Severe acute maternal morbidity reporting in Australia: Why is it so hard?

Adverse outcomes associated with pregnancy, including severe acute maternal morbidity (SAMM) and mortality, are internationally regarded as important indicators of quality of maternity services. Varied definitions and processes are barriers for SAMM recording, reporting and review. Identifying and documenting these cases of SAMM is a critical first step. Case reviews allow exploration of factors contributing to SAMM. Translation of the lessons learnt into practice improvement strategies and dissemination of this knowledge is essential for continual quality improvement. This review will outline the current status of SAMM review internationally and in Australia.

Synthesis and Characterization of Paclitaxel-Loaded PEGylated Liposomes by the Microfluidics Method.

For cancer therapy, paclitaxel (PX) possesses several limitations, including limited solubility and untargeted effects. Loading PX into nanoliposomes to enhance PX solubility and target their delivery as a drug delivery system has the potential to overcome these limitations. Over the other conventional method to prepare liposomes, a microfluidic system is used to formulate PX-loaded PEGylated liposomes. The impact of changing the flow rate ratio (FRR) between the aqueous and lipid phases on the particle size and polydispersity index (PDI) is investigated. Moreover, the effect of changing the polyethylene glycol (PEG) lipid ratio on the particle size, PDI, stability, encapsulation efficiency % (EE %), and release profile is studied. The physicochemical characteristics of the obtained formulation were analyzed by dynamic light scattering, FTIR spectroscopy, and AFM. This work aims to use microfluidic technology to produce PEGylated PX-loaded liposomes with a diameter of <200 nm, low PDI < 0.25 high homogeneity, and viable 28 day stability. The results show a significant impact of FRR and PEG lipid ratio on the empty liposomes' physicochemical characteristics. Among the prepared formulations, two formulations produce size-controlled, low PDI, and stable liposomes, which make them preferable for PX encapsulation. The average EE % was >90% for both formulations, and the variation in the PEG lipid ratio affected the EE % slightly; a high packing for PX was reported at different drug concentrations. A variation in the release profiles was notified for the different PEG lipid ratios.

Suicide crises among women and mothers during and around the time of pregnancy: Prevalence and timing of initial contact with first responders and health services.

OBJECTIVES: Suicide is a leading cause of maternal mortality. Suicidality during and around the time of pregnancy can have detrimental impacts on a child's development and outcomes. This paper examines prevalence, demographic characteristics, and timing of initial contact with first responders and health services for a cohort of women who experienced suicidality during and around the time of pregnancy. METHODS: Findings are drawn from the Partners in Prevention (PiP) study, a population-wide linked data set of suicide-related attendances by police or paramedics in Queensland, Australia. A sub-cohort of women was identified, who were between 6 months preconception and 2 years postpartum at the time of a suicide-related contact with police or paramedics (PiP-Maternal). Findings are compared to other girls and women who had a suicide-related contact with police or paramedics (PiP-Female). Prevalence, demographic characteristics, timing of contact with first responders and health services, re-presentations, and mortality are reported. RESULTS: The PiP-Maternal cohort comprised 3020 individuals and 3400 births. Women in the PiP-Maternal cohort were younger, more likely to be of Aboriginal and/or Torres Strait Islander descent and live outside of a major city than the PiP-Female cohort. There were high rates of out-of-hours calls to police and ambulance, and similar perceived seriousness of the call between women in the PiP-Maternal and PiP-Female cohorts. Women in the PiP-Maternal cohort were less likely to be admitted to an emergency department within 24 hours, even after matching on covariates. Prevalence of suicidality for women who were pregnant and up to 2 years postpartum was 1.32% (95% CI = [1.27, 1.37]). CONCLUSION: Vulnerabilities and high rates of contact with police or paramedics, coupled with lower levels of follow-up, highlight the critical need to improve service responses for women with mental health needs during these phases of life.

