Treatment Of Episodes Research Articles

Pilot study comparing sleep logs to a commercial wearable device in describing the sleep patterns of physicians-in-training.

With the increasing burden of professional burnout in physicians, attention is being paid to optimizing sleep health, starting in training. The multiple dimensions of physicians' sleep are not well described due to obstacles to easily and reliably measuring sleep. This pilot study tested the feasibility of using commercial wearable devices and completing manual sleep logs to describe sleep patterns of medical students and residents. Prospective pilot study of 50 resident physicians and medical students during a single year of training. Participants completed a manual sleep log while concurrently wearing the Fitbit Inspire device for 14-consecutive days over three clinical rotations of varying work schedules: light, medium, and heavy clinical rotations. Study completion was achieved in 24/50 (48%) participants. Overall correlation coefficients between the sleep log and Fitbit were statistically low; however, the discrepancies were acceptable, i.e., Fitbit underestimated time in bed and total sleep time by 4.3 and 2.7 minutes, respectively. Sleep onset time and waketime were within 8 minutes, with good agreement. Treatment of sleep episodes during the day led to variance in the data. Average missingness of collected data did not vary between medical students or residents or by rotation type. When comparing the light to heavy rotations, hours slept went from 7.7 (±0.64) to 6.7 (±0.88), quality-of-life and sleep health decreased and stress, burnout, and medical errors increased. Burnout was significantly associated with worse sleep health, hours worked, and quality-of-life. Prospective data collection of sleep patterns using both sleep logs and commercial wearable devices is burdensome for physicians-in-training. Using commercial wearable devices may increase study success as long as attention is paid to daytime sleep. In future studies investigating the sleep of physicians, the timing of data collection should account for rotation type.

Bevacizumab-Based Therapies in Malignant Tumors-Real-World Data on Effectiveness, Safety, and Cost.

For this purpose, we conducted an open, observational, retrospective study involving all patients treated for solid malignant tumors in the Bucharest Institute of Oncology with "Prof. Dr. Al. Trestioreanu" with Bevacizumab-based systemic therapy, between 2017 and 2021. The study consisted of 657 treatment episodes in 625 patients (F/B = 1.62/1, with a median age of 57.6 years) which were treated for malignant tumors (majority colorectal, non-small cell lung, ovarian, and breast cancer). First-line treatment was administered in 229 patients, and the rest received Bevacizumab as second or subsequent lines of treatment. The overall response rate to Bevacizumab-based therapies was around 60-65% across all indication except for subsequent treatment lines in colorectal and ovarian cancers, where lower values were recorded (27.1%, and 31.5% respectively). Median PFS for the entire cohort was 8.2 months (95% CI 6.8-9.6), and the median OS was 13.2 months (95% CI 11.5-14.9). Usual bevacizumab-related toxicities were observed, including bleeding, hypertension, wound-healing complications, gastrointestinal perforation, other types of fistulas, septic complications, and thromboembolic events. Although the clinical benefits are undeniable, the addition of Bevacizumab to standard chemotherapy increased the overall treatment cost by 213%. Bevacizumab remains a high-cost therapy, but it can add to clinical benefits (like overall survival, progression-free survival, and response rate) when used in conjunction with standard chemotherapy. Similar results as those presented in various controlled trials are observable even on unselected cohorts of patients in the uncontrolled conditions of "real-world" oncological practice. Off-label usage is encountered in clinical practice, and this aspect should be monitored given the potential adverse effects of the therapy.

High-Dose Opioid Prescribing in Individuals with Acute Pain: Assessing the Effects of US State Opioid Policies.

