Tuberculosis and diabetes: increased hospitalisations and mortality associated with renal impairment.

BACKGROUND: Diabetes mellitus (DM) triples a person's risk of active tuberculosis (TB) and is associated with increased mortality. It is unclear whether diabetes status and/or the associated renal dysfunction is associated with poor TB outcomes in New Zealand, which has high diabetes screening. AIM: To characterise the population of TB-DM and TB-alone to assess the effect of diabetes status and renal function on hospitalisation and mortality. METHODS: Clinical records from all adult patients diagnosed with TB in Auckland over a 6-year period (2010-2015) were reviewed. Baseline demographics, clinical presentation and microbiological data were assessed to compare the rates of hospitalisation and mortality between those with TB-DM and TB-alone. Statistical significance was defined as P < 0.05. RESULTS: A total of 701 patients was identified with TB; 120 (17%) had an unknown diabetes status and were excluded, and 135 had co-existing diabetes. The TB-DM and TB-alone groups had similar distribution of TB site and proportions of Mycobacterium tuberculosis culture positivity. Univariate analysis showed TB-DM patients had statistically significantly higher proportions of acute hospitalisation and mortality. Multivariate logistic regression showed only a reduced estimated glomerular filtration rate (eGFR) accounted for the higher rates of hospitalisation, with the odds of hospitalisation increasing by 2% for every unit decrease in eGFR. The odds of mortality increased by 6% for every year increase in age, and the odds of mortality increased by 3% for every unit reduction in eGFR. CONCLUSIONS: Diabetes is associated with higher TB hospitalisation and mortality; however, this is likely mediated by increased age and chronic kidney disease.

Tiotropium treatment for bronchiectasis: a randomised, placebo-controlled, crossover trial.

BACKGROUND: Tiotropium via the HandiHaler device is an established long-acting, anticholinergic bronchodilator that prevents exacerbations and improves lung function in patients with chronic obstructive pulmonary disease. We hypothesised that tiotropium would reduce pulmonary exacerbations and improve lung function in patients with stable bronchiectasis and airflow limitation, and assessed the effect of tiotropium on these outcomes. METHODS: In a randomised, double-blind, two-period crossover trial, we recruited adult patients from three hospitals in New Zealand. Patients were excluded if they had a smoking history of >20 pack-years. Patients were assigned to either the tiotropium-placebo or placebo-tiotropium sequence in a 1:1 ratio, using randomly permuted blocks stratified by centre. Participants and investigators were masked to treatment allocation. Eligible patients received tiotropium 18 µg via HandiHaler daily for 6 months followed by 6 months of placebo, or vice versa, with a washout period of 4 weeks. The primary end-point was rate of event-based exacerbations during the 6-month period. Primary analyses were carried out in an intention-to-treat set. RESULTS: 90 patients were randomly assigned and 85 completed both treatment cycles. The rate of exacerbations was 2.17 per year under the tiotropium treatment and 2.27 per year under placebo (rate ratio 0.96, 95% CI 0.72-1.27; p=0.77). Tiotropium, compared with placebo, improved forced expiratory volume in 1 s by 58 mL (95% CI 23-92 mL; p=0.002). Adverse events were similar under both treatments. CONCLUSIONS: Tiotropium via HandiHaler over 6 months significantly improved lung function but not frequency of exacerbations. Further research is required to understand the clinical context and significance of these findings.

Clostridioides difficile infection in US hospitals: a national inpatient sample study.

