume of information available for the management of enuresis, the majority of research has been conducted outside Australia. Therefore, the purpose of this work was to produce management guidelines for nocturnal enuresis in children specific to Australian clinical practice. INCLUSION CRITERIA: This review considered systematic reviews or concurrently controlled trials (randomised controlled trials (RCT), pseudo-randomised controlled trials, controlled clinical trials (CCT), interrupted time series (ITS) and controlled before and after trials (CBA)), for examining effectiveness of interventions to manage nocturnal enuresis in children up to the age of 16 years. SEARCH STRATEGY: A systematic search of the literature was performed to identify all available evidence. Cochrane and other health technology assessment websites were searched for existing systematic reviews. For recent randomised controlled trials and controlled trials (1990 to 2007) Pubmed, Embase, and CINAHL databases were searched. Reference lists of all retrieved articles were searched for relevant trials. These reviews and guidelines were summarised and presented to an advisory panel of nurse continence advisors and clinicians to ensure relevance to Australian clinical practice. METHODOLOGICAL QUALITY: Methodological quality of all studies was assessed by two reviewers using the JBI critical appraisal forms for experimental studies located within the JBI-MAStARI software. This tool was used to identify all sources of bias. Where disagreement existed between the two reviewers a third reviewer adjudicated. RESULTS: Seven systematic reviews, eight new trials and two guidelines were used in the development of these guidelines.Briefly management recommendations include: CONCLUSIONS: Despite the high prevalence of nocturnal enuresis and the negative psychosocial sequelae that can arise from this condition, management is both readily available and effective. IMPLICATIONS FOR PRACTICE: The practice of managing nocturnal enuresis in children should start with addressing both daytime wetting and any evidence of constipation. Following this, less invasive behavioural therapies should be attempted. If these measures fail then the use of alarms with or without short-term administration of desmopressin could be attempted. Other interventions have yet to be proven to be definitively effective and should be considered with caution.It should be emphasized however, that the vast majority of children will become continent at some future time point, with or without the benefit of interventions. IMPLICATIONS FOR RESEARCH: While it is clear that some behavioural methods, alarms and desmopressin can be effective interventions, the evidence for other treatments is not so definitive. The observation however that even alarms and/or desmopressin do not work for all children suggests that research to establish the effectiveness of other interventions (especially behavioural and complementary treatments) should be performed in the form of large, carefully designed RCTs.

A systematic review of topical skin care in aged care facilities.

AIM: This systematic review aimed to evaluate the best available evidence regarding the effectiveness of topical skin care interventions for residents of aged care facilities. INTRODUCTION: Natural changes to skin, as well as increased predisposition to pressure sores and incontinence, means residents of aged care facilities readily require topical skin care. A range of interventions exist that aim to maintain or improve the integrity of skin of older adults. METHODS: Pubmed, Embase, Current Contents, CINAHL and The Cochrane Library databases were searched, as well as Health Technology Assessment websites up to April 2003. Systematic reviews and randomized or non-randomized controlled trials were evaluated for quality and data were independently extracted by two reviewers. RESULTS: The effectiveness of topical skin interventions was variable and dependent on the skin condition being treated. Studies examined the effectiveness of washing products on incontinence irritated skin. Disposable bodyworns may prevent deterioration of skin condition better than non-disposable underpads or bodyworns. Clinisan, a no-rinse cleanser may reduce the incidence of incontinence associated pressure ulcers when compared with soap and water. CONCLUSION: In general the quality of evidence for interventions to improve or maintain the skin condition in the older person was poor and more research in this area is needed. RELEVANCE TO CLINICAL PRACTICE: Skin care is a major issue for nurses working with older people. On the basis of this review no clear recommendations can be made. This lack of strong evidence for nurses to base effective practice decisions is problematic. However, the 'best' evidence suggests that disposable bodyworns are a good investment in the fight against skin deterioration. No rinse cleansers are to be preferred over soap and the use of the bag bath appears to be a useful practice to reduce the risk of dry skin (a risk factor for breaches in skin integrity).

Effectiveness of topical skin care provided in aged care facilities.

