Maternal dietary intervention during lactation impacts the maternal faecal and human milk microbiota.

AIMS: To determine the effect of a two-week reduced fat and sugar and increased fibre maternal dietary intervention on the maternal faecal and human milk (HM) microbiomes. METHODS AND RESULTS: Faecal swabs and HM samples were collected from mothers (n = 11) immediately pre-intervention, immediately post-intervention, and 4 and 8 weeks post-intervention, and were analysed using full-length 16S rRNA gene sequencing. Maternal macronutrient intake was assessed at baseline and during the intervention. Maternal fat and sugar intake during the intervention were significantly lower than pre-intervention (P = <0.001, 0.005, respectively). Significant changes in the bacterial composition of maternal faeces were detected after the dietary intervention, with decreases in the relative abundance of Bacteroides caccae (P = <0.001) and increases in the relative abundance of Faecalibacillus intestinalis (P = 0.006). In HM, the diet resulted in a significant increase in Cutibacterium acnes (P = 0.001) and a decrease in Haemophilus parainfluenzae (P = <0.001). The effect of the diet continued after the intervention, with faecal swabs and HM samples taken 4 and 8 weeks after the diet showing significant differences compared to baseline. CONCLUSION: This pilot study demonstrates that short-term changes in maternal diet during lactation can alter the bacterial composition of the maternal faeces and HM.

Exposure to low-level ambient air pollution and the relationship with lung and bladder cancer in older men, in Perth, Western Australia.

BACKGROUND: Air pollution is a cause of lung cancer and is associated with bladder cancer. However, the relationship between air pollution and these cancers in regions of low pollution is unclear. We investigated associations between fine particulate matter (PM2.5), nitrogen dioxide, and black carbon (BC), and both these cancers in a low-pollution city. METHODS: A cohort of 11,679 men ≥65 years old in Perth (Western Australia) were followed from 1996-1999 until 2018. Pollutant concentrations, as a time-varying variable, were estimated at participants' residential addresses using land use regression models. Incident lung and bladder cancer were identified through the Western Australian Cancer Registry. Risks were estimated using Cox proportional-hazard models (age as the timescale), adjusting for smoking, socioeconomic status, and co-pollutants. RESULTS: Lung cancer was associated with PM2.5 and BC in the adjusted single-pollutant models. A weak positive association was observed between ambient air pollution and squamous cell lung carcinoma but not lung adenocarcinoma. Positive associations were observed with bladder cancer, although these were not statistically significant. Associations were attenuated in two-pollutant models. CONCLUSION: Low-level ambient air pollution is associated with lung, and possibly bladder, cancer among older men, suggesting there is no known safe level for air pollution as a carcinogen.

Ambient air pollution and risk of incident dementia in older men living in a region with relatively low concentrations of pollutants: The Health in Men Study.

BACKGROUND: In areas with moderate to severe air pollution, pollutant concentrations are associated with dementia risk. It is unclear whether the same relationship is present in regions with lower ambient air pollution. OBJECTIVE: To determine whether exposure to air pollution is associated with risk of incident dementia in general, and Alzheimer's disease and vascular dementia in particular, in older men living in a relatively low ambient air pollution region. METHODS: The cohort comprised 11,243 men residing in Perth, Australia. Participants were aged ≥65 years and free of a dementia diagnosis at time of recruitment in 1996-1999. Incident dementia was identified from recruitment to 2018 via ICD diagnosis codes and subsequent study waves. Concentrations for three air pollutants, nitrogen dioxide (NO2), fine particulate matter less than 2.5 µm in diameter (PM2.5), and black carbon (BC) were estimated at participants' home addresses using land-use regression models. We used Cox proportional hazards regression models adjusting for smoking status, physical activity, BMI, education, and socio-economic status. RESULTS: Of 3053 (27.2%) incident cases of dementia, 1670 (54.7%) and 355 (11.6%) had documented Alzheimer's disease and vascular dementia. The average concentration of NO2 was 13.5 (SD 4.4) µg/m3, of PM2.5 was 4.54 (SD 1.6) µg/m3 and of BC was 0.97 (SD 0.29) ×10-5 m-1. None of the air pollutants were associated with incident dementia or Alzheimer's disease. In the unadjusted model, increased exposure to PM2.5 was associated with an increased risk of vascular dementia (for a 5 µg/m3 increase: HR 1.62, 95% CI 1.13, 2.31). However, this association was attenuated following adjustment for confounders (HR 1.39, 95% CI 0.93, 2.08). NO2 and BC were not associated with vascular dementia incidence. DISCUSSION: Exposure to air pollution is not associated with increased risk of incident dementia in older men living in a region with relatively low ambient air pollution.

