Association between testosterone and cognitive performance in postmenopausal women: a systematic review of observational studies.

This review was conducted to explore the association between endogenous testosterone blood concentrations and cognitive performance among community dwelling postmenopausal women. We searched Ovid MEDLINE, EMBASE, PsycINFO and Web of Science databases for observational studies with at least 100 postmenopausal participants. The results were categorized by study design, reporting of total or free testosterone and risk of bias assessments, narratively. Ten of the 26 articles retrieved for full-text review met the inclusion criteria, six provided cross-sectional data, seven provided longitudinal data and one provided case-control data. Cognitive performance tests differed between studies. Eight studies measured testosterone by immunoassay, one by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and one did not specify their methodology. Eleven different cognitive domains were tested by 37 different instruments. Irrespective of the study design, the findings were inconsistent and inconclusive. Both positive and inverse associations were reported for each of global cognition and immediate and delayed verbal recall. The majority of studies reported no association between total or free testosterone and cognitive performance. Although this review did not demonstrate an association between testosterone and cognitive performance in postmenopausal women, the findings should be considered inconclusive due to the imprecision of testosterone measurement and the methodological heterogeneity of the included studies.

Cancer case trends following the onset of the COVID-19 pandemic: A community-based observational study with extended follow-up.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted health care delivery worldwide. Cancer is a leading cause of death, and the impact of the pandemic on cancer diagnoses is an important public health concern. METHODS: This cross-sectional study retrospectively analyzed the electronic medical records of 80,138 cancer patients diagnosed between January 1, 2019, and May 31, 2021. Outcome measures included weekly number of new cancer cases and trends in weekly cancer cases, before and after the pandemic; patient demographics; and positive COVID-19 test rates. RESULTS: Beginning March 4, 2020, defined as the onset of the pandemic, weekly cancer cases declined precipitously (-110.0 cases per week [95% confidence interval, -190.2 to -29.8]) for 4 weeks, followed by a moderate recovery (+23.7 cases per week [9.1 to 38.4]) of 10 weeks duration. Thereafter, weekly cancer cases trended slowly back toward pre-COVID-19 baseline levels. Following the pandemic onset, there was a cumulative year-over-year decline in cancer cases overall of 7.3%, including a 20.2%, 14.3%, and 12.8% decline in nonmelanoma skin cancer, breast cancer, and prostate cancer, respectively. Changes in case volumes were accompanied by variations in patient characteristics, including region, age, gender, race, insurance coverage, and COVID-19 positive test rates (P < .01 for all). Among patients tested for COVID-19, 5.3% had a positive result. CONCLUSIONS: The data in this study demonstrate a substantial reduction in cancer diagnoses following the onset of COVID-19, which appear to reach expected pre-COVID norms 12 months later. The largest reduction was noted among cancers that are typically screen-detected or identified as part of a routine wellness examination.

Remote ischaemic conditioning: defining critical criteria for success-report from the 11th Hatter Cardiovascular Workshop.

The Hatter Cardiovascular Institute biennial workshop, originally scheduled for April 2020 but postponed for 2 years due to the Covid pandemic, was organised to debate and discuss the future of Remote Ischaemic Conditioning (RIC). This evolved from the large multicentre CONDI-2-ERIC-PPCI outcome study which demonstrated no additional benefit when using RIC in the setting of ST-elevation myocardial infarction (STEMI). The workshop discussed how conditioning has led to a significant and fundamental understanding of the mechanisms preventing cell death following ischaemia and reperfusion, and the key target cyto-protective pathways recruited by protective interventions, such as RIC. However, the obvious need to translate this protection to the clinical setting has not materialised largely due to the disconnect between preclinical and clinical studies. Discussion points included how to adapt preclinical animal studies to mirror the patient presenting with an acute myocardial infarction, as well as how to refine patient selection in clinical studies to account for co-morbidities and ongoing therapy. These latter scenarios can modify cytoprotective signalling and need to be taken into account to allow for a more robust outcome when powered appropriately. The workshop also discussed the potential for RIC in other disease settings including ischaemic stroke, cardio-oncology and COVID-19. The workshop, therefore, put forward specific classifications which could help identify so-called responders vs. non-responders in both the preclinical and clinical settings.

