Exploring potential anti-inflammatory effects of medicinal cannabis.

PURPOSE: Inflammation is thought to play a key role in malignant disease and may play a significant part in the expression of cancer-related symptoms. Cannabidiol (CBD) is a bioactive compound in cannabis and is reported to have significant anti-inflammatory properties. METHOD: Serial C-reactive protein (CRP) levels were measured in all participants recruited to a randomised controlled trial of CBD versus placebo in patients with symptoms related to advanced cancer. A panel of inflammatory cytokines was measured over time in a subset of these patients. RESULTS: There was no difference between the two arms in the trajectory of CRP or cytokine levels from baseline to day 28. CONCLUSION: We were unable to demonstrate an anti-inflammatory effect of CBD in cancer patients. TRIAL REGISTRATION: ANZCTR 26180001220257, registered 20/07/2018.

The risk of recurrent small-for-gestational-age infants at term is dependent on the number of previously affected births.

BACKGROUND: Small-for-gestational-age infants are at a substantially increased risk of perinatal complications, but the risk of recurrent small-for-gestational-age is not well known, particularly because there are many demographic and obstetrical factors that interact and modify this risk. We investigated the relationship between previous small-for-gestational-age births and the risk of recurrence at term in a large Australian cohort. OBJECTIVE: We aimed to identify key demographic and obstetrical variables that influence the risk of recurrence of a small-for-gestational-age infant at term. The primary outcome measure was the odds of recurrence of small-for-gestational-age in subsequent pregnancies up to a maximum of 4 consecutive term births. STUDY DESIGN: This was a retrospective analysis of women who had more than 1 consecutive nonanomalous, singleton, term live births between July 1997 and September 2018 at the Mater Mother's Hospital in Brisbane, Australia. Women with multiple pregnancy, preterm birth, or major congenital malformations were excluded. Small-for-gestational-age was defined as birthweight at the <10th centile. We calculated the odds of recurrence depending on the number of previous small-for-gestational-age infants and if only the preceding infant was small-for-gestational-age. The study population was dichotomized into small-for-gestational-age and non-small-for-gestational-age for each consecutive pregnancy. Univariate analyses compared baseline demographic and obstetrical characteristics followed by logistic regression modeling to determine the odds of recurrence in the second, third, and fourth pregnancies. RESULTS: The final study comprised 24,819 women. The proportion of women who had a small-for-gestational-age infant in their first pregnancy was 9.4%, whereas the proportion of women who had a small-for-gestational-age infant in their second, third, and fourth pregnancies after the birth of a previous small-for-gestational-age infant were 20.5% (479 of 2338), 24.6% (63 of 256), and 30.4% (14 of 46), respectively. Regardless of parity, the odds of recurrence increased if the preceding infant was small-for-gestational-age. The odds of recurrence increased markedly if there was more than 1 previous small-for-gestational-age infant. In women with 3 previous small-for-gestational-age infants, the adjusted odds of another small-for-gestational-age infant were 66.00 (95% confidence interval, 11.35-383.76). Maternal age, body mass index, ethnicity, and smoking were significant risk factors for recurrent small-for-gestational-age. However, maternal diabetes mellitus or hypertension, either in a previous or current pregnancy, did not influence the risk of recurrence. CONCLUSION: The risk of recurrence in a subsequent pregnancy increased if there was a previous small-for-gestational-age birth. Women with consecutive small-for-gestational-age infants were at the highest risk of recurrence. Our results highlight that women with a previous small-for-gestational-age infant are at a substantial risk of another small infant and need to be counseled and monitored appropriately.

Oral medicinal cannabinoids to relieve symptom burden in the palliative care of patients with advanced cancer: a double-blind, placebo controlled, randomised clinical trial of efficacy and safety of cannabidiol (CBD).