How state opioid policy environments with multiple concurrent policies affect opioid prescribing to individuals with acute pain is unknown. To examine how prescription drug monitoring programs (PDMPs), pain management clinic regulations, initial prescription duration limits, and mandatory continued medical education affected total and high-dose prescribing. A county-level multiple-policy difference-in-difference event study framework. A total of 2,425,643 individuals in a large national commercial insurance deidentified claims database (aged 12-64 years) with acute pain diagnoses and opioid prescriptions from 2007 to 2019. The total number of acute pain opioid treatment episodes and number of episodes containing high-dose (> 90 morphine equivalent daily dosage (MEDD)) prescriptions. Approximately 7.5% of acute pain episodes were categorized as high-dose episodes. Prescription duration limits were associated with increases in the number of total episodes; no other policy was found to have a significant impact. Beginning five quarters after implementation, counties in states with pain management clinic regulations experienced a sustained 50% relative decline in the number of episodes containing > 90 MEDD prescriptions (95 CIs: (Q5: - 0.506, - 0.144; Q12: - 1.000, - 0.290)). Mandated continuing medical education regarding the treatment of pain was associated with a 50-75% relative increase in number of high-dose episodes following the first year-and-a-half of enactment (95 CIs: (Q7: 0.351, 0.869; Q12: 0.413, 1.107)). Initial prescription duration limits were associated with an initial relative reduction of 25% in high-dose prescribing, with the effect increasing over time (95 CI: (Q12: - 0.967, - 0.335). There was no evidence that PDMPs affected high-dose opioids dispensed to individuals with acute pain. Other high-risk prescribing indicators were explored as well; no consistent policy impacts were found. State opioid policies may have differential effects on high-dose opioid dispensing in individuals with acute pain. Policymakers should consider effectiveness of individual policies in the presence of other opioid policies to address the ongoing opioid crisis.

Clinical factors associated with hyponatremia correction during treatment with oral Urea.

Oral urea is being used more commonly to treat hyponatremia, but factors contributing to the correction rate are unknown. We hypothesized that clinically relevant factors can be identified to help guide hyponatremia correction with oral urea. Retrospective study in two university hospitals including hospitalized patients with hyponatremia (plasma sodium < 135mmol/L) treated with oral urea. Linear mixed-effects models were used to identify factors associated with hyponatremia correction. Rates of overcorrection, osmotic demyelination and treatment discontinuation were also assessed. We included 161 urea treatment episodes in 140 patients (median age 69 years, 46% females, 93% syndrome of inappropriate antidiuresis). Oral urea succeeded fluid restriction in 117 treatment episodes (73%), was combined with fluid restriction in 104 treatment episodes (65%) and was given as only treatment in 27 treatment episodes (17%). A median dose of 30 grams/day of urea for 4 days (interquartile range 2-7 days) increased plasma sodium from 127 to 134mmol/L and normalized hyponatremia in 47% of treatment episodes. Older age (ß 0.09, 95%CI 0.02 to 0.16), lower baseline plasma sodium (ß -0.65, 95%CI -0.78 to -0.62), and higher cumulative urea dose (ß 0.03, 95%CI -0.02 to -0.03) were independently associated with a greater rise in plasma sodium. Concurrent fluid restriction was associated with a greater rise in plasma sodium only during the first 48h of treatment (ß 1.81, 95%CI 0.40 to 3.08). Overcorrection occurred in 5 cases (3%), no cases of osmotic demyelination were identified, and oral urea was discontinued in 11 cases (11%) due to side-effects. During treatment with oral urea, older age, higher cumulative dose, lower baseline plasma sodium and initial fluid restriction are associated with a greater correction rate of hyponatremia. These factors may guide clinicians to achieve a gradual correction of hyponatremia with oral urea.

A reference architecture for personal health data spaces using decentralized content-addressable storage networks.

This paper addresses the dilemmas of accessibility, comprehensiveness, and ownership related to health data. To resolve these dilemmas, we propose and justify a novel, globally scalable reference architecture for a Personal Health Data Space (PHDS). This architecture leverages decentralized content-addressable storage (DCAS) networks, ensuring that the data subject retains complete control and ownership of their personal health data. In today's globalized world, where people are increasingly mobile for work and leisure, healthcare is transitioning from episodic symptom-based treatment toward continuity of care. The main aims of this are patient engagement, illness prevention, and active and healthy longevity. This shift, along with the secondary use of health data for societal benefit, has intensified the challenges associated with health data accessibility, comprehensiveness, and ownership. The study is structured around four health data use case scenarios from the Estonian National Health Information System (EHIS): primary medical use, medical emergency use, secondary use, and personal use. We analyze these use cases from the perspectives of accessibility, comprehensiveness, and ownership. Additionally, we examine the security, privacy, and interoperability aspects of health data. The proposed architectural solution allows individuals to consolidate all their health data into a unified Personal Health Record (PHR). This data can come from various healthcare institutions, mobile applications, medical devices for home use, and personal health notes. The comprehensive PHR can then be shared with healthcare providers in a semantically interoperable manner, regardless of their location or the information systems they use. Furthermore, individuals maintain the autonomy to share, sell, or donate their anonymous or pseudonymous health data for secondary use with different systems worldwide. The proposed reference architecture aligns with the principles of the European Health Data Space (EHDS) initiative, enhancing health data management by providing a secure, cost-effective, and sustainable solution.

