A Balancing Act: A Systematic Review and Metasynthesis of Family-Focused Practice in Adult Mental Health Services.

Parental mental illness is a major international public health concern given its implications for whole families, including children. Family-focused practice (FFP), an approach that emphasises a "whole-family" approach to care, provides an opportunity to mitigate the significant risks associated with parental mental health difficulties. The positive benefits associated with FFP have led to a shift in policy and practice towards prioritising FFP within adult mental health services. However, evidence suggests that FFP remains scarce and is not routine. Research has identified the important role of practitioners in facilitating FFP. The current review identified, synthesised and appraised the international qualitative literature examining adult mental health practitioners' implementation experiences of FFP. It aimed to provide an evidence-informed account of practitioner experiences of FFP delivery and to identify key recommendations to enhance future FFP outcomes in AMHS. Ovid Medline, PsycInfo, CINAHL plus, EMBASE and Web of Science Core Collection were searched systematically, in line with PRISMA guidance, up to January 2022. The Critical Appraisal Skills Programme (CASP) was used to undertake the quality appraisal prior to a thematic synthesis being conducted. The review was registered on PROSPERO. Nineteen papers, spanning 17 years of research with 469 practitioners, were included. Three main themes and 14 subthemes were developed, representing different aspects of practitioner experiences of FFP delivery. Practitioners' approach to FFP was variable and influenced by their beliefs about FFP, perceived roles and responsibilities, competence, service setting, and personal parenting status. Practitioners engaged in a balancing act to maintain a dual focus on their service-users and their children, to navigate powerful emotions, and consider multiple perspectives in a biomedical organisational structure that advocates individualised treatment. Although working together unified teams, a greater need for external interagency collaboration was identified. The use of strength-based approaches with clients and dedicated staff resources, within clear guidelines and frameworks, was reported to be necessary to maximise FFP delivery. This review proposes a complex FFP dynamic whereby practitioners engage in a constant balancing act between FFP stakeholders to achieve meaningful FFP outcomes for service-users and their families. Service recommendations are provided.

Maternal and fetal characteristics for predicting risk of Cesarean section following induction of labor: pooled analysis of PROBAAT trials.

OBJECTIVE: Induction of labor (IOL) is one of the most widely used obstetric interventions. However, one-fifth of IOLs result in Cesarean section (CS). We aimed to assess maternal and fetal characteristics that influence the likelihood of CS following IOL, according to the indication for CS. METHODS: This was a secondary analysis of pooled data from four randomized controlled trials, including women undergoing IOL at term who had a singleton pregnancy and an unfavorable cervix, intact membranes and the fetus in cephalic presentation. The main outcomes of this analysis were CS for failure to progress (FTP) and CS for suspected fetal compromise (SFC). Restricted cubic splines were used to determine whether continuous maternal and fetal characteristics had a non-linear relationship with outcome. Optimal cut-offs for those characteristics with a non-linear pattern were determined based on the maximum area under the receiver-operating-characteristics curve. Adjusted odds ratios (aOR) were computed, using multivariable logistic regression analysis, for the associations between optimally categorized characteristics and outcome. RESULTS: Of a total of 2990 women undergoing IOL, 313 (10.5%) had CS for FTP and 227 (7.6%) had CS for SFC. The risk of CS for FTP was increased in women aged 31-35 years compared with younger women (aOR, 1.51 (95% CI, 1.15-1.99)), in nulliparous compared with parous women (aOR, 8.07 (95% CI, 5.34-12.18)) and in Sub-Saharan African compared with Caucasian women (aOR, 2.09 (95% CI, 1.33-3.28)). Higher body mass index (BMI) increased incrementally the risk of CS for FTP (aOR, 1.06 (95% CI, 1.04-1.08)). High birth-weight percentile was also associated with an increased risk of CS due to FTP (aOR, 2.66 (95% CI, 1.74-4.07) for birth weight between the 80.0th and 89.9th percentiles and aOR, 4.08 (95% CI, 2.75-6.05) for birth weight ≥ 90th percentile, as compared with birth weight between the 20.0th and 49.9th percentiles). For CS due to SFC, higher maternal age (aOR, 1.09 (95% CI, 1.05-1.12)) and BMI (aOR, 1.05 (95% CI, 1.03-1.08)) were associated with an incremental increase in risk. The risk of CS for SFC was increased in nulliparous compared with parous women (aOR, 5.91 (95% CI, 3.76-9.28)) and in South Asian compared with Caucasian women (aOR, 2.50 (95% CI, 1.23-5.10)). Birth weight < 10.0th percentile increased significantly the risk of CS due to SFC (aOR, 1.93 (95% CI, 1.22-3.05)), as compared with birth weight between the 20.0th and 49.9th percentiles. Bishop score did not demonstrate a significant association with the risk of CS for FTP or for SFC. CONCLUSIONS: In women undergoing IOL, maternal age, BMI, parity, ethnicity and birth-weight percentile are predictors of CS due to FTP and of CS due to SFC, but the direction and magnitude of the associations differ according to the indication for CS. These characteristics should be considered in combination with the Bishop score to stratify the risk of CS for different indications in women undergoing IOL. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Menstrual fluid endometrial stem/progenitor cell and supernatant protein content: cyclical variation and indicative range.

