De Novo Metastatic Prostate Cancer Presenting With Atypical Lower-Limb Skeletal Metastases Detected on 68Ga-PSMA PET/CT.

ABSTRACT: Metastatic prostate cancer to the appendicular skeleton is rare. We present an 86-year-old man with undiagnosed prostate cancer presenting with unilateral foot pain. CT and MRI demonstrated a sclerotic midfoot suggestive of an infiltrative process. In view of an elevated PSA, metastatic disease was suspected, and bone scan confirmed osteoblastically active pelvic and lower-limb skeletal lesions. Subsequent prostate biopsy confirmed prostate adenocarcinoma. Staging 68Ga-PSMA PET/CT demonstrated PSMA-avid intraprostatic malignancy with pelvic and right lower-limb skeletal metastases. This is an unusual case of de novo 68Ga-PSMA-avid metastatic prostate cancer with atypical lower-limb skeletal metastases presenting with foot pain.

CURATE.AI-assisted dose titration for anti-hypertensive personalized therapy: study protocol for a multi-arm, randomized, pilot feasibility trial using CURATE.AI (CURATE.AI ADAPT trial).

Aims: Artificial intelligence-driven small data platforms such as CURATE.AI hold potential for personalized hypertension care by assisting physicians in identifying personalized anti-hypertensive doses for titration. This trial aims to assess the feasibility of a larger randomized controlled trial (RCT), evaluating the efficacy of CURATE.AI-assisted dose titration intervention. We will also collect preliminary efficacy and safety data and explore stakeholder feedback in the early design process. Methods and results: In this open-label, randomized, pilot feasibility trial, we aim to recruit 45 participants with primary hypertension. Participants will be randomized in 1:1:1 ratio into control (no intervention), home blood pressure monitoring (active control; HBPM), or CURATE.AI arms (intervention; HBPM and CURATE.AI-assisted dose titration). The home treatments include 1 month of two-drug anti-hypertensive regimens. Primary endpoints assess the logistical (e.g. dose adherence) and scientific (e.g. percentage of participants for which CURATE.AI profiles can be generated) feasibility, and define the progression criteria for the RCT in a 'traffic light system'. Secondary endpoints assess preliminary efficacy [e.g. mean change in office blood pressures (BPs)] and safety (e.g. hospitalization events) associated with each treatment protocol. Participants with both baseline and post-treatment BP measurements will form the intent-to-treat analysis. Following their involvement with the CURATE.AI intervention, feedback from CURATE.AI participants and healthcare providers will be collected via exit survey and interviews. Conclusion: Findings from this study will inform about potential refinements of the current treatment protocols before proceeding with a larger RCT, or potential expansion to collect additional information. Positive results may suggest the potential efficacy of CURATE.AI to improve BP control. Trial registration number: NCT05376683.

Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization.

The human gut microbiota can restrict the growth of pathogens to prevent them from colonizing the intestine ('colonization resistance'). However, antibiotic treatment can kill members of the gut microbiota ('gut commensals') and reduce competition for nutrients, making these nutrients available to support the growth of pathogens. This disturbance can lead to the growth and expansion of pathogens within the intestine (including antibiotic-resistant pathogens), where these pathogens can exploit the absence of competitors and the nutrient-enriched gut environment. In this review, we discuss nutrient competition between the gut microbiota and pathogens. We also provide an overview of how nutrient competition can be harnessed to support the design of next-generation microbiome therapeutics to restrict the growth of pathogens and prevent the development of invasive infections.

Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites.

