A moderate spinal contusion injury in rats alters bone turnover both below and above the level of injury with sex-based differences apparent in long-term recovery.

Spinal cord injury (SCI) leads to significant sublesional bone loss and high fracture rates. While loss of mechanical loading plays a significant role in SCI-induced bone loss, animal studies have demonstrated mechanical loading alone does not fully account for loss of bone following SCI. Indeed, we have shown that bone loss occurs below the level of an incomplete moderate contusion SCI, despite the resumption of weight-bearing and stepping. As systemic factors could also impact bone after SCI, bone alterations may also be present in bone sites above the level of injury. To examine this, we assessed bone microarchitecture and bone turnover in the supralesional humerus in male and female rats at two different ages following a moderate contusion injury in both sub-chronic (30 days) and chronic (180 days) time points after injury. At the 30-day timepoint, we found that both young and adult male SCI rats had decrements in trabecular bone volume at the supralesional proximal humerus (PH), while female SCI rats were not different from age-matched shams. At the 180-day timepoint, there were no statistical differences between SCI and sham groups, irrespective of age or sex, at the supralesional proximal humerus. At the 30-day timepoint, all SCI rats had lower BFR and higher osteoclast-covered trabecular surfaces in the proximal humerus compared to age-matched sham groups generally matching the pattern of SCI-induced changes in bone turnover seen in the sublesional proximal tibia. However, at the 180-day timepoint, only male SCI rats had lower BFR at the supralesional proximal humerus while female SCI rats had higher or no different BFR than their age-matched counterparts. Overall, this preclinical study demonstrates that a moderate contusion SCI leads to alterations in bone turnover above the level of injury within 30-days of injury; however male SCI rats maintained lower BFR in the supralesional humerus into long-term recovery. These data further highlight that bone loss after SCI is not driven solely by disuse. Additionally, these data allude to potential systemic factors exerting influence on bone following SCI and highlight the need to consider treatments for SCI-induced bone loss that impact both sublesional and systemic factors.

Impact of COVID-19 on people with non-functioning spleens in Australia.

BACKGROUND: COVID-19 has had enormous impact on health and social systems, with stringent public health measures enacted across Australia. The virus itself disproportionately affects immunocompromised individuals including people without functioning spleens. We thus sought to characterise the psychological and physical impact of COVID-19 and such measures upon this oft-neglected patient group. METHODS: Adults ≥ 18 years old identified from the Spleen Australia (SA) database were invited to participate in an online survey in November to December 2021 to assess the impact of the COVID-19 pandemic. Stata (v17, StataCorps, Texas, USA) was used to conduct descriptive and frequency analyses. RESULTS: 2864 respondents were surveyed. The majority were female (1473/2838, 51.9%), Australian-born (2257/2835, 79.6%), and living in Victoria (1755/2822, 62.2%). The largest age group was 61-70 years-old (841/2858, 29.4%). Trauma was the commonest reason for asplenia (826/2724, 30.3%). Respondents reported the pandemic reduced their ability to visit a GP (753/2864, 26.3%), access food (153/2864, 5.3%), medications (179/2864, 6.3%) or spleen-specific vaccines (120/2864, 4.2%), maintain relationships (503/2864, 17.6%), or care for children (127/2864, 4.4%). 84.8% of participants reported at least one impact of COVID, including negative physical health (1463/2864, 51.1%), mental health (733/2864, 25.6%) and financial repercussions (509/2864, 17.8%). 96.9% (2743/2831) had received at least one dose of COVID-19 vaccines. CONCLUSIONS: Overall, we found detailed evidence of the negative psychological and physical impacts of the pandemic upon this cohort. We recommend that providers consider people without functioning spleens as requiring extra social and psychological support in circumstances such as the COVID-19 pandemic.

Intrathecal minocycline does not block the adverse effects of repeated, intravenous morphine administration on recovery of function after SCI.

