Health Economic Studies of Surfactant Replacement Therapy in Neonates with Respiratory Distress Syndrome: A Systematic Literature Review.

BACKGROUND: Neonatal respiratory distress syndrome (RDS) is one of the most common problems for preterm infants, and symptoms include tachypnoea, grunting, retractions and cyanosis, which occur immediately after birth. Treatment with surfactants has reduced morbidity and mortality rates associated with neonatal RDS. OBJECTIVE: The objective of this review is to describe the treatment costs, healthcare resource utilization (HCRU) and economic evaluations of surfactant use in the treatment of neonates with RDS. METHODS: A systematic literature review (SLR) was performed to identify available economic evaluations and costs associated with neonatal RDS. Electronic searches were conducted in Embase, MEDLINE, MEDLINE In-Process, NHS EED, DARE and HTAD to identify studies published between 2011 and 2021. Supplementary searches of reference lists, conference proceedings, websites of global health technology assessment bodies and other relevant sources were conducted. Publications were screened by two independent reviewers for inclusion and followed the population, interventions, comparators and outcomes framework eligibility criteria. Quality assessment of the identified studies was performed. RESULTS: Eight publications included in this SLR met all eligibility criteria: three conference abstracts and five peer-reviewed original research articles. Four of these publications evaluated costs/HCRU, and five (three abstracts and two peer-reviewed articles) investigated economic evaluations (two from Russia, and one each from Italy, Spain and England). The main cost drivers and causes of increased HCRU were invasive ventilation, duration of hospitalization and RDS-associated complications. There were no significant differences in neonatal intensive care unit (NICU) length of stay or NICU total costs between infants treated with beractant (Survanta®), calfactant (Infasurf®) or poractant alfa (Curosurf®). However, treatment with poractant alfa was associated with reduced total costs compared with no treatment, continuous positive airway pressure (CPAP) alone or calsurf (Kelisu®), due to shorter duration of hospitalization and fewer complications. Early use of the surfactant after birth was more clinically effective and cost-effective than late intervention in infants with RDS. Poractant alfa was found to be cost-effective and cost-saving compared to beractant for the treatment of neonatal RDS in two Russian studies. CONCLUSION: There were no significant differences in NICU length of stay or NICU total costs between surfactants evaluated for treating neonates with RDS. However, early use of surfactant was found to be more clinically effective and cost-effective than late treatment. Treatment with poractant alfa was found to be cost-effective versus beractant and cost-saving compared with CPAP alone or beractant or CPAP in combination with calsurf. Limitations included the small number of studies, the geographic scope of the studies and the retrospective study design of the cost-effectiveness studies.

PHARMACEUTICAL BENEFITS ADVISORY COMMITTEE RECOMMENDATIONS IN AUSTRALIA.

OBJECTIVES: The aim of this study was to examine submissions made to the Pharmaceutical Benefits Advisory Committee (PBAC) and assess whether the predicted financial impact was associated with a recommendation. The second objective was to assess whether the financial and utilization estimates for listing the proposed medicine were reliable. METHODS: Data were extracted from public summary documents of major submissions considered by the PBAC from 2012 to 2014. Information collected included whether submissions were accepted, rejected, or deferred; estimated use; and financial impact. For those submissions that were recommended in 2012 and listed on the Pharmaceutical Benefits Scheme (PBS) by January 2014, a comparison was made between predicted and actual use and cost in 2014, based on PBS utilization. RESULTS: In 2012 to 2014, the PBAC considered 142 unique major submissions; of those, 65 were recommended for listing. A higher financial cost to the government was a statistically significant factor in predicting rejection (p = .004 for cost > AUD 30 million Australian dollars [20.7 million Euros] compared with cost-saving). Of the submissions that were recommended in 2012 and listed by 2014, the actual use was higher than predicted for 5/19 medications. The estimated cost was outside the predicted bracket of cost for 10/19 medications, with 8/19 medications having threefold underestimated expenditure, and 2/19 items having lower than predicted expenditure. CONCLUSIONS: This study highlights that the predicted financial impact of a medication to the PBS budget is associated with a PBAC recommendation and also highlights that predicted use may not reflect actual prescribing practices.

An economic evaluation alongside a randomised controlled trial on psycho-education counselling intervention offered by midwives to address women's fear of childbirth in Australia.

