A universal 3D imaging sensor on a silicon photonics platform.

Accurate three-dimensional (3D) imaging is essential for machines to map and interact with the physical world1,2. Although numerous 3D imaging technologies exist, each addressing niche applications with varying degrees of success, none has achieved the breadth of applicability and impact that digital image sensors have in the two-dimensional imaging world3-10. A large-scale two-dimensional array of coherent detector pixels operating as a light detection and ranging system could serve as a universal 3D imaging platform. Such a system would offer high depth accuracy and immunity to interference from sunlight, as well as the ability to measure the velocity of moving objects directly11. Owing to difficulties in providing electrical and photonic connections to every pixel, previous systems have been restricted to fewer than 20 pixels12-15. Here we demonstrate the operation of a large-scale coherent detector array, consisting of 512 pixels, in a 3D imaging system. Leveraging recent advances in the monolithic integration of photonic and electronic circuits, a dense array of optical heterodyne detectors is combined with an integrated electronic readout architecture, enabling straightforward scaling to arbitrarily large arrays. Two-axis solid-state beam steering eliminates any trade-off between field of view and range. Operating at the quantum noise limit16,17, our system achieves an accuracy of 3.1 millimetres at a distance of 75 metres when using only 4 milliwatts of light, an order of magnitude more accurate than existing solid-state systems at such ranges. Future reductions of pixel size using state-of-the-art components could yield resolutions in excess of 20 megapixels for arrays the size of a consumer camera sensor. This result paves the way for the development and proliferation of low-cost, compact and high-performance 3D imaging cameras that could be used in applications from robotics and autonomous navigation to augmented reality and healthcare.

SARS-CoV-2 Viral Replication Persists in the Human Lung for Several Weeks after Symptom Onset.

Rationale: In the upper respiratory tract, replicating (culturable) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recoverable for ∼4-8 days after symptom onset, but there is a paucity of data about the frequency and duration of replicating virus in the lower respiratory tract (i.e., the human lung).Objectives: We undertook lung tissue sampling (needle biopsy) shortly after death in 42 mechanically ventilated decedents during the Beta and Delta waves. An independent group of 18 ambulatory patients served as a control group.Methods: Lung biopsy cores from decedents underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling, and immunohistochemistry.Measurements and Main Results: Thirty-eight percent (16 of 42) of mechanically ventilated decedents had culturable virus in the lung for a median of 15 days (persisting for up to 4 wk) after symptom onset. Lung viral culture positivity was not associated with comorbidities or steroid use. Delta but not Beta variant lung culture positivity was associated with accelerated death and secondary bacterial infection (P < 0.05). Nasopharyngeal culture was negative in 23.1% (6 of 26) of decedents despite lung culture positivity. This hitherto undescribed biophenotype of lung-specific persisting viral replication was associated with an enhanced transcriptomic pulmonary proinflammatory response but with concurrent viral culture positivity.Conclusions: Concurrent rather than sequential active viral replication continues to drive a heightened proinflammatory response in the human lung beyond the second week of illness and was associated with variant-specific increased mortality and morbidity. These findings have potential implications for the design of interventional strategies and clinical management of patients with severe coronavirus disease (COVID-19).

Glycan degradation promotes macroautophagy.

Macroautophagy promotes cellular homeostasis by delivering cytoplasmic constituents to lysosomes for degradation [Mizushima, Nat. Cell Biol. 20, 521-527 (2018)]. However, while most studies have focused on the mechanisms of protein degradation during this process, we report here that macroautophagy also depends on glycan degradation via the glycosidase, α-l-fucosidase 1 (FUCA1), which removes fucose from glycans. We show that cells lacking FUCA1 accumulate lysosomal glycans, which is associated with impaired autophagic flux. Moreover, in a mouse model of fucosidosis-a disease characterized by inactivating mutations in FUCA1 [Stepien et al., Genes (Basel) 11, E1383 (2020)]-glycan and autophagosome/autolysosome accumulation accompanies tissue destruction. Mechanistically, using lectin capture and mass spectrometry, we identified several lysosomal enzymes with altered fucosylation in FUCA1-null cells. Moreover, we show that the activity of some of these enzymes in the absence of FUCA1 can no longer be induced upon autophagy stimulation, causing retardation of autophagic flux, which involves impaired autophagosome-lysosome fusion. These findings therefore show that dysregulated glycan degradation leads to defective autophagy, which is likely a contributing factor in the etiology of fucosidosis.