A prospective cohort study comparing neonatal outcomes of waterbirth and land birth in an Australian tertiary maternity unit.

BACKGROUND: Maternal preference for warm water immersion (WWI) and waterbirth is increasing, but adoption into obstetric guidelines and clinical practice remains limited. Concerns regarding safety and a paucity of evidence have been cited as reasons for the limited adoption and uptake. AIM: The aim was to investigate maternal and neonatal outcomes after WWI and/or waterbirth compared with land birth. MATERIALS AND METHODS: A prospective cohort study was conducted in an Australian public maternity hospital between 2019 and 2020. Maternal and neonatal outcomes for 1665 women who had a vaginal birth were studied. Primary outcome was admission to the neonatal unit (NNU). Secondary outcomes included neonatal antibiotic administration, maternal intrapartum fever, epidural use and perineal injury. Multivariate logistical regression analyses compared the outcomes between three groups: waterbirth, WWI only and land birth. RESULTS: NNU admissions for a suspected infectious condition were significantly higher in the land birth group (P = 0.035). After accounting for labour duration, epidural use and previous birth mode, no significant difference was detected between groups in the odds of NNU admission (P = 0.167). No babies were admitted to NNU with water inhalation or drowning. Women birthing on land were more likely to be febrile (2 vs 0%; P = 0.007); obstetric anal sphincter injury and postpartum haemorrhage were similar between groups. Regional analgesia use was significantly lower in the WWI group compared to the land birth group (21.02 vs 38.58%; P = <0.001). There was one cord avulsion in the waterbirth group (0.41%). CONCLUSION: Maternal and neonatal outcomes were similar between groups, with no increased risk evident in the waterbirth and WWI groups.

Effect of surgeon volume on long-term quality of life outcomes following tension-free vaginal tape surgery.

INTRODUCTION AND HYPOTHESIS: The role of the general obstetrician/gynaecologist completing routine urogynaecology procedures is controversial, and some research has suggested that these patients should be referred to high-volume subspecialists. In response to recent public and regulatory scrutiny of vaginal mesh procedures, credentialling guidelines have been released in Australia requiring surgeons to demonstrate a minimum caseload prior to performing tension-free vaginal tape (TVT) surgery for incontinence. Hence, a retrospective cohort study was conducted to evaluate the long-term quality of life outcomes of TVT procedures for high- and low-volume surgeons. METHODS: One hundred seventy patients who had undergone TVT surgery between 1 May 2011 and 1 May 2016 in the Sunshine Coast health district were invited to complete the UDI-6 (Urinary Distress Inventory) and IIQ-7 (Incontinence Impact Questionnaire) surveys. Perioperative information was accessed from available health records. Mean UDI-6 and IIQ-7 scores were compared for high- and low-volume groups, and the groups were assessed for confounding factors. RESULTS: Of the 170 patients eligible, 83 completed the surveys (47.2%). No differences in UDI-6 or IIQ-7 scores were found between high- and low-volume surgeons (p > 0.05). High-volume surgeons completed more concomitant procedures amongst survey respondents (p < 0.05), though this was not reproduced when considering all 170 patients eligible for the study. There were no significant differences in age, ASA (American Society of Anaesthesiologists) score or complication rate amongst survey respondents. CONCLUSIONS: Amongst the patients surveyed, high- and low-volume surgeons had similar long-term quality of life outcomes for TVT surgery, without any significant difference in complication rate.

Reduction in preterm birth rates during and after the COVID-19 lockdown in Queensland Australia.