Opioids are among the most effective analgesics for the management of pain in the acute phase of a spinal cord injury (SCI), and approximately 80% of patients are treated with morphine in the first 24 h following SCI. We have found that morphine treatment in the first 7 days after SCI increases symptoms of pain at 42 days post-injury and undermines the recovery of locomotor function in a rodent model. Prior research has implicated microglia/macrophages in opioid-induced hyperalgesia and the development of neuropathic pain. We hypothesized that glial activation may also underlie the development of morphine-induced pain and cell death after SCI. Supporting this hypothesis, our previous studies found that intrathecal and intravenous morphine increase the number of activated microglia and macrophages present at the spinal lesion site, and that the adverse effects of intrathecal morphine can be blocked with intrathecal minocycline. Recognizing that the cellular expression of opioid receptors, and the intracellular signaling pathways engaged, can change with repeated administration of opioids, the current study tested whether minocycline was also protective with repeated intravenous morphine administration, more closely simulating clinical treatment. Using a rat model of SCI, we co-administered intravenous morphine and intrathecal minocycline for the first 7 days post injury and monitored sensory and locomotor recovery. Contrary to our hypothesis and previous findings with intrathecal morphine, we found that minocycline did not prevent the negative effects of morphine. Surprisingly, we also found that intrathecal minocycline alone is detrimental for locomotor recovery after SCI. Using ex vivo cell cultures, we investigated how minocycline and morphine altered microglia/macrophage function. Commensurate with published studies, we found that minocycline blocked the effects of morphine on the release of pro-inflammatory cytokines but, like morphine, it increased glial phagocytosis. While phagocytosis is critical for the removal of cellular and extracellular debris at the spinal injury site, increased phagocytosis after injury has been linked to the clearance of stressed but viable neurons and protracted inflammation. In sum, our data suggest that both morphine and minocycline alter the acute immune response, and reduce locomotor recovery after SCI.

The PRotective Effect of Maternal Immunisation on preTerm birth: characterising the Underlying mechanisms and Role in newborn immune function: the PREMITUR study protocol.

Maternal immunisation, a low cost and high efficacy intervention is recommended for its pathogen specific protection. Evidence suggests that maternal immunisation has another significant impact: reduction of preterm birth (PTB), the single greatest cause of childhood morbidity and mortality globally. Our overarching question is: how does maternal immunisation modify the immune system in pregnant women and/or their newborn to reduce adverse pregnancy outcomes and enhance the newborn infant's capacity to protect itself from infectious diseases during early childhood? To answer this question we are conducting a multi-site, prospective observational cohort study collecting maternal and infant biological samples at defined time points during pregnancy and post-partum from nulliparous women. We aim to enrol 400 women and determine the immune trajectory in pregnancy and the impact of maternal immunisation (including influenza, pertussis and/or COVID-19 vaccines) on this trajectory. The results are expected to identify areas that can be targeted for future intervention studies.

Successful expanded clinic network collaboration and patient tracing for retention in HIV care.