Assessment of endpoint definitions in curative-intent trials for mucosal head and neck squamous cell carcinomas: Head and Neck Cancer International Group consensus recommendations.

Robust time-to-event endpoint definitions are crucial for the assessment of treatment effect and the clinical value of trial interventions. Here, the Head and Neck Cancer International Group investigated endpoint use in phase 3 trials and trials considered potentially practice-changing published between 2008 and 2021 in the curative-intent setting for patients with mucosal head and neck squamous cell carcinoma. Of the 92 trials reviewed, we show that all core components of endpoint reporting were heterogeneous, including definitions of common terms, such as overall survival and progression-free survival. Our report highlights the urgent need for harmonisation of fundamental components of clinical trial endpoints and the engagement of all stakeholders to ensure the transparent reporting of endpoint details.

Vertical integration of KTN on SOI wafer.

Optical modulators play an important role in communication systems, and silicon has been a focal point in this field thanks to its compatibility with CMOS fabrication. However, silicon's lack of inherent electro-optic behavior makes it suboptimal for modulation purposes. Conversely, potassium tantalate niobate (KTN) materials boast an improved electro-optic coefficient, presenting a path for improving modulation efficiency. However, limited research exists on KTN materials due to the difficulties associated with their fabrication. Here, a fabrication methodology is described for wafer-scale vertical integration of KTN material onto silicon-on-insulator (SOI) wafers. The resulting devices exhibit a propagation loss of 3.3 dBmm1 and a transition loss within the range of 0.46 to 0.76 dB, which are in agreement with simulations. This method tackles the fabrication challenges and showcases the potential of utilising KTN as the integration material on silicon platform for future optical modulators.

Neurological manifestations of COVID-19 in adults and children.

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.

Haematoma block is the most efficient technique for closed forearm fracture reduction: a retrospective cohort study.

BACKGROUND: Forearm fractures are a common ED presentation. This study aimed to compare the resource utilisation of three anaesthetic techniques used for closed forearm fracture reduction in the ED: haematoma block (HB), Bier's block (BB) and procedural sedation (PS). METHODS: A retrospective multicentre cohort study was conducted of adult patients presenting to either Port Macquarie Base Hospital ED or Kempsey District Hospital ED in New South Wales, Australia, from January 2018 to June 2021. Patients requiring a closed reduction in the ED were included. ED length of stay (LOS) was compared using a likelihood ratio test. Successful reduction on the first attempt and the number of ED specialists present for each method were both modelled with a linear regression. Staff utilisation by the level of training, cost of consumables and complications for each group were presented as descriptive statistics. RESULTS: A total of 226 forearm fractures were included. 84 used HB, 35 BB and 107 PS. The mean ED LOS was lowest for HB (187.7 min) compared with BB (227.2 min) and PS (239.3 min) (p=0.023). The number of ED specialists required for PS was higher when compared with HB and BB (p=0.001). The cost of consumables and a total number of staff were considerably lower for HB compared with PS and BB methods. PS had the highest proportion of successful reductions on the first attempt (94.4%) compared with BB (88.6%) and HB (76.2%) (p=0.006). More patients experienced complications from PS (17.8%) compared with BB (14.3%) and HB (13.1%). CONCLUSIONS: In this study, the HB method was the most efficient as it was associated with a shorter ED LOS, lower cost and staff resource utilisation. Although PS had a significantly greater proportion of successful reductions on the first attempt, HB had fewer complications than BB and PS. EDs with limited resources should consider using HB or BB as the initial technique for fracture reduction with PS used for failed HB or when regional blocks are contraindicated.

Screening for Body Dysmorphic Disorder in Plastic Surgery Patients.