BACKGROUND: Preventative strategies for preterm birth are lacking. Recent evidence proposed COVID-19 lockdowns may have contributed to changes in preterm birth. AIMS: To determine the prevalence of preterm birth and birth outcomes during and after the COVID-19 lockdown at the Sunshine Coast University Hospital and the overall state of Queensland, Australia. METHODS: Retrospective cohort analysis of all births in Queensland including the Sunshine Coast University Hospital, during two epochs, April 1-May 31, 2020 (lockdown) and June 1-July 31, 2020 (post-lockdown), compared to antecedent calendar-matched periods in 2018-2019. Prevalence of preterm birth, stillbirth, and late terminations were examined. RESULTS: There were 64 989 births in Queensland from April to July 2018-2020. At the Sunshine Coast University Hospital, there was a significantly higher chance of birth at term during both lockdown (odds ratio (OR) 1.81, 95% CI 1.17, 2.79; P = 0.007) and post-lockdown (OR 2.01, 95% CI 1.27, 3.18; P = 0.003). At the same centre, prevalence of preterm birth was 5.5% (30/547) during lockdown, compared to 9.1% (100/1095) in previous years, a 40.0% relative reduction (P = 0.016). At this centre during lockdown, emergency caesareans concurrently decreased (P < 0.01) and instrumental vaginal births increased (P < 0.01). In Queensland overall, there was a nonsignificant decrease in the prevalence of preterm birth during lockdown. CONCLUSIONS: There is a link between lockdown and a reduction in the prevalence of preterm birth on the Sunshine Coast. The cause is speculative at present, although increased influenza vaccination rates, decreased transmission of infections, and improved air quality may have been favourable in reducing preterm birth. Further research is needed to determine a causal link.

Manufacturing of 3D-Printed Microfluidic Devices for the Synthesis of Drug-Loaded Liposomal Formulations.

Microfluidic technique has emerged as a promising tool for the production of stable and monodispersed nanoparticles (NPs). In particular, this work focuses on liposome production by microfluidics and on factors involved in determining liposome characteristics. Traditional fabrication techniques for microfluidic devices suffer from several disadvantages, such as multistep processing and expensive facilities. Three-dimensional printing (3DP) has been revolutionary for microfluidic device production, boasting facile and low-cost fabrication. In this study, microfluidic devices with innovative micromixing patterns were developed using fused deposition modelling (FDM) and liquid crystal display (LCD) printers. To date, this work is the first to study liposome production using LCD-printed microfluidic devices. The current study deals with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes with cholesterol (2:1) prepared using commercial and 3D-printed microfluidic devices. We evaluated the effect of microfluidic parameters, chip manufacturing, material, and channel design on liposomal formulation by analysing the size, PDI, and ζ-potential. Curcumin exhibits potent anticancer activity and it has been reported that curcumin-loaded liposomes formulated by microfluidics show enhanced encapsulation efficiency when compared with other reported systems. In this work, curcumal liposomes were produced using the developed microfluidic devices and particle sizing, ζ-potential, encapsulation efficiency, and in vitro release studies were performed at 37 °C.

Resilience and workplace stress in Australian and New Zealand obstetrics and gynaecology trainees: A cross-sectional survey.

BACKGROUND: Obstetrics and gynaecology training is a demanding vocation; there is a paucity of data on trainee resilience and well-being in this field. AIM: To investigate resilience, support and perceived levels of stress and burnout in Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) trainees. MATERIALS AND METHODS: A cross-sectional survey of RANZCOG trainees in Australia and New Zealand (n = 638) was distributed electronically in May 2018. RESULTS: Two-hundred and thirty-one (36%) valid responses were received. The mean resilience score was moderate (mean = 77; SD = 11). Resilience was significantly associated with general health (F = 7.5, P = 0.007), depression in the last two weeks (F = 4.4, P = 0.013) and seriously considering leaving the program at some point (F = 15.4, P < 0.001). Most participants (204; 88%) stated improvements could be made to the level of trainee support; with over half identifying the support they received from RANZCOG to be low or very low (132; 57%). One-third of participants (76; 33%) rated the support from their direct supervisor as low to very low. Over half of all participants identified high to very high responses to: burnout (127; 55%); personal stress (134; 58%); workplace stress (143; 62%) and depression (103; 45%). CONCLUSION: RANZCOG trainees exhibit moderate resilience levels, yet they report high levels of perceived stress, depression and burnout and low-level support from direct supervisors. This may highlight the need for enhanced support and working conditions to allow trainees to remain resilient and thrive in their careers.

