Combinatorial biosynthesis in yeast leads to over 200 diterpenoids.

Diterpenoids form a diverse group of natural products, many of which are or could become pharmaceuticals or industrial chemicals. The modular character of diterpene biosynthesis and the promiscuity of the enzymes involved make combinatorial biosynthesis a promising approach to generate libraries of diverse diterpenoids. Here, we report on the combinatorial assembly in yeast of ten diterpene synthases producing (+)-copalyl diphosphate-derived backbones and four cytochrome P450 oxygenases (CYPs) in diverse combinations. This resulted in the production of over 200 diterpenoids. Based on literature and chemical database searches, 162 of these compounds can be considered new-to-Nature. The CYPs accepted most substrates they were given but remained regioselective with few exceptions. Our results provide the basis for the systematic exploration of the diterpenoid chemical space in yeast using sequence databases.

Effectiveness of patient reminders on influenza vaccination coverage among adults with chronic conditions: A feasibility study in Australian general practices.

BACKGROUND: Influenza vaccination is recommended for Australians 18+ years old with medical risk factors, but coverage is suboptimal. We aimed to examine whether automatic, opportunistic patient reminders (SMS and/or printed) before appointments with a general practitioner increased influenza vaccination uptake. METHODS: This clustered non-randomised feasibility study in Australian general practice included patients aged 18-64 years with at least one medical risk factor attending participating practices between May and September 2021. Software installed at intervention practices identified unvaccinated eligible patients when they booked an appointment, sent vaccination reminders (SMS on booking and 1 h before appointments), and printed automatic reminders on arrival. Control practices provided usual care. Clustered analyses adjusted for sociodemographic differences among practices were performed using logistic regression. RESULTS: A total of 12,786 at-risk adults attended 16 intervention practices (received reminders = 4066; 'internal control' receiving usual care = 8720), and 5082 individuals attended eight control practices. Baseline influenza vaccination uptake (2020) was similar in intervention and control practices (∼34%). After the intervention, uptake was similar in all groups (control practices = 29.3%; internal control = 30.0%; intervention = 31.6% (p-value = 0.203). However, SMS 1 h before appointments increased vaccination coverage (39.3%, adjusted OR = 1.65; 95%CI 1.20;2.27; number necessary to treat = 13), especially when combined with other reminder forms. That effect was more evident among adults with chronic respiratory, rheumatologic, or inflammatory bowel disease. CONCLUSION: These findings indicate that automated SMS reminders delivered at proximate times to appointments are a low-cost strategy to increase influenza vaccination among adults at higher risk of severe disease attending Australian general practices.

Implementing FAIR data management within the German Network for Bioinformatics Infrastructure (de.NBI) exemplified by selected use cases.

This article describes some use case studies and self-assessments of FAIR status of de.NBI services to illustrate the challenges and requirements for the definition of the needs of adhering to the FAIR (findable, accessible, interoperable and reusable) data principles in a large distributed bioinformatics infrastructure. We address the challenge of heterogeneity of wet lab technologies, data, metadata, software, computational workflows and the levels of implementation and monitoring of FAIR principles within the different bioinformatics sub-disciplines joint in de.NBI. On the one hand, this broad service landscape and the excellent network of experts are a strong basis for the development of useful research data management plans. On the other hand, the large number of tools and techniques maintained by distributed teams renders FAIR compliance challenging.

Longitudinal follow-up by MR angiography reveals progressive dilatation of the distal aorta after aortic root replacement in Marfan syndrome.