The intestine is the primary colonisation site for carbapenem-resistant Enterobacteriaceae (CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Broad-spectrum antibiotics disrupt colonisation resistance mediated by the gut microbiota, promoting the expansion of CRE within the intestine. Here, we show that antibiotic-induced reduction of gut microbial populations leads to an enrichment of nutrients and depletion of inhibitory metabolites, which enhances CRE growth. Antibiotics decrease the abundance of gut commensals (including Bifidobacteriaceae and Bacteroidales) in ex vivo cultures of human faecal microbiota; this is accompanied by depletion of microbial metabolites and enrichment of nutrients. We measure the nutrient utilisation abilities, nutrient preferences, and metabolite inhibition susceptibilities of several CRE strains. We find that CRE can use the nutrients (enriched after antibiotic treatment) as carbon and nitrogen sources for growth. These nutrients also increase in faeces from antibiotic-treated mice and decrease following intestinal colonisation with carbapenem-resistant Escherichia coli. Furthermore, certain microbial metabolites (depleted upon antibiotic treatment) inhibit CRE growth. Our results show that killing gut commensals with antibiotics facilitates CRE colonisation by enriching nutrients and depleting inhibitory microbial metabolites.

Use of multiple epinephrine doses in anaphylaxis: A systematic review and meta-analysis.

BACKGROUND: Regulatory bodies recommend that all patients at risk of anaphylaxis be prescribed 2 epinephrine autoinjectors, which they should carry at all times. This is in contrast to some guidelines. The proportion of anaphylaxis reactions that are treated with multiple doses of epinephrine has not been systematically evaluated. OBJECTIVE: Our aim was to undertake a systematic review and meta-analysis of published studies reporting epinephrine treatment for anaphylaxis in which data relating to the number of doses administered were available. METHODS: We searched the Medline, Embase, and Cochrane databases for relevant studies reporting at least 10 anaphylaxis events (due to food or venom) from 1946 until January 2020. Data were extracted in duplicate for the meta-analysis, and the risk of bias was assessed. The study was registered under the PROSPERO identifier CRD42017069109. RESULTS: A total of 86 studies (36,557 anaphylaxis events) met the inclusion criteria (20 of the studies [23%] were prospective studies; 64 [74%] reported reactions in the community, and 22 [26%] included food challenge data). Risk of bias was assessed as low in 50 studies. Overall, 7.7% of anaphylaxis events from any cause (95% CI = 6.4-9.1) were treated with multiple doses of epinephrine. When only epinephrine-treated reactions for which subsequent doses were administered by a health care professional were considered, 11.1% of food-induced reactions (95% CI = 9.4-13.2) and 17.1% of venom-induced reactions (95% CI = 11.3-25.0) were treated with more than 1 epinephrine dose. Heterogeneity was moderate to high in the meta-analyses, but at sensitivity analysis this estimate was not affected by study design or anaphylaxis definition. CONCLUSION: Around 1 in 10 anaphylaxis reactions are treated with more than 1 dose of epinephrine.

Identifying Patients With Cirrhosis Who Might Avoid Screening Endoscopy Based on Serum Albumin and Bilirubin and Platelet Counts.

The presence of gastroesophageal varices is a major complication of portal hypertension associated with significant morbidity and mortality.1 The Baveno VI criteria state that patients with liver stiffness measurement (LSM) <20 kPa by transient elastography (TE) and platelet count >150,000/µL can avoid screening endoscopy for high-risk varix (HRV).2 However, because TE is not widely available, the Baveno VI criteria could not be applied in many clinical settings. As such, we aim to determine a concise clinical criterion as an alternative noninvasive tool to predict absence of HRV among patients with compensated cirrhosis to avoid screening esophagogastroduodenoscopy (EGD).

Clinical utilization of magnetic resonance enterography in small bowel Crohn's disease management: a retrospective tertiary centre experience.