OBJECTIVE: The rate of caesarean section continues to increase, and there is evidence that childbirth fear is a contributing factor. Insufficient evidence is available on the impact of reducing childbirth fear on health-related quality of life and health service use. We undertook an economic evaluation of a psycho-education counselling intervention offered by midwives to address women's fear of childbirth in Australia. METHODS: Pregnant women (n = 339) with high childbirth fear were randomised to a midwife-led psycho-education intervention for childbirth fear or to usual care. This paper presents the economic evaluation of the intervention based on health-related quality of life and health service use from recruitment to six weeks postpartum (n = 184). RESULTS: The changes in health-related quality of life after birth (EQ-5D-3L: 0.016 vs. 0.010, p = 0.833, for usual care and intervention) and total health care use cost (AUS$10,110 vs. AUS$9980, p = 0.819) were similar between groups. The intervention did not increase costs; however, in a post hoc analysis, the interventions might be cost-effective for those women with very high childbirth fear. CONCLUSION: This brief psycho-education intervention by midwives did not improve the health-related quality of life of women, and had no impact on overall cost.

Triple therapy in type 2 diabetes; a systematic review and network meta-analysis.

Aims. The purpose was to evaluate the evidence for triple therapy regimen using medicines available in Australia for type 2 diabetes. Methods. A systematic literature review was performed to update the relevant evidence from 2002 to 2014 on triple therapy for type 2 diabetes. A multiple-treatments network meta-analysis was undertaken to summarise the comparative efficacy and harms of different triple therapies. Results. Twenty seven trials were identified, most were six months of duration. The following combinations were included in the network meta-analysis: metformin (MET) + sulfonylureas (SU) (used as reference combination); MET + SU+ dipeptidyl peptidase 4 inhibitors (DPP-4-i); MET + SU+ thiazolidinediones (TZD); MET + SU+ glucagon-like peptide-1 receptor agonists (GLP-1-RA); MET + SU+ insulins; MET + TZD + DPP-4-i; and MET + SU+ sodium/glucose cotransporter 2 inhibitors (SGLT2-i). For HbA1c reduction, all triple therapies were statistically superior to MET+SU dual therapy, except for MET + TZD + DPP-4-i. None of the triple therapy combinations demonstrated differences in HbA1c compared with other triple therapies. MET + SU + SGLT2-i and MET + SU + GLP-1-RA resulted in significantly lower body weight than MET + SU + DPP-4-i, MET+SU+insulin and MET + SU + TZDs; MET + SU + DPP-4-i resulted in significantly lower body weight than MET + SU + insulin and MET + SU + TZD. MET + SU + insulin, MET + SU + TZD and MET + SU + DPP-4-i increased the odds of hypoglycaemia when compared to MET + SU. MET + SU + GLP-1-RA reduced the odds of hypoglycaemia compared to MET + SU + insulin. Conclusion. Care when choosing a triple therapy combination is needed as there is often a risk of increased hypoglycaemia events associated with this regimen and there are very limited data surrounding the long-term effectiveness and safety of combined therapies.

Effects of a midwife psycho-education intervention to reduce childbirth fear on women's birth outcomes and postpartum psychological wellbeing.