STUDY QUESTION: Does natural variation exist in the endometrial stem/progenitor cell and protein composition of menstrual fluid across menstrual cycles in women? SUMMARY ANSWER: Limited variation exists in the percentage of some endometrial stem/progenitor cell types and abundance of selected proteins in menstrual fluid within and between a cohort of women. WHAT IS KNOWN ALREADY: Menstrual fluid is a readily available biofluid that can represent the endometrial environment, containing endometrial stem/progenitor cells and protein factors. It is unknown whether there is natural variation in the cellular and protein content across menstrual cycles of individual women, which has significant implications for the use of menstrual fluid in research and clinical applications. STUDY DESIGN, SIZE, DURATION: Menstrual fluid was collected from 11 non-pregnant females with regular menstrual cycles. Participants had not used hormonal medications in the previous 3 months. Participants collected menstrual fluid samples from up to five cycles using a silicone menstrual cup worn on Day 2 of menstrual bleeding. PARTICIPANTS/MATERIALS, SETTING, METHODS: Menstrual fluid samples were centrifuged to separate soluble proteins and cells. Cells were depleted of red blood cells and CD45+ leucocytes. Menstrual fluid-derived endometrial stem/progenitor cells were characterized using multicolour flow cytometry including markers for endometrial stem/progenitor cells N-cadherin (NCAD) and stage-specific embryonic antigen-1 (SSEA-1) (for endometrial epithelial progenitor cells; eEPC), and sushi domain containing-2 (SUSD2) (for endometrial mesenchymal stem cells; eMSC). The clonogenicity of menstrual fluid-derived endometrial cells was assessed using colony forming unit assays. Menstrual fluid supernatant was analyzed using a custom magnetic Luminex assay. MAIN RESULTS AND THE ROLE OF CHANCE: Endometrial stem/progenitor cells are shed in menstrual fluid and demonstrate clonogenic properties. The intraparticipant agreement for SUSD2+ menstrual fluid-derived eMSC (MF-eMSC), SSEA-1+ and NCAD+SSEA-1+ MF-eEPC, and stromal clonogenicity were moderate-good (intraclass correlation; ICC: 0.75, 0.56, 0.54 and 0.52, respectively), indicating limited variability across menstrual cycles. Endometrial inflammatory and repair proteins were detectable in menstrual fluid supernatant, with five of eight (63%) factors demonstrating moderate intraparticipant agreement (secretory leukocyte protein inhibitor (SLPI), lipocalin-2 (NGAL), lactoferrin, follistatin-like 1 (FSTL1), human epididymis protein-4 (HE4); ICC ranges: 0.57-0.69). Interparticipant variation was limited for healthy participants, with the exception of key outliers of which some had self-reported menstrual pathologies. LARGE SCALE DATA: N/A. There are no OMICS or other data sets relevant to this study. LIMITATIONS, REASONS FOR CAUTION: The main limitations to this research relate to the difficulty of obtaining menstrual fluid samples across multiple menstrual cycles in a consistent manner. Several participants could only donate across <3 cycles and the duration of wearing the menstrual cup varied between 4 and 6 h within and between women. Due to the limited sample size used in this study, wider studies involving multiple consecutive menstrual cycles and a larger cohort of women will be required to fully determine the normal range of endometrial stem/progenitor cell and supernatant protein content of menstrual fluid. Possibility for selection bias and true representation of the population of women should also be considered. WIDER IMPLICATIONS OF THE FINDINGS: Menstrual fluid is a reliable source of endometrial stem/progenitor cells and related endometrial proteins with diagnostic potential. The present study indicates that a single menstrual sample may be sufficient in characterizing a variety of cellular and protein parameters across women's menstrual cycles. The results also demonstrate the potential of menstrual fluid for identifying endometrial and menstrual abnormalities in both research and clinical settings as a non-invasive method for assessing endometrial health. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Australian National Health and Medical Research Council to C.E.G. (Senior Research Fellowship 1024298 and Investigator Fellowship 1173882) and to J.E. (project grant 1047756), the Monash IVF Research Foundation to C.E.G. and the Victorian Government's Operational Infrastructure Support Program. K.A.W., M.L.D.-T., S.G.S. and J.E. declare no conflicts of interest. C.E.G. reports grants from NHMRC, during the conduct of the study; grants from EndoFound USA, grants from Ferring Research Innovation, grants from United States Department of Defence, grants from Clue-Utopia Research Foundation, outside the submitted work. CEF reports grants from EndoFound USA, grants from Clue-Utopia Research Foundation, outside the submitted work.