OBJECTIVES: To define and compare growth rates of the distal aorta in Marfan patients with and without aortic root replacement using serial MR angiography (MRA). METHODS: We retrospectively included 136 Marfan patients with a total of 645 MRAs who underwent a median of five MRAs (range: 2-13) at 1.5 T and 3 T in annual intervals. Of these, 41 patients (34.8 ± 12 years) had undergone aortic root replacement. The remaining 95 patients (29.0 ± 17 years) still had a native aorta and served as the control group. Thoracic aortic diameters were independently measured at eleven predefined levels. Estimated growth rates were calculated using a mixed effects model adjusted for sex, age, BMI, and medication. RESULTS: Marfan patients with aortic root replacement revealed the highest mean estimated growth rate in the proximal descending aorta (0.77 mm/year, CI: 0.31-1.21). Mean growth rates at all levels of the distal thoracic aorta were significantly higher in patients with aortic root replacement (0.28-0.77 mm/year) when compared to patients without aortic root replacement (0.03-0.07 mm/year) (all p < 0.001). Antihypertensive medication, gender, and BMI had no significant impact on the distal aortic growth rates. CONCLUSION: Distal thoracic aortic diameters increase at a significantly higher rate in Marfan patients with aortic root replacement compared to Marfan patients without aortic root replacement. Further studies are warranted to investigate if the increased growth rate of the distal thoracic aorta after aortic root replacement is caused by altered hemodynamics due to the rigid aortic root graft or due to the general genetic disposition of post-operative Marfan patients. CLINICAL RELEVANCE STATEMENT: High growth rates of the distal aorta after aortic root replacement underline the need for careful life-long aortic imaging of Marfan patients after aortic root replacement. KEY POINTS: • Aortic growth rates in Marfan patients with aortic root replacement are highest in the mid-aortic arch, the proximal- and mid-descending aorta. • Growth rates of the distal thoracic aorta are significantly higher in Marfan patients with aortic root replacement compared to Marfan patients without aortic root replacement. • Antihypertensive medication, gender, and BMI have no significant impact on distal aortic growth rates in Marfan patients.

Bi-planar calibration method for templating of hip joint arthroplasty: phantom study and proof of concept.

PURPOSE: Calibration of radiographs is a critical step in digital templating for hip arthroplasty. Calibration errors of > 1.5% lead to over- or undersizing of the templated implants and may affect logistics and patient safety. Contemporary calibration methods are known to be imprecise with average errors of 6.5% and wide variance. A novel bi-planar radiograph-based calibration method is proposed, and a phantom study was conducted as proof of concept. METHODS: A spherical external calibration marker (ECM) is placed in front of the pubic symphysis of a pelvic bone model at twelve different positions. For each marker position, standard anteroposterior radiographs and four corresponding lateral radiographs with different degrees of rotation (0°-30°) are taken (overall, 60 radiographs). Calibration factors are calculated for an internal calibration marker (ICM) at the centre of the right hip (reference) and the ECM using a novel algorithm. Rotation and marker positions simulate foreseeable use errors and misplacements and aim to test robustness of the method against these errors. RESULTS: ECM calibration factor was 125.9% (range 124.7-127.2), and the mean ICM calibration factor was 126.6% (range 126.2-127.1) ([Formula: see text]). Four images (8.3%) were beyond the 1% error threshold (all with 30° rotation). The mean difference was 0.79% (SD 0.49). CONCLUSION: The bi-planar method precisely predicts the true calibration factor of the hip joint plane under various conditions. In lateral radiographs, rotation of up to 20° did not adversely affect the precision and all images had calibration errors below the threshold for clinical significance.

It is time to update sun safety campaigns to recognise population diversity: Findings from two citizens' juries in Australia.