INTRODUCTION: The Australian medical board, the Australian Health Practitioner Regulation Agency (AHPRA) has recently introduced new regulations mandating providers of cosmetic surgery undertake a clinical screen for body dysmorphic disorder (BDD) in all potential cosmetic surgery patients. The assessment must be conducted by the surgeon using a validated psychological screening tool. The aims of this paper are to discuss the key clinical characteristics of BDD before reviewing currently validated screening tools that would meet this new regulatory requirement, and which may be most applicable to a busy plastic surgery practice. METHODS: A literature search identified 1164 titles, of which 229 titles were retrieved for abstract screening. Six studies were identified that validated BDD screening tools in a setting relevant to cosmetic plastic surgery. RESULTS: Six validated screening were identified: BDD Questionnaire (BDDQ), BDD Questionnaire Dermatology Version (BDDQ-DV), BDD Questionnaire Aesthetic Surgery (BDDQ-AS), Cosmetic Procedure Screening Questionnaire (COPS), Body Dysmorphia Symptom Scale (BDSS) and the BDD Screening Test (BDD-ST). Our group practice has chosen to adopt the BDDQ-AS to meet the AHPRA regulator requirement for BDD screening based on its robust validation and ease of use in clinical practice, consisting of a seven-item self-report questionnaire that can be reliably completed in 1-2 minutes in most cases. CONCLUSION: Of the six screening tools for body dysmorphic disorder available for use in clinical practice that have been validated in a cosmetic population setting, we have chosen to use the BDD Questionnaire Aesthetic Surgery (BDDQ-AS). To date all available validated screening tools are based on the DSM-IV, and further work to develop a validated screening tool based on the revised definition of BDD in the DSM-V is recommended, with a particular focus on items relating to repetitive physical or mental behaviours. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Lost Therapeutic Benefit of Delayed Low-Density Lipoprotein Cholesterol Control in Statin-Treated Patients and Cost-Effectiveness Analysis of Lipid-Lowering Intensification.

OBJECTIVES: Attainment of low-density lipoprotein cholesterol (LDL-C) therapeutic goals in statin-treated patients remains suboptimal. We quantified the health economic impact of delayed lipid-lowering intensification from an Australian healthcare and societal perspective. METHODS: A lifetime Markov cohort model (n = 1000) estimating the impact on coronary heart disease (CHD) of intensifying lipid-lowering treatment in statin-treated patients with uncontrolled LDL-C, at moderate to high risk of CHD with no delay or after a 5-year delay, compared with standard of care (no intensification), starting at age 40 years. Intensification was tested with high-intensity statins or statins + ezetimibe. LDL-C levels were extracted from a primary care cohort. CHD risk was estimated using the pooled cohort equation. The effect of cumulative exposure to LDL-C on CHD risk was derived from Mendelian randomization data. Outcomes included CHD events, quality-adjusted life-years (QALYs), healthcare and productivity costs, and incremental cost-effectiveness ratios (ICERs). All outcomes were discounted annually by 5%. RESULTS: Over the lifetime horizon, compared with standard of care, achieving LDL-C control with no delay with high-intensity statins prevented 29 CHD events and yielded 30 extra QALYs (ICERs AU$13 205/QALY) versus 22 CHD events and 16 QALYs (ICER AU$20 270/QALY) with a 5-year delay. For statins + ezetimibe, no delay prevented 53 CHD events and gave 45 extra QALYs (ICER AU$37 271/QALY) versus 40 CHD events and 29 QALYs (ICER of AU$44 218/QALY) after a 5-year delay. CONCLUSIONS: Delaying attainment of LDL-C goals translates into lost therapeutic benefit and a waste of resources. Urgent policies are needed to improve LDL-C goal attainment in statin-treated patients.

Race and ethnicity in the COVID-19 Critical Care Consortium: demographics, treatments, and outcomes, an international observational registry study.

BACKGROUND: Improving access to healthcare for ethnic minorities is a public health priority in many countries, yet little is known about how to incorporate information on race, ethnicity, and related social determinants of health into large international studies. Most studies of differences in treatments and outcomes of COVID-19 associated with race and ethnicity are from single cities or countries. METHODS: We present the breadth of race and ethnicity reported for patients in the COVID-19 Critical Care Consortium, an international observational cohort study from 380 sites across 32 countries. Patients from the United States, Australia, and South Africa were the focus of an analysis of treatments and in-hospital mortality stratified by race and ethnicity. Inclusion criteria were admission to intensive care for acute COVID-19 between January 14th, 2020, and February 15, 2022. Measurements included demographics, comorbidities, disease severity scores, treatments for organ failure, and in-hospital mortality. RESULTS: Seven thousand three hundred ninety-four adults met the inclusion criteria. There was a wide variety of race and ethnicity designations. In the US, American Indian or Alaska Natives frequently received dialysis and mechanical ventilation and had the highest mortality. In Australia, organ failure scores were highest for Aboriginal/First Nations persons. The South Africa cohort ethnicities were predominantly Black African (50%) and Coloured* (28%). All patients in the South Africa cohort required mechanical ventilation. Mortality was highest for South Africa (68%), lowest for Australia (15%), and 30% in the US. CONCLUSIONS: Disease severity was higher for Indigenous ethnicity groups in the US and Australia than for other ethnicities. Race and ethnicity groups with longstanding healthcare disparities were found to have high acuity from COVID-19 and high mortality. Because there is no global system of race and ethnicity classification, researchers designing case report forms for international studies should consider including related information, such as socioeconomic status or migration background. *Note: "Coloured" is an official, contemporary government census category of South Africa and is a term of self-identification of race and ethnicity of many citizens of South Africa.