Human Milk Oligosaccharides and Bacterial Profile Modulate Infant Body Composition during Exclusive Breastfeeding.

Human milk is a complex and variable ecosystem fundamental to the development of newborns. This study aimed to investigate relationships between human milk oligosaccharides (HMO) and human milk bacterial profiles and infant body composition. Human milk samples (n = 60) were collected at two months postpartum. Infant and maternal body composition was measured with bioimpedance spectroscopy. Human milk bacterial profiles were assessed using full-length 16S rRNA gene sequencing and 19 HMOs were quantitated using high-performance liquid chromatography. Relative abundance of human milk bacterial taxa were significantly associated with concentrations of several fucosylated and sialylated HMOs. Individual human milk bacteria and HMO intakes and concentrations were also significantly associated with infant anthropometry, fat-free mass, and adiposity. Furthermore, when data were stratified based on maternal secretor status, some of these relationships differed significantly among infants born to secretor vs non-secretor mothers. In conclusion, in this pilot study the human milk bacterial profile and HMO intakes and concentrations were significantly associated with infant body composition, with associations modified by secretor status. Future research designed to increase the understanding of the mechanisms by which HMO and human milk bacteria modulate infant body composition should include intakes in addition to concentrations.

A comparison of the opinions of intensive care unit staff and family members of the treatment intensity received by patients admitted to an intensive care unit: A multicentre survey.

BACKGROUND: Achieving shared decision-making in the intensive care unit (ICU) is challenging because of limited patient capacity, leading to a reliance on surrogate decision-makers. Prior research shows that ICU staff members often perceive that patients receive inappropriate or futile treatments while some surrogate decision-makers of patients admitted to the ICU report inadequate communication with physicians. Therefore, understanding the perceptions of both ICU staff and surrogate decision-makers around wishes for ICU treatments is an essential component to improve these situations. OBJECTIVES: The objectives of this study were to compare perceptions of ICU staff with surrogate decision-makers about the intensity and appropriateness of treatments received by patients and analyse the causes of any incongruence. METHODS: A multicentred, single-day survey of staff and surrogate decision-makers of ICU inpatients was conducted across four Australian ICUs in 2014. Patients were linked to a larger prospective observational study, allowing comparison of patient outcomes. RESULTS: Twelve of 32 patients were identified as having a mismatch between staff and surrogate decision-maker perceptions. For these 12 patients, all 12 surrogate decision-makers believed that the treatment intensity the patient was receiving was of the appropriate intensity and duration. Mismatched patients were more likely to be emergency admissions to ICU compared with nonmismatched patients (0.0% vs 42.1%, p = 0.012) and have longer ICU admissions (7.5 vs 3, p = 0.022). There were no significant differences in perceived communication (p = 0.61). CONCLUSIONS: Family members did not share the same perceptions of treatment with ICU staff. This may result from difficulty in prognostication; challenges in conveying poor prognoses to surrogate decision-makers; and the accuracy of surrogate decision-makers.

Implementing Endobronchial Ultrasound-Guided (EBUS) for Staging and Diagnosis of Lung Cancer: A Cost Analysis.

BACKGROUND Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and guide sheath (EBUS-GS) are gaining popularity for diagnosis and staging of lung cancer compared to CT-guided transthoracic needle aspiration (CT-TTNA), blind fiber-optic bronchoscopy, and mediastinoscopy. This paper aimed to examine predictors of higher costs for diagnosing and staging lung cancer, and to assess the effect of EBUS techniques on hospital cost. MATERIAL AND METHODS Hospital costs for diagnosis and staging of new primary lung cancer patients presenting in 2007-2008 and 2010-2011 were reviewed retrospectively. Multiple linear regression was used to determine relationships with hospital cost. RESULTS We reviewed 560 lung cancer patient records; 100 EBUS procedures were performed on 90 patients. Higher hospital costs were associated with: EBUS-TBNA performed (p<0.0001); increasing inpatient length of stay (p<0.0001); increasing number of other surgical/diagnostic procedures (p<0.0001); whether the date of management decision fell within an inpatient visit (p<0.0001); and if the patient did not have a CT-TTNA, then costs increased as the number of imaging events increased (interaction p<0.0001). Cohort was not significantly related to cost. Location of the procedure (outside vs. inside theater) was a predictor of lower one-day EBUS costs (p<0.0001). Cost modelling revealed potential cost saving of $1506 per EBUS patient if all EBUS procedures were performed outside rather than in the theater ($66,259 per annum). CONCLUSIONS EBUS-TBNA only was an independent predictor of higher cost for diagnosis and staging of lung cancer. Performing EBUS outside compared to in the theater may lower costs for one-day procedures; potential future savings are considerable if more EBUS procedures could be performed outside the operating theater.