ISSUE ADDRESSED: While the links between sun exposure and skin cancer are well known, the benefits of sun exposure, particularly as a source of vitamin D, are less well known. This paper reports on a deliberative study exploring public perspectives about sun exposure harms and benefits. METHODS: Two citizens' juries were conducted in Brisbane and Adelaide to consider questions about sun exposure, vitamin D and health promotion. Members of the general population (jurors) listened to evidence from expert witnesses about the harms and benefits of sun exposure. Most witness sessions extended for 60 min, with 6 sessions over 2 days. At each citizens' jury, jurors were asked to listen to expert testimony, consider the evidence and make policy recommendations. The planning and design of the citizens' juries were informed by well-established citizens' jury methods. RESULTS: Jurors proposed that Australia needs improved public information about the harms and benefits of sun exposure. They argued for information that supports personal decision-making that accounts for differences in skin tone and geographical region. Jurors agreed that Australia needs an updated sun safety campaign that reflects new research and addresses diversity. A one-size-fits-all approach to sun protection may no longer be appropriate. CONCLUSIONS: While a new campaign should address both harms and benefits, jurors felt the need for skin cancer prevention outweighs the desirability of generating vitamin D through sun exposure. More nuanced public health messages are needed, which balance the need for skin protection and vitamin D, and acknowledge the diversity of Australia's population. SO WHAT?: Previous research studies are typically siloed into the separate areas of vitamin D or skin cancer research. This study incorporated both topics and pooled the views of participants in two citizens' juries who agreed on the need for improved information about the harms and benefits of sun exposure to reflect a modern Australian population.

Localization Defines Streptozotocin/5-FU Response in Primary Pancreatic Neuroendocrine Tumours.

INTRODUCTION: Incidence of pancreatic neuroendocrine tumours (pNETs) is on the rise. The only curative treatment is surgical resection in localized or oligo-metastatic disease. However, patients may present with locally advanced or unresectable primary tumours. So far, no conversion therapy to achieve resectability has been established, which is partly due to lack of data on primary tumour response to therapies. Here, we specifically evaluate the primary tumour response to streptozocin/5-FU in a large cohort of metastatic pNET patients. METHODS: Five ENETS centres in Germany contributed 84 patients to the study cohort for retrospective analysis. RESULTS: Overall response rate (ORR) in primary tumours was 34% and disease control rate (DCR) 88%. ORR was different in metastases at 44% and DCR at 70%. Partial remission in primary tumours was more frequent among those located in pancreatic tail than that in pancreatic head (49% vs. 14%, p = 0.03). Correspondingly, metastases from tumours originating from pancreatic tail responded more frequently than metastases originating from pancreatic head (88.5% vs. 41.7%, p = 0.005). The median PFS of the primary tumours was longer than that in metastases (31 months vs. 16 months; p = 0.04). Considerable downsizing of the primary tumour was rare and occurred primarily in tumours located in the pancreatic tail. CONCLUSION: STZ/5-FU can achieve disease stabilization in a high proportion of metastatic pNET patients. In the majority of cases however it does not induce substantial downsizing of the primary tumour, thus possibly limiting its potential as conversion chemotherapy. Furthermore, the difference in response rate observed between different primary tumour locations warrants further exploration.

Dynamic Mediolateral Patellar Translation Is a Sex- and Size-Independent Parameter of Adult Proximal Patellar Tracking Using Dynamic 3 Tesla Magnetic Resonance Imaging.