Genomic Epidemiology of Salmonella enterica Circulating in Surface Waters Used in Agriculture and Aquaculture in Central Mexico.

Salmonella enterica can survive in surface waters (SuWa), and the role of nonhost environments in its transmission has acquired increasing relevance. In this study, we conducted comparative genomic analyses of 172 S. enterica isolates collected from SuWa across 3 months in six states of central Mexico during 2019. S. enterica transmission dynamics were assessed using 87 experimental and 112 public isolates from Mexico collected during 2002 through 2019. We also studied genetic relatedness between SuWa isolates and human clinical strains collected in North America during 2005 through 2020. Among experimental isolates, we identified 41 S. enterica serovars and 56 multilocus sequence types (STs). Predominant serovars were Senftenberg (n = 13), Meleagridis, Agona, and Newport (n = 12 each), Give (n = 10), Anatum (n = 8), Adelaide (n = 7), and Infantis, Mbandaka, Ohio, and Typhimurium (n = 6 each). We observed a high genetic diversity in the sample under study, as well as clonal dissemination of strains across distant regions. Some of these strains are epidemiologically important (ST14, ST45, ST118, ST132, ST198, and ST213) and were genotypically close to those involved in clinical cases in North America. Transmission network analysis suggests that SuWa are a relevant source of S. enterica (0.7 source/hub ratio) and contribute to its dissemination as isolates from varied sources and clinical cases have SuWa isolates as common ancestors. Overall, the study shows that SuWa act as reservoirs of various S. enterica serovars of public health significance. Further research is needed to better understand the mechanisms involved in SuWa contamination by S. enterica, as well as to develop interventions to contain its dissemination in food production settings. IMPORTANCE Surface waters are heavily used in food production worldwide. Several human pathogens can survive in these waters for long periods and disseminate to food production environments, contaminating our food supply. One of these pathogens is Salmonella enterica, a leading cause of foodborne infections, hospitalizations, and deaths in many countries. This research demonstrates the role of surface waters as a vehicle for the transmission of Salmonella along food production chains. It also shows that some strains circulating in surface waters are very similar to those implicated in human infections and harbor genes that confer resistance to multiple antibiotics, posing a risk to public health. This study contributes to expand our current knowledge on the ecology and epidemiology of Salmonella in surface waters.

"Custom" Plate in a Day-Accurate Predictive Hole Fabrication Using Point-of-Care 3-Dimensional Printing.

PURPOSE: In computer surgical planned (CSP) fibular reconstructions of the mandible, custom plates facilitate accurate and efficient transfer of the digital plan intraoperatively by a way of predrilled fixation holes. Stock plates are more easily accessible and are more economical but typically preclude the utilization of these predictive holes. The purpose of this article is to describe an accurate and economical alternative to custom plates, while still having the ability to create predictive holes for plate alignment and execution of a digital surgical plan. METHODS: An in vitro accuracy study was performed on a point-of-care resin-printed predictive hole guide termed "prebent plate analog" (PPA). Twenty stock 2.0 reconstruction plates prebent against a 3-dimensional printed mandibular model reconstructed with a 2-piece fibula were used to fabricate 20 PPAs. The proximal and distal 4 holes of each prebent plate and corresponding PPA were assessed using a heat map overlay, measuring difference in millimeters between matching points of the predictive hole segments. The median distance from the points of reference in the PPA versus the prebent plate was calculated for each predictive hole position in addition to the average error of the PPA to the stock plate. RESULTS: Eighteen PPAs were used for statistical analysis; 2 were damaged in transport. The mean error between the body (-0.265) and condylar segments (-0.116 mm) and mean difference in error between the proximal predictive holes (-0.124 mm) and distal predictive holes (-0.215 mm) on the PPA were not statistically different (P = .061, P = .314 general estimating equation regression, respectively). The mean error across the PPA predictive holes and corresponding holes of the prebent plates was -0.194 mm (P < .001, general estimating equation regression). CONCLUSIONS: The PPA is a precise and accurate analog that faithfully replicates the position of proximal and distal components of a prebent stock plate, thereby allowing for predictive hole placement in lieu of a custom plate in fibula mandibular reconstruction cases.