BACKGROUND: Despite improvements in medical care, patients with advanced cancer still experience substantial symptom distress. There is increasing interest in the use of medicinal cannabinoids, but there is little high quality evidence to guide clinicians. This study aims to define the role of cannabidiol (CBD) in the management of symptom burden in patients with advanced cancer undergoing standard palliative care. METHODS AND DESIGN: This study is a multicentre, randomised, placebo controlled, two arm, parallel trial of escalating doses of oral CBD. It will compare efficacy and safety outcomes of a titrated dose of CBD (100 mg/mL formulation, dose range 50 mg to 600 mg per day) against placebo. There is a 2-week patient determined titration phase, using escalating doses of CBD or placebo to reach a dose that achieves symptom relief with tolerable side effects. This is then followed by a further 2-week assessment period on the stable dose determined in collaboration with clinicians. DISCUSSION: A major strength of this study is that it will target symptom burden as a whole, rather than just individual symptoms, in an attempt to describe the general improvement in wellbeing previously reported by some patients in open label, non controlled trials of medicinal cannabis. Randomisation with placebo is essential because of the well-documented over reporting of benefit in uncontrolled trials and high placebo response rates in cancer pain trials. This will be the first placebo controlled clinical trial to evaluate rigorously the efficacy, safety and acceptability of CBD for symptom relief in advanced cancer patients. This study will provide the medical community with evidence to present to patients wishing to access medicinal cannabis for their cancer related symptoms. TRIAL REGISTRATION NUMBER: ALCTRN12618001220257 Registered 20/07/2018.

Identification of bacteria and fungi sampled from the conjunctival surface of normal horses in South-East Queensland, Australia.

OBJECTIVE: To identify bacteria and fungi found on the conjunctival surface of normal horse eyes; to investigate potential risk factors for these microflora; and to determine their susceptibility to common topical ophthalmic antimicrobials. ANIMALS STUDIED: A total of 95 client-owned horses were studied. PROCEDURES: Horses within sub-tropical Australia (South-East Queensland) were sampled once between April 2012 and March 2013. A conjunctival swab was taken from each eye and cultured for aerobic bacteria and fungi. Organisms were identified by colony morphology and phenotype. Antimicrobial disk diffusion susceptibility testing for commonly used antimicrobials was performed. RESULTS: Positive bacterial cultures were returned from 187/190 (98.4%) eyes from 94/95 (98.9%) horses. The most common species included Staphylococcus spp. (25.2% of total bacterial isolates), Bacillus cereus (17.4%), Bacillus spp. (14.1%), and Corynebacterium spp. (8.9%). Most bacterial isolates were susceptible to neomycin and fluoroquinolones. Positive fungal cultures were returned from 111/190 (58.4%) eyes from 73 (76.8%) horses. The most common species identified included: Penicillium spp. (16.7% of fungal isolates), Aspergillus spp. (15.4%), and Scopulariopsis spp. (10.3%). Most (≥90%) molds were susceptible to ketoconazole, voriconazole, itraconazole, and miconazole. Yeasts were most susceptible to ketoconazole. There was no significant effect of breed, age, sex, purpose, or housing of the horse or climatic conditions on bacterial or fungal culture status. CONCLUSIONS: Bacteria and fungi were commonly isolated from the eyes of healthy horses. The antibiotic and antifungal susceptibilities identified can be used as a guide for empirical therapy after cytology in the treatment of corneal ulceration in horses.

Birth-weight centiles and the risk of serious adverse neonatal outcomes at term.

BACKGROUND: Birth-weight is an important determinant of perinatal outcome with low birth-weight being a particular risk factor for adverse consequences. AIM: To investigate the impact of neonatal sex, mode of birth and gestational age at birth according to birth-weight centile on serious adverse neonatal outcomes in singleton term pregnancies. MATERIALS AND METHODS: This was a retrospective cohort study of singleton term births at the Mater Mother's Hospital, Brisbane, Australia. Serious adverse neonatal outcome was defined as a composite of severe acidosis at birth (pH ≤7.0 and/or lactate ≥6 mmol/L and/or base excess ≤-12 mmol/L), Apgar <3 at 5 min, neonatal intensive-care unit admission and antepartum or neonatal death. The main exposure variable was birth-weight centile. RESULTS: Of the 69,210 babies in our study, the overall proportion of serious adverse neonatal outcomes was 9.1% (6327/69,210). Overall, neonates in the <3rd birth-weight centile category had the highest adjusted odds ratio (OR) for serious adverse neonatal outcomes [OR 3.53, 95% confidence interval (CI) 3.06-4.07], whilst those in the ≥97th centile group also had elevated odds (OR 1.51, 95% CI 1.30-1.75). Regardless of birth modality, smaller babies in the <3rd centile group had the highest adjusted OR and predicted probability for serious adverse neonatal outcomes. When stratified by sex, male babies consistently demonstrated a higher predicted probability of serious adverse neonatal outcomes across all birth-weight centiles. The adjusted odds, when stratified by gestational age at birth, were the highest from 37+0 to 38+6 weeks in the <3rd centile group (OR 5.97, 95% CI 4.60-7.75). CONCLUSIONS: Low and high birth-weights are risk factors for serious adverse neonatal outcomes. The adjusted OR appears to be greatest for babies in the <3rd birth-weight centile group, although an elevated risk was also found in babies within the ≥97th centile category.