Impact of Raised Serum Cobalt Levels From Recalled Articular Surface Replacement Hip Prostheses on the Visual Pathway.

BACKGROUND: The articular surface replacement (ASR) was recalled in 2010 because of higher than expected revision rates. Patients reported symptoms of neurologic dysfunction including poor vision. This cohort study, using objective measurements, aimed to establish whether a higher incidence of visual function defects exists in ASR patients. METHODS: Thirty-three ASR patients and 33 non-ASR controls (control 1) were recruited. Data were compared with normative population data from the visual electrophysiology database (control 2). Patients underwent investigations for serum cobalt levels, psychophysical visual tests, and extensive electrophysiological visual testing. RESULTS: After excluding 2 subjects with pre-existing eye disease, data from 33 ASR patients were compared with the 2 control cohorts. The median serum cobalt level in the ASR group (median, 52 nmol/L [interquartile range, 14-151 nmol/L]) was significantly higher than that in the control 1 cohort (median, 7 nmol/L [interquartile range, 5-14 nmol/L]; P < .0001). The photoreceptor function of patients with an ASR of the hip showed significantly larger electroretinography mixed rod-cone b-wave amplitudes than both control 1 and control 2 cohorts (P = .0294 and .0410, respectively). Abnormalities in macular function as reflected by multifocal and scotopic electroretinography were more prevalent in control 1 (P = .0445 and .0275, respectively). Optic nerve pathway measurements using visual-evoked potential latency was significantly longer in the ASR group compared with those in the control 2 cohort (P = .0201). There were no statistical differences in visual acuity. CONCLUSION: A statistically significant disturbance in visual electrophysiology was found in the ASR group when compared with the control groups. These differences did not translate to identifiable clinical visual deficits. Orthopedic surgeons need to be aware of the possibility of visual dysfunction in patients with ASR and other metal-on-metal hip arthroplasties; however, routine visual testing is not recommended.

Characterisation of human milk bacterial DNA profiles in a small cohort of Australian women in relation to infant and maternal factors.

Human milk is composed of complex microbial and non-microbial components that shape the infant gut microbiome. Although several maternal and infant factors have been associated with human milk microbiota, no study has investigated this in an Australian population. Therefore, we aimed to investigate associations between human milk bacterial composition of Australian women and maternal factors (body mass index (BMI), mode of delivery, breast pump use, allergy, parity) and infant factors (sex, mode of feeding, pacifier use, and introduction of solids). Full-length 16S rRNA gene sequencing was used to characterise milk bacterial DNA profiles. Milk from mothers with a normal BMI had a higher relative abundance of Streptococcus australis than that of underweight mothers, while milk from overweight mothers had a higher relative abundance of Streptococcus salivarius compared with underweight and obese mothers. Mothers who delivered vaginally had a higher relative abundance of Streptococcus mitis in their milk compared to those who delivered via emergency caesarean section. Milk of mothers who used a breast pump had a higher relative abundance of Staphylococcus epidermidis and Streptococcus parasanguinis. Milk of mothers whose infants used a pacifier had a higher relative abundance of S. australis and Streptococcus gwangjuense. Maternal BMI, mode of delivery, breast pump use, and infant pacifier use are associated with the bacterial composition of human milk in an Australian cohort. The data from this pilot study suggests that both mother and infant can contribute to the human milk microbiome.

Long-term exposure to low-concentration PM2.5 and heart disease in older men in Perth, Australia: The Health in Men Study.

Exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM2.5) is associated with increased risk of heart disease, but less is known about the relationship at low concentrations. This study aimed to determine the dose-response relationship between long-term PM2.5 exposure and risk of incident ischemic heart disease (IHD), incident heart failure (HF), and incident atrial fibrillation (AF) in older men living in a region with relatively low ambient air pollution. Methods: PM2.5 exposure was estimated for 11,249 older adult males who resided in Perth, Western Australia and were recruited from 1996 to 1999. Participants were followed until 2018 for the HF and AF outcomes, and until 2017 for IHD. Cox-proportional hazards models, using age as the analysis time, and adjusting for demographic and lifestyle factors were used. PM2.5 was entered as a restricted cubic spline to model nonlinearity. Results: We observed a mean PM2.5 concentration of 4.95 µg/m3 (SD 1.68 µg/m3) in the first year of recruitment. After excluding participants with preexisting disease and adjusting for demographic and lifestyle factors, PM2.5 exposure was associated with a trend toward increased incidence of IHD, HF, and AF, but none were statistically significant. At a PM2.5 concentration of 7 µg/m3 the hazard ratio for incident IHD was 1.04 (95% confidence interval [CI] = 0.86, 1.25) compared with the reference category of 1 µg/m3. Conclusions: We did not observe a significant association between long-term exposure to low-concentration PM2.5 air pollution and IHD, HF, or AF.