Pregnancy and development of diabetes in First Nations and non-First Nations women in Alberta, Canada.

AIM: To conduct a retrospective population-based study to examine the risk of developing diabetes after delivery in First Nations and non-First Nations women in Alberta. METHODS: Delivery records (1999-2014) were linked to provincial administrative data, which allowed for a maximum follow-up of 16 years after delivery. Prevalence of pregnancy risk factors were compared by First Nations status. Hazard ratios for diabetes after delivery by First Nations status, high pre-pregnancy body weight (≥91 kg) and gestational diabetes status were estimated using the Cox proportional hazards model. RESULTS: Age-adjusted prevalence of gestational diabetes (7.9% vs 4.6%; P<0.0001), high pre-pregnancy body weight (18.8% vs 10.2%; P<0.0001) and diabetes after delivery (3.9% vs 1.1%; P<0.0001) were higher in First Nations women than in non-First Nations women. Development of diabetes after delivery was higher with First Nations status (hazard ratio 3.0, 95% CI 2.6-3.4), high pre-pregnancy body weight (hazard ratio 3.6, 95% CI 3.3-4.0) and gestational diabetes status (hazard ratio 19.2, 95% CI 17.9-20.6). The highest risk was within First Nations women with high pre-pregnancy body weight and gestational diabetes (hazard ratio 54.8, 95% CI 45.2-66.5) compared to women without these three risk factors. Reduced prenatal visits per pregnancy (8.4 vs 10.7; P<0.0001) and delayed first prenatal visit (time to delivery 23.7 vs 26.7 weeks; P<0.0001) were observed in First Nations women compared to non-First Nations women. CONCLUSION: First Nations women are at greater risk of developing diabetes after pregnancy, with gestational diabetes being the strongest predictor. Strategies that target the specific needs of First Nations women before, during and after pregnancy are required.

Health-care providers' views of menopause and its management: a qualitative study.

OBJECTIVE: This study aimed to explore Australian health-care providers' knowledge of menopause and its consequences, and their views about menopause-related health care. METHODS: This was a cross-sectional qualitative study of Australian general practitioners (GPs), gynecologists (GYs) and pharmacists (PHs). Recruitment was ultimately achieved through professional networks and cold calling. RESULTS: There were equal numbers of GPs, GYs and PHs, and equal numbers of males and females in each group. All participants demonstrated sound understanding of menopause and its consequences. A strong theme was recognition of high usage of complementary and alternative medicines (CAMs) by women for menopausal symptoms. Most participants highlighted lack of efficacy evidence for most CAMs, but the majority of GPs and PHs considered CAMs to 'have a role'. Most supported menopausal hormone therapy (MHT) when symptoms impaired quality of life. Limitations to comprehensive care included knowledge gaps and lack of time. CONCLUSIONS: Australian health-care providers appeared knowledgeable about menopause, but uncertain about its management. MHT prescription appeared limited to women with severe symptoms despite lifestyle modification and a trial of CAMs. The upskilling of clinicians providing care for women at midlife, with respect to the indications for and prescribing of MHT, urgently needs to be addressed.

Guideline on the peri-operative management of patients with sickle cell disease: Guideline from the Association of Anaesthetists.

Sickle cell disease is a multisystem disease characterised by chronic haemolytic anaemia, painful vaso-occlusive crises and acute and chronic end-organ damage. It is one of the most common serious inherited single gene conditions worldwide and has a major impact on the health of affected individuals. Peri-operative complications are higher in patients with sickle cell disease compared with the general population and may be sickle or non-sickle-related. Complications may be reduced by meticulous peri-operative care and transfusion, but unnecessary transfusion should be avoided, particularly to reduce the risk of allo-immunisation. Planned surgery and anaesthesia for patients with sickle cell disease should ideally be undertaken in centres with experience in caring for these patients. In an emergency, advice should be sought from specialists with experience in sickle cell disease through the haemoglobinopathy network arrangements. Emerging data suggest that patients with sickle cell disease are at increased risk of COVID-19 infection but may have a relatively mild clinical course. Outcomes are determined by pre-existing comorbidities, as for the general population.