Diagnostic Performance of Cerebroplacental Ratio Thresholds at Term for Prediction of Low Birthweight and Adverse Intrapartum and Neonatal Outcomes in a Term, Low-Risk Population.

OBJECTIVES: To investigate the screening performance and best threshold centile (5th vs. 10th) of the cerebroplacental ratio (CPR) in low-risk, term pregnancies to predict low birthweight and adverse intrapartum and neonatal outcomes in a term, low-risk population. METHODS: This was a blinded, prospective, cross-sectional study of low-risk singleton pregnancies at term. Women attended fortnightly from 36 weeks for CPR and estimated fetal weight assessment. Intrapartum and neonatal outcomes were recorded. Primary outcomes assessed were low birthweight, cesarean section for intrapartum fetal compromise, and composite adverse neonatal outcome. RESULTS: A total of 483 women participated in the study. The CPR 10th centile (1.48) threshold resulted in the best screening performance. Sensitivities for low birthweight, cesarean section for intrapartum fetal compromise, and composite adverse neonatal outcome of 41.9, 61.1, and 38.3% were achieved for false-positive rates of 17.7, 17.7, and 15.2%, respectively. The corresponding areas under the receiver operating characteristic curves were 0.62, 0.72, and 0.62. CONCLUSION: The CPR 10th centile resulted in the best screening performance, although this would be considered fair at best. The CPR 10th centile may be useful as part of a risk stratification tool for prediction of low birthweight and adverse intrapartum and neonatal outcomes.

Screening Performance of Placental Growth Factor for the Prediction of Low Birth Weight and Adverse Intrapartum and Neonatal Outcomes in a Term Low-Risk Population.

INTRODUCTION: Fetuses who fail to reach their genetic growth potential are thought to have sub-optimal placental function. Low placental growth factor (PlGF) levels have been shown to be predictive of placentally mediated conditions, such as pre-eclampsia or fetal growth restriction. We investigated the screening performance of PlGF for the prediction of low birth weight (<10th centile for gestation) and adverse intrapartum and neonatal outcomes in apparently low-risk term pregnancies. MATERIALS AND METHODS: Maternal PlGF levels were measured fortnightly in a blinded, prospective, observational study from 36 weeks of pregnancy. Women and clinicians were blinded to PlGF results, and pregnancies were managed according to local policies and guidelines. Intrapartum and neonatal outcomes were recorded. PlGF was analysed for association with, and predictive capacity for, low birth weight, caesarean section for intrapartum fetal compromise (CS-IFC) and adverse neonatal outcomes. RESULTS: A total of 438 women were included in the final analysis. Lower PlGF levels were associated with low birth weight, CS-IFC and adverse neonatal outcome. For a false-positive rate of 10 and 20%, respectively, the corresponding sensitivities were 9.7-11.1% and 22.2-26.8%. CONCLUSION: As a sole predictor for low birth weight, CS-IFC and adverse neonatal outcome, PlGF was poor as a test.

Sildenafil in Pregnancy: A Systematic Review of Maternal Tolerance and Obstetric and Perinatal Outcomes.