Management of Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Cytomegalovirus (CMV) is a type of double-stranded deoxyribonucleic acid virus belonging to the herpesviridae family. Following a primary infection, the virus becomes latent in various types of white blood cells. Cytomegalovirus infection can remain latent or become active, especially in immunocompromised individuals, such as those undergoing hematopoietic stem cell transplantation (HSCT), where CMV reactivation can occur. In this context, CMV infection is common and associated with high rates of morbidity and mortality. Pneumonia is one of the most serious complications, with mortality rates exceeding 50%. Additionally, even in the absence of organ-specific disease, CMV infection is related to increased mortality unrelated to hematologic neoplasm recurrence. Given the frequency and severity of this infection in HSCT patients, it is crucial to implement effective strategies for monitoring, prevention, and treatment. This guideline was developed to identify patient groups that benefit from a systematic approach to CMV infection and to define the most appropriate strategy for each group. Monitoring CMV viral load in peripheral blood is crucial, especially in patients at moderate to high risk of active infection. Primary prophylaxis with letermovir (an antiviral drug) is recommended to reduce the incidence of active infection, especially in high-risk patients. Secondary prophylaxis with valganciclovir (antiviral drug) is recommended after an episode of active infection, while preemptive and disease treatment is based on monitoring viral load and clinical response. The aim of this guideline is to improve the approach to CMV infection in HSCT patients, ensuring an effective and safe preventive and therapeutic approach.

Comparative Risk of Serious Infection With Vedolizumab vs Anti-Tumor Necrosis Factor in Inflammatory Bowel Disease: Results From Nationwide Swedish Registers.

We aimed to assess the risk of serious infection in patients with inflammatory bowel disease (IBD) treated with vedolizumab compared with those treated with anti-tumor necrosis factors (TNF) and the general population. In this Swedish cohort study, treatment episodes were identified from nationwide health registers. We used Cox regression with propensity score-matched cohorts to estimate hazard ratios (HRs) for incident serious infections, defined as infections requiring hospital admission. During 1,376 treatment episodes in Crohn's disease, the rate of serious infections per 100 person-years (PY) was 5.18 (95% CI = 3.98-6.63) with vedolizumab vs 3.54 (95% CI = 2.50-4.85) with anti-TNF; HR = 1.72 (95% CI = 1.12-2.65), partly explained by more gastrointestinal infections. Compared with the rate of 0.75/100 PY (95% CI = 0.59-0.92) in a matched general population cohort, vedolizumab demonstrated higher risk (HR = 7.00; 95% CI = 5.04-9.72). During 1,294 treatment episodes in ulcerative colitis, the corresponding rates were 3.74/100 PY (95% CI = 2.66-5.11) with vedolizumab vs 3.42/100 PY (95% CI = 2.31-4.89) with anti-TNF; HR = 0.80 (95% CI = 0.47-1.36) during the initial 1.1 years and HR = 2.03 (95% CI = 0.65-6.32) after 1.1 years (truncated due to nonproportional hazards). Pneumonia accounted for 40% of all infections among anti-TNF, whereas no case was observed among vedolizumab episodes. Compared with the rate of 0.69/100 PYs (95% CI = 0.53-0.87) in a matched general population cohort, vedolizumab showed an HR of 5.45 (95% CI = 3.67-8.11). Vedolizumab was associated with increased risks of serious infections compared with anti-TNF in Crohn's disease but not in ulcerative colitis. Nonetheless, the panorama of serious infections seemed to differ between the drugs. Our findings underscore the importance of clinical awareness of infections and the safety profile of the 2 therapies.

Efficacy and tolerability of monoamine oxidase inhibitors for the treatment of depressive episodes in mood disorders: A systematic review and network meta-analysis.