BACKGROUND: High levels of childbirth fear impact birth preparation, obstetric outcomes and emotional wellbeing for around one in five women living in developed countries. Higher rates of obstetric intervention and caesarean section (CS) are experienced in fearful women. The efficacy of interventions to reduce childbirth fear is unclear, with no previous randomised controlled trials reporting birth outcomes or postnatal psychological wellbeing following a midwife led intervention. METHOD: Between May 2012 and June 2013 women in their second trimester of pregnancy were recruited. Women with a fear score ≥ 66 on the Wijma Delivery Expectancy / Experience Questionnaire (W-DEQ) were randomised to receive telephone psycho-education by a midwife, or usual maternity care. A two armed non-blinded parallel (1:1) multi-site randomised controlled trial with participants allocated in blocks of ten and stratified by hospital site and parity using an electronic centralised computer service. The outcomes of the RCT on obstetric outcomes, maternal psychological well-being, parenting confidence, birth satisfaction, and future birth preference were analysed by intention to treat and reported here. RESULTS: 1410 women were screened for high childbirth fear (W-DEQ ≥66). Three hundred and thirty-nine (n = 339) women were randomised (intervention n = 170; controls n = 169). One hundred and eighty-four women (54 %) returned data for final analysis at 6 weeks postpartum (intervention n = 91; controls n = 93). Compared to controls the intervention group had a clinically meaningful but not statistically significant reduction in overall caesarean section (34 % vs 42 %, p = 0.27) and emergency CS rates (18 % vs 25 %, p = 0.23). Fewer women in the intervention group preferred caesarean section for a future pregnancy (18 % vs 30 %, p = 0.04). All other obstetric variables remained similar. There were no differences in postnatal depression symptoms scores, parenting confidence, or satisfaction with maternity care between groups, but a lower incidence of flashbacks about their birth in the intervention group compared to controls (14 % vs 26 %, p = 0.05). Postnatally women who received psycho-education reported that the 'decision aid' helped reduce their fear (53 % vs 37 %, p = 0.02). CONCLUSION: Following a brief antenatal midwife-led psycho-education intervention for childbirth fear women were less likely to experience distressing flashbacks of birth and preferred a normal birth in a future pregnancy. A reduction in overall CS rates was also found. Psycho-education for fearful women has clinical benefits for the current birth and expectations of future pregnancies. TRIAL REGISTRATION: Australian New Zealand Controlled Trials Registry ACTRN12612000526875 , 17th May 2012.

A randomized controlled trial of a psycho-education intervention by midwives in reducing childbirth fear in pregnant women.

BACKGROUND: Childbirth fear is associated with increased obstetric interventions and poor emotional and psychological health for women. The purpose of this study is to test an antenatal psycho-education intervention by midwives in reducing women's childbirth fear. METHODS: Women (n = 1,410) attending three hospitals in South East Queensland, Australia, were recruited into the BELIEF trial. Participants reporting high fear were randomly allocated to intervention (n = 170) or control (n = 169) groups. All women received a decision-aid booklet on childbirth choices. The telephone counseling intervention was offered at 24 and 34 weeks of pregnancy. The control group received usual care offered by public maternity services. Primary outcome was reduction in childbirth fear (WDEQ-A) from second trimester to 36 weeks' gestation. Secondary outcomes were improved childbirth self-efficacy, and reduced decisional conflict and depressive symptoms. Demographic, obstetric & psychometric measures were administered at recruitment, and 36 weeks of pregnancy. RESULTS: There were significant differences between groups on postintervention scores for fear of birth (p < 0.001) and childbirth self-efficacy (p = 0.002). Decisional conflict and depressive symptoms reduced but were not significant. CONCLUSION: Psycho-education by trained midwives was effective in reducing high childbirth fear levels and increasing childbirth confidence in pregnant women. Improving antenatal emotional well-being may have wider positive social and maternity care implications for optimal childbirth experiences.

Yes, the government should tax soft drinks: findings from a citizens' jury in Australia.

Taxation has been suggested as a possible preventive strategy to address the serious public health concern of childhood obesity. Understanding the public's viewpoint on the potential role of taxation is vital to inform policy decisions if they are to be acceptable to the wider community. A Citizens' Jury is a deliberative method for engaging the public in decision making and can assist in setting policy agendas. A Citizens' Jury was conducted in Brisbane, Australia in May 2013 to answer the question: Is taxation on food and drinks an acceptable strategy to the public in order to reduce rates of childhood obesity? Citizens were randomly selected from the electoral roll and invited to participate. Thirteen members were purposively sampled from those expressing interest to broadly reflect the diversity of the Australian public. Over two days, participants were presented with evidence on the topic by experts, were able to question witnesses and deliberate on the evidence. The jurors unanimously supported taxation on sugar-sweetened drinks but generally did not support taxation on processed meats, snack foods and foods eaten/ purchased outside the home. They also supported taxation on snack foods on the condition that traffic light labelling was also introduced. Though they were not specifically asked to deliberate strategies outside of taxation, the jurors strongly recommended more nutritional information on all food packaging using the traffic light and teaspoon labelling systems for sugar, salt and fat content. The Citizens' Jury suggests that the general public may support taxation on sugar-sweetened drinks to reduce rates of obesity in children. Regulatory reforms of taxation on sugar-sweetened drinks and improved labelling of nutritional information on product packaging were strongly supported by all members of the jury. These reforms should be considered by governments to prevent childhood obesity and the future burden on society from the consequences of obesity.