PURPOSE: To provide normal values for physiological patellofemoral tracking in a representative group of healthy individuals, as well as sex differences, using real-time 3T-magnetic resonance imaging (MRI) and to test for the reliability of the presented technique. METHODS: One hundred knees of healthy individuals with no history of patellofemoral symptoms were scanned with dynamic MRI sequences, during repetitive cycles of flexion (40°) and full extension. Within a 30-seconds time-frame, three simultaneous, transverse slices were acquired. Dynamic mediolateral patellar translation (dMPT) and dynamic patellar tilt (dPT) were measured on two occasions by two independent examiners. Common radiological parameters were measured using static MRI, and correlations were calculated. RESULTS: 100 knees (53 right, 47 left; age: 26.7 ± 4.4 years; BMI: 22.5 ± 3.1) of 57 individuals (27 females, 30 males) were included. Mean height was 170.1 ± 7.7 cm in women and 181.8 ± 6.4 cm in men. Average patella diameter was 37.9 ± 2.7 (95% CI 37.1-38.7) mm in women and 42.4 ± 3.2 (95% CI 41.5-43.3) mm in men. In females, the patellar diameters and intercondylar distances were significantly smaller than in males (P < .001). Radiological parameters for patellar maltracking were within the normal range. During the range of motion, mean dMPT was 1.7 ± 2.4 (95% CI .9-2.5) mm in females and 1.8 ± 2.7 (95% CI 1.1-2.6) mm in males (P = .766). Mean dPT was 1.3 ± 2.9° (95% CI .4-2.1°) in females and -0.2 ± 3.8° (95% CI -1.2-.9°) in males (P = .036). Neither dMPT nor dPT was correlated with height, BMI, or patellar diameter. Intercondylar distance correlated weakly with dPT (r = -.241; P = .041). Intra- and interrater reliability were excellent for dMPT and dPT. CONCLUSION: Dynamic mediolateral patellar translation is a size- and sex-independent parameter for proximal patellar tracking. In healthy individuals without patellofemoral abnormalities normal dMPT proximal to the trochlea groove was 1.7 ± 2.5 (1.2-2.2) mm, independent of size or sex. Normal dPT showed a dependency on sex and was 1.3 ± 2.9 (.4-2.1)° in women and -0.2 ± 3.8 (-1.2-0.9)° in men. LEVEL OF EVIDENCE: Level II, diagnostic study.

Semi-quantitative magnetic resonance imaging scoring of the knee detects previous injuries in professional soccer players.

PURPOSE: The medical examination ("medical") is an important procedure in professional soccer since it has high economic relevance. In addition to clinical tests, magnetic resonance imaging (MRI) is used to assess joint health. In the present study, the reliability of semiquantitative knee MRI during the "medical" in professional soccer was tested, and its relationship with clinical data and days missed due to knee injury was observed. METHODS: In this cross-sectional study, between 2012 and 2019, 69 newly assigned players (age 18-35 years) from a professional soccer club underwent MRI (3.0 T) of both knee joints during their "medical". Reported knee injuries and previously missed days due to injury were obtained from player anamnesis and the "transfermarkt.com" database. Based on the established "Whole-Organ Magnetic Resonance Imaging Score" (WORMS), two independent radiologists graded the MRI results. Further evaluation was based on the mean score of both knees. RESULTS: The mean WORMS for all subjects was 13.9 (median 10.5, range 0-61). Players with previous injuries had significantly higher scores than players without reported injuries (22.1 ± 17.7 vs. 8.9 ± 4.4, p < 0.002). Three outliers (previously undetected injuries) in the group of players without reported injuries were observed (6.7%). The WORMS was significantly correlated with a prior knee injury (r: 0.424, p < 0.0001) and days missed due to injury (r: 0.489, p < 0.001). Age was correlated with the WORMS (r: 0.386, p < 0.001). In a linear regression model, prior injury was the only significant predictor of a high WORMS (p = 0.001). The WORMS was a significant predictor of days missed due to injury (p < 0.0002) and prior injury (sensitivity: 78%, specificity: 91%, p = 0.006). The intraclass correlation coefficient was excellent (0.89). CONCLUSION: Semiquantitative knee MRI for WORMS determination during the soccer "medical" is a robust and reliable method. Prior injury, even in players without documented trauma, was detected by the WORMS, and previously missed days due to injury were correlated with the semiquantitative MR knee score. LEVEL OF EVIDENCE: Level III.

[Neoehrlichiosis as a cause of feaver of unknown origin]. / Neoehrlichiose als Ursache eines Fiebers unklarer Genese.

Establishing a diagnosis in cases of fever of unknown origin (FUO) in immunocompromised patients can be difficult. In 25-35% infectious diseases are the underlying cause. This article reports the case of a 74-year-old woman with a 5-month history of fever. Through open biopsy of the femoral shaft and microbiological analysis, a diagnosis of neoehrlichiosis could be established. After initiation of treatment with doxycycline, the symptoms quickly resolved resulting in a complete recovery.