Management of Zygomaticomaxillary Complex Fractures Utilizing Intraoperative 3-Dimensional Imaging: The ZYGOMAS Protocol.

PURPOSE: Utilization of technology to aid in the assessment, planning, and management of complex craniomaxillofacial injuries is increasingly common. Limited data exist regarding the implication of intraoperative CT/3-Dimensional imaging on decision making in the management of zygomaticomaxillary complex (ZMC) fractures. This study characterizes the utilization of the intraoperative CT scanner for ZMC fracture surgery and analyzes the impact of the intraoperative CT scanner on fracture management. Using these findings, we sought to propose an algorithm to guide the appropriate utilization of intraoperative 3-Dimensional imaging in ZMC fracture surgery. METHODS: This retrospective case series evaluates the use of the intraoperative CT scanner for orbitozygomatic trauma surgery at a level 1 trauma center from February 2011 to September 2016. We evaluated the preoperative CT images assessing for the number of displaced sutures, the presence of adjacent fractures requiring fixation, the presence of comminution of the zygomaticomaxillary buttress or body of the zygoma, as well as the number of axes displaced ≥ 5 mm. This information was evaluated to provide guidance on the appropriate utilization of the intraoperative scanner in ZMC fracture management. RESULTS: A total of 71 patients were identified to have intraoperative facial CT scans and surgery for ZMC fractures over the study time period. There was a 23.9% (17/71) CT directed revision rate. There was a significantly increased likelihood of CT directed revision for fractures with adjacent fractures requiring fixation, and those with ≥ 2 axes displaced ≥ 5 mm. Using these findings, we proposed the ZYGOMAS algorithm outlining the indications for use of intraoperative CT in management of ZMC fractures. CONCLUSIONS: If available, intraoperative CT/3-Dimensional imaging should be utilized in the management of ZMC fractures with the requirement for orbital floor reconstruction, where adjacent fractures require fixation and/or when ≥ 2 axes are displaced ≥ 5 mm.

Variation in menopausal vasomotor symptoms outcomes in clinical trials: a systematic review.

BACKGROUND: There is substantial variation in how menopausal vasomotor symptoms are reported and measured among intervention studies. This has prevented meaningful comparisons between treatments and limited data synthesis. OBJECTIVES: To review systematically the outcome reporting and measures used to assess menopausal vasomotor symptoms from randomised controlled trials of treatments. SEARCH STRATEGY: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to May 2018. SELECTION CRITERIA: Randomised controlled trials with a primary outcome of menopausal vasomotor symptoms in women and a sample size of at least 20 women per study arm. DATA COLLECTION AND ANALYSIS: Data about study characteristics, primary vasomotor-related outcomes and methods of measuring them. MAIN RESULTS: The search identified 5591 studies, 214 of which were included. Forty-nine different primary reported outcomes were identified for vasomotor symptoms and 16 different tools had been used to measure these outcomes. The most commonly reported outcomes were frequency (97/214), severity (116/214), and intensity (28/114) of vasomotor symptoms or a composite of these outcomes (68/214). There was little consistency in how the frequency and severity/intensity of vasomotor symptoms were defined. CONCLUSIONS: There is substantial variation in how menopausal vasomotor symptoms have been reported and measured in treatment trials. Future studies should include standardised outcome measures which reflect the priorities of patients, clinicians, and researchers. This is most effectively achieved through the development of a Core Outcome Set. This systematic review is the first step towards development of a Core Outcome Set for menopausal vasomotor symptoms. TWEETABLE SUMMARY: Menopausal hot flushes and night sweats have been reported in 49 different ways in clinical research. A core outcome set is urgently required.

Mammographic density and breast cancer screening.