The cost-effectiveness and consumer acceptability of taxation strategies to reduce rates of overweight and obesity among children in Australia: study protocol.

BACKGROUND: Childhood obesity is a recognised public health problem and around 25% of Australian children are overweight or obese. A major contributor is the obesogenic environment which encourages over consumption of energy dense nutrient poor food. Taxation is commonly proposed as a mechanism to reduce consumption of poor food choices and hence reduce rates of obesity and overweight in the community. METHODS/DESIGN: An economic model will be developed to assess the lifetime benefits and costs to a cohort of Australian children by reducing energy dense nutrient poor food consumption through taxation mechanisms. The model inputs will be derived from a series of smaller studies. Food options for taxation will be derived from literature and expert opinion, the acceptability and impact of price changes will be explored through a Citizen's Jury and a discrete choice experiment and price elasticities will be derived from the discrete choice experiment and consumption data. DISCUSSION: The health care costs of managing rising levels of obesity are a challenge for all governments. This study will provide a unique contribution to the international knowledge base by engaging a variety of robust research techniques, with a multidisciplinary focus and be responsive to consumers from diverse socio-economic backgrounds.

Study protocol for reducing childbirth fear: a midwife-led psycho-education intervention.

BACKGROUND: Childbirth fear has received considerable attention in Scandinavian countries, and the United Kingdom, but not in Australia. For first-time mothers, fear is often linked to a perceived lack of control and disbelief in the body's ability to give birth safely, whereas multiparous women may be fearful as a result of previous negative and/or traumatic birth experiences. There have been few well-designed intervention studies that test interventions to address women's childbirth fear, support normal birth, and diminish the possibility of a negative birth experience. METHODS/DESIGN: Pregnant women in their second trimester of pregnancy will be recruited and screened from antenatal clinics in Queensland, Australia. Women reporting high childbirth fear will be randomly allocated to the intervention or control group. The psycho-educational intervention is offered by midwives over the telephone at 24 and 34 weeks of pregnancy. The intervention aims to review birth expectations, work through distressing elements of childbirth, discuss strategies to develop support networks, affirm that negative childbirth events can be managed and develop a birth plan. Women in the control group will receive standard care offered by the public funded maternity services in Australia. All women will receive an information booklet on childbirth choices. Data will be collected at recruitment during the second trimester, 36 weeks of pregnancy, and 4-6 weeks after birth. DISCUSSION: This study aims to test the efficacy of a brief, midwife-led psycho-education counselling (known as BELIEF: Birth Emotions - Looking to Improve Expectant Fear) to reduce women's childbirth fear. 1) Relative to controls, women receiving BELIEF will report lower levels of childbirth fear at term; 2) less decisional conflict; 3) less depressive symptoms; 4) better childbirth self-efficacy; and 5) improved health and obstetric outcomes. TRIAL REGISTRATION: Australian New Zealand Controlled Trials Registry ACTRN12612000526875.

Cost-effectiveness of a coronary heart disease secondary prevention program in patients with myocardial infarction: results from a randomised controlled trial (ProActive Heart).

BACKGROUND: Participation in coronary heart disease (CHD) secondary prevention programs is low. Telephone-delivered CHD secondary prevention programs may overcome the treatment gap. The telephone-based health coaching ProActive Heart trial intervention has previously been shown to be effective for improving health-related quality of life, physical activity, body mass index, diet, alcohol intake and anxiety. As a secondary aim, the current study evaluated the cost-effectiveness of the ProActive Heart intervention compared to usual care. METHODS: 430 adult myocardial infarction patients were randomised to a six-month CHD secondary prevention 'health coaching' intervention or 'usual care' control group. Primary outcome variables were health-related quality of life (SF-36) and physical activity (Active Australia Survey). Data were collected at baseline, six-months (post-intervention) and 12 months (six-months post-intervention completion) for longer term effects. Cost-effectiveness data [health utility (SF-6D) and health care utilisation] were collected using self-reported (general practitioner, specialist, other health professionals, health services, and medication) and claims data (hospitalisation rates). Intervention effects are presented as mean differences (95% CI), p-value. RESULTS: Improvements in health status (SF-6D) were observed in both groups, with no significant difference between the groups at six [0.012 (-0.016, 0.041), p = 0.372] or 12 months [0.011 (-0.028, 0.051) p = 0.738]. Patients in the health coaching group were significantly more likely to be admitted to hospital due to causes unrelated to cardiovascular disease (p = 0.042). The overall cost for the health coaching group was higher ($10,574 vs. $8,534, p = 0.021), mainly due to higher hospitalisation (both CHD and non-CHD) costs ($6,841 vs. $4,984, p = 0.036). The incremental cost-effectiveness ratio was $85,423 per QALY. CONCLUSIONS: There was no intervention effect measured using the SF-36/SF-6D and ProActive Heart resulted in significantly increased costs. The cost per QALY gained from ProActive Heart was high and above acceptable limits compared to usual care.