Implementation and evaluation of a quality improvement initiative to reduce late gestation stillbirths in Australia: Safer Baby Bundle study protocol.

BACKGROUND: In 2015, the stillbirth rate after 28 weeks (late gestation) in Australia was 35% higher than countries with the lowest rates globally. Reductions in late gestation stillbirth rates have steadily improved in Australia. However, to amplify and sustain reductions, more needs to be done to reduce practice variation and address sub-optimal care. Implementing bundles for maternity care improvement in the UK have been associated with a 20% reduction in stillbirth rates. A similar approach is underway in Australia; the Safer Baby Bundle (SBB) with five elements: 1) supporting women to stop smoking in pregnancy, 2) improving detection and management of fetal growth restriction, 3) raising awareness and improving care for women with decreased fetal movements, 4) improving awareness of maternal safe going-to-sleep position in late pregnancy, 5) improving decision making about the timing of birth for women with risk factors for stillbirth. METHODS: This is a mixed-methods study of maternity services across three Australian states; Queensland, Victoria and New South Wales. The study includes evaluation of 'targeted' implementer sites (combined total approximately 113,000 births annually, 50% of births in these states) and monitoring of key outcomes state-wide across all maternity services. Progressive implementation over 2.5 years, managed by state Departments of Health, commenced from mid-2019. This study will determine the impact of implementing the SBB on maternity services and perinatal outcomes, specifically for reducing late gestation stillbirth. Comprehensive process, impact, and outcome evaluations will be conducted using routinely collected perinatal data, pre- and post- implementation surveys, clinical audits, focus group discussions and interviews. Evaluations explore the views and experiences of clinicians embedding the SBB into routine practice as well as women's experience with care and the acceptability of the initiative. DISCUSSION: This protocol describes the evaluation of the SBB initiative and will provide evidence for the value of a systematic, but pragmatic, approach to strategies to reduce the evidence-practice gaps across maternity services. We hypothesise successful implementation and uptake across three Australian states (amplified nationally) will be effective in reducing late gestation stillbirths to that of the best performing countries globally, equating to at least 150 lives saved annually. TRIAL REGISTRATION: The Safer Baby Bundle Study was retrospectively registered on the ACTRN12619001777189 database, date assigned 16/12/2019.

Survey of Australian maternity hospitals to inform development and implementation of a stillbirth prevention 'bundle of care'.