BACKGROUND: Hypervirulent strains of Clostridioides difficile have altered the landscape of hospital and community outbreaks. We aim to examine and compare spatiotemporal trends, incidence, hospital teaching status, mortality, and cost associated with hospital-acquired Clostridioides difficile infection (HCDI) and community-acquired Clostridioides difficile infection (CCDI). METHODS: Retrospective cohorts were studied using data from the Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) from 2006 to 2015. RESULTS: A total of 76,124 cases of HCDI and 190,641 cases of CCDI were identified within the study period. The incidence of HCDI decreased from 8555 in 2006 to 7191 in 2015. Mortality also decreased during the same period (5.9% in 2006 to 1.4% 2015, p < 0.0001). Conversely, CCDI cases increased from 13,823 in 2006 to 20,637 in 2015. CCDI mortality decreased during the same period (4.3% in 2006 to 1.9% 2015, p < 0.0001). Rural hospital centers experienced the sharpest decline in HCDI mortality compared to urban and urban teaching centers (3.8%, p < 0.0001 vs 2.8%, p < 0.0001 vs 2.1%, p < 0.0001). Multivariate logistic regression indicated that increasing age (p = 0.0001), increasing hospital length of stay (p = 0.0001), and Medicare insurance (p = 0.002) were significant predictors of mortality for CDI mortality. Geospatial mapping of CCDI and HCDI revealed that the Eastern and Southern US experienced the largest incidence of CDI over 10 years. CONCLUSION: The incidence of HCDI has decreased in the past decade while the incidence of CCDI hospitalization is sharply on the rise. While hospital length of stay and mortality has decreased over time, the cost of treating CDI remains high.

Safety and tolerability of experimental hookworm infection in humans with metabolic disease: study protocol for a phase 1b randomised controlled clinical trial.

BACKGROUND: Abdominal obesity and presence of the metabolic syndrome (MetS) significantly increase the risk of developing diseases such as Type 2 diabetes mellitus (T2DM) with escalating emergence of MetS and T2DM constituting a significant public health crisis worldwide. Lower prevalence of inflammatory and metabolic diseases such as T2DM in countries with higher incidences of helminth infections suggested a potential role for these parasites in the prevention and management of certain diseases. Recent studies confirmed the potential protective nature of helminth infection against MetS and T2DM via immunomodulation or, potentially, alteration of the intestinal microbiota. This Phase 1b safety and tolerability trial aims to assess the effect of inoculation with helminths on physical and metabolic parameters, immune responses, and the microbiome in otherwise healthy women and men. METHODS: Participants eligible for inclusion are adults aged 18-50 with central obesity and a minimum of one additional feature of MetS recruited from the local community with a recruitment target of 54. In a randomised, double-blind, placebo-controlled design, three groups will receive either 20 or 40 stage three larvae of the human hookworm Necator americanus or a placebo. Eligible participants will provide blood and faecal samples at their baseline and 6-monthly assessment visits for a total of 24 months with an optional extension to 36 months. During each scheduled visit, participants will also undergo a full physical examination and complete diet (PREDIMED), physical activity, and patient health (PHQ-9) questionnaires. Outcome measurements include tolerability and safety of infection with Necator americanus, changes in metabolic and immunological parameters, and changes in the composition of the faecal microbiome. DISCUSSION: Rising cost of healthcare associated with obesity-induced metabolic diseases urgently calls for new approaches in disease prevention. Findings from this trial will provide valuable information regarding the potential mechanisms by which hookworms, potentially via alterations in the microbiota, may positively influence metabolic health. TRIAL REGISTRATION: The protocol was registered on ANZCTR.org.au on 05 June 2017 with identifier ACTRN12617000818336. Alternatively, a Google search using the above trial registration number will yield a direct link to the trial protocol within the ANZCTR website.

Private Keeping of Dangerous Wild Animals in Great Britain.

We analysed the licences issued by British local government authorities under the Dangerous Wild Animals Act 1976, which regulates the private keeping of wild animals categorised as "dangerous", to assess the scope and scale of private keeping of dangerous wild animals in Great Britain. Results are compared with historical data from England and Wales, showing that there has been an overall decrease both in the total population of dangerous wild animals privately kept under licence and the number of licences, resulting primarily from a decrease in the farming of wild boar and ostrich, and from certain other species no longer requiring a licence to be kept. Nonetheless, the private keeping of dangerous wild animals remains prevalent, with a total population of 3950 animals kept under licence, and at least one-third of local authorities in Britain licensing keepers of one or more such animals. The population of non-farmed dangerous taxa has increased by 59% in 20 years, with notable increases in crocodilians (198%), venomous snakes (94%), and wild cats (57%). We present evidence that the average cost of a licence to keep dangerous wild animals has fallen over time, and that there is a negative association between cost and licensing. The current schedule of species categorised as dangerous is compared to a formally recognised list of species kept in zoos assessed by risk to the public. Problems with the legislation, enforcement of the licensing system, and animal welfare for privately kept dangerous wild animals are identified and discussed.