A non-randomised trial investigating the cost-effectiveness of Midwifery Group Practice compared with standard maternity care arrangements in one Australian hospital.

OBJECTIVE: to compare cost-effectiveness of two models of maternity service delivery: Midwifery Group Practice (MGP) at a birth centre and standard care (SC). DESIGN: a prospective non-randomised trial. SETTING: an Australian metropolitan hospital. METHOD: women at 36 weeks gestation were approached in the birth centre or hospital antenatal clinics between March and December 2008. Of 170 consecutive women who met birth centre eligibility criteria, 70% (n=119) were recruited to the study. Women (MGP n=52 or standard care n=50) were followed through to 6 weeks postpartum. Publically funded care costs were collected from women's diaries, handheld pregnancy health records, medical records and the hospital accounting system. MAIN OUTCOME MEASURES: health-care costs to the hospital and government. ANALYSIS: generalised linear models with covariates of age, nulliparity, private health insurance (yes/no) and household income category. FINDINGS: women receiving MGP care were less likely to experience induction of labour, required fewer antenatal visits, received more postnatal care, and neonates were less likely to be admitted to special care nursery than those receiving standard care. Statistically significant lower costs were found for women and babies receiving MGP care compared with women receiving standard care during pregnancy, labour and birth and postpartum to 6 weeks. MGP resulted in lower costs for the hospital ($AUD4,696 vs. $AUD5,521 p<0.001) and the government ($AUD4,722 vs. $AUD5,641 p<0.001). When baby costs were excluded MGP care remained statistically significantly cheaper than standard care. CONCLUSION: for women at low-risk of birth complications, Midwifery Group Practice was cost effective, and women experienced fewer obstetric interventions compared with standard maternity care. The evidence suggests Midwifery Group Practice is safe and economically viable.

Present and past carers' health: some considerations.

We sought to examine the mental and physical health and health-related quality of life of current and past carers compared to non-carers, using two instruments--the Short Form-12 (SF-12) and the EuroQol 5-dimension (EQ-5D). A total of 249 participants (34 current carers, 14 previous carers, 197 non-carers, 4 non-respondents) completed a baseline self-report survey at randomization into the larger study. Previous carers demonstrated moderate to severe anxiety or depressive symptoms measured with the EQ-5D (P < 0.001), reported on the SF-12 that they accomplished less because of emotional problems (P = 0.01) and more likely to have 'felt down' (P = 0.01) and used more health-care services than current or non-carers. Current carers tended towards a higher level of emotional problems and limitations to mobility than non-carers. This study indicates major differences in the well-being of these three cohorts. Health practitioners should pay particular attention to the mental health and health related quality of life of previous carers.

Hypoxanthine plus xanthine oxidase causes profound natriuresis without affecting renal blood flow autoregulation.