BACKGROUND: 'Bundles of care' are being implemented to improve key practice gaps in perinatal care. As part of our development of a stillbirth prevention bundle, we consulted with Australian maternity care providers. OBJECTIVE: To gain the insights of Australian maternity care providers to inform the development and implementation of a bundle of care for stillbirth prevention. METHODS: A 2018 on-line survey of hospitals providing maternity services included 55 questions incorporating multiple choice, Likert items and open text. A senior clinician at each site completed the survey. The survey asked questions about practices related to fetal growth restriction, decreased fetal movements, smoking cessation, intrapartum fetal monitoring, maternal sleep position and perinatal mortality audit. The objectives were to assess which elements of care were most valued; best practice frequency; and, barriers and enablers to implementation. RESULTS: 227 hospitals were invited with 83 (37%) responding. All proposed elements were perceived as important. Hospitals were least likely to follow best practice recommendations "all the time" for smoking cessation support (<50%), risk assessment for fetal growth restriction (<40%) and advice on sleep position (<20%). Time constraints, absence of clear guidelines and lack of continuity of carer were recognised as barriers to implementation across care practices. CONCLUSIONS: Areas for practice improvement were evident. All elements of care were valued, with increasing awareness of safe sleeping position perceived as less important. There is strong support from maternity care providers across Australia for a bundle of care to reduce stillbirth.

Description of a method for inducing fetal growth restriction in the spiny mouse.

Intrauterine or fetal growth restriction (IUGR) is a major complication of pregnancy and leads to significant perinatal morbidities and mortality. Typically, induction of IUGR in animals involves the complete occlusion or ablation of vessels to the uterus or placenta, acutely impairing blood flow and fetal growth, usually with high fetal loss. We aimed to produce a model of reduced fetal growth in the spiny mouse with minimal fetal loss. At 27 days gestational age (term is 38-39 days), a piece of silastic tubing was placed around the left uterine artery to prevent the further increase of uterine blood flow with advancing gestation to induce IUGR (occluded). Controls were generated from sham surgeries without placement of the tubing. Dams were humanely euthanized at 37 days gestational age and all fetuses and placentas were weighed and collected. Of the 17 dams that underwent surgery, 15 carried their pregnancies to 37 days gestational age and 95% of fetuses survived to this time. The difference in fetal body weight between occluded and control was ~21% for fetuses in the left uterus side: there were no differences for fetuses in the right uterus side. Offspring from the occluded group had significantly lower brain, liver, lung, kidney and carcass weights compared with shams. Preventing the gestation-related increase of uterine blood flow induced significant growth restriction in the fetal spiny mouse, with minimal fetal loss. This technique could be readily adapted for other small animal.

Comparison of preterm and term equivalent age MRI for the evaluation of preterm brain injury.

OBJECTIVE: To compare information obtained from preterm magnetic resonance imaging (MRI; 31-34 weeks) brain scan to that done at term equivalent age. STUDY DESIGN: Prospective observational study of premature infants with evidence or suspicion of parenchymal brain injury on cranial ultrasound. Brain injury on two scans scored using a scoring system and analyzed. RESULTS: Fourteen infants with a median (range) gestation at birth of 28 (25-29) weeks and birth weight of 1254 (680-1557) grams were studied. There was a strong correlation between the brain injury scores for the two scans (Spearman ρ=0.87, P=0.001) with excellent agreement between two radiologists (interclass correlation coefficient 0.9-0.94). There was also a high level of agreement between the preterm and term MRI two scores (Intraclass correlation coefficient, 0.79 (0.53-0.94)). CONCLUSIONS: Preterm MRI is a feasible option for the assessment of preterm brain injury and analysis of data obtained from scan at preterm age is comparable to that obtained at term equivalent age.

Integrated analysis of genetic variation and gene expression reveals novel variant for increased warfarin dose requirement in African Americans.