Effect of Cold Storage on the Viable and Total Bacterial Populations in Human Milk.

Expression and cold storage of human milk is a common practice. Current guidelines for cold storage of expressed milk do not take into account the impact on the milk microbiome. Here, we investigated the impact of cold storage on viable bacterial populations in human milk. Freshly expressed milk samples (n = 10) were collected and analysed immediately, stored at 4 °C for four days, −20 °C for 2.25 months and 6 months, and −80 °C for 6 months. Samples were analysed using propidium monoazide (PMA; a cell viability dye) coupled with full-length 16S rRNA gene. An aliquot of each sample was additionally analysed without PMA to assess the impact of cold storage on the total DNA profile of human milk. Cold storage significantly altered the composition of both the viable microbiome and total bacterial DNA profile, with differences in the relative abundance of several OTUs observed across each storage condition. However, cold storage did not affect the richness nor diversity of the samples (PERMANOVA all p > 0.2). Storage of human milk under typical and recommended conditions results in alterations to the profile of viable bacteria, with potential implications for infant gut colonisation and infant health.

The Viable Microbiome of Human Milk Differs from the Metataxonomic Profile.

Bacteria in human milk contribute to the establishment of the infant gut microbiome. As such, numerous studies have characterized the human milk microbiome using DNA sequencing technologies, particularly 16S rRNA gene sequencing. However, such methods are not able to differentiate between DNA from viable and non-viable bacteria. The extent to which bacterial DNA detected in human milk represents living, biologically active cells is therefore unclear. Here, we characterized both the viable bacterial content and the total bacterial DNA content (derived from viable and non-viable cells) of fresh human milk (n = 10). In order to differentiate the living from the dead, a combination of propidium monoazide (PMA) and full-length 16S rRNA gene sequencing was used. Our results demonstrate that the majority of OTUs recovered from fresh human milk samples (67.3%) reflected DNA from non-viable organisms. PMA-treated samples differed significantly in their bacterial composition compared to untreated samples (PERMANOVA p < 0.0001). Additionally, an OTU mapping to Cutibacterium acnes had a significantly higher relative abundance in PMA-treated (viable) samples. These results demonstrate that the total bacterial DNA content of human milk is not representative of the viable human milk microbiome. Our findings raise questions about the validity of conclusions drawn from previous studies in which viability testing was not used, and have broad implications for the design of future work in this field.

The prevalence of perceptions of mismatch between treatment intensity and achievable goals of care in the intensive care unit: a cross-sectional study.

PURPOSE: To describe the prevalence of perceptions of patients receiving a mismatch in treatment intensity, as perceived by intensive care unit (ICU) healthcare providers, and to assess the congruence of perceptions between providers. METHODS: In this cross-sectional, observational study conducted in 21 ICUs in Australia and New Zealand, patient prevalence data was linked to an ICU staff survey to describe the extent to which patient treatment intensity was matched to the perceived prognosis and patient wishes. RESULTS: Of the 307 study patients, 62 (20.2%) were reported to be receiving a mismatch in treatment intensity by at least one ICU healthcare professional. For reported mismatch, there was consensus amongst staff members for 52/62 (84%) of patients. Patients were significantly more likely to receive mismatched treatments if they were more severely unwell (APACHE II score > 20 vs. ≤ 20), odds ratio OR 2.35, 95% confidence interval (CI) 1.63-3.37, p < 0.0001, if they were an emergency admission (OR 3.05, CI 1.18-7.89, p = 0.0212) or if they had an advance care directive (OR 3.68, 95% CI 1.66-8.16, p = 0.0013). CONCLUSIONS: Being more severely unwell, being an emergency admission or having an advance care directive made patients more likely to be perceived as having a mismatch between the intensity of treatments provided and either the achievable goals of care, expected prognosis or patient's wishes.

Derivation of a clinical decision-making aid to improve the insertion of clinically indicated peripheral intravenous catheters and promote vessel health preservation. An observational study.