INTRODUCTION: This systematic review evaluates maternal tolerance and obstetric and perinatal outcomes following sildenafil citrate (SC) use in human pregnancy. DATA SOURCES: Scopus, PubMed, Cochrane Library, Web of Science, Embase, and Google Scholar were searched. Relevant full-text studies including case series and reports in English were included. Publications were excluded if the pregnancy was terminated or if SC was used only at conception. RESULTS: Sixteen studies were included (n = 165). Indications for use and outcomes were variably reported. Maternal outcomes reported were headache (45.8%, 49/107), visual disturbances (17.3%, 14/81), dyspepsia/epigastric pain (15.8%, 15/95), and hypotension (0%, 0/39). There were more caesarean (83.3%, 55/66) than vaginal deliveries (16.7%, 11/66) and postpartum haemorrhage occurred in 3.9% (3/76) of women exposed to SC. Neonatal outcomes including nursery admission (67.3%, 35/52), Apgar scores <7 at 5 min (7.1%, 4/56), and cord arterial pH <7.1 (0%, 0/17) were reported. Stillbirths (4.3%, 3/69) and neonatal deaths (3.9%, 5/129) were comparable to SC-naïve groups. There were no congenital malformations (0%, 0/35). CONCLUSIONS: Despite limited data, overall there does not appear to be any severe adverse maternal side effects nor any increase in the rate of stillbirths, neonatal deaths, or congenital anomalies attributed to SC.

Impact of Maternal Body Mass Index on Intrapartum and Neonatal Outcomes in Brisbane, Australia, 2007 to 2013.

BACKGROUND: The aim of this study was to evaluate the influence of maternal body mass index on intrapartum and neonatal outcomes at one of the largest maternity hospitals in Australia. METHODS: A retrospective cross-sectional study of 55,352 term singleton deliveries at the Mater Mothers' Hospital in Brisbane, Australia, was conducted. The study cohort was stratified into six groups based on the World Health Organization's body mass index classification. The normal body mass index category was the reference group for all comparisons. Multivariate logistic regression was used to examine the effect of maternal body mass index, adjusted for maternal age, ethnicity, parity, and preexisting conditions (e.g., diabetes mellitus and hypertension), on selected intrapartum and neonatal outcomes. RESULTS: Women in the overweight and Obese I, II, and III categories were more likely to have chronic or gestational hypertension/preeclampsia, and preexisting or gestational diabetes mellitus. They also had an increased risk for induction of labor, elective and emergency cesarean, and postpartum hemorrhage. Underweight women were less likely to require induction of labor and emergency cesarean. Infants born to women with increased body mass index were more likely to require neonatal resuscitation, neonatal intensive care unit admission, and have lower Apgar scores at 5 minutes. CONCLUSION: There is an increased risk of adverse intrapartum and neonatal outcomes for women who are overweight and obese, with the risks increasing with rising body mass index. Appropriately targeted weight management strategies and health education may yield improved maternal and perinatal outcomes if effectively implemented before pregnancy. These may particularly be of benefit in the teenage cohort that has yet to embark on pregnancy.

Impact of mode of delivery after 32 weeks' gestation on neonatal outcome in dichorionic diamniotic twins.

AIM: The purpose of this study was to investigate neonatal outcome of dichorionic diamniotic twins born beyond 32 weeks' gestation according to mode of delivery at a major tertiary center in Australia. METHODS: This was a retrospective cohort study of women with dichorionic diamniotic twins delivering at ≥32 weeks' gestation at a large tertiary maternity center in Australia using data from a maternity database. Primary and secondary outcomes included mode of delivery, birthweight, stillbirth, Apgar score, neonatal unit admission, neonatal resuscitation, death and respiratory distress. RESULTS: Of 1261 women, 82.9% (1045/1261; 2090 babies) delivered at ≥32 weeks' gestation. The mode of delivery for these babies was as follows: normal vaginal delivery, 419 (20%); instrumental delivery, 179 (8.6%); emergency cesarean section, 658 (31.5%); and elective cesarean section, 834 (39.9%). Babies delivered by emergency cesarean section or instrumental vaginal delivery had worse outcome. In contrast, the lowest complications were seen in the uncomplicated vaginal delivery and elective cesarean section cohorts. CONCLUSIONS: Neonatal outcome was worse for those delivering via emergency cesarean section or instrumental vaginal delivery compared with elective cesarean section or uncomplicated vaginal delivery. The rate of uncomplicated vaginal delivery, however, was low, with only 14.8% of women delivering both babies vaginally without any form of intervention.

Systematic review and metaanalysis of perinatal outcomes after radiofrequency ablation and bipolar cord occlusion in monochorionic pregnancies.