BACKGROUND: There are more than 7,800 people living with human immunodeficiency virus (HIV) in Victoria, Australia. Crucial in maximising the individual and population level benefits from antiretroviral therapy (ART) is understanding how to achieve patient retention in care and the factors that drive it. This study was an expansion of a 2015 assessment of HIV-care retention in Victoria, which sought out to determine whether the inclusion of a broader range of HIV-healthcare sites would yield more accurate estimates of retention in HIV-care. We aimed to improve our understanding of HIV-care retention in Victoria, Australia, identify people living with HIV (PLHIV) with unknown outcomes, and attempt to re-engage PLHIV in care. METHODS: A network of 15 HIV-care sites was established in Victoria, Australia across diverse care settings which ranged from low-caseload rural sites to high-caseload metropolitan GP clinics and hospitals. Individuals who had an HIV viral load (VL) performed in both calendar years of 2016 and 2017 were classified as retained in care. Individuals with a VL test in 2016 but not in 2017 were considered to potentially have unknown outcomes as they may have been receiving care elsewhere, have disengaged from care or died. For this group, an intervention of cross-referencing partially de-identified data between healthcare sites, and contact tracing individuals who still had unknown outcomes was performed. RESULTS: For 5223 individuals considered to be retained in care across 15 healthcare sites in the study period, 49 had unconfirmed transfers of care to an alternative provider and 79 had unknown outcomes. After the intervention, the number of unconfirmed care transfers was reduced to 17 and unknown outcomes reduced to 51. These changes were largely attributed to people being reclassified as confirmed transfers of care. Retention in care estimates that did not include the patient outcome of confirmed transfer of care ranged from 76.2 to 95.8% and did not alter with the intervention. However, retention in care estimates which considered confirmed transfers and those that re-entered care at a new site as retained in care significantly increased across five of the sites with estimates ranging from 80.9 to 98.3% pre-intervention to 83.3-100% post-intervention. Individuals whose outcomes remained unknown post-intervention were more often men who have sex with men (MSM) when compared to other categories (person who injects drugs (PWID), combined PWID/MSM, men who identify as heterosexual or unknown) (74.5% vs. 53.5%, [p = 0.06]) and receiving ART at their last HIV-care visit (84.3% vs. 67.8% [p = 0.09]). CONCLUSION: This study confirmed high retention in HIV-care and low numbers of people disengaged from HIV-care in Victoria. This was demonstrated across a larger number of sites with varying models of care than a prior assessment in 2015. These data align with national and state targets aiming for 95% of PLHIV retained in HIV-care.

The Impact of the COVID-19 Pandemic on People with HIV in Victoria, Australia: 1 Year Later.

In the first year of the COVID-19 pandemic, Australia had <30,000 COVID-19 cases. Formerly stringent public health measures are now relaxed and vaccinations are available. We compared pandemic impacts on Victorians with HIV (people with HIV [PWHIV]) over time. Two surveys were developed with HIV stakeholder groups appraising demographics, concern, and pandemic impacts. The latter included vaccination, mental health, and quality of life questions. Recruitment was through social media and Alfred and Monash Health HIV-clinics (first survey August 26 to November 26, 2020; second survey October 30, 2021 to January 31, 2022). The surveys had 153 and 95 respondents, respectively. Demographics were similar. Most reported negatively impacted mental health (68%). Most (56%) required mental health services, of these, 39% could not access them. Rates of concern increased. Ninety percent had two COVID-19 vaccinations. Both surveys demonstrated HIV and non-HIV-care provision. PWHIV reported concern and negative impacts. Improved mental health services access is needed to optimize PWHIV quality of life.

How COVID-19 has impacted immunisation service delivery in Australia: a national study.

OBJECTIVE: The objective of this study was to determine the impact the COVID-19 pandemic had on the delivery of adult, maternal and childhood immunisation services in Australia in 2020 prior to the rollout of COVID-19 vaccines, and to understand the adaptations made at a service delivery level that may have contributed to the successful delivery of immunisation services during the first year of the pandemic. METHODS: An electronic survey was sent to immunisation providers and pharmacists in all states and territories in Australia between November 2020 and December 2020. It explored interruption to the delivery of immunisation services, strategies implemented to maintain services, prioritisation of populations, and self-reported challenges and solutions initiated by providers. RESULTS: A total of 850 people responded to the survey. Of these, the most common professional groups identified were pharmacists followed by nurse immunisers, nurses/midwives and general practitioners. Several changes were implemented including relocation of vaccination clinics, change to bookings rather than walk-in appointments, infection prevention measures, clients waiting in cars pre- and post-vaccination and reduced observation period post-vaccination. CONCLUSION: The pandemic has provided opportunities for services to trial new and innovative strategies such as electronic pre-assessment, electronic consent and drive-through vaccination services. IMPLICATIONS FOR PUBLIC HEALTH: Immunisation providers mostly viewed these changes positively and intend to continue many post-pandemic. The experience gained from the trialling of these strategies may be adapted for vaccine delivery and National Immunisation Program vaccines beyond the pandemic.

A clinical trial of non-invasive imaging with an anti-HIV antibody labelled with copper-64 in people living with HIV and uninfected controls.