Essentials Genetic variants controlling gene regulation have not been explored in pharmacogenomics. We tested liver expression quantitative trait loci for association with warfarin dose response. A novel predictor for increased warfarin dose response in African Americans was identified. Precision medicine must take into account population-specific variation in gene regulation. SUMMARY: Background Warfarin is commonly used to control and prevent thromboembolic disorders. However, because of warfarin's complex dose-requirement relationship, safe and effective use is challenging. Pharmacogenomics-guided warfarin dosing algorithms that include the well-established VKORC1 and CYP2C9 polymorphisms explain only a small proportion of inter-individual variability in African Americans (AAs). Objectives We aimed to assess whether transcriptomic analyses could be used to identify regulatory variants associated with warfarin dose response in AAs. Patients/Methods We identified a total of 56 expression quantitative trait loci (eQTLs) for CYP2C9, VKORC1 and CALU derived from human livers and evaluated their association with warfarin dose response in two independent AA warfarin patient cohorts. Results We found that rs4889606, a strong cis-eQTL for VKORC1 (log10 Bayes Factor = 12.02), is significantly associated with increased warfarin daily dose requirement (ß = 1.1; 95% confidence interval [CI] 0.46 to 1.8) in the discovery cohort (n = 305) and in the replication cohort (ß = 1.04; 95% CI 0.33 -1.7; n = 141) after conditioning on relevant covariates and the VKORC1 -1639G>A (rs9923231) variant. Inclusion of rs4889606 genotypes, along with CYP2C9 alleles, rs9923231 genotypes and clinical variables, explained 31% of the inter-patient variability in warfarin dose requirement. We demonstrate different linkage disequilibrium patterns in the region encompassing rs4889606 and rs9923231 between AAs and European Americans, which may explain the increased dose requirement found in AAs. Conclusion Our approach of interrogating eQTLs identified in liver has revealed a novel predictor of warfarin dose response in AAs. Our work highlights the utility of leveraging information from regulatory variants mapped in the liver to uncover novel variants associated with drug response and the importance of population-specific research.

Post-term surveillance and birth outcomes in South Asian-born compared with Australian-born women.

OBJECTIVE: To determine if apparently healthy post-term South Asian-born (SA) women were more likely to have abnormal post-term fetal surveillance than Australian- and New Zealand-born (AUS/NZ) women, whether those abnormalities were associated with increased rates of obstetric intervention and adverse perinatal outcomes, and whether SA women and their babies were at higher risk of adverse outcomes in the post-term period irrespective of their post-term surveillance outcomes. STUDY DESIGN: Post-term surveillance and perinatal outcomes of 145 SA and 272 AUS/NZ nulliparous women with a singleton post-term pregnancy were compared in a retrospective multicentre cohort analysis. RESULTS: Post-term SA women were not significantly more likely to have a low amniotic fluid index (AFI) than AUS/NZ women. However, they were nearly four times more likely (odds ratio 3.75; 95% CI 1.49-9.44) to have an abnormal CTG (P=0.005). Irrespective of maternal region of birth having an abnormal cardiotocography (CTG) or AFI was not associated with adverse intrapartum or perinatal outcomes. However, post-term SA women were significantly more likely than AUS/NZ women to have intrapartum fetal compromise (P=0.03) and an intrapartum cesarean section (P=0.002). Babies of SA women were more also significantly likely to be admitted to the Special Care Nursery or Neonatal Intensive Care Unit (P=0.02). CONCLUSION: Post-term SA women experience higher rates of fetal compromise (antenatal and intrapartum) and obstetric intervention than AUS/NZ women. Irrespective of maternal region of birth an abnormal CTG or AFI was not predictive of adverse outcomes.

Maternal creatine in pregnancy: a retrospective cohort study.

OBJECTIVE: To estimate creatine concentrations in maternal plasma and urine, and establish relationships with maternal characteristics, diet and fetal growth. DESIGN: Retrospective cohort study. SETTING: Lyell McEwin Hospital, Adelaide, Australia. POPULATION: A biobank of plasma and urine samples collected at 13, 18, 30 and 36 weeks' gestation from 287 pregnant women from a prospective cohort of asthmatic and non-asthmatic women. METHODS: Creatine was measured by enzymatic analysis. Change in creatine over pregnancy was assessed using the Friedman test. Linear mixed models regression was used to determine associations between maternal factors and diet with creatine across pregnancy and between creatine with indices of fetal growth at birth. MAIN OUTCOME MEASURES: Maternal creatine concentrations, associations between maternal factors and creatine and between creatine and fetal growth parameters. RESULTS: Maternal smoking, body mass index, asthma and socio-economic status were positively and parity negatively associated with maternal plasma and/or urine creatine. Maternal urine creatine concentration was positively associated with birthweight centile and birth length. After adjustment, each µmol/l increase in maternal urinary creatine was associated with a 1.23 (95% CI 0.44-2.02) unit increase in birthweight centile and a 0.11-cm (95% CI 0.03-0.2) increase in birth length. CONCLUSIONS: Maternal factors and fetal growth measures are associated with maternal plasma and urine creatine concentrations. TWEETABLE ABSTRACT: Maternal creatine is altered by pregnancy; fetal growth measures are associated with maternal creatine concentrations.