BACKGROUND: It is well established that the idle peripheral intravenous catheter (PIVC) provides no therapeutic value and is a clinical, economic and above all, patient concern. This study aimed to develop a decision aid to assist with clinical decision making to promote clinically indicated peripheral intravenous catheter (CIPIVC) insertion in the emergency department (ED) setting. Providing evidence for a uniform process could assist clinicians in a decision-making process for PIVC insertion. This could enable patients receive appropriate vascular access healthcare. METHODS: We performed a secondary analysis of data from a multicentre cohort of emergency department clinicians who performed PIVC insertion. We defined CIPIVC a priori as one used for a specific clinical treatment and or procedure such as prescribed intravenous (IV) fluids; prescribed IV medication; or IV contrast (for computerized tomography scans). We sought to refute or validate an assumption if the clinician performing or requesting the insertion decided the patient was >80% likely to need a PIVC. Using logistic regression, we derived a decision aid for CIPIVCs. RESULTS: In 817 patients undergoing PIVC insertion, we observed 68% of these to be CIPIVCs. Admitted patients were significantly more likely to have a CIPIVC, Odds Ratio (OR) = 3.05, 95% confidence interval (CI) = 2.17-4.30, p = <0.0001. Before insertion, patients who definitely needed IV fluids/medicines OR = 3.30, 95% CI = 2.02-5.39, p = <0.0001 and who definitely needed a contrast scan OR = 3.04, 95% CI = 1.15-8.03, p = 0.0250 were significantly more likely to have a device inserted for a clinical indication. Patients who presented with an existing vascular access device were more likely to have a new CIPIVC inserted for use OR = 4.35, 95% CI = 1.58-11.95, p = 0.0043. The clinician's pre-procedural judgment of the likelihood of therapeutic use >80% was independently associated with CIPIVC; OR 3.16, 95% CI = 2.06-4.87, p<0.0001. The area under the receiver operating characteristic curve was 0.81, and at the best cut-off, the model had a specificity of 0.81, sensitivity of 0.71, a positive predictive value of 0.89 and negative predictive value of 0.57. CONCLUSIONS: Using the derived decision aid, clinicians could ask:- "Does this patient need A-PIVC?" Clinicians can decide to insert a CIPIVCs when: (i) Admission to hospital is anticipated and when (ii) a Procedure requires a PIVC, e.g., computerised tomography scans and where an existing suitable vascular access device is not present and or; (iii) there is an indication for IV fluids and or medicines that cannot be tolerated enterally and are suitable for dilution in peripheral veins; and, (iv) the Clinician's perceived likelihood of use is greater than 80%.

Factors associated with peripheral intravenous cannulation first-time insertion success in the emergency department. A multicentre prospective cohort analysis of patient, clinician and product characteristics.

OBJECTIVES: This study aimed to identify the incidence of and factors associated with peripheral intravenous catheter/cannula (PIVC) first time insertion success (FTIS) in the emergency department (ED). DESIGN: Prospective cohort study. SETTING: Two tertiary EDs in Western Australia. PARTICIPANTS: 879 ED patients. PRIMARY OUTCOME: To identify factors affecting FTIS using univariate and multivariate logistic regression modelling. We created four models: patient factors only; clinician factors only; products and technology factors only and all factors model. We assessed each model's performance using area under the receiver operating characteristic curve. RESULTS: A total of 1201 PIVCs were inserted in 879 patients. The mean age was 60.3 (SD 22) years with slightly more females (52%). The FTIS rate was 73%, with 128 (15%) requiring a second attempt and 83 (9%) requiring three or more attempts. A small percentage (3%) had no recorded number of subsequent attempts. FTIS was related to the following patient factors: age (for a 1-year increase in age: OR 0.99, 95% CI 0.983 to 0.998; p=0.0097); and target vein palpability: (always palpable vs never palpable: OR 3.53 95% CI 1.64 to 7.60; only palpable with tourniquet vs never palpable: OR 2.20, 95% CI 1.06 to 4.57; p=0.0014). Clinician factors related to FTIS include: clinicians with greater confidence (p<0.0001) and insertion experience (301-1000 vs <301: OR 1.54, 95% CI 1.02 to 2.34; >1000 vs <301: OR 2.07, 95% CI 1.41 to 3.04; p=0.0011). The final all factors model combining patient factors; clinician factors and product and technology factors has greater discriminative ability than specific factors models. It has a sensitivity of 74.26%, specificity of 57.69%, positive predictive value of 82.87% and negative predictive value of 44.85%. CONCLUSION: A clinical decision, matching patients who have no palpable veins and are older, with clinicians with greater confidence and experience, will likely improve FTIS. TRIALREGISTRATION NUMBER: ANZCTRN12615000588594; Results.