The aim of this study was to analyze perinatal outcomes after selective reduction in monochorionic pregnancies with the use of either radiofrequency ablation (RFA) or bipolar cord occlusion (BCO). This was a systematic review and metaanalysis that included all studies with ≥5 cases that described perinatal outcomes after BCO or RFA that were identified in PubMed, Embase, Web of Science, COCHRANE, CINAHL, Academic Search Premier, Science Direct, and MEDLINE that were published between 1965 and July 2014. For count data, incidence risk ratios (IRR; 95% confidence interval [CI]) were calculated with BCO as the reference standard. The analysis included 481 cases of BCO and 320 cases of RFA from 17 studies. The mean median gestations at procedure were 21.1 ± 1.2 weeks (BCO) and 18.8 ± 2.5 weeks (RFA; P = .03). The rate of cotwin death was higher in the RFA group (14.7%) vs the BCO group (10.6%; IRR, 1.38; 95% CI, 0.93-2.05; P = .11). The live birth rate was 81.3% for the RFA group and 86.7% in the BCO group (IRR, 0.93; 95% CI, 0.80-1.09; P = .41). BCO had higher neonatal death rates (8.1%) vs RFA (4.5%; IRR, 0.56; 95% CI, 0.30-1.04; P = .07). Overall survival was 76.8% for RFA and 79.1% for BCO (IRR, 0.97; 95% CI, 0.82-1.14; P = .72); however, none of these differences were statistically significant. Preterm premature rupture of membranes occurred in 17.7% of RFA cases and 28.2% of the BCO cases (IRR, 0.63; 95% CI, 0.43-0.91; P = .01). The mean median gestational age at delivery was 34.7 ± 1.7 weeks in the RFA group and 35.1 ± 1.6 weeks in the BCO group. Our data do not demonstrate clearly the superiority of 1 procedure over the other. The clinical situation and preference of the operator are important considerations. Rates of preterm delivery and preterm premature rupture of membranes remain substantial for both procedures.

Prenatal extra-abdominal bowel dilatation is a risk factor for intrapartum fetal compromise for fetuses with gastroschisis.

OBJECTIVE: The aim of this study was to investigate the prenatal ultrasound features that were associated with intrapartum fetal distress in fetuses with gastroschisis. METHODS: This was a retrospective observational study of all cases of gastroschisis referred to and delivering at the Mater Mothers' Hospital in Brisbane, Australia. Maternal demographics, prenatal ultrasound features including the presence of bowel dilatation, umbilical artery and middle cerebral artery Doppler indices and amniotic fluid volume as well as intrapartum outcome details were analysed using univariate and multivariate logistic regression to ascertain factors predictive of intrapartum compromise. RESULTS: The study cohort included 155 cases of gastroschisis over a 16-year period. The overall perinatal loss rate was 5.9% (four intrauterine fetal deaths, four neonatal deaths and one termination of pregnancy). The live birth rate was 96.8% (150/155). Fetal heart rate abnormalities occurred in 55.1% of cases. The overall caesarean section rate was 40.9% (63/154), of which 63.5% (40/63) was emergency procedures. Both univariate and multivariate analysis confirmed that only extra-abdominal bowel dilatation was a risk factor for intrapartum fetal compromise necessitating emergency delivery. CONCLUSIONS: Extra-abdominal bowel dilatation is a risk factor for intrapartum fetal compromise (OR 2.2; 95%CI 1.03-4.7) and emergent delivery.

Psychological distress and physical symptoms in advanced cancer: cross-sectional study.

OBJECTIVES: Patients with advanced cancer experience varying physical and psychological symptoms throughout the course of their illness. Depression, anxiety and stress affect overall well-being. This study investigates the correlation between emotional distress and physical symptoms in a cohort of patients with advanced cancer. METHODS: There were 238 patients included in this study. Data from participants in two medicinal cannabis randomised controlled trials were analysed. Patients were aged over 18 years and had advanced cancer. Edmonton Symptom Assessment System, and Depression, Anxiety and Stress Scale (DASS-21) were assessed for all patients at baseline. RESULTS: Moderate-severe depression was reported in 29.8% and moderate-severe anxiety was reported in 47.9% of patients. The emotional subscales of DASS-21 (depression, anxiety, stress) correlated with total symptom distress score (p<0.001) and overall well-being (p<0.001). Depression was correlated with physical symptoms of fatigue, nausea, poor appetite and dyspnoea. Anxiety was correlated with fatigue and dyspnoea. Stress was correlated with fatigue, nausea and dyspnoea. CONCLUSIONS: Depression, anxiety and stress were common in this population. The relationship between physical and psychological well-being is complex. A holistic approach to symptom management is required to improve quality of life in patients with advanced cancer.