[Intimal pulmonary sarcoma: A case report of a rare differential diagnosis of chronic thromboembolic pulmonary hypertension]. / Das intimale Sarkom der Pulmonalarterie ­ Fallbericht einer seltenen Differenzialdiagnose der chronisch thromboembolischen pulmonalen Hypertonie.

Pulmonary angiosarcoma is a rare and malignant disease of the blood vessels. Initially, it can be misdiagnosed as chronic thromboembolic hypertension (CTEPH). In CTEPH, there is increased pressure and resistance of the pulmonary arteries following persistent obstruction of pulmonary circulation from (recurrent) thromboembolism despite adequate anticoagulative treatment.A 76-year-old patient was referred to our centre for pulmonary hypertension after a central, left-sided, subacute pulmonary thromboembolism had been observed 7 months earlier. It was treated with apixaban, but the patient described persistent dyspnoea and cough. We observed severely reduced diffusion capacity, ineffective ventilation during cardiopulmonary exercise testing and right heart strain on echocardiograph, signs that are in agreement with suspected CTEPH. Computer tomography of the chest showed a persistent, size-constant obliteration of the left main pulmonary artery, and ventilation perfusion scan confirmed complete interruption of perfusion. We suspected malignancy; PET-CT scan confirmed metabolically active lesions. Histopathological examination of a sample obtained from the lesion by endobronchial ultrasound-guided needle aspiration showed a sarcomatous tumour with amplification of the MDM2-gene. We diagnosed an intimal angiosarcoma of the left pulmonary artery and referred the patient to pneumectomy.Angiosarcoma of the pulmonary arteries is a rare differential diagnosis of persistent thrombotic lesion and suspected CTEPH. In 2015 there were less than 300 cases described.Pulmonary angiosarcoma should be considered if: lesion occupies the entire lumen of pulmonary arteries with dilatation, contrast enhancement and infiltration of the wall in radiological examination, FDG-PET CT reveals metabolically active lesions, no pulmonary thromboembolism was documented in the anamnesis, increase in size is seen despite anticoagulation, patient presents with B symptoms.Diagnosis confirmed by biopsy, resection of tumour and removal of metastases is the therapeutic standard. Median survival remains poor. Further research is needed for improved diagnosis and treatment.

Analysis of bacterial communities in a municipal duck pond during a phytoplankton bloom and isolation of Anatilimnocola aggregata gen. nov., sp. nov., Lacipirellula limnantheis sp. nov. and Urbifossiella limnaea gen. nov., sp. nov. belonging to the phylum Planctomycetes.

Waterbodies such as lakes and ponds are fragile environments affected by human influences. Suitable conditions can result in massive growth of phototrophs, commonly referred to as phytoplankton blooms. Such events benefit heterotrophic bacteria able to use compounds secreted by phototrophs or their biomass as major nutrient source. One example of such bacteria are Planctomycetes, which are abundant on the surfaces of marine macroscopic phototrophs; however, less data are available on their ecological roles in limnic environments. In this study, we followed a cultivation-independent deep sequencing approach to study the bacterial community composition during a cyanobacterial bloom event in a municipal duck pond. In addition to cyanobacteria, which caused the bloom event, members of the phylum Planctomycetes were significantly enriched in the cyanobacteria-attached fraction compared to the free-living fraction. Separate datasets based on isolated DNA and RNA point towards considerable differences in the abundance and activity of planctomycetal families, indicating different activity peaks of these families during the cyanobacterial bloom. Motivated by the finding that the sampling location harbours untapped bacterial diversity, we included a complementary cultivation-dependent approach and isolated and characterized three novel limnic strains belonging to the phylum Planctomycetes.

A generally applicable lightweight method for calculating a value structure for tools and services in bioinformatics infrastructure projects.