Monoamine oxidase inhibitors (MAOIs) are considered third-line treatments for treatment resistant depression; however, they are underused in clinical practice. This study aimed to assess the efficacy, tolerability, and acceptability of MAOIs for the treatment of depression in comparison with other antidepressant treatments. A systematic review and network meta-analysis of randomised clinical trials was performed to compare the efficacy, tolerability and acceptability between MAOIs and other antidepressant treatments for the treatment of depressive episodes. A total of 83 double-blinded, randomised controlled trials were included in the analysis, with 7765 participants assigned to an active treatment and 1844 assigned to placebo. Several MAOIs, including isocarboxazid, phenelzine, tranylcypromine and moclobemide, showed significantly higher efficacy compared with placebo. The tolerability and acceptability of MAOIs was comparable to other antidepressants. A disproportionate number of studies investigating the most commonly used MAOIs, such as moclobemide and phenelzine, and a lack of specific studies focusing on treatment-resistant and atypical depression. MAOIs are similar in efficacy to other antidepressants for the treatment of depression. However, more studies are needed comparing MAOI treatment in people with treatment-resistant, atypical and bipolar depression.

S47 - Trends in Buprenorphine Dosage and Days Supplied for New Treatment Episodes, 2010-2019

S47 - Trends in Buprenorphine Dosage and Days Supplied for New Treatment Episodes, 2010-2019

S44 - Prescription Opioid Tapering Patterns Prior to Discontinuation of Long-Term, High-Dosage Treatment Episodes Among Adult Medicaid Enrollees

S44 - Prescription Opioid Tapering Patterns Prior to Discontinuation of Long-Term, High-Dosage Treatment Episodes Among Adult Medicaid Enrollees

Hospital-Treated Infections and Risk of Disability Worsening in Multiple Sclerosis.

To investigate the association between infections and disability worsening in people with multiple sclerosis (MS) treated with either B-cell depleting therapy (rituximab) or interferon-beta/glatiramer acetate (IFN/GA). This cohort study spanned from 2000 to 2021, using data from the Swedish MS Registry linked to national health care registries, comprising 8,759 rituximab and 7,561 IFN/GA treatment episodes. The risk of hospital-treated infection was estimated using multivariable Cox models. The association between infections and increase in Expanded Disability Status Scale (EDSS) scores was assessed using a doubly robust generalized estimating equations model. Additionally, a piece-wise exponential model analyzed events of increased disability beyond defined cut-off values, controlling for relapses, and MRI activity. Compared with IFN/GA, rituximab displayed increased risk of both inpatient- and outpatient-treated infections (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.50-2.90 and HR, 1.37; 95% CI, 1.13-1.67, respectively). An inpatient-treated infection was associated with a 0.19-unit increase in EDSS (95% CI, 0.12-0.26). Degree of worsening was greatest for progressive MS, and under IFN/GA treatment, which unlike rituximab, was more commonly associated with MRI activity. After controlling for relapses and MRI activity, inpatient-treated infections were associated with disability worsening in people with relapsing-remitting MS treated with IFN/GA (HR, 2.01; 95% CI, 1.59-2.53), but not in those treated with rituximab. Compared to IFN/GA, rituximab doubled the infection risk, but reduced the risk of subsequent disability worsening. Further, the risk of worsening after hospital-treated infection was greater with progressive MS than with relapsing-remitting MS. Infection risk should be considered to improve long term outcomes. ANN NEUROL 2024.

Treatment modification patterns of glucose-lowering agents in Saudi Arabia: A retrospective real-world data analysis

AimThe growing number of antidiabetics has broadened therapeutic options, leading to heterogeneity in prescribing patterns. Studies identifying antidiabetics modification patterns are lacking in Saudi Arabia. Therefore, the aim of this study is to describe modification patterns in Saudi patients. MethodsPatients ≥ 18 years old with at least one antidiabetic between 2016 and 2022 were included. Follow-up started from the earliest to the last prescription.Two modification types were evaluated: “add-on,” prescribing new antidiabetics within a treatment episode, and “switching”, starting a new treatment episode after the preceding ends. Descriptive statistics were used to characterize patients and estimate events proportions. ResultsOf 122,291 patients, 47.2 % had treatment interruption or modification, totaling 303,781 events. Interruptions accounted for 54 %, add-on for 11 %, and switching for 35 %. The median time to first event was 159 days. The most add-on included dipeptidyl peptidase-4 inhibitor (DPP-4) inhibitors to biguanide and sulfonylurea (8 %), and sulfonylurea to biguanide (8 %). Among 106,405 switching events, 23 % shifted from dual to monotherapy and 17 % from monotherapy to dual therapy. ConclusionNearly half of patients experienced modifications or interruptions, with notable shifts between monotherapies and dual therapies. These findings highlight the evolving landscape of treatment patterns in Saudi Arabia and guide future research and decision-making.