BACKGROUND: A research priority in finding a cure for HIV is to establish methods to accurately locate and quantify where and how HIV persists in people living with HIV (PLWH) receiving suppressive antiretroviral therapy (ART). Infusing copper-64 (64Cu) radiolabelled broadly neutralising antibodies targeting HIV envelope (Env) with CT scan and positron emission tomography (PET) identified HIV Env in tissues in SIV infected non-human primates . We aimed to determine if a similar approach was effective in people living with HIV (PLWH). METHODS: Unmodified 3BNC117 was compared with 3BNC117 bound to the chelator MeCOSar and 64Cu (64Cu-3BNC117) in vitro to assess binding and neutralization. In a clinical trial 64Cu-3BNC117 was infused into HIV uninfected (Group 1), HIV infected and viremic (viral load, VL >1000 c/mL; Group 2) and HIV infected aviremic (VL <20 c/mL; Group 3) participants using two dosing strategies: high protein (3mg/kg unlabeled 3BNC117 combined with <5mg 64Cu-3BNC117) and trace (<5mg 64Cu-3BNC117 only). All participants were screened for 3BNC117 sensitivity from virus obtained from viral outgrowth. Magnetic resonance imaging (MRI)/PET and pharmacokinetic assessments (ELISA for serum 3BNC117 concentrations and gamma counting for 64Cu) were performed 1, 24- and 48-hours post dosing. The trial (clincialtrials.gov NCT03063788) primary endpoint was comparison of PET standard uptake values (SUVs) in regions of interest (e.g lymph node groups and gastrointestinal tract). FINDINGS: Comparison of unmodified and modified 3BNC117 in vitro demonstrated no difference in HIV binding or neutralisation. 17 individuals were enrolled of which 12 were dosed including Group 1 (n=4, 2 high protein, 2 trace dose), Group 2 (n=6, 2 high protein, 4 trace) and Group 3 (n=2, trace only). HIV+ participants had a mean CD4 of 574 cells/microL and mean age 43 years. There were no drug related adverse effects and no differences in tissue uptake in regions of interest (e.g lymph node gut, pharynx) between the 3 groups. In the high protein dosing group, serum concentrations of 3BNC117 and gamma counts were highly correlated demonstrating that 64Cu-3BNC117 remained intact in vivo. INTERPRETATION: In PLWH on or off ART, the intervention of infusing 64Cu-3BNC117 and MRI/PET imaging over 48 hours, was unable to detect HIV-1 env expression in vivo. Future studies should investigate alternative radiolabels such as zirconium which have a longer half-life in vivo. FUNDING: Funded by the Alfred Foundation, The Australian Centre for HIV and Hepatitis Virology Research with additional support from the Division of AIDS, National Institute of Allergy and Infectious Disease, US National Institutes of Health (USAI126611). JHM and SRL are supported by the Australian National Health and Medical Research Council.

The Impact of the COVID-19 Pandemic on People Living with HIV in Victoria, Australia.

As of January 12, 2021, Australia has reported 28,634 COVID-19 cases. Most (20,411) cases are from the state of Victoria. In response to rising infections and community transmission in July 2020, on August 2nd, several restrictions were imposed for the following 111 days, including an 8pm curfew, a travel restriction to 5 km from home, and closure of nonessential services. It is unknown how this affected people living with HIV (PLHIV), who already experience disproportionate levels of mental health issues, comorbidity, and stigma. An online survey was designed with HIV community-based organizations to investigate the impact of the pandemic on Victorian PLHIV. Participants were recruited voluntarily both through social media and Infectious Diseases clinics at participating hospitals. There were 153 respondents. Most were male (77%), aged between 30 and 60 years (77%), and Australian-born (63%). Forty-three percent, 31%, and 25% reported negative impacts upon personal relationships, employment, and income, respectively. HIV care continued with 95% and 98% being able to access their HIV provider and antiretroviral therapy (ART), respectively. Telehealth was used by 92% and was largely well received. PLHIV reported worry about physical health (68%), mental health (66%), finances (50%),z and accommodation (25%). Fifty percent of participants reported weight gain and 27% increased alcohol intake. This study demonstrated the widespread negative effects of the COVID-19 pandemic on PLHIV in Victoria, although provision of HIV care and ART continued uninterrupted. This highlighted the importance of mental health support and social welfare programs during times of health care and societal strain.