Sustainable noncommercial bioinformatics infrastructures are a prerequisite to use and take advantage of the potential of big data analysis for research and economy. Consequently, funders, universities and institutes as well as users ask for a transparent value model for the tools and services offered. In this article, a generally applicable lightweight method is described by which bioinformatics infrastructure projects can estimate the value of tools and services offered without determining exactly the total costs of ownership. Five representative scenarios for value estimation from a rough estimation to a detailed breakdown of costs are presented. To account for the diversity in bioinformatics applications and services, the notion of service-specific 'service provision units' is introduced together with the factors influencing them and the main underlying assumptions for these 'value influencing factors'. Special attention is given on how to handle personnel costs and indirect costs such as electricity. Four examples are presented for the calculation of the value of tools and services provided by the German Network for Bioinformatics Infrastructure (de.NBI): one for tool usage, one for (Web-based) database analyses, one for consulting services and one for bioinformatics training events. Finally, from the discussed values, the costs of direct funding and the costs of payment of services by funded projects are calculated and compared.

Repositories for Taxonomic Data: Where We Are and What is Missing.

Natural history collections are leading successful large-scale projects of specimen digitization (images, metadata, DNA barcodes), thereby transforming taxonomy into a big data science. Yet, little effort has been directed towards safeguarding and subsequently mobilizing the considerable amount of original data generated during the process of naming 15,000-20,000 species every year. From the perspective of alpha-taxonomists, we provide a review of the properties and diversity of taxonomic data, assess their volume and use, and establish criteria for optimizing data repositories. We surveyed 4113 alpha-taxonomic studies in representative journals for 2002, 2010, and 2018, and found an increasing yet comparatively limited use of molecular data in species diagnosis and description. In 2018, of the 2661 papers published in specialized taxonomic journals, molecular data were widely used in mycology (94%), regularly in vertebrates (53%), but rarely in botany (15%) and entomology (10%). Images play an important role in taxonomic research on all taxa, with photographs used in >80% and drawings in 58% of the surveyed papers. The use of omics (high-throughput) approaches or 3D documentation is still rare. Improved archiving strategies for metabarcoding consensus reads, genome and transcriptome assemblies, and chemical and metabolomic data could help to mobilize the wealth of high-throughput data for alpha-taxonomy. Because long-term-ideally perpetual-data storage is of particular importance for taxonomy, energy footprint reduction via less storage-demanding formats is a priority if their information content suffices for the purpose of taxonomic studies. Whereas taxonomic assignments are quasifacts for most biological disciplines, they remain hypotheses pertaining to evolutionary relatedness of individuals for alpha-taxonomy. For this reason, an improved reuse of taxonomic data, including machine-learning-based species identification and delimitation pipelines, requires a cyberspecimen approach-linking data via unique specimen identifiers, and thereby making them findable, accessible, interoperable, and reusable for taxonomic research. This poses both qualitative challenges to adapt the existing infrastructure of data centers to a specimen-centered concept and quantitative challenges to host and connect an estimated $ \le $2 million images produced per year by alpha-taxonomic studies, plus many millions of images from digitization campaigns. Of the 30,000-40,000 taxonomists globally, many are thought to be nonprofessionals, and capturing the data for online storage and reuse therefore requires low-complexity submission workflows and cost-free repository use. Expert taxonomists are the main stakeholders able to identify and formalize the needs of the discipline; their expertise is needed to implement the envisioned virtual collections of cyberspecimens. [Big data; cyberspecimen; new species; omics; repositories; specimen identifier; taxonomy; taxonomic data.].

The UNITE database for molecular identification of fungi: handling dark taxa and parallel taxonomic classifications.