Predictors of retention in heroin-assisted treatment in Denmark 2010–2018 – A record-linkage study

IntroductionWhile randomized-controlled trials have shown that heroin-assisted treatment (HAT) is superior to methadone maintenance alone in treatment of refractory clients, little is known about client factors associated with retention in HAT in routine care. MethodsThis retrospective cohort study assessed predictors of retention in first treatment episode among a consecutive cohort of clients admitted to HAT in Denmark from 2010 to 2018, who could be matched to the Danish population register and for whom a Short Form Health Survey (SF-36) was available at admission (N = 432). The study derived predictors from client self-reports at intake and administrative data available in national registers. Cox proportional hazards regression modelled retention in treatment. ResultsThe one-year retention rate was 69.63 % (95 % CI 65.06 %–73.74 %), and the median time in treatment was 2.45 years (95 % CI, 1.83–3.12). Bivariate analyses showed that retention was lower for clients who had recent cocaine or benzodiazepine use and among those who had experienced an overdose in the year prior to enrollment in HAT. Age below 40, recent illegal activity, poorer emotional wellbeing, previous residential treatment experience, and previous intensive outpatient treatment were also predictors of dropout from HAT. ConclusionsThis observational study found that retention in HAT in routine care was similar to rates observed in randomized-controlled trials conducted in other countries. The results suggest that addressing polysubstance use as part of the HAT program may promote long-term retention, as may directing resources to certain subgroups identified at intake, including clients under 40 years and those who report recent criminal activity, emotional problems, or overdoses. The findings that previous residential treatment and intensive outpatient treatment were associated with dropout were unexpected.

Early versus late initiation of infliximab for refractory uveitis in a cohort of Egyptian BD patients

Introduction Behçet’s syndrome is a multisystem inflammatory disease characterized by recurrent oral aphthous ulcers, genital ulcers, skin lesions, and uveitis. Ocular involvement, occurring roughly in 50% of patients, is one of the most feared complications of Behçet’s syndrome. Recurrent severe uveitis leads to irreversible severe vision loss. Purpose The main goals in the management of patients with Behçet’s uveitis are rapid resolution of intraocular inflammation, prevention of recurrent attacks, and achievement of complete remission and preservation of vision. Corticosteroids are generally used for the treatment of acute episodes of inflammation. According to the updated EULAR recommendations for the management of BS ‘any patient with BS and inflammatory eye disease affecting the posterior segment should be on a treatment regime such as azathioprine, cyclosporine-A, interferon alpha or monoclonal tumor necrosis factor alpha antagonists. Methods Infliximab has been increasingly used in the treatment of Behçet’s syndrome patients with uveitis when they are refractory to conventional immunosuppressive therapy. However, there is no consensus on the best time to start anti- tumor necrosis factor alpha therapy. In our study we evaluated the outcome of early initiation of infliximab for refractory uveitis in cohort of Egyptian Behçet’s syndrome patients. Conclusion Early administration of Intravenous Infliximab therapy for severe sight-threatening uveitis and chorioretinitis in Egyptian Behçet’s syndrome patients has a favorable value regarding BCVA. Multidisciplinary approach in managing Behçet’s uveitis is mandatory to reach better functional visual outcome.