Mammographic density, which is determined by the relative amounts of fibroglandular tissue and fat in the breast, varies between women. Mammographic density is associated with a range of factors, including age and body mass index. The description of mammographic density has been transformed by the digitalization of mammography, which has allowed automation of the assessment of mammographic density, rather than using visual inspection by a radiologist. High mammographic density is important because it is associated with reduced sensitivity for the detection of breast cancer at the time of mammographic screening. High mammographic density is also associated with an elevated risk of developing breast cancer. Mammographic density appears to be on the causal pathway for some breast cancer risk factors, but not others. Mammographic density needs to be considered in the context of a woman's background risk of breast cancer. There is intense debate about the use of supplementary imaging for women with high mammographic density. Should supplementary imaging be used in women with high mammographic density and a clear mammogram? If so, what modalities of imaging should be used and in which women? Trials are underway to address the risks and benefits of supplementary imaging.

Why do we need cohort studies?

Cohort studies play an important role in medical research but it is important to understand their limitations. Some large ongoing cohort studies continue to provide critical insights into the causes of chronic disease. Confounding is a major challenge but can be dealt with during both the design and analysis phases of a cohort study. Planning for inclusion of potential confounders in the analysis should be part of the study protocol. The STROBE guidelines have improved the performance and reporting of cohort studies.

When you are making plans to publish research, you need to plan for data sharing.

Open data is another step on the pathway of strengthening medical research. Allowing access to data facilitates testing the reproducibility of research findings. It also allows for the testing of new hypotheses, the incorporation of individual level data into meta-analyses and the development of very large data sets in which to develop and test new algorithms. There are now many data repositories that researchers can use to share their protocols, syntax and data. There are strategies both for managing what other researchers do with publically available data and for rewarding researchers who share their data. There is a strong ethical argument for making data publically available and research participants are generally supportive of this approach.

Australian women's understanding of menopause and its consequences: a qualitative study.

BACKGROUND: This study was undertaken to determine women's knowledge of menopause and its consequences, and their menopause-related health-care experiences. METHODS: Participants were recruited to this cross-sectional qualitative study from a nationally, representative sample of Australian women. Recruitment was stratified by age to achieve groups of premenopausal (PRE), perimenopausal (PERI), early postmenopausal (E-POST), and late postmenopausal (L-POST) women. RESULTS: The 32 participants were aged 46-69 years: 10 PRE, three PERI, 11 E-POST and eight L-POST women. All understood that menopause meant the end of reproductive function and were aware of menopause-associated symptoms. Most PRE and E-POST women referred to lifestyle changes to optimize health, and self-help and complementary therapies to manage symptoms. E-POST and L-POST women were more likely to nominate seeing a doctor for overall health and symptom management. Menopausal hormone therapy (MHT) was viewed negatively, with shared perceptions of cancer risk and over-prescription. A strong theme was lack of knowledge of long-term menopause sequelae, with only four women nominating osteoporosis. CONCLUSIONS: Our in-depth qualitative study would suggest that, while Australian midlife women have a good understanding of the immediate effects of menopause, their lack of knowledge of the long-term consequences is concerning. Despite the effectiveness and safety of MHT, the overall attitude to MHT remains negative.

Contemporary Techniques in Orbital Reconstruction: A Review of the Literature and Report of a Case Combining Surgical Navigation, Computer-Aided Surgical Simulation, and a Patient-Specific Implant.

PURPOSE: Complex orbital fractures can be surgically challenging because the orbital cavity contains several vital anatomic structures and visibility is limited. We present a case in which computer-aided surgical simulation (CASS), surgical navigation (SN), and a patient-specific implant (PSI) were used. Furthermore, the reported data regarding this topic were systematically searched and investigated. PATIENTS AND METHODS: A patient with a complex, failed orbital reconstruction was referred to our department. Despite the use of advanced tools, including a preformed PSI using a 1:1 mirrored, individual 3-dimensional model, several challenges remained. A systematic search of the relevant databases, scientific journals, and bibliographies of the included reports was conducted. Clinical studies involving CASS and SN in the treatment of at least 5 patients reported between 2016 and 2018 were included. RESULTS: The final reconstruction was planned virtually, and a milled PSI was produced and implanted under guidance of SN. The clinical outcome was acceptable to the patient. The literature search showed that superior results can be obtained when CASS and SN are involved in the treatment regimen. The average technical accuracy for SN has been reported to be less than 1 mm, and volume restoration has been reported to be significantly superior to that achieved with traditional methods. CONCLUSIONS: New technological advancements such as CASS involving SN seem to improve the outcomes of orbital reconstruction, especially in complex cases. Furthermore, planning, execution, and evaluation will be facilitated. Real-time guidance can also be used as a training tool for novice surgeons; however, factors such as financial investments, challenges in implementation, and a steep learning curve must be considered.