Gastric rupture following nasopharyngeal catheter oxygen delivery-a report of two cases.

Iatrogenic gastric distension and subsequent rupture following nasal or nasopharyngeal catheter oxygen delivery is a rare but life-threatening condition that requires urgent laparotomy. We report two cases recently encountered at our institution. Both patients exhibited symptoms of abdominal pain and distension following oxygen delivery involving a nasopharyngeal catheter during procedural sedation. Oxygen flow rates were 4 l/minute in both cases. The diagnosis was made by urgent imaging. Both patients survived following laparotomy and repair of gastric rupture. Seventeen cases have been reported previously in the literature. We recommend avoidance of nasal or nasopharyngeal catheters and the use of alternative oxygen delivery methods such as nasal prongs and face masks.

The relationship between body composition and knee structure in patients with human immunodeficiency virus.

Obesity is a risk factor for osteoarthritis. Antiretroviral therapy (ART)-treated HIV-infected patients are frequently affected by overweight and obesity, and may be at increased risk of osteoarthritis. BMI however is a measure which does not discriminate adipose from non-adipose body mass, or fat distribution, which may have different effects. This study aimed to examine relationships between body composition and knee cartilage volume, as assessed by magnetic resonance imaging in HIV infection. 35 ART-treated HIV-infected men aged 51.7 years (mean) 7.9 (SD) and 18 healthy men aged 49.5 years (mean) 6.4 (SD) participated. Cartilage volume was measured on magnetic resonance imaging of the dominant knee using validated methods. Body composition was measured using dual x-ray absorptiometry. HIV-infected participants had less total body and gynoid fat (kg) (p = 0.04 and p = 0.007, respectively) and more percent android fat mass and percent trunk fat mass (p = 0.001 and p < 0.001, respectively) than controls. In HIV-infected participants there was an inverse association between total body fat mass and average tibial cartilage volume (R = -8.01, 95% CI -15.66, -0.36). Also, in HIV-infected participants there was an inverse association between android fat mass and average cartilage volume (R = -90.91, 95% CI -158.66, -23.16). This preliminary study found that both total body and android fat mass were inversely related to average knee cartilage volume in ambulant, ART-treated HIV-infected adults. These findings are features of early knee osteoarthritis and this may be of future significance in HIV.

Ethnicity-specific pharmacogenetics: the case of warfarin in African Americans.

Using a derivation cohort (N=349), we developed the first warfarin dosing algorithm that includes recently discovered polymorphisms in VKORC1 and CYP2C9 associated with warfarin dose requirement in African Americans (AAs). We tested our novel algorithm in an independent cohort of 129 AAs and compared the dose prediction to the International Warfarin Pharmacogenetics Consortium (IWPC) dosing algorithms. Our algorithm explains more of the phenotypic variation (R(2)=0.27) than the IWPC pharmacogenomics (R(2)=0.15) or clinical (R(2)=0.16) algorithms. Among high-dose patients, our algorithm predicted a higher proportion of patients within 20% of stable warfarin dose (45% vs 29% and 2% in the IWPC pharmacogenomics and clinical algorithms, respectively). In contrast to our novel algorithm, a significant inverse correlation between predicted dose and percent West African ancestry was observed for the IWPC pharmacogenomics algorithm among patients requiring ⩾60 mg per week (ß=-2.04, P=0.02).

Aromatase inhibitors associated with knee subchondral bone expansion without cartilage loss.