Effect of Multilevel Upper Airway Surgery vs Medical Management on the Apnea-Hypopnea Index and Patient-Reported Daytime Sleepiness Among Patients With Moderate or Severe Obstructive Sleep Apnea: The SAMS Randomized Clinical Trial.

Importance: Many adults with obstructive sleep apnea (OSA) use device treatments inadequately and remain untreated. Objective: To determine whether combined palatal and tongue surgery to enlarge or stabilize the upper airway is an effective treatment for patients with OSA when conventional device treatment failed. Design, Setting, and Participants: Multicenter, parallel-group, open-label randomized clinical trial of upper airway surgery vs ongoing medical management. Adults with symptomatic moderate or severe OSA in whom conventional treatments had failed were enrolled between November 2014 and October 2017, with follow-up until August 2018. Interventions: Multilevel surgery (modified uvulopalatopharyngoplasty and minimally invasive tongue volume reduction; n = 51) or ongoing medical management (eg, advice on sleep positioning, weight loss; n = 51). Main Outcomes and Measures: Primary outcome measures were the apnea-hypopnea index (AHI; ie, the number of apnea and hypopnea events/h; 15-30 indicates moderate and >30 indicates severe OSA) and the Epworth Sleepiness Scale (ESS; range, 0-24; >10 indicates pathological sleepiness). Baseline-adjusted differences between groups at 6 months were assessed. Minimal clinically important differences are 15 events per hour for AHI and 2 units for ESS. Results: Among 102 participants who were randomized (mean [SD] age, 44.6 [12.8] years; 18 [18%] women), 91 (89%) completed the trial. The mean AHI was 47.9 at baseline and 20.8 at 6 months for the surgery group and 45.3 at baseline and 34.5 at 6 months for the medical management group (mean baseline-adjusted between-group difference at 6 mo, -17.6 events/h [95% CI, -26.8 to -8.4]; P < .001). The mean ESS was 12.4 at baseline and 5.3 at 6 months in the surgery group and 11.1 at baseline and 10.5 at 6 months in the medical management group (mean baseline-adjusted between-group difference at 6 mo, -6.7 [95% CI, -8.2 to -5.2]; P < .001). Two participants (4%) in the surgery group had serious adverse events (1 had a myocardial infarction on postoperative day 5 and 1 was hospitalized for observation following hematemesis of old blood). Conclusions and Relevance: In this preliminary study of adults with moderate or severe OSA in whom conventional therapy had failed, combined palatal and tongue surgery, compared with medical management, reduced the number of apnea and hypopnea events and patient-reported sleepiness at 6 months. Further research is needed to confirm these findings in additional populations and to understand clinical utility, long-term efficacy, and safety of multilevel upper airway surgery for treatment of patients with OSA. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12614000338662.

Surgical approach to hysterectomy and barriers to using minimally invasive methods.

Minimally invasive approaches to hysterectomy have been shown to be safe, effective and have recovery advantages over open hysterectomy, yet in Australia 36% of hysterectomies are still conducted by open surgery. In 2006, a survey of Australian gynaecological specialists found the main impediment to increasing laparoscopic hysterectomy to be a lack of surgical skills training opportunities. We resurveyed specialists to explore contemporary factors influencing surgeons' approaches to hysterectomy; 258 (estimated ~19%) provided analysable responses. Despite >50% of surveyed specialists wishing to practise laparoscopic hysterectomy in the future, lack of surgical skills, arising from the lack of training opportunities, remains the main impediment.

An official American Thoracic Society statement: continuous positive airway pressure adherence tracking systems. The optimal monitoring strategies and outcome measures in adults.