A review of the toxicological and environmental hazards and risks of tetrahydrofuran.

We present in this paper a review of the toxicological and environmental hazards, exposures and risks of tetrahydrofuran (THF; CASRN 109-99-9). THF is a polar solvent and monomer that is easily absorbed by all routes of exposure. The acute toxicity of THF is low to moderate by all routes. Irreversible corrosive damage to the eye can result from direct contact. However, THF is neither a skin irritant, nor sensitizer. Studies in vitro and in vivo have shown that THF is not mutagenic. Chronic studies have found benign tumors in the kidneys of male rats and in the livers of female mice. These findings have been examined, and although a mode of action is not known, the weight of evidence suggests that these tumors are likely not relevant to human health, but instead secondary to rodent-specific modes of action. THF produces transient sedative effects in rats at high concentrations but no significant neurobehavioral changes or neuropathology in sub-chronic studies. There were no specific effects reported on reproduction or developmental toxicity in rats or mice, with non-specific developmental toxicity observed only in the presence of significant maternal toxicity. The log K(ow) value for THF is less than 3, indicating a low potential for bioaccumulation. THF is inherently biodegradable, thus is not expected to be environmentally persistent. THF does not present an ecotoxicity hazard based on test results in fish, aquatic invertebrates and plants. Exposures to THF in the workplace, to consumers and via environmental releases were modeled and all found to fall below the derived toxicity thresholds.

Patient perceptions of barriers to the early diagnosis of lung cancer and advice for health service improvement.

BACKGROUND AND OBJECTIVE: Patient and systematic factors within primary and secondary care contribute to delay in timely diagnosis of lung cancer. This qualitative study aimed to explore New Zealand service users' experiences of the pathway to lung cancer diagnosis, identify factors contributing to delay and provide advice for service improvement. METHODS: Two samples were recruited. Patients who presented to a hospital emergency department with suspicious symptoms (n = 19) were interviewed individually. Those with confirmed lung cancer (n = 20) took part in a focus group. Similar semi-structured interview schedules were used. Interviews and focus groups were audiorecorded and thematic analyses performed. Evident commonality led to an integrated interpretation. RESULTS: Patient delay was common but most had seen a GP before referral. No ED participant had seen a respiratory specialist prior ED admission, but after that, most had a seamless pathway. This contrasts with long waits for outpatient participants. Two central themes, 'access to health services' and 'processes of care', described factors influencing delay. Subthemes highlighted issues relating to symptom interpretation, health beliefs, provider continuity, relationships and perceived expertise that contributed to patient and GP delay. System complexity, information systems and resourcing issues were identified as barriers at the primary-secondary care interface and within secondary care. CONCLUSION: Reasons for diagnostic delay are complex and multifactorial. Solutions include community initiatives to educate and resource at-risk patients to seek help, supporting and resourcing primary care to increase timely referral and implementing strategies to reduce system complexity for GPs and patients, and the employment of care coordinators.

Data crowdsourcing on psychomotor and cognitive effects of cannabis via mobile app.