UNITE (https://unite.ut.ee/) is a web-based database and sequence management environment for the molecular identification of fungi. It targets the formal fungal barcode-the nuclear ribosomal internal transcribed spacer (ITS) region-and offers all ∼1 000 000 public fungal ITS sequences for reference. These are clustered into ∼459 000 species hypotheses and assigned digital object identifiers (DOIs) to promote unambiguous reference across studies. In-house and web-based third-party sequence curation and annotation have resulted in more than 275 000 improvements to the data over the past 15 years. UNITE serves as a data provider for a range of metabarcoding software pipelines and regularly exchanges data with all major fungal sequence databases and other community resources. Recent improvements include redesigned handling of unclassifiable species hypotheses, integration with the taxonomic backbone of the Global Biodiversity Information Facility, and support for an unlimited number of parallel taxonomic classification systems.

Assessment, referral and management of obstructive sleep apnea by Australian general practitioners: a qualitative analysis.

BACKGROUND: The high and increasing demand for obstructive sleep apnea (OSA) care has exceeded the capacity of specialist sleep services prompting consideration of whether general practitioners could have an enhanced role in service delivery. However, little is known about the current involvement, experiences and attitudes of Australian general practitioners towards OSA. The purpose of this study was to provide an in-depth analysis of Australian general practitioners' experiences and opinions regarding their care of patients with OSA to inform the design and implementation of new general practice models of care. METHODS: Purposive sampling was used to recruit participants with maximum variation in age, experience and location. Semi-structured interviews were conducted and were analysed using Thematic Analysis. RESULTS: Three major themes were identified: (1) General practitioners are important in recognising symptoms of OSA and facilitating a diagnosis by others; (2) Inequities in access to the assessment and management of OSA; and (3) General practitioners currently have a limited role in the management of OSA. CONCLUSIONS: When consulting with patients with symptoms of OSA, general practitioners see their primary responsibility as providing a referral for diagnosis by others. General practitioners working with patients in areas of greater need, such as rural/remote areas and those of socio-economic disadvantage, demonstrated interest in being more involved in OSA management. Inequities in access to assessment and management are potential drivers for change in future models of care for OSA in general practice.

Primary care management of chronic insomnia: a qualitative analysis of the attitudes and experiences of Australian general practitioners.

BACKGROUND: Chronic insomnia is a highly prevalent disorder, with ten to thirty percent of Australian adults reporting chronic difficulties falling asleep and/or staying asleep such that it causes significant daytime impairment. Current Australian general practice guidelines recommend cognitive behavioural therapy for insomnia (CBTi) as first line treatment for insomnia, however research suggests that most general practice consultations for insomnia result in a prescription for hypnotic or sedative medicines. Although the first point of contact for patients experiencing symptoms of insomnia is often general practice, little is known about the current role, experiences and capacity of Australian general practitioners to manage insomnia. This study aimed to address that gap by exploring the attitudes and opinions of general practitioners regarding insomnia management, to inform the development and implementation of new models of best practice insomnia care within general practice. METHODS: A descriptive, pragmatic qualitative study. Purposive sampling was used to recruit practising Australian general practitioners, varying in age, years of experience and geographic location. Semi-structured interviews were conducted, and data analysed using thematic analysis.  RESULTS: Twenty-eight general practitioners participated in the study. Three major themes were identified: 1) Responsibility for insomnia care; 2) Complexities in managing insomnia; and 3) Navigating treatment pathways. Whilst general practitioners readily accepted responsibility for the management of insomnia, provision of care was often demanding and difficult within the funding and time constraints of general practice. Patients presenting with comorbid mental health conditions and insomnia, and decision-making regarding long-term use of benzodiazepines presented challenges for general practitioners. Whilst general practitioners confidently provided sleep hygiene education to patients, their knowledge and experience of CBTi, and access and understanding of specialised referral pathways for insomnia was limited.  CONCLUSIONS: General practitioners report that whilst assessing and managing insomnia can be demanding, it is an integral part of general practice. Insomnia presents complexities for general practitioners. Greater clarity about funding options, targeted education about effective insomnia treatments, and referral pathways to specialist services, such as benzodiazepine withdrawal support and psychologists, would benefit insomnia management within general practice.