BACKGROUND: Continuous positive airway pressure (CPAP) is considered the treatment of choice for obstructive sleep apnea (OSA), and studies have shown that there is a correlation between patient adherence and treatment outcomes. Newer CPAP machines can track adherence, hours of use, mask leak, and residual apnea-hypopnea index (AHI). Such data provide a strong platform to examine OSA outcomes in a chronic disease management model. However, there are no standards for capturing CPAP adherence data, scoring flow signals, or measuring mask leak, or for how clinicians should use these data. METHODS: American Thoracic Society (ATS) committee members were invited, based on their expertise in OSA and CPAP monitoring. Their conclusions were based on both empirical evidence identified by a comprehensive literature review and clinical experience. RESULTS: CPAP usage can be reliably determined from CPAP tracking systems, but the residual events (apnea/hypopnea) and leak data are not as easy to interpret as CPAP usage and the definitions of these parameters differ among CPAP manufacturers. Nonetheless, ends of the spectrum (very high or low values for residual events or mask leak) appear to be clinically meaningful. CONCLUSIONS: Providers need to understand how to interpret CPAP adherence tracking data. CPAP tracking systems are able to reliably track CPAP adherence. Nomenclature on the CPAP adherence tracking reports needs to be standardized between manufacturers and AHIFlow should be used to describe residual events. Studies should be performed examining the usefulness of the CPAP tracking systems and how these systems affect OSA outcomes.

Risks and benefits of hysteroscopy and endometrial sampling as a standard procedure for assessing serendipitous findings of endometrial thickening in postmenopausal women.

A retrospective study was undertaken of 35 asymptomatic postmenopausal women undergoing hysteroscopy, dilatation and curettage (H D&C) for an incidental finding of thickened endometrium to assess the rate of significant pathological findings, cost per finding and complication rate of any procedures performed. This study found one case of endometrial adenocarcinoma (1/35; 3%) at an estimated cost per significant finding of $507,116 with an estimated 11.6 complication events per finding.

Has the incidence of hypoxic ischaemic encephalopathy in Queensland been reduced with improved education in fetal surveillance monitoring?

BACKGROUND: Hypoxic ischaemic encephalopathy (HIE) is secondary to intrapartum asphyxia and the fifth largest cause of death of children under five. Incorrect use and interpretation of intrapartum cardiotocographs has been identified as a contributing factor to the development of HIE. Therefore, RANZCOG introduced the Fetal Surveillance Education Program (FSEP) to improve education and practice of intrapartum care. AIM: To investigate the incidence of HIE throughout Queensland between 2003 and 2011 during the introduction and implementation of RANZCOG FSEP. METHODS: The incidence of HIE admissions at each hospital in Queensland (2003-2011) was collated from Queensland Health Statistics Centre. RANZCOG FSEP provided data regarding course attendees throughout Queensland (2006-2011). Hospitals were grouped into four regions. Statistical analysis was conducted using Stata(TM) (version 12.0) - data appeared to follow a damped harmonic model. RESULTS: The posteducation (2006-2011) HIE rate was significantly lower (P = 0.02) than the pre-education (2003-2005) rate. The final model predicted a stabilisation of HIE occurrence rate at approximately 160 events/100,000 live births by 2012. This rate was stable if the level of education was maintained but rose back to the initial rate of 250 events/100,000 live births if the education participation was discontinued. CONCLUSIONS: This study identified a significant reduction in the incidence of HIE--a potentially life-threatening newborn condition--between 2003 and 2011, during and following FSEP implementation. Notwithstanding the inevitable limitations of state-based data collection, these results are encouraging. For such improvements to be sustained, education must reach all staff engaged in intrapartum care and be regularly repeated.

Microfluidic encapsulation of enzymes and steroids within solid lipid nanoparticles.