Cannabidiol oil or placebo in advanced cancer-disease progression and survival: a secondary analysis.

OBJECTIVES: Medical cannabinoids have become increasingly popular over the last decade. Preclinical trials suggest cannabinoids, for example, cannabidiol (CBD), may provide an anticancer effect; however, good-quality clinical information supporting this is lacking. We assessed the effect of CBD treatment on disease progression and survival in patients enrolled in a study of CBD versus placebo for symptom management in patients with advanced cancer (MEDCAN-1). METHODS: We reviewed the clinical records of all patients enrolled in the MEDCAN-1 Study (CBD vs placebo) at days 14, 28 and 56 of study follow-up, for evidence of disease progression. The proportion of participants with disease progression by treatment arm at each time point was compared, as was survival between both groups from study entry to the censor date (end of study period) and the effect of treatment arm and disease progression status on survival. RESULTS: Of the 135 patient records assessed, 128 were included in the final analysis. 36% (n=46) had progressive disease documented at day 28, rising to 49.2% (n=63) by day 56. No significant difference in disease progression was noted between the two groups at days 14 (p=0.33), 28 (p=0.67) or 56 (p=0.50). There was no difference in survival between both groups from study entry to censor date (p=0.38). Disease progression at day 14 was highly predictive of mortality (p<0.001). CONCLUSIONS: In this substudy analysis, treatment with CBD oil did not affect disease progression or survival over the course of 56 days in patients with advanced cancer.

Medicinal Cannabis (MedCan 3): a randomised, multicentre, double-blind, placebo-controlled trial to assess THC/CBD (1:20) to relieve symptom burden in patients with cancer-a study protocol for a randomised controlled trial.

BACKGROUND: Distressing symptoms are common in advanced cancer. Medicinal cannabinoids are commonly prescribed for a variety of symptoms. There is little evidence to support their use for most indications in palliative care. This study aims to assess a 1:20 delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) cannabinoid preparation in the management of symptom distress in patients with advanced cancer undergoing palliative care. METHODS AND DESIGN: One hundred and fifty participants will be recruited across multiple sites in Queensland, Australia. A teletrial model will facilitate the recruitment of patients outside of major metropolitan areas. The study is a pragmatic, multicenter, randomised, placebo-controlled, two-arm trial of escalating doses of an oral 1:20 THC/CBD medicinal cannabinoid preparation (10 mg THC:200 mg CBD/mL). It will compare the efficacy and safety outcomes of a titrated dose range of 2.5 mg THC/50mgCBD to 30 mg THC/600 mg CBD per day against a placebo. There is a 2-week patient-determined titration phase, to reach a dose that achieves symptom relief or intolerable side effects, with a further 2 weeks of assessment on the final dose. The primary objective is to assess the effect of escalating doses of a 1:20 THC/CBD medicinal cannabinoid preparation against placebo on change in total symptom distress score, with secondary objectives including establishing a patient-determined effective dose, the effect on sleep quality and overall quality of life. Some patients will be enrolled in a sub-study which will more rigorously evaluate the effect on sleep. DISCUSSION: MedCan-3 is a high-quality, adequately powered, placebo-controlled trial which will help demonstrate the utility of a THC:CBD 1:20 oral medicinal cannabis product in reducing total symptom distress in this population. Secondary outcomes may lead to new hypotheses regarding medicinal cannabis' role in particular symptoms or in particular cancers. The sleep sub-study will test the feasibility of using actigraphy and the Insomnia Severity Index (ISI) in this cohort. This will be the first large-scale palliative care randomised clinical trial to utilise the teletrial model in Australia. If successful, this will have significant implications for trial access for rural and remote patients in Australia and internationally. TRIAL REGISTRATION: ANZCTR ACTRN12622000083796 . Protocol number 001/20. Registered on 21 January 2022. Recruitment started on 8 August 2022.

Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes.

Vitamin D is synthesised in the skin through the action of UVB radiation (sunlight), and 25-hydroxy vitamin D (25OHD) measured in serum as a marker of vitamin D status. Several studies, mostly conducted in high latitudes, have shown an association between type 1 diabetes mellitus (T1DM) and low serum 25OHD. We conducted a case-control study to determine whether, in a sub-tropical environment with abundant sunlight (latitude 27.5°S), children with T1DM have lower serum vitamin D than children without diabetes. Fifty-six children with T1DM (14 newly diagnosed) and 46 unrelated control children participated in the study. Serum 25OHD, 1,25-dihydroxy vitamin D (1,25(OH)(2) D) and selected biochemical indices were measured. Vitamin D receptor (VDR) polymorphisms Taq1, Fok1, and Apa1 were genotyped. Fitzpatrick skin classification, self-reported daily hours of outdoor exposure, and mean UV index over the 35 d prior to blood collection were recorded. Serum 25OHD was lower in children with T1DM (n = 56) than in controls (n = 46) [mean (95%CI) = 78.7 (71.8-85.6) nmol/L vs. 91.4 (83.5-98.7) nmol/L, p = 0.02]. T1DM children had lower self-reported outdoor exposure and mean UV exposure, but no significant difference in distribution of VDR polymorphisms. 25OHD remained lower in children with T1DM after covariate adjustment. Children newly diagnosed with T1DM had lower 1,25(OH)(2) D [median (IQR) = 89 (68-122) pmol/L] than controls [121 (108-159) pmol/L, p = 0.03], or children with established diabetes [137 (113-153) pmol/L, p = 0.01]. Children with T1DM have lower 25OHD than controls, even in an environment of abundant sunlight. Whether low vitamin D is a risk factor or consequence of T1DM is unknown.

Human intravenous immunoglobulin use for hematological immune-mediated disease in dogs.

OBJECTIVE: To report on survival rates and risk factors in dogs with immune-mediated hemolytic anemia (IMHA) and immune-mediated thrombocytopenia (ITP) treated with human IV immunoglobulin (hIVIG; Privigen). We hypothesized that hIVIG could be used as a salvage treatment to improve survival and reduce the requirement for ongoing blood transfusion therapy in IMHA and ITP patients. ANIMALS: 52 client-owned dogs with IMHA or ITP were included, comprising 31 females (28 spayed and 3 entire) and 21 males (19 castrated and 2 entire). Miniature Schnauzers were the most common breed (5), with a further 24 different breeds identified. PROCEDURES: A retrospective cohort study was conducted between January 2006 and January 2022 that assessed the survival rates, risk factors, and need for ongoing transfusion in dogs with IMHA and ITP treated with hIVIG compared with those not receiving hIVIG. RESULTS: Of 36 dogs that did not receive hIVIG, 29 (80%) survived and 7 (24%) died, and of 16 dogs administered hIVIG, 11 (69%) survived and 5 (31%) died (P = .56). No effect of PCV at admission or age on the risk of death was detected (OR, 1.00; 95% CI, 0.94 to 1.08; P = .89; and OR, 1.10; 95% CI, 0.85 to 1.47; P = .47, respectively). CLINICAL RELEVANCE: This was the largest study to date of dogs with hematological immune-mediated disease treated with hIVIG. There was no difference in survival rates for dogs that received hIVIG versus those treated with standard immunosuppression. The benefit of hIVIG as a salvage treatment appears limited.

Phase IIb Randomized, Placebo-Controlled, Dose-Escalating, Double-Blind Study of Cannabidiol Oil for the Relief of Symptoms in Advanced Cancer (MedCan1-CBD).