Using EMPOWER in daily life: a qualitative investigation of implementation experiences.

BACKGROUND: Digital self-management tools blended with clinical triage and peer support have the potential to improve access to early warning signs (EWS) based relapse prevention in schizophrenia care. However, the implementation of digital interventions in psychosis can be poor. Traditionally, research focused on understanding how people implement interventions has focused on the perspectives of mental health staff. Digital interventions are becoming more commonly used by patients within the context of daily life, which means there is a need to understand implementation from the perspectives of patients and carers. METHODS: Semi-structured one-on-one interviews with 16 patients who had access to the EMPOWER digital self-management intervention during their participation in a feasibility trial, six mental health staff members who supported the patients and were enrolled in the trial, and one carer participant. Interviews focused on understanding implementation, including barriers and facilitators. Data were coded using thematic analysis. RESULTS: The intervention was well implemented, and EMPOWER was typically perceived positively by patients, mental health staff and the carer we spoke to. However, some patients reported negative views and reported ideas for intervention improvement. Patients reported valuing that the app afforded them access to things like information or increased social contact from peer support workers that went above and beyond that offered in routine care. Patients seemed motivated to continue implementing EMPOWER in daily life when they perceived it was creating positive change to their wellbeing, but seemed less motivated if this did not occur. Mental health staff and carer views suggest they developed increased confidence patients could self-manage and valued using the fact that people they support were using the EMPOWER intervention to open up conversations about self-management and wellbeing. CONCLUSIONS: The findings from this study suggest peer worker supported digital self-management like EMPOWER has the potential to be implemented. Further evaluations of these interventions are warranted, and conducting qualitative research on the feasibility gives insight into implementation barriers and facilitators, improving the likelihood of interventions being usable. In particular, the views of patients who demonstrated low usage levels would be valuable.

Rapidly evolving gangrenous vasculitis in a critically ill patient with ulcerative colitis: a case report.

Ulcerative colitis is a disease characterised by non-granulomatous submucosal inflammation ranging from isolated proctitis to colitis. Extra-intestinal manifestations of the condition occur in multiple organ systems, with dermatological complications occurring commonly. This case report aims to highlight an uncommon dermatological complication of ulcerative colitis with particular focus on patient care and management.

Dogmalysis.

Air medical and critical care providers encounter the extremes of being both in-hospital and out-of-hospital clinicians, work in unpredictable environments, and treat patients with the most significant injury patterns and diagnoses. These demands highlight the need to recognize unique mental challenges for those who work in the air medical environment and the process by which providers make decisions. Patients who present with a high-acuity/low-volume pathology generate particularly difficult situations with abundant opportunity for both celebrations of performance and learning from mistakes. There are times when the desired option of therapy is not available, the most appropriate destination is not feasible, or the crew is unable to address every aspect of patient care with resources that are immediately available. Although it is logical to make decisions based on anatomic and physiological knowledge, the absence of an actual answer does not necessitate the acceptance of consensus. Dogmalysis refers to the dissolution of authoritative tenets held as established opinion without adequate grounds. This article highlights the importance of dogmalysis, the value of honest scientific reflection, and the aggressive seeking of evidence-based answers as it pertains to the air medical environment.

Dynamic dentin: A quantitative microscopic assessment of age and spatial changes to matrix architecture, peritubular dentin, and collagens types I and III.

To investigate age and site-related changes to human dentin collagen, sound human teeth collected from donors aged 13-29 (young) and 50-74 (aged) years (n = 9/group) were cut to shallow and deep sites. Dentin collagen orientation and fibril bundling was investigated using the Picrosirius Red (PSR) stain observed under cross-polarized light microscopy (Pol), and collagen distribution was investigated using Confocal Laser Scanning Microscopy (CLSM). Collagen types III to I distribution in peritubular dentin (PTD) was revealed using Herovici stain and brightfield microscopy. Image analysis software and linear mixed modelling quantified outcomes. In situ dentin collagen was observed using Xenon Plasma Focussed Ion Beam Scanning Electron Microscopy (Xe PFIB-SEM). The PSR-Pol analysis revealed less coherently aligned and more bundled collagen fibrils in aged dentin (P = 0.005). Deep inner dentin collagen in both groups were less coherently aligned with reduced bundling. Regardless of age, CLSM showed collagen distribution remained stable; and more collagen type III was detectable in PTD located in inner dentin (Young: P = 0.006; Aged: P = 0.008). Observations following Xe PFIB-SEM cross-sectioning showed apatite-like deposits surrounding large intratubular collagen fibers, and evidence of smaller intertubular dentin collagen fibrils in situ. In conclusion, aging changes collagen network architecture, but not distribution or content.