BACKGROUND: Magnetic resonance enterography (MRE) is the mainstay imaging modality in the evaluation of small bowel Crohn's disease (CD) activity and its associated complications. Few studies have assessed the indications for ordering it and its association with management changes. The objective was to identify the current clinical utilization of MRE and associated management changes in patients with established small bowel CD. METHODS: A retrospective audit was conducted on all patients with established CD who underwent MRE at a tertiary centre from November 2014 to December 2017. Clinical indications, radiological findings and management changes were obtained from patient records. RESULTS: A total of 220 patients underwent a total of 287 MRE examinations. The most common indications for ordering MREs were based on patient symptoms (n = 204, 71.1%) and routine disease surveillance (n = 57, 19.9%). The most common radiological findings were inflammation (n = 156, 54.4%) and strictures (n = 98, 34.1%). Management changes post MRE occurred in 152 of 287 (53%) cases. Of the 152 patients, 87 (57.2%) had changes in medical management, 40 (26.3%) had surgical or endoscopic intervention and 25 (16.4%) had both medical and surgical management changes. Management changes following MRE in patients with new or concerning symptoms were significantly higher than in surveillance patients (OR 4.1, P = 0.000003). CONCLUSION: This study provides a foundation for understanding the current utilization of MRE in small bowel CD at a tertiary centre. However, its role in altering management particularly within surveillance patients is yet to be defined. Future prospective trials are required to better delineate its role and develop an algorithm for small bowel CD management.

Conflicting perceptions between health care professionals and patients on the psychological morbidity following miscarriage.

BACKGROUND: Miscarriage is common and may result in significant psychological morbidity for women. Recent research has revealed that health care professionals often tend to neglect this factor. This negligence may lead to delayed diagnosis and appropriate care. AIMS: To assess health care professionals' and patients' attitudes towards the psychological impact of miscarriage. METHODS: A prospective, cross-sectional survey of nearly 3000 subjects was conducted. Of these, 1269 were health care professionals and 1519 were pregnant women or their spouses. Their perceptions of the psychological impact of miscarriage, in comparison with postnatal depression were studied. RESULTS Health care professionals were less aware of the psychological impact of miscarriage compared with postnatal depression (91.9 vs 98.4%, P = 0.02). Furthermore, they believed that the psychological impact of miscarriage was less than that of postnatal depression (79.9 vs 88.9%, P < 0.001). However, more patients believed that psychological impact after miscarriage can seriously affect women (59.0 vs for health care professionals 38.3%, P < 0.001). A higher proportion of patients compared with health care professionals (85.2 vs 74.3%, P < 0.001) believed that routine psychological support should be provided after miscarriage, but few agreed that primary health professionals were the most suitable people to provide this care although most health care professionals thought this to be appropriate (9.1 vs 59.7%, P < 0.001). CONCLUSION: Health care professionals should be more aware of the psychological morbidity associated with miscarriage and also be sensitive to a currently unmet need for psychological care.

Detecting postnatal depression in Chinese men: a comparison of three instruments.

Postnatal depression affects both men and women. The detection of postnatal depression is important, yet there are few validated screening tools on Chinese men. The goals of the present study were to compare the psychometric properties of the Edinburgh Postnatal Depression Scale (EPDS), the Beck Depression Inventory (BDI), and the Patient Health Questionnaire - Depression Module (PHQ-9) in screening for postnatal depression among Chinese fathers in Hong Kong. The prevalence of depression at 8 weeks postpartum was also estimated. A prospective cohort of 551 men completed the EPDS, BDI, and PHQ-9 at 8 weeks postpartum. Clinical diagnosis of depression was established with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), non-patient version (SCID-NP). The criterion validity of the instruments was evaluated against this clinical diagnosis. The EPDS was significantly more accurate than the BDI and PHQ-9 in detecting postnatal depression among Chinese men. With a cut-off score of 10 or more, the EPDS has a sensitivity of 91%, specificity of 97%, positive predictive value of 57%, and negative predictive value of 99%. Approximately 3.1% men met the DSM-IV criteria for depression at 8 weeks postpartum. The prevalence rate of postnatal depression in Chinese men is comparable to their Western counterparts. The Chinese EPDS is a valid instrument for detecting postnatal depression in men. It could be applied as a supplementary assessment tool in Chinese fathers who may be reluctant to disclose their depressive symptoms in face-to-face interviews.