Four Practical Reconstructive Techniques Using the Transantral Approach to the Orbital Floor Without the Need for an Endoscope.

Fractures of the orbital floor have traditionally been treated through transorbital approaches. Transconjunctival approaches risk entropion, whereas transcutaneous approaches risk ectropion or hypertrophic scarring. The intraoral transantral approach to the orbital floor has the advantage of minimizing the risk of any eyelid changes while providing appropriate access to reduce the herniated orbital contents and restore orbital volume. This article describes 4 plating methods for reconstructing a fractured orbital floor using a transantral approach. Many prior descriptions of transantral treatment of the orbital floor have relied heavily on the use of an endoscope. This article describes an osteotomy technique that does not require an endoscope but requires only a high-quality headlight for visualization.

The Biaxial Double-Barrel Fibula Flap-A Simplified Technique for Fibula Maxillary Reconstruction.

PURPOSE: Previously described techniques for microvascular fibula reconstruction of Brown Class II to IV maxillectomy defects are complex, require multiple osteotomies, result in a short pedicle, and inadequately reconstruct the dental alveolus in preparation for endosseous implants. This report describes a simplified technique for Brown Class II to IV defects that re-creates facial support, allows for dental reconstruction with appropriately positioned implants, and maintains adequate pedicle length. MATERIALS AND METHODS: A retrospective chart review was performed of all patients with Brown Class II to IV maxillectomy defects immediately reconstructed with a biaxial double-barrel fibula flap technique. The reconstructive surgeon evaluated each patient at least 1 month after reconstruction for enophthalmos, facial symmetry, nasal patency, satisfactory jaw position, deglutition, intelligible speech, and intraoperative need for vein grafting. RESULTS: The sample was composed of 6 patients (mean age, 54 yr; range, 33 to 78 yr; 67% women) who underwent reconstruction with the biaxial double-barrel fibula flap technique for Brown Class II to IV defects. None of these patients required vein grafting. None of these patients had flap failure. Diagnoses for these patients were a hybrid odontogenic tumor (n = 1), squamous cell carcinoma (n = 3), adenoid cystic carcinoma (n = 1), and sinonasal melanoma (n = 1). All 6 patients had excellent facial contour and malar projection, regular oral intake, 100% intelligible speech, and a new maxillary skeletal Class I relation without need for intraoperative vein grafting. One patient developed enophthalmos related to inferior rectus sacrifice and removal of orbital fat. Complications included development of nasal synechia and occlusion of the maxillary sinus ostium (n = 1). CONCLUSIONS: The biaxial double-barrel fibula flap technique achieves the goals of providing adequate facial support and an alveolar segment amenable to implant dentistry. It allows for intelligible speech, deglutition, orbital support, and separation of the oronasal, orbital, and sinus cavities. In addition, it minimizes the need for vein grafting.

Does Mandible-First Sequencing Increase Maxillary Surgical Accuracy in Bimaxillary Procedures?