International assessment of interobserver reproducibility of flap delineation in head and neck carcinoma.

Background: Several reports have suggested that radiotherapy after reconstructive surgery for head and neck cancer (HNC), could have deleterious effects on the flaps with respect to functional outcomes. To predict and prevent toxicities, flap delineation should be accurate and reproducible. The objective of the present study was to evaluate the interobserver variability of frequent types of flaps used in HNC, based on the recent GORTEC atlas.Materials and methods: Each member of an international working group (WG) consisting of 14 experts delineated the flaps on a CT set from six patients. Each patient had one of the five most commonly used flaps in HNC: a regional pedicled pectoralis major myocutaneous flap, a local pedicled rotational soft tissue facial artery musculo-mucosal (FAMM) (2 patients), a fasciocutaneous radial forearm free flap, a soft tissue anterolateral thigh (ALT) free flap, or a fibular free flap. The WG's contours were compared to a reference contour, validated by a surgeon and a radiologist specializing in HNC. Contours were considered as reproducible if the median Dice Similarity Coefficient (DSC) was > 0.7.Results: The median volumes of the six flaps delineated by the WG were close to the reference contour value, with approximately 50 cc for the pectoral, fibula, and ALT flaps, 20 cc for the radial forearm, and up to 10 cc for the FAMM. The volumetric ratio was thus close to the optimal value of 100% for all flaps. The median DSC obtained by the WG compared to the reference for the pectoralis flap, the FAMM, the radial forearm flap, ALT flap, and the fibular flap were 0.82, 0.40, 0.76, 0.81, and 0.76, respectively.Conclusions: This study showed that the delineation of four main flaps used for HNC was reproducible. The delineation of the FAMM, however, requires close cooperation between radiologist, surgeon and radiation oncologist because of the poor visibility of this flap on CT and its small size.

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study.

BACKGROUND: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). METHODS: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. RESULTS: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). CONCLUSIONS: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

Switching, Persistence and Adherence to Statin Therapy: a Retrospective Cohort Study Using the Australian National Pharmacy Data.

BACKGROUND: Statins are widely prescribed for the primary and secondary prevention of cardiovascular disease (CVD), but their effectiveness is dependent on the level of adherence and persistence. OBJECTIVES: This study aimed to explore the patterns of switching, adherence and persistence among the Australian general population with newly dispensed statins. METHODS: A retrospective cohort study was conducted using a random sample of data from the Australian national prescription claims data. Switching, adherence to and persistence with statins were assessed for people starting statins from 1 January 2015 to 31 December 2019. Switching was defined as either switching to another intensity of statin, to another statin or to a non-statin agent. Non-persistence to treatment was defined as discontinuation (i.e. ≥90 days with no statin) of coverage. Adherence was measured using proportion of days covered (PDC), and patients with PDC < 0.80 were considered non-adherent. Cox proportional hazard models were used to compare discontinuation, switching and reinitiation between different statins. RESULTS: A cohort of 141,062 people dispensed statins and followed over a median duration of 2.5 years were included. Of the cohort, 29.3% switched statin intensity, 28.4% switched statin type, 3.7% switched to ezetimibe and in 2.7%, ezetimibe was added as combination therapy during the study period. Overall, 58.8% discontinued statins based on the 90-day gap criteria, of whom 55.2% restarted. The proportion of people non-adherent was 24.0% at 6 months to 49.0% at 5 years. People on low and moderate intensity statins were more likely to discontinue compared to those on high-intensity statins (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.31), (HR 1.28, 95%CI 1.14-1.42), respectively. Compared to maintaining same statin type and intensity, switching statins, which includes up-titration (HR 0.77, 95%CI 0.70 to 0.86) was associated with less likelihood of discontinuation after reinitiation. CONCLUSIONS: Long-term persistence and adherence to statins remains generally poor among Australians, which limits the effectiveness of these medicines and the consequent health impact they may provide for individuals (and by extension, the population impact when poor persistence and adherence is considered in the statin-taking population). Switching between statins is prevalent in one third of statin users, although any clinical benefit of the observed switching trend is unknown. This, combined with the high volume of statin prescriptions, highlights the need for better strategies to address poor persistence and adherence.