BACKGROUND: The profound estrogen depletion caused by aromatase inhibitors (AIs) is associated with musculoskeletal symptoms, but the underlying pathophysiology remains unclear. OBJECTIVE: To assess the effects of AI therapy on structural changes in knee cartilage and subchondral bone over 2 years in postmenopausal women. Setting and participants Thirty women with breast cancer, mean age 58.5 (standard deviation ± 5.6) years and 62 healthy controls, mean age 56.5 (standard deviation ± 4.6) years. MAIN OUTCOME MEASURES: Annualized changes in tibial cartilage volume and subchondral bone area, and worsening of tibiofemoral cartilage defects from paired knee magnetic resonance imaging 2 years apart were compared between the two groups. RESULTS: The AI-treated women had significantly greater expansion of the tibial plateau than the control group. The mean annualized differences, after adjusting for age, body mass index and baseline bone area, were 22.1 mm(2) (95% confidence interval (CI) 7.6-36.6, p = 0.003) for the medial tibial plateau and 19.1 mm(2) (95% CI 9.6-28.5, p < 0.001) for the lateral tibial plateau. The annual change in tibial cartilage volume and the worsening of cartilage defects did not differ between women taking AI therapy and controls. CONCLUSIONS: AI therapy is associated with knee subchondral bone expansion knee with no effect on knee cartilage in postmenopausal women without pre-existing joint symptoms. This suggests the effect of severe estrogen depletion on knee is on bone, with the tibial bone expansion most likely a response to mechanical load in the setting of bone loss. Whether this then results in an increased risk of knee osteoarthritis will need to be determined.

Bone marrow lesions predict increase in knee cartilage defects and loss of cartilage volume in middle-aged women without knee pain over 2 years.

OBJECTIVE: Bone marrow lesions (BML) are important in established knee osteoarthritis, predicting pain and progression of disease. Whether BML are also associated with longitudinal changes in knee structure in an asymptomatic population is unknown. METHODS: 148 healthy pain-free women in middle age with no history of knee injury or clinical knee osteoarthritis who had a magnetic resonance imaging (MRI) scan performed on their dominant knee at baseline, had another MRI 2 years later to assess whether having a BML present at baseline affected change in tibiofemoral cartilage defects and tibial cartilage volume. RESULTS: BML were present in 14.9% of women at baseline. The risk of progression of total tibiofemoral cartilage defects was significantly higher when a very large BML was present (odds ratio 5.55, 95% CI 1.04 to 29.6) compared with when no BML was present, after adjusting for potential confounders. In the lateral compartment, the rate of cartilage volume loss was significantly greater when a BML was present after adjusting for confounders (regression coefficient 39.2 mm(3), 95% CI 11.1 to 67.2, p = 0.007). CONCLUSIONS: In healthy women without pain at baseline, large BML were associated with both progression of cartilage defects in the whole tibiofemoral joint and more rapid lateral tibial cartilage loss. These data suggest that the relationship between BML and knee cartilage in healthy women is similar to that described in established osteoarthritis. It is possible that BML may predict an increased risk of knee osteoarthritis and facilitate the identification of novel interventions to prevent disease.

Change in knee angle influences the rate of medial tibial cartilage volume loss in knee osteoarthritis.

OBJECTIVES: Identifying factors that influence the rate of cartilage loss at the knee may help to prevent or delay the progression of knee osteoarthritis (OA). Changes in knee alignment alter knee joint load and may affect the rate of cartilage loss. The aim of this study was to determine whether change in knee alignment between baseline and 2 years is associated with a change in knee cartilage volume in knee OA in the subsequent 2.5 years. METHODS: Seventy-eight adults with symptomatic knee OA were recruited using a combined strategy. Radiographs were performed at time 0 and 2 years to determine change in knee alignment, measured on a continuous scale. Magnetic Resonance Imaging was performed at 2 and 4.5 years to determine annual percentage change in medial and lateral tibial cartilage volumes. RESULTS: In multivariate analyses, for every 1 degrees change toward genu valgum, there is an associated 0.44% reduction in the rate of annual medial tibial cartilage volume loss (95% CI: -0.85%, -0.04%, P=0.03). Similarly, because our measures of change in alignment and cartilage volume were continuous, these results also implied that for every 1 degrees change toward genu varum, there was an associated 0.44% increase in the rate of annual medial tibial cartilage volume loss. Change in knee angle did not significantly affect the rate of loss of the lateral tibial cartilage volume (P=0.95). CONCLUSION: Our results have demonstrated that progressive change toward genu valgum reduced the annual rate of medial tibial cartilage volume loss in people with knee OA, without expediting the rate of lateral tibial cartilage volume loss. These findings suggest that methods to reduce varus alignment may delay the progression of medial tibiofemoral OA and warrant further investigation.