In an effort to educate consumers of cannabis, we created a downloadable application (app) for mobile phones that collects data on the neuropsychological effects related to cannabis use. In particular, the app assessed four domains, these being: (i) psychomotor compensation, (ii) time estimation, (iii) sustained attention, and (iv) response inhibition. These tests were presented as a sequence of video games to be completed in under 10 min. Included in the analysis were 213 users who indicated that they were intoxicated from cannabis at the moment of app use. The control group contained individuals who reported using the app while sober (n = 137). A machine learning model was applied to the data to determine whether a particular pattern of performance was predictive of intoxication, and these results were used to inform the creation of a composite score that reflected aggregate performance for all four (i-iv) video games. Relative to the control group, the largest performance decrements were discovered within the initial 120 min after self-administration. These deficits abated as the time-since-use lengthened, and this pattern was consistent with the time-course of subjectively reported intoxication. Although significant limitations in interpretation exist due to the naturalistic and self-report data collection method, this proof-of-concept study points toward the potential utility of mobile app detection of cannabis effect. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Invitation methods for Indigenous New Zealand Maori in lung cancer screening: Protocol for a pragmatic cluster randomized controlled trial.

Lung cancer screening can significantly reduce mortality from lung cancer. Further evidence about how to optimize lung cancer screening for specific populations, including Aotearoa New Zealand (NZ)'s Indigenous Maori (who experience disproportionately higher rates of lung cancer), is needed to ensure it is equitable. This community-based, pragmatic cluster randomized trial aims to determine whether a lung cancer screening invitation from a patient's primary care physician, compared to from a centralized screening service, will optimize screening uptake for Maori. Participating primary care practices (clinics) in Auckland, Aotearoa NZ will be randomized to either the primary care-led or centralized service for delivery of the screening invitation. Clinic patients who meet the following criteria will be eligible: Maori; aged 55-74 years; enrolled in participating clinics in the region; ever-smokers; and have at least a 2% risk of developing lung cancer within six years (determined using the PLCOM2012 risk prediction model). Eligible patients who respond positively to the invitation will undertake shared decision-making with a nurse about undergoing a low dose CT scan (LDCT) and an assessment for Chronic Obstructive Pulmonary Disease (COPD). The primary outcomes are: 1) the proportion of eligible population who complete a risk assessment and 2) the proportion of people eligible for a CT scan who complete the CT scan. Secondary outcomes include evaluating the contextual factors needed to inform the screening process, such as including assessment for Chronic Obstructive Pulmonary Disease (COPD). We will also use the RE-AIM framework to evaluate specific implementation factors. This study is a world-first, Indigenous-led lung cancer screening trial for Maori participants. The study will provide policy-relevant information on a key policy parameter, invitation method. In addition, the trial includes a nested analysis of COPD in the screened Indigenous population, and it provides baseline (T0 screen round) data using RE-AIM implementation outcomes.

Effect of experimental hookworm infection on insulin resistance in people at risk of type 2 diabetes.

The reduced prevalence of insulin resistance and type 2 diabetes in countries with endemic parasitic worm infections suggests a protective role for worms against metabolic disorders, however clinical evidence has been non-existent. This 2-year randomised, double-blinded clinical trial in Australia of hookworm infection in 40 male and female adults at risk of type 2 diabetes assessed the safety and potential metabolic benefits of treatment with either 20 (n = 14) or 40 (n = 13) Necator americanus larvae (L3) or Placebo (n = 13) (Registration ACTRN12617000818336). Primary outcome was safety defined by adverse events and completion rate. Homoeostatic model assessment of insulin resistance, fasting blood glucose and body mass were key secondary outcomes. Adverse events were more frequent in hookworm-treated participants, where 44% experienced expected gastrointestinal symptoms, but completion rates were comparable to Placebo. Fasting glucose and insulin resistance were lowered in both hookworm-treated groups at 1 year, and body mass was reduced after L3-20 treatment at 2 years. This study suggests hookworm infection is safe in people at risk of type 2 diabetes and associated with improved insulin resistance, warranting further exploration of the benefits of hookworms on metabolic health.

A systematic review of methodological principles and delivery of surgical simulation bootcamps.