PURPOSE: To determine whether cannabidiol (CBD) oil can improve symptom distress in patients with advanced cancer receiving palliative care. METHODS: Participants were adults with advanced cancer and symptom distress (Edmonton Symptom Assessment Scale [ESAS] total score of ≥ 10/90) who received titrated CBD oil 100 mg/mL, 0.5 mL once daily to 2 mL three times a day, or matched placebo for 28 days. The primary outcome was ESAS total symptom distress score (TSDS) at day 14. Response was defined as a decrease in TSDS by ≥ 6 at day 14. Secondary outcomes were ESAS TSDS over time, individual symptom scores, patient-determined effective dose, opioid use, Global Impression of Change, depression, anxiety, quality of life, and adverse events. RESULTS: Of the 144 patients randomly assigned, the planned sample size of 58 participants on CBD and 63 on placebo reached the primary analysis point (day 14). The unadjusted change in TSDS from baseline to day 14 was -6.2 (standard deviation, 14.5) for placebo and -3.0 (standard deviation, 15.2) for CBD with no significant difference between arms (P = .24). Similarly, there was no detected difference in proportion of responders (placebo: 37 of 63 [58.7%], CBD: 26 of 58 [44.8%], P = .13). All components of ESAS improved (fell) over time with no difference between arms. The median dose of participant-selected CBD was 400 mg per day with no correlation with opioid dose. There was no detectable effect of CBD on quality of life, depression, or anxiety. Adverse events did not differ significantly between arms apart from dyspnea that was more common with CBD. Most participants reported feeling better or much better at days 14 (53% CBD and 65% placebo) and 28 (70% CBD and 64% placebo). CONCLUSION: CBD oil did not add value to the reduction in symptom distress provided by specialist palliative care alone.

Drug dependence epidemiology in palliative care medicinal cannabis trials.

OBJECTIVES: Drug dependence is becoming increasingly common and meeting palliative care patients with substance use disorders is inevitable. However, data on substance use in these patients are lacking. This study aims to evaluate the prevalence of drug dependence in palliative care patients with advanced cancer and correlate with symptom distress and opioid use. METHODS: Palliative care patients with advanced cancer interested in participation in a medicinal cannabis trial were required to complete Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), Edmonton Symptom Assessment Scale (ESAS) and record of concomitant medications including baseline opioid use as part of the eligibility screen. RESULTS: Of the 182 participants, 167 (92%) reported lifetime alcohol and 132/182 (73%) lifetime tobacco use. No participant reached the threshold criteria for high risk of drug dependence with majority being low risk. There was no correlation between ASSIST score, ESAS and oral morphine equivalent. CONCLUSION: This study identified alcohol and tobacco as the main substances used in this group of patients and that most were of very low risk for drug dependence. This suggests routine drug screening for palliative care patient may not be justified, but the high possibility of questionnaire bias is acknowledged.

Importance of hepatic fibrosis in cystic fibrosis and the predictive value of liver biopsy.

UNLABELLED: Cystic fibrosis liver disease (CFLD), which results from progressive hepatobiliary fibrosis, is an important cause of morbidity and mortality, but it is difficult to identify before portal hypertension (PHT) ensues. Clinical signs, serum alanine aminotransferase (ALT) levels, and ultrasound (US) are widely applied, but their value in predicting the presence of cirrhosis, the development of PHT, or adverse outcomes is undetermined. The potential gold standard, liver biopsy, is not standard practice and, notwithstanding sampling error considerations, has not been systematically evaluated. Forty patients with cystic fibrosis (median age = 10.6 years) with abnormal clinical, biochemical, and US findings were subjected to dual-pass percutaneous liver biopsy. Clinical outcomes were recorded over 12 years of follow-up (median = 9.5 years for survivors). Logistic regression and receiver operating characteristic analyses were applied to predict hepatic fibrosis (which was assessed by fibrosis staging and quantitative immunohistochemistry) and the occurrence of PHT. PHT occurred in 17 of 40 patients (42%), including 6 of 7 (17%) who died during follow-up. Clinical examination, serum ALT levels, and US findings failed to predict either the presence of liver fibrosis or the development of PHT. Fibrosis staging on liver biopsy, where the accuracy was improved by dual passes (P = 0.002, nonconcordance = 38%), predicted the development of PHT (P < 0.001), which occurred more frequently and at a younger age in those with severe fibrosis. CONCLUSION: Clinical modalities currently employed to evaluate suspected CFLD help to identify a cohort of children at risk for liver disease and adverse outcomes but do not predict an individual's risk of liver fibrosis or PHT development. Liver fibrosis on biopsy predicts the development of clinically significant liver disease. Dual passes help to address sampling concerns. Liver biopsy has a relevant role in the management of patients with suspected CFLD and deserves more widespread application.