The natural history of bone marrow lesions in community-based adults with no clinical knee osteoarthritis.

OBJECTIVE: Although bone marrow lesions (BML) have been implicated in the pathogenesis of osteoarthritis, their natural history in a healthy population is unknown. This study in a healthy, pain-free population aimed to examine the natural history of BML; factors associated with incidence and progression of BML over 2 years and whether incident BML are associated with the development of pain. METHODS: 271 subjects with no clinical knee osteoarthritis, being pain free at baseline, underwent magnetic resonance imaging of their dominant knee at baseline and 2 years later. The presence of BML was assessed. RESULTS: In knees initially free of BML, incident BML developed in 14% of people over the study period. Increased body mass index (BMI; odds ratio (OR) 1.15, 95% CI 1.06 to 1.2, p = 0.001) was associated with incident BML. Those who developed a BML were more likely to develop knee pain compared with those in whom no BML developed (OR 4.2, 95% CI 1.2 to 15.1, p = 0.03). Among those in whom BML were present at baseline, 46% completely resolved. There was no association between age, gender and BMI and persistence of BML over 2 years. CONCLUSION: In this healthy population, the rate of incident BML is lower than previously described in a population with osteoarthritis. Incident BML are associated with increased BMI and the development of pain. Approximately half the BML present at baseline resolved. These data suggest that in pain-free people with no clinical knee osteoarthritis, BML are reversible and may provide a target for interventions aimed at the prevention of knee osteoarthritis.

Imaging of knee osteoarthritis.

New imaging modalities are broadening the possibilities in osteoarthritis (OA) research, and are offering new insights to help better understand the pathogenesis of this disease. Although knee radiographs are widely employed in epidemiological and clinical studies to assess structural pathology, joint radiographs provide limited outcome measures in knee OA, and other more valid, reliable and sensitive imaging modalities are now available. In particular, magnetic resonance imaging can directly visualize articular cartilage and other joint structures, such as bone and soft tissue, that are now recognized as part of the disease process. This chapter will examine imaging modalities in the assessment of knee OA, and the impact of these on our understanding of the pathogenesis of this disease.

Bone marrow lesions predict progression of cartilage defects and loss of cartilage volume in healthy middle-aged adults without knee pain over 2 yrs.

OBJECTIVE: In knee OA, the presence of bone marrow lesions (BMLs) predicts pain and progression of disease. Their occurrence has been described in healthy, pain-free subjects, but whether their presence affects change in cartilage is unknown. METHODS: Two hundred and seventy-one healthy community-dwelling adults with no history of knee injury, knee pain or clinical knee OA had an MRI performed on their dominant knee at baseline and 2 yrs later to assess the relationship between the presence of BMLs at baseline and change in tibiofemoral cartilage defects and tibial cartilage volume over 2 yrs. RESULTS: BMLs were present in 37 (14%) subjects. Cartilage defects were more likely to progress rather than remain stable or regress in subjects with BMLs compared with those without BMLs (P = 0.04). The odds of cartilage defects progressing in the tibiofemoral compartment of the knee where BMLs were present compared with where BMLs were absent was 2.6 (95% CI 1.2, 5.3; P = 0.01). Where 'very large' BMLs were present, there was a trend for increased annual tibial cartilage volume loss (46.4 mm(3)/yr; P = 0.07). CONCLUSIONS: These data suggest that BMLs are associated with change in knee cartilage over 2 yrs in asymptomatic subjects. Increased progression of cartilage defects is seen with increasing size of BMLs. It will be important to determine in future studies whether BMLs directly cause change in cartilage over 2 yrs, or act as a marker of another factor that facilitates these changes.