BACKGROUND: Enhanced superoxide (O2-.) production by xanthine oxidase in ischemia/reperfusion has been implicated in structural damage. The reperfusion phase is accompanied by decreased tubular sodium reabsorption, which has been partly attributed to enhanced action of O2-. In the present study we assessed whether intrarenal increases of O2-. accomplished by concomitant intrarenal hypoxanthine and intravenous xanthine oxidase (HX/XO) infusion would decrease or increase sodium excretion, and whether HX/XO infusion could be responsible for the diminished efficacy of renal blood flow (RBF) autoregulation in ischemia/reperfusion. METHODS: In the first group of Sprague-Dawley rats, renal sodium handling was measured before and during O2-. infusion. In the second group, renal hemodynamics and RBF autoregulation were assessed. RESULTS: Intrarenal O2-. infusion dramatically increased urine flow from 14.5 +/- 2.0 microL/min to 46.3 +/- 4.4 microL/min, urinary excretion of sodium (UNaV) from 1.7 +/- 0.4 micromol/min to 8.6 +/- 0.9 micromol/min, and fractional excretion of sodium FENa from 1.2 +/- 0.4% to 7.6 +/- 1.2%. Urinary excretion of thiobarbituric acid reactive substances (TBARS), a measure of lipid peroxidation, increased during HX/XO infusion. These changes were completely reversible. Glomerular filtration rate (GFR) decreased from 1.12 +/- 0.08 during baseline to 0.79 +/- 0.06 during HX/XO (P < 0.05) and tended to increase toward baseline during recovery (0.84 +/- 0.06 mL/min/g kidney weight). HX/XO did not significantly affect mean arterial pressure (MAP). HX/XO decreased RBF in the second group from 8.4 +/- 0.6 mL/min/g kidney weight to 7.4 +/- 0.5 mL/min/g kidney weight (P < 0.05) and renal vascular resistance (RVR) slightly increased from 13.8 +/- 0.9 units under baseline conditions to 15.1 +/- 1.1 units during HX/XO infusion (P < 0.05). HX/XO did not significantly affect RBF autoregulation. Proteinuria and glucosuria were absent and light microscopy revealed no renal morphologic changes. CONCLUSION: Intrarenal O2-. infusion (1) dramatically increased sodium and volume excretion and (2) did not affect autoregulation of RBF. Thus, superoxide can markedly affect glomerulotubular balance by diverging actions on renal hemodynamics and reabsorptive function and could mediate the functional tubular consequences of ischemia/reperfusion.

Impaired renal blood flow autoregulation in two-kidney, one-clip hypertensive rats is caused by enhanced activity of nitric oxide.

Increases in renal perfusion pressure will induce shear stress-mediated nitric oxide (NO) release, which could oppose autoregulation of renal blood flow (RBF). Although cardiac, cerebral, and mesenteric autoregulation is enhanced during nitric oxide (NO) synthesis inhibition, this has not been reported for renal autoregulation of blood flow. In the present study, the lower limit and efficiency of RBF autoregulation (as assessed by the degree of compensation) were studied before and during NO inhibition in normotensive Sprague Dawley rats (control; n = 9) and in the non-clipped kidney of two-kidney, one-clip Goldblatt hypertensive animals (2K1C; n = 9; 3 wk; 0.25-mm silver clip). In both groups, renal autoregulation curves were obtained before and during infusion of N(G) -nitro-L-arginine (L-NNA) (bolus 1.5 mg/kg intravenously, infusion 10 microg/kg per min intravenously), using a transit-time flow probe around the left renal artery. In control rats, mean arterial pressure (MAP) increased, RBF decreased, and renal vascular resistance (RVR) increased in response to L-NNA infusion. The lower limit of autoregulation in control animals did not significantly change during L-NNA infusion (78 +/- 3 to 70 +/- 2 mmHg). The degree of compensation in these rats slightly increased during L-NNA infusion, however, this was only significant below 90 mmHg. The 2K1C rats had elevated MAP under baseline conditions. L-NNA infusion resulted in a decrease in RBF and an increase in MAP and RVR. During L-NNA infusion, RVR in 2K1C rats greatly exceeded RVR in control rats. A significant decrease was observed in the lower limit of autoregulation from 85 +/- 3 to 72 +/- 5 mmHg (P < 0.05). In the contralateral kidney of 2K1C rats, the degree of compensation was lower than in control rats under baseline conditions. L-NNA infusion resulted in significantly higher degrees of compensation compared to baseline. In conclusion, the contralateral kidney displayed a high NO dependency, as RBF greatly decreased and RVR dramatically increased in response to L-NNA infusion. The contralateral kidney of 2K1C rats exhibited impaired RBF autoregulation, which was improved by NO inhibition, as judged from a decrease in the lower limit of autoregulation and an increase in the degree of compensation. This study indicates that perfusion pressure-dependent NO release can oppose autoregulation in the kidney. However, the enhanced influence of NO on pressure-dependent RBF may facilitate the preservation of renal function in the nonclipped kidney of 2K1C rats.