Prevalence of suicidal ideation in patients with chronic non-cancer pain referred to a behaviorally based pain program.

BACKGROUND: Patients with chronic pain often experience co-occurring depression and in some cases suicidal ideation. It is critical to discover risk factors for suicide in this vulnerable patient population. OBJECTIVE: To assess the prevalence of suicidal ideation and identify potential risk factors in patients with chronic non-cancer pain. STUDY DESIGN: Retrospective chart review. SETTING: Four hundred and sixty-six patients with chronic non-cancer pain referred to a behaviorally based pain program in a community health system. METHODS: Data collected included pain intensity and level of pain interference (Brief Pain Inventory), pain duration, pain site, depression level (Beck Depression Inventory Fast Screen for Medical Patients), anxiety (Beck Anxiety Inventory), personal and family psychiatric and substance use disorder history, level of isolation, and demographic data. Univariate and logistic regression analyses were performed. RESULTS: Results showed a high rate of suicidal ideation in this patient population (28%). Univariate analyses stratified by level of suicide (no suicidal ideation or passive/active suicidal ideation) revealed statistically significant group differences on pain location (extremity P = 0.046, generalized P = 0.047), work disruption (P = 0.049), social withdrawal (P < 0.001), pre-pain history of depression (P < 0.001), family history of depression (P < 0.001), and history of sexual/physical abuse (P < 0.001). Logistic regression revealed that history of sexual/physical abuse (Beta = 0.825; P = 0.020; OR = 2.657 [95% CI = 1.447 - 4.877]), family history of depression (Beta = 0.471; P = 0.006; OR = 1.985 [95% CI = 1.234 - 3.070]), and being socially withdrawn (Beta = 0.482; P < 0.001; OR = 2.226 [95% CI = 1.431 - 3.505]) were predictive of suicidal ideation. LIMITATIONS: Measure of depression was not included in data analysis to reduce effect of co-linearity. Also the study population was a specialty pain clinic allowing for possible subject selection bias. CONCLUSIONS: Results of this study are consistent with the prevailing literature on pain and suicide demonstrating a high prevalence of suicidal ideation in the chronic pain population. Novel predictive variables were also identified that will provide the basis for developing a risk stratification model that can be further tested prospectively in chronic pain patients.

Comparison of the quality of life of early and advanced stage ovarian cancer survivors.

OBJECTIVE: The objective of this study was to compare the long-term adjustment and QOL of early and advanced stage ovarian cancer survivors (OCS). METHODS: Early and advanced OCS >3 years from diagnosis with no evidence of recurrent cancer were interviewed. The following surveys were administered: EORTC QLQ-C30 (overall QOL) and QLQ-OV28 (ovarian specific issues), MHI-17 (anxiety, depression and global well-being), CALGB sexual functioning, FACT Fatigue, Beck's Hopelessness Scale, Fear of Recurrence (FOR), PCL-C post-traumatic stress disorder (PTSD), Unmet Needs, FACT-Spirituality (FACT-Sp), complementary therapy (CAM use), and MOS Social Support Survey (MOS). The results of the surveys were compared between the early and advanced stage groups. RESULTS: 42 advanced and 58 early stage patients were interviewed. The majority of survivors scored above the medical outpatient norm for emotional status (71% of early stage and 64% of advanced stage survivors). Overall QOL, fatigue, hopelessness, spirituality, social support, degree to which unmet needs were met and use of complementary therapy, did not differ between the two groups. No advanced stage OCS had diagnosable PTSD scores, while 6.9% of early stage survivors had scores indicative of PTSD. Decreased sexual interest attributed to cancer and anxiety when getting CA-125 testing were of concern for both groups. OCS used on average 5 CAM to improve their QOL. CONCLUSION: Regardless of staging, OCS experience similarly overall positive QOL and adjustment, though PTSD, sexual problems and fear of recurrence are still important for some survivors.