BACKGROUND: The growth of "bootcamp style" simulation training in surgical practice has been exponential over the last decade. Developing and delivering a surgical bootcamp requires a significant investment. This systematic review aims to identify the key components that allow for a successful and rewarding surgical bootcamp course to be implemented that can be applied to all surgical specialities. METHODS: To understand the surgical bootcamp principles and delivery mechanisms, we searched peer-reviewed, English language studies published between 2000 and 21. RESULTS: From 137 articles, 14 studies with a Medical Education Research Quality Instrument Score of >11.5 were included. Most studies followed the core components; delivery at transition (12), mapping syllabus (13), multimodality delivery (14), and deliberate practice with formative feedback (12) apart from 1:1 training by only 2 studies. CONCLUSIONS: Our review suggests that Surgical bootcamp can be an extremely useful education tool for trainees if 5 pillars of a boot camp are respected.

Practicing internal medicine onboard the USNS COMFORT in the aftermath of the Haitian earthquake.

On 12 January 2010, a 7.0-magnitude earthquake devastated the island nation of Haiti, leading to the world's largest humanitarian effort in over 6 decades. The catastrophe caused massive destruction of homes and buildings and overwhelmed the Haitian health care system. The United States responded immediately with a massive relief effort, sending U.S. military forces and civilian volunteers to Haiti's aid and providing a tertiary care medical center aboard the USNS COMFORT hospital ship. The COMFORT offered sophisticated medical care to a geographically isolated population and helped to transfer resource-intensive patients from other treatment facilities. Working collaboratively with the surgical staff, ancillary services, and nursing staff, internists aboard the COMFORT were integral to supporting the mission of the hospital ship and provided high-level care to the casualties. This article provides the perspective of the U.S. Navy internists who participated in the initial response to the Haitian earthquake disaster onboard the COMFORT.

Socioeconomic inequalities in cancer survival in New Zealand: the role of extent of disease at diagnosis.

We examined socioeconomic inequalities in cancer survival in New Zealand among 132,006 people ages 15 to 99 years who had a cancer registered (1994-2003) and were followed up to 2004. Relative survival rates (RSR) were calculated using deprivation-specific life tables. A census-based measure of socioeconomic position (New Zealand deprivation based on the 1996 census) based on residence at the time of cancer registration was used. All RSRs were age-standardized, and further standardization was used to investigate the effect of extent of disease at diagnosis on survival. Weighted linear regression was used to estimate the deprivation gap (slope index of inequality) between the most and least deprived cases. Socioeconomic inequalities in cancer survival were evident for all of the major cancer sites, with the deprivation gap being particularly high for prostate (-0.15), kidney and uterus (both -0.14), bladder (-0.12), colorectum (-0.10), and brain (+0.10). Accounting for extent of disease explained some of the inequalities in survival from breast and colorectal cancer and melanoma and all of the deprivation gaps in survival of cervical cancer; however, it did not affect RSRs for cancers of the kidney, uterus, and brain. No substantial differences between the total compared with the non-Maori population were found, indicating that the findings were not due to confounding by ethnicity. In summary, socioeconomic disparities in survival were consistent for nearly all cancer sites, persisted in ethnic-specific analyses, and were only partially explained by differential extent of disease at diagnosis. Further investigation of reasons for persisting inequalities is required.

Neural basis and recovery of spatial attention deficits in spatial neglect.

The syndrome of spatial neglect is typically associated with focal injury to the temporoparietal or ventral frontal cortex. This syndrome shows spontaneous partial recovery, but the neural basis of both spatial neglect and its recovery is largely unknown. We show that spatial attention deficits in neglect (rightward bias and reorienting) after right frontal damage correlate with abnormal activation of structurally intact dorsal and ventral parietal regions that mediate related attentional operations in the normal brain. Furthermore, recovery of these attention deficits correlates with the restoration and rebalancing of activity within these regions. These results support a model of recovery based on the re-weighting of activity within a distributed neuronal architecture, and they show that behavioral deficits depend not only on structural changes at the locus of injury, but also on physiological changes in distant but functionally related brain areas.

Urinary Alpha-1-Acid Glycoprotein Is a Sensitive Marker of Glomerular Protein Leakage at Altitude.