A 1-year longitudinal study of psychological morbidity after miscarriage.

OBJECTIVE: To examine the 1-year longitudinal course of psychological outcomes after miscarriage. DESIGN: Longitudinal observational study. SETTING: University-affiliated teaching hospital. PATIENT(S): 280 miscarrying women and 150 nonpregnant women. INTERVENTION(S): Psychological outcomes were assessed using the 12-item General Health Questionnaire (GHQ-12) and Beck Depression Inventory (BDI) immediately, 3 months, 6 months, and 12 months after miscarriage. MAIN OUTCOME MEASURE(S): Scores on GHQ-12 and BDI. RESULT(S): Half (55%) of the miscarrying women scored high (>or=4) on the GHQ-12 immediately, 25% at 3 months; 17.8% at 6 months, and 10.8% at 1 year after miscarriage; 26.8% of the patients scored high on the BDI (>or=12) immediately, 18.4% at 3 months, 16.4% at 6 months, and 9.3% at 1 year after miscarriage. Patients who were initially more distressed continued to score higher on both the GHQ-12 and the BDI along the 1-year course when compared with those who were initially less distressed. When compared with the nonpregnant controls, the miscarrying women scored statistically significantly higher on the GHQ-12 and BDI; the differences became not statistically significant only 1 year after miscarriage. CONCLUSION(S): A statistically significant proportion of patients reported psychological morbidity shortly after miscarriage, but their level of distress reduced over time until they were comparable with the controls 1 year later. Patients who were initially more distressed continued to be throughout the 1-year course.

Antenatal taboos among Chinese women in Hong Kong.

OBJECTIVE: to identify the antenatal taboos commonly practised by pregnant Hong Kong Chinese women; to explore the health beliefs behind these taboos; and to examine how pregnant women perceived and reacted to the cultural tradition. DESIGN: general ethnography and in-depth interviews, followed by a quantitative self-reported survey. SETTING: Antenatal clinic of a university-affiliated hospital in Hong Kong. PARTICIPANTS: consecutive samples of 60 women for in-depth interviews, and 832 women for the survey. MEASUREMENTS: an inventory on the adherence and attitude towards antenatal taboos, and the Beck Depression Inventory that measures severity of depression. FINDINGS: antenatal taboos were still commonly observed by contemporary Chinese women. Miscarriage, fetus malformation and fetal ill-health were the key cultural fears that drove contemporary Chinese women to observe the traditional taboos. About one-quarter and one-tenth of the women, respectively, felt unhappy and disputed with their families about the taboos. These women had significantly higher levels of depression in late pregnancy and during childbirth. IMPLICATIONS FOR PRACTICE: health-care practitioners should be aware of the benefits and risks of traditional antenatal taboos on maternal health. Although some taboos can be socio-morally protective, the tension created by the observation of cultural tradition in modernity may impair maternal psychological well-being. Health-care providers in Western countries should be vigilant of the complex cultural tension faced by migrant Chinese mothers.

Fetal methylmercury exposure as measured by cord blood mercury concentrations in a mother-infant cohort in Hong Kong.

This study was designed to examine newborn infants in Hong Kong prenatally exposed to levels of methylmercury considered to increase risk of neurotoxic effects and to examine subject characteristics that modify the degree of prenatal mercury exposure. Mercury concentrations in 1057 sets of maternal and cord blood samples and 96 randomly selected maternal hair samples were measured. Subject characteristics were measured or collected by questionnaire. Of the 1057 cord blood samples collected only 21.6% had mercury concentrations less than 29 nmol/L (5.8 micro g/L). Median maternal hair mercury concentration was 1.7 ppm. The geometric mean cord to maternal blood mercury ratio was 1.79 to 1. Increasing maternal fish consumption and maternal age were found to be associated with increased cord blood mercury concentrations. Marine fish consumption increased cord blood mercury concentrations more than freshwater fish (5.09%/kg vs 2.86%/kg). Female babies, maternal alcohol consumption and increasing maternal height were associated with decreased cord blood mercury concentrations. Pregnant women in Hong Kong consume large amounts of fish and as a result, most of their offspring have been prenatally exposed to moderately high levels of mercury. In this population, pregnant women should choose freshwater over marine fish and limit fish consumption.