The production of solid lipid nanoparticles (SLNs) is challenging, especially when considering the incorporation of biologics. A novel in-house method of microfluidic production of biologic-encapsulated SLNs is proposed, using a variety of base materials for formulation to help overcome the barriers presented during manufacture and administration. Trypsin is used as a model drug for hydrophilic encapsulation whilst testosterone is employed as a positive non-biologic lipophilic control active pharmaceutical ingredient. Particle sizes obtained ranged from 160 to 320 nm, and a lead formulation has been identified from the combinations assayed, allowing for high encapsulation efficiencies (47-90%, respectively) of both the large hydrophilic and the small hydrophobic active pharmaceutical ingredients (APIs). Drug release profiles were analysed in vitro to provide useful insight into sustained kinetics, providing data towards future in vivo studies, which displayed a slow prolonged release for testosterone and a quicker burst release for trypsin. The study represents a large leap forward in the field of SLN production, especially in the field of difficult-to-encapsulate molecules, and the technique also benefits from being more environmentally sustainable due to the use of microfluidics.

Respiratory internal kinematics of the tongue base and soft palate in obese minipigs with obstructive sleep apnea.

It is largely unknown how the tongue base and soft palate deform to alter the configuration of the oropharyngeal airway during respiration. This study is to address this important gap. After live sleep monitoring of five Yucatan and two Panepinto minipigs to verify obstructive sleep apnea (OSA), eight and four ultrasonic crystals were implanted into the tongue base and soft palate to circumscribe a cubic and square region, respectively. The 3D and 2D deformational changes of the circumscribed regions were measured simultaneously with electromyographic activity of the oropharyngeal muscles during spontaneous respiration under sedated sleep. The results indicated that both obese Yucatan and Panepinto minipigs presented spontaneous OSA, but not in three nonobese Yucatan minipigs. During inspiration, the tongue base showed elongation in both dorsal and ventral regions but thinning and thickening in the anterior and posterior regions, respectively. The widths showed opposite directions, widening in the dorsal but narrowing in the ventral regions. The soft palate expanded in both length and width. Compared to normal controls, obese/OSA ones showed similar directions of deformational changes, but the magnitude of change was two times larger in the tongue base and soft palate, and obese/OSA Panepinto minipigs presented 10 times larger changes in all dimensions of both the tongue base and the soft palate. The distance changes between the dorsal surface of tongue base and soft palate during inspiration increased in normal but decreased in obese OSA minipigs.

Co-delivery of VEGF and amoxicillin using LP-coated co-axial electrospun fibres for the potential treatment of diabetic wounds.

Diabetic complications present throughout a wide range of body tissues, however one of the most widely recognised complications remains to be chronic diabetic wounds. Current treatment options largely rely on standard wound treatment routines which provide no promotion of wound healing mechanisms at different physiological stages of repair. Recently materials produced using novel additive manufacturing techniques have been receiving attention for applications in wound care and tissue repair. Additive manufacturing techniques have recently been used in the interest of targeted drug delivery and production of novel materials resembling characteristics of native tissues. The potential to exploit these highly tailorable manufacturing techniques for the design of novel wound care remedies is highly desirable. In the present study two additive manufacturing techniques are combined to produce a scaffold for the treatment of diabetic wounds. The combination of microfluidic manufacturing of an antimicrobial liposome (LP) formulation and a coaxial electrospinning method incorporating both antimicrobial and proangiogenic factors allowed dual delivery of therapeutics to target both infection and lack of vascularisation at wound sites. The coaxial fibres comprised of a polyvinyl alcohol (PVA) core containing vascular endothelial growth factor (VEGF) and a poly (l-lactide-co-ε-caprolactone) (PLCL) shell blended with amoxicillin (Amox). Additionally, a liposomal formulation was produced to incorporate Amox and adhered to the surface of fibres loaded with Amox and VEGF. The liposomal loading provided the potential to deliver a much higher, more clinically relevant dose of Amox without detrimentally changing the mechanical properties of the material. The growth factor release was sustained up to 7-days in vitro. The therapeutic effect of the antibiotic loading was analysed using a disk diffusion method with a significant increase in zone diameter following LP adhesion, proving the full scaffold system had improved efficacy against both Gram-positive and Gram-negative strains. Additionally, the dual-loaded scaffolds show enhanced potential for supporting vascular growth in vitro, as demonstrated via a viability assay and tubule formation studies. Results showed a significant increase in the average total number of tubes from 10 in control samples to 77 in samples fully-loaded with Amox and VEGF.