PURPOSE: In bimaxillary procedures, it is important to know how the chosen sequence affects the surgical outcome. The purpose of this study was to explore whether the theoretical advantages of using the mandible-first procedure were supported by clinical data. MATERIALS AND METHODS: The authors performed a retrospective investigation on a cohort compiled from 3 published retrospective studies. The sample was composed of patients treated at the Radboud University Nijmegen Medical Centre (Nijmegen, the Netherlands) from 2010 to 2014 and the Odense University Hospital (Odense, Denmark) from 2011 to 2015. The inclusion criterion was bimaxillary surgery without maxillary segmentation. The exclusion criterion was lack of a virtual surgical plan. The primary outcome variable was surgical accuracy, defined as the mean difference between the obtained outcome and the virtual surgical plan. The primary predictor variable was the comparison between mandible-first and maxilla-first sequencing. Secondary predictors were inferior maxillary repositioning and counterclockwise (CCW) rotation. The confounding variable was the virtually planned reposition. Results were analyzed by mixed-model regression encompassing all variables, followed by a detailed analysis of positive results using 2-sample t tests. RESULTS: Overall, 145 patients were included for analysis (98 women; mean age, 28 years). Operating on the mandible first notably influenced maxillary positioning and placed the maxilla 1.5 mm posterior and with 1.4° of CCW rotation compared with virtual surgical planning. The interaction of surgical sequence with maxillary rotation showed similar surgical accuracy between maxilla-first surgery with clockwise rotation and mandible-first surgery with CCW rotation. Inferior maxillary repositioning resulted in the maxilla being placed 1.7 mm (maxilla-first sequence) and 2.0 mm (mandible-first sequence) posterior to the planned position. CONCLUSION: Surgical accuracy was considerably influenced by sequencing in bimaxillary procedures. It remains important to know how the chosen sequence affects the surgical outcome so that the virtual surgical plan can be adjusted accordingly.

Pregnancy in Diabetes: challenges and opportunities for improving pregnancy outcomes.

Our aim was to review the data from the National Pregnancy in Diabetes (NPID) audit, and to identify the challenges and opportunities for improving pregnancy outcomes in women with diabetes. We reviewed three years of NPID data and relevant diabetes and obstetric literature, and found that there has been little change in pregnancy preparation or outcomes over the past 3 years, with substantial clinic-to clinic variations in care. Women with Type 2 diabetes remain less likely to take 5 mg preconception folic acid (22.8% vs. 41.8%; P < 0.05), and more likely to take potentially harmful medications (statin and/or ACE inhibitor 13.0% vs. 1.8%; P < 0.05) than women with Type 1 diabetes. However, women with Type 1 diabetes are less likely to achieve the recommended glucose control target of HbA1c < 48 mmol/mol (6.5%) (14.9% vs. 38.1%; P < 0.05). The following opportunities for improvement were identified. First, the need to integrate reproductive health into the diabetes care plans of all women with diabetes aged 15-50 years. Second, to develop more innovative approaches to improve uptake of pre-pregnancy care in women with Type 2 diabetes in primary care settings. Third, to integrate insulin pump, continuous glucose monitoring and automated insulin delivery technologies into the pre-pregnancy and antenatal care of women with Type 1 diabetes. Fourth, to improve postnatal care with personalized approaches targeting women with previous pregnancy loss, congenital anomaly and perinatal mortality. A nationwide commitment to delivering integrated reproductive and diabetes healthcare interventions is needed to improve the health outcomes of women with diabetes.

Inhibition of apoptosis exacerbates fatigue-damage tendon injuries in an in vivo rat model.

Tendinopathy is a common and progressive musculoskeletal disease. Increased apoptosis is an end-stage tendinopathy manifestation, but its contribution to the pathology of the disease is unknown. A previously established in vivo model of fatigue damage accumulation shows that increased apoptosis is correlated with the severity of induced tendon damage, even in early onset of the disease, supporting its implication in the pathogenesis of the disease. Consequently, this study aimed to determine: (1) whether apoptosis could be inhibited after fatigue damage and (2) whether its inhibition could lead to remodeling of the extracellular matrix (ECM) and pericellular matrix (PCM), to ultimately improve the mechanical properties of fatigue-damaged tendons. The working hypothesis was that, despite the low vascular nature of the tendon, apoptosis would be inhibited, prompting increased production of matrix proteins and restoring tendon mechanical properties. Rats received 2 or 5 d of systemic pan-caspase inhibitor (Q-VD-OPh) or dimethyl sulfoxide (DMSO) carrier control injections starting immediately prior to fatigue loading and were sacrificed at days 7 and 14 post-fatigue-loading. Systemic pan-caspase inhibition for 2 d led to a surprising increase in apoptosis, but inhibition for 5 d increased the population of live cells that could repair the fatigue damage. Further analysis of the 5 d group showed that effective inhibition led to an increased population of cells producing ECM and PCM proteins, although typically in conjunction with oxidative stress markers. Ultimately, inhibition of apoptosis led to further deterioration in mechanical properties of fatigue-damaged tendons.