Psychological responses of pregnant women to an infectious outbreak: a case-control study of the 2003 SARS outbreak in Hong Kong.

OBJECTIVE: The aim of the present study was to examine the behavioral and psychological responses of pregnant women during the 2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong. METHODS: Ethnographic interviews were first conducted to identify the common psychological and behavioral responses to the outbreak. This was followed by a case-control study of 235 consecutive pregnant women recruited during the SARS epidemic, and a historical cohort of 939 pregnant women recruited a year before the outbreak. Both cohorts completed standardized rating scales on depression, anxiety, and social support. RESULTS: Women in the SARS cohort adopted behavioral strategies to mitigate their risk of contracting infection. However, pregnant women tended to overestimate the risk of contracting SARS and nearly a third of the women were homebound. The anxiety level of the SARS cohort was slightly higher than that of the pre-SARS control. No statistical difference was found between the depression levels of the two cohorts. CONCLUSION: The improved social support experienced by pregnant women during SARS might have buffered the stress associated with an outbreak. However, clinicians should monitor for overestimation of infectious risk among pregnant women.

A prevalence study of antenatal depression among Chinese women.

BACKGROUND: There has thus far been no empirical research on the occurrence of antenatal psychiatric morbidity in Chinese population. Epidemiological studies in western societies generally show that depressive episodes occur in 10-20% of pregnant women. Longitudinal studies have demonstrated that antenatal depression is one of the most powerful predictors of postnatal depression. There is also a growing literature that shows that antenatal psychological distress can adversely affect maternal and foetal well being. METHODS: At 38 weeks of pregnancy, 238 consecutive women were invited to return for psychiatric assessment. The participants were interviewed using the non-patient version of the Structured Clinical Interview for DSM-IV (SCID-NP). RESULTS: Seventy women (29%) declined to participate, and another 11 (5%) defaulted the SCID interview. Among the 157 women interviewed, the 1-month prevalence of antenatal depression was 4.4%. The 1-month prevalence of all psychiatric diagnoses was 6.4%. The prevalence of antenatal depression and all psychiatric diagnoses for the entire pregnancy was 6.4% and 8.3%, respectively. LIMITATIONS: About a third of eligible subjects did not participate in the study. CONCLUSIONS: A significant proportion of Chinese women suffer from psychiatric morbidity during pregnancy. Depressive disorders are by far the commonest morbidity in the study population. Given the scope of the morbidity and the potential impact on obstetric and neonatal outcomes, early screening and treatment are warranted.

Ethnoepidemiology of postnatal depression. Prospective multivariate study of sociocultural risk factors in a Chinese population in Hong Kong.

BACKGROUND: Although there have been many studies of the biological and psychosocial causations of postnatal depression, studies of sociocultural risk factors are rare. AIMS: To investigate the sociocultural risk factors of postnatal depression using ethnographically informed epidemiological methods. METHOD: A total of 959 women were assessed at their first ante-partum visit (baseline), in the third trimester, immediately after delivery, and 3 months postpartum. Six domains of risk factors were examined. The dependent variable was postnatal depression (as defined by the Edinburgh Postnatal Depression Scale) at 3 months post-partum. RESULTS: Conflict with mother-in-law, marital dissatisfaction, past depression and antenatal depression independently predicted the occurrence of postnatal depression. The cultural practice of peiyue - a Chinese post-partum custom of mandated family support - was associated with better social support and a slightly lower risk of postnatal depression. CONCLUSIONS: Sociocultural aspects of the immediate puerperium shape maternal emotional well-being. In-law conflict is an important source of household distress in many Asian societies. The findings have implications for clinical practice and future studies.