Effect of dentine site on resin and cement adaptation tested using X-ray and electron microscopy to evaluate bond durability and adhesive interfaces.

Glass ionomer (GI) cements and self-etch (SE) or universal adhesives after etching (ER) adapt variably with dentine. Dentine characteristics vary with depth (deep/shallow), location (central/peripheral), and microscopic site (intertubular/peritubular). To directly compare adhesion to dentine, non-destructive imaging and testing are required. Here, GI, ER, and SE adapted at different dentine depths, locations, and sites were investigated using micro-CT, xenon plasma focused ion beam scanning electron microscopy (Xe PFIB-SEM), and energy dispersive X-ray spectroscopy (EDS). Extracted molars were prepared to deep or shallow slices and treated with the three adhesives. Micro-CT was used to compare changes to air volume gaps, following thermocycling, and statistically analysed using a quantile regression model and Fisher's exact test. The three adhesives performed similarly across dentine depths and locations, yet no change or overall increases and decreases in gaps at all dentine depths and locations were measured. The Xe PFIB-SEM-milled dentine-adhesive interfaces facilitated high-resolution characterization, and element profiling revealed variations across the tooth-material interfaces. Dentine depth and location had no impact on adhesive durability, although microscopic differences were observed. Here we demonstrate how micro-CT and Xe PFIB-SEM can be used to compare variable dental materials without complex multi-stage specimen preparation to minimize artefacts.

Physical therapy for facial nerve paralysis (Bell's palsy): An updated and extended systematic review of the evidence for facial exercise therapy.

OBJECTIVE: To conduct a systematic review of the effectiveness of facial exercise therapy for facial palsy patients, updating an earlier broader Cochrane review; and to provide evidence to inform the development of telerehabilitation for these patients. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Cochrane Library, PEDro and AMED for relevant studies published between 01 January 2011 and 30 September 2020. METHODS: Predetermined inclusion/exclusion criteria were utilised to shortlist abstracts. Two reviewers independently appraised articles, systematically extracted data and assessed the quality of individual studies and reviews (using GRADE and AMSTAR-2, respectively). Thematic analysis used for evidence synthesis; no quantitative meta-analysis conducted. The review was registered with PROSPERO (CRD42017073067). RESULTS: Seven new randomised controlled trials, nine observational studies, and three quasi-experimental or pilot studies were identified (n = 854 participants). 75% utilised validated measures to record changes in facial function and/or patient-rated outcomes. High-quality trials (4/7) all reported positive impacts; as did observational studies rated as high/moderate quality (3/9). The benefit of therapy at different time points post-onset and for cases of varying clinical severity is discussed. Differences in study design prevented data pooling to strengthen estimates of therapy effects. Six new review articles identified were all rated critically low quality. CONCLUSION: The findings of this targeted review reinforce those of the earlier more general Cochrane review. New research studies strengthen previous conclusions about the benefits of facial exercise therapy early in recovery and add to evidence of the value in chronic cases. Further standardisation of study design/outcome measures and evaluation of cost-effectiveness are recommended.

Modified Posterior Arm Flap for Axillary Hidradenitis Suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, inflammatory condition of the apocrine sweat glands present in 1% to 4% of the adult population, with twice greater prevalence in females. Surgical excision is the criterion-standard treatment for advanced, grade III disease, characterized by extensive and recurrent abscesses and interconnected sinus tracts. Numerous reconstructive methods have been used to cover the resulting defects, including secondary intention healing, use of skin grafts, and a wide range of locoregional flaps. METHODS: The modified posterior arm flap has been developed for reconstruction of axillary defects after radical excision of HS. Based on perforating vessels from the axillary artery first identified by Masquelet, a brachioplasty-like incision is used to keep the donor site closure relatively hidden on the posteromedial aspect of the inner arm. RESULTS: Eight modified posterior arm flaps have been undertaken in 6 patients, all women (mean age, 35 years; range, 22-51 years) from 2014 to 2019. All patients had complete resolution of their HS symptoms with no incidences of recurrence at mean follow-up of 15 months. All reported satisfaction with the aesthetic and functional outcomes of the procedure. DISCUSSION: We present a novel modification of the posterior arm flap for the treatment of advanced axillary HS with good functional and aesthetic outcomes and no incidences of recurrence.