Is it time to stop using statistical significance?

The important first step in the critical appraisal of a randomised trial is not an evaluation of the statistical analyses. The most important aspect to consider when reviewing a study of a new drug is the appropriateness and quality of the trial design and methods The next most important aspect is the effect size of different treatments and its clinical significance. Rather than reporting statistical significance, studies should report the difference between treatments and its precision Over-reliance on statistical significance and p values may lead to incorrect conclusions. Trial reports about drugs should therefore avoid the term statistical significance and quote p values with caution.

MDCT in the Setting of Suspected Colonic Diverticulitis: Prevalence and Diagnostic Yield for Diverticulitis and Alternative Diagnoses.

OBJECTIVE. The purpose of this study was to determine the prevalence and demographic distribution of colonic diverticulitis (CD) and alternative diagnoses (AD), as well as the diagnostic accuracy of MDCT in patients with suspected CD. MATERIALS AND METHODS. This study retrospectively included 1069 patients (560 women) undergoing MDCT for the evaluation of suspected CD. The prevalence of CD and AD was determined and the diagnostic accuracy of MDCT calculated. The final clinical diagnosis derived from the discharge report served as the standard of reference. Prevalence of diagnoses by age, sex, and admission status were compared using Cochran-Armitage, chi-square, and Fisher exact tests. RESULTS. Prevalence of CD was 52.5% (561/1069) and of AD was 39.9% (427/1069). In the remaining 7.6% (81/1069) no final clinical diagnosis was established. The most frequent AD were appendicitis (12.6%, 54/427), infectious colitis (10.5%, 45/427), infectious gastroenteritis (8.2%, 35/427), urolithiasis (6.1%, 26/427), and pyelonephritis (4.9%, 21/427). The prevalence of diverticulitis and AD varied statistically significantly according to both age (p < 0.001) and admission status (p < 0.001). Also, the prevalence of the 10 most frequent specific AD varied statistically significantly according to sex (p = 0.022). CT had a sensitivity and specificity of 99.1% and 99.8% for diagnosing CD and 92.7% and 98.8% for AD, respectively. CONCLUSION. In about 40% of patients with suspected diverticulitis a broad spectrum of AD is causative for symptoms. MDCT provides high diagnostic accuracy in the diagnosis of diverticulitis and AD. The prevalence of diagnoses is related to admission status and demographic data; in particular age-related AD have to be considered in patients with clinically suspected diverticulitis.

Implementation of a 24-Hour Teleradiology Service for Cruise Ships: A Pilot Study.

OBJECTIVE. The purpose of this study was to introduce a 24-hour teleradiology service for cruise ships as a novel concept in maritime telemedicine. SUBJECTS AND METHODS. One cruise ship equipped with a mobile radiography unit and digital storage imaging plates was involved in this pilot study. Radiographs were transmitted via satellite internet to a tertiary hospital on shore for image interpretation by expert radiologists. Use of a virtual private network (VPN) enabled secure data transfer. Radiographs and patient data were automatically integrated into the PACS and radiology information system of the radiology department at the hospital. Images were analyzed by the staff radiologist at the hospital, and reports were immediately returned via e-mail through the VPN tunnel. RESULTS. Seventy-five radiographs of 47 patients were obtained on board within 2 months. All datasets were successfully transmitted. Most of the examinations (35 [≈ 75%]) were skeletal radiographs; the other 12 (≈ 25%) were chest radiographs. The turnaround time for the radiology reports was within 30 minutes in 43 cases (≈ 92%). In four cases (≈ 8%), delay was due to technical and organizational issues at the tertiary hospital. CONCLUSION. With the objective of supporting ship physicians with expert analyses of radiographs, a secure and stable method of image and radiology report transmission between an onboard hospital and a land-based radiology department was established.