Background The 2001 Australian census revealed that adults aged 65 years and over constituted 12.6% of the population, up from 12.1% in 1996. It is projected that this figure will rise to 21% or 5.1 million Australians by 2031. In 1998, 6% (134 000) of adults in Australia aged 65 years and over were residing in nursing homes or hostels and this number is also expected to rise. As skin ages, there is a decreased turnover and replacement of epidermal skin cells, a thinning subcutaneous fat layer and a reduced production of protective oils. These changes can affect the normal functions of the skin such as its role as a barrier to irritants and pathogens, temperature and water regulation. Generally, placement in a long-term care facility indicates an inability of the older person to perform all of the activities of daily living such as skin care. Therefore, skin care management protocols should be available to reduce the likelihood of skin irritation and breakdown and ultimately promote comfort of the older person. Objectives The objective of this review was to determine the best available evidence for the effectiveness and safety of topical skin care regimens for older adults residing in long-term aged care facilities. The primary outcome was the incidence of adverse skin conditions with patient satisfaction considered as a secondary outcome. Search strategy A literature search was performed using the following databases: PubMed (NLM) (1966-4/2003), Embase (1966-4/2003), CINAHL (1966-4/2003), Current Contents (1993-4/2003), Cochrane Library (1966-2/2003), Web of Science (1995-12/2002), Science Citation Index Expanded and ProceedingsFirst (1993-12/2002). Health Technology Assessment websites were also searched. No language restrictions were applied. Selection criteria Systematic reviews of randomised controlled trials, randomised and non-randomised controlled trials evaluating any non-medical intervention or program that aimed to maintain or improve the integrity of skin in older adults were considered for inclusion. Participants were 65 years of age or over and residing in an aged care facility, hospital or long-term care in the community. Studies were excluded if they evaluated pressure-relieving techniques for the prevention of skin breakdown. Data collection and analysis Two independent reviewers assessed study eligibility for inclusion. Study design and quality were tabulated and relative risks, odds ratios, mean differences and associated 95% confidence intervals were calculated from individual comparative studies containing count data. Results The resulting evidence of the effectiveness of topical skin care interventions was variable and dependent upon the skin condition outcome being assessed. The strongest evidence for maintenance of skin condition in incontinent patients found that disposable bodyworn incontinence protection reduced the odds of deterioration of skin condition compared with non-disposable bodyworns. The best evidence for non-pressure relieving topical skin care interventions on pressure sore formation found the no-rinse cleanser Clinisan to be more effective than soap and water at maintaining healthy skin (no ulcers) in elderly incontinent patients in long-term care. The quality of studies examining the effectiveness of topical skin care interventions on the incidence of skin tears was very poor and inconclusive. Topical skin care for prevention of dermatitis found that Sudocrem could reduce the redness of skin compared with zinc cream if applied regularly after each pad change, but not the number of lesions. Topical skin care on dry skin found the Bag Bath/Travel Bath no-rinse skin care cleanser to be more effective at preventing overall skin dryness and most specifically flaking and scaling when compared with the traditional soap and water washing method in residents of a long-term care facility. Information on the safety of topical skin care interventions is lacking. Therefore, because of the lack of evidence, no recommendation on the safety on any intervention included in this review can be made.

Effectiveness of topical skin care provided in aged care facilities.

BACKGROUND: The 2001 Australian census revealed that adults aged 65 years and over constituted 12.6% of the population, up from 12.1% in 1996. It is projected that this figure will rise to 21% or 5.1 million Australians by 2031. In 1998, 6% (134 000) of adults in Australia aged 65 years and over were residing in nursing homes or hostels and this number is also expected to rise. As skin ages, there is a decreased turnover and replacement of epidermal skin cells, a thinning subcutaneous fat layer and a reduced production of protective oils. These changes can affect the normal functions of the skin such as its role as a barrier to irritants and pathogens, temperature and water regulation. Generally, placement in a long-term care facility indicates an inability of the older person to perform all of the activities of daily living such as skin care. Therefore, skin care management protocols should be available to reduce the likelihood of skin irritation and breakdown and ultimately promote comfort of the older person. OBJECTIVES: The objective of this review was to determine the best available evidence for the effectiveness and safety of topical skin care regimens for older adults residing in long-term aged care facilities. The primary outcome was the incidence of adverse skin conditions with patient satisfaction considered as a secondary outcome. SEARCH STRATEGY: A literature search was performed using the following databases: PubMed (NLM) (1966-4/2003), Embase (1966-4/2003), CINAHL (1966-4/2003), Current Contents (1993-4/2003), Cochrane Library (1966-2/2003), Web of Science (1995-12/2002), Science Citation Index Expanded and ProceedingsFirst (1993-12/2002). Health Technology Assessment websites were also searched. No language restrictions were applied. SELECTION CRITERIA: Systematic reviews of randomised controlled trials, randomised and non-randomised controlled trials evaluating any non-medical intervention or program that aimed to maintain or improve the integrity of skin in older adults were considered for inclusion. Participants were 65 years of age or over and residing in an aged care facility, hospital or long-term care in the community. Studies were excluded if they evaluated pressure-relieving techniques for the prevention of skin breakdown. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed study eligibility for inclusion. Study design and quality were tabulated and relative risks, odds ratios, mean differences and associated 95% confidence intervals were calculated from individual comparative studies containing count data. RESULTS: The resulting evidence of the effectiveness of topical skin care interventions was variable and dependent upon the skin condition outcome being assessed. The strongest evidence for maintenance of skin condition in incontinent patients found that disposable bodyworn incontinence protection reduced the odds of deterioration of skin condition compared with non-disposable bodyworns. The best evidence for non-pressure relieving topical skin care interventions on pressure sore formation found the no-rinse cleanser Clinisan to be more effective than soap and water at maintaining healthy skin (no ulcers) in elderly incontinent patients in long-term care. The quality of studies examining the effectiveness of topical skin care interventions on the incidence of skin tears was very poor and inconclusive. Topical skin care for prevention of dermatitis found that Sudocrem could reduce the redness of skin compared with zinc cream if applied regularly after each pad change, but not the number of lesions. Topical skin care on dry skin found the Bag Bath/Travel Bath no-rinse skin care cleanser to be more effective at preventing overall skin dryness and most specifically flaking and scaling when compared with the traditional soap and water washing method in residents of a long-term care facility.Information on the safety of topical skin care interventions is lacking. Therefore, because of the lack of evidence, no recommendation on the safety on any intervention included in this review can be made.