Liposomal encapsulation of amoxicillin via microfluidics with subsequent investigation of the significance of PEGylated therapeutics.

With an increasing concern of global antimicrobial resistance, the efforts to improve the formulation of a narrowing library of therapeutic antibiotics must be confronted. The liposomal encapsulation of antibiotics using a novel and sustainable microfluidic method has been employed in this study to address this pressing issue, via a targeted, lower-dose medical approach. The study focusses upon microfluidic parameter optimisation, formulation stability, cytotoxicity, and future applications. Particle sizes of circa. 130 nm, with viable short-term (28-day) physical stability were obtained, using two different non-cytotoxic liposomal formulations, both of which displayed suitable antibacterial efficacy. The microfluidic method allowed for high encapsulation efficiencies (≈77 %) and the subsequent in vitro release profile suggested high limits of antibiotic dissociation from the nanovessels, achieving 90% release within 72 h. In addition to the experimental data, the growing use of poly(ethylene) glycol (PEG) within lipid-based formulations is discussed in relation to anti-PEG antibodies, highlighting the key pharmacological differences between PEGylated and non-PEGylated formulations and their respective advantages and drawbacks. It's surmised that in the case of the formulations used in this study, the addition of PEG upon the liposomal membrane would still be a beneficial feature to possess owing to beneficial features such as stability, antibiotic efficacy and the capacity to further modify the liposomal membrane.

Sleep apnea multi-level surgery trial: long-term observational outcomes.

STUDY OBJECTIVES: The sleep apnea multi-level surgery (SAMS) randomized clinical trial showed surgery improved outcomes at 6 months compared to ongoing medical management in patients with moderate or severe obstructive sleep apnea (OSA) who failed continuous positive airway pressure therapy. This study reports the long-term outcomes of the multi-level surgery as a case series. METHODS: Surgical participants were reassessed >2 years postoperatively with the same outcomes reported in the main SAMS trial. Primary outcomes were apnea-hypopnea index (AHI) and Epworth sleepiness scale (ESS), with secondary outcomes including other polysomnography measures, symptoms, quality of life, and adverse events. Long-term effectiveness (baseline to long-term follow-up [LTFU]) and interval changes (6 month to LTFU) were assessed using mixed effects regression models. Control participants were also reassessed for rate of subsequent surgery and outcomes. RESULTS: 36/48 (75%) of surgical participants were reevaluated (mean (standard deviation)) 3.5 (1.0) years following surgery, with 29 undergoing polysomnography. AHI was 41/h (23) at preoperative baseline and 21/h (18) at follow-up, representing persistent improvement of -24/h (95% CI -32, -17; p < 0.001). ESS was 12.3 (3.5) at baseline and 5.5 (3.9) at follow-up, representing persistent improvement of -6.8 (95% CI -8.3, -5.4; p < 0.001). Secondary outcomes were improved long term, and adverse events were minor. Interval change analysis suggests stability of outcomes. 36/43 (84%) of the control participants were reevaluated, with 25 (69%) reporting subsequent surgery, with symptom and quality of life improvements. CONCLUSION: Multi-level upper airway surgery improves OSA burden with long-term maintenance of treatment effect in adults with moderate or severe OSA in whom conventional therapy failed. CLINICAL TRIAL: Multi-level airway surgery in patients with moderate-severe obstructive sleep apnea (OSA) who have failed medical management to assess change in OSA events and daytime sleepiness; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366019&isReview=true; ACTRN12614000338662.