Talks, Ben J., Susie B. Bradwell, John Delamere, Will Rayner, Alex Clarke, Chris T. Lewis, Owen D. Thomas, and Arthur R. Bradwell. Urinary alpha-1-acid glycoprotein is a sensitive marker of glomerular protein leakage at altitude. High Alt Med Biol. 19:295-298, 2018.-Proteinuria is an established feature of ascent to altitude and may be caused by a loss of negative charges on glomerular capillary walls (GCWs). To test this hypothesis, we measured two similar sized but oppositely charged proteins in urine: negatively charged alpha-1-acid glycoprotein (α1-AGP, 41-43 kDa) and positively charged dimeric lambda free light chains (λ-FLCs, 50 kDa). Twenty-four-hour urinary leakage was compared with albumin, a 66 kDa negatively charged protein. We studied 23 individuals (ages 23-78 years, male = 17) at baseline (140 m) and daily during an expedition to 5035 m. The results showed a significant increase in median urinary leakage of α1-AGP (p < 0.0001; 6.85-fold) and albumin (p = 0.0006; 1.65-fold) with ascent to altitude, but no significant increase in leakage of λ-FLCs (p = 0.39; 1.14-fold). α1-AGP correlated with the daily ascent profile (p = 0.0026) and partial pressure of oxygen (p = 0.01), whereas albumin showed no correlation (p = 0.19). Urinary α1-AGP was a more sensitive marker of altitude proteinuria than urinary albumin and λ-FLCs, and supported the possibility of loss of GCW negative charges at altitude.

Using a cluster randomized controlled trial to determine the effects of intervention of battery and hardwired smoke alarms in New South Wales, Australia: Home fire safety checks pilot program.

INTRODUCTION: In 2014, Fire & Rescue New South Wales piloted the delivery of its home fire safety checks program (HFSC) aimed at engaging and educating targeted top "at risk" groups to prevent and prepare for fire. This pilot study aimed to assess the effectiveness of smoke alarms using a cluster randomized controlled trial. METHODS: Survey questionnaires were distributed to the households that had participated in the HFSC program (intervention group). A separate survey questionnaire was distributed to the control group that was identified with similar characteristics to the intervention group in the same suburb. To adjust for potential clustering effects, generalized estimation equations with a log link were used. RESULTS: Multivariable analyses revealed that battery and hardwired smoking alarm usage increased by 9% and 3% respectively among the intervention group compared to the control group. Females were more likely to install battery smoke alarms than males. Respondents who possessed a certificate or diploma (AOR=1.31, 95% CI 1.00-1.70, P=0.047) and those who were educated up to years 8-12 (AOR=1.32, 95% CI 1.06-1.64, P=0.012) were significantly more likely to install battery smoke alarms than those who completed bachelor degrees. Conversely, holders of a certificate or diploma and people who were educated up to years 8-12 were 31% (AOR=0.69, 95% CI 0.52-0.93, P=0.014) and 24% (AOR=0.76, 95% CI 0.60-0.95, P=0.015) significantly less likely to install a hardwired smoke alarm compared to those who completed bachelor degrees. CONCLUSIONS: This pilot study provided evidence of the benefit of the HFSC in New South Wales. PRACTICAL APPLICATIONS: Fire safety intervention programs, like HFSC, need to be targeted to male adults with lower level of schooling even when they are aware of their risks.

A tele-ultrasound needs analysis in Queensland.

A tele-ultrasound survey was distributed to clinicians and sonographers in regional and rural sites throughout Queensland. In all, 28 centres were invited to complete a profile questionnaire, and 27 centres were invited to complete a case-log. Twenty-five of the 28 questionnaires were returned (89% response rate). Twenty-two of the 27 case-logs were returned (81% response rate). Obstetric ultrasound was the most frequently performed ultrasound examination, accounting for 846 (35%) of the 2,410 recorded during the two-week survey period. The respondents considered that 182 cases would have benefited from further consultation: 79% for diagnostic advice, 13% for patient management advice and 8% for advice on examination technique. Six hospitals appeared to have the greatest need for a tele-ultrasound service. There was a strong preference for the store-and-forward transmission of static images: 70% preferred this modality, in comparison with 19% who preferred realtime transmission and 11% who preferred store-and-forward transmission of video clips.