Real-world severe COVID-19 outcomes associated with use of antivirals and neutralising monoclonal antibodies in Scotland

We sought to investigate the incidence of severe COVID-19 outcomes after treatment with antivirals and neutralising monoclonal antibodies, and estimate the comparative effectiveness of treatments in community-based individuals. We conducted a retrospective cohort study investigating clinical outcomes of hospitalisation, intensive care unit admission and death, in those treated with antivirals and monoclonal antibodies for COVID-19 in Scotland between December 2021 and September 2022. We compared the effect of various treatments on the risk of severe COVID-19 outcomes, stratified by most prevalent sub-lineage at that time, and controlling for comorbidities and other patient characteristics. We identified 14,365 individuals treated for COVID-19 during our study period, some of whom were treated for multiple infections. The incidence of severe COVID-19 outcomes (inpatient admission or death) in community-treated patients (81% of all treatment episodes) was 1.2% (n = 137/11894, 95% CI 1.0-1.4), compared to 32.8% in those treated in hospital for acute COVID-19 (re-admissions or death; n = 40/122, 95% CI 25.1-41.5). For community-treated patients, there was a lower risk of severe outcomes (inpatient admission or death) in younger patients, and in those who had received three or more COVID-19 vaccinations. During the period in which BA.2 was the most prevalent sub-lineage in the UK, sotrovimab was associated with a reduced treatment effect compared to nirmaltrelvir + ritonavir. However, since BA.5 has been the most prevalent sub-lineage in the UK, both sotrovimab and nirmaltrelvir + ritonavir were associated with similarly lower incidence of severe outcomes than molnupiravir. Around 1% of those treated for COVID-19 with antivirals or neutralising monoclonal antibodies required hospital admission. During the period in which BA.5 was the prevalent sub-lineages in the UK, molnupiravir was associated with the highest incidence of severe outcomes in community-treated patients.

Self-help groups and opioid use disorder treatment: An investigation using a machine learning-assisted robust causal inference framework

ObjectivesThis study investigates the impact of participation in self-help groups on treatment completion among individuals undergoing medication for opioid use disorder (MOUD) treatment. Given the suboptimal adherence and retention rates for MOUD, this research seeks to examine the association between treatment completion and patient-level factors. Specifically, we evaluated the causal relationship between self-help group participation and treatment completion for patients undergoing MOUD. MethodsWe used the Substance Abuse and Mental Health Services Administration’s (SAMHSA) Treatment Episode Data Set: Discharges (TEDS-D) from 2015 to 2019. The data are filtered by the patient’s opioid use history, demographics, treatment modality, and other relevant information. In this observational study, machine learning models (Lasso Regression, Decision Trees, Random Forest, and XGBoost) were developed to predict treatment completion. Outcome Adaptive Elastic Net (OAENet) was used to select confounders and outcome predictors, and the robust McNemars test was used to evaluate the causal relationship between self-help group participation and MOUD treatment completion. ResultsThe machine-learning models showed a strong association between participation in self-help groups and treatment completion. Our causal analysis demonstrated an average treatment effect on treated (ATT) of 0.260 and a p-value < 0.0001 for the robust McNemars test. ConclusionsOur study demonstrates the importance of participation in self-help groups for MOUD treatment recipients. We found that participation in MOUD along with self-help groups caused higher chances of treatment completion than MOUD alone. This suggests that policymakers should consider further integrating self-help groups into the treatment for OUD to improve the adherence and completion rate.

Excess mortality among individuals who have undergone addiction treatment: a study from Greenland

In Greenland, where addiction-related concerns significantly affect well-being, research has explored alcohol’s impact on health and mortality. However, no studies have focused on mortality among those who received addiction treatment. This study investigates whether individuals treated for addiction in Greenland experience elevated mortality rates compared to the general population. The study encompassed individuals receiving addiction treatment through the national system between 2012 and December 31, 2022. Data on treatment were sourced from the National Addiction Database, and Statistics Greenland. Person-years at risk were calculated and used to estimate crude mortality rates (CMRs). Adjusted standardized mortality rates (SMRs), accounting for age, sex, and calendar year, were estimated using an indirect method based on observed and expected deaths. Of the 3286 in treatment, 53.9% were women, with a median age of 37. About a third had undergone multiple treatment episodes, and 60.1% received treatment in 2019 or later. The cohort was followed for a median of 2.89 years, yielding 12,068 person-years. The overall CMR was 7.79 deaths per 1000 person-years, with a SMR of 1.42 (95% confidence interval: 1.15; 1.74). Significantly, SMRs differed by age at treatment entry, with younger groups exhibiting higher SMRs (p value = .021). This study found that individuals seeking treatment for addiction problems in Greenland had a higher mortality rate than the general population. Importantly, these SMRs were substantially lower than those observed in clinical populations in other countries.

Blood Gene Signature as a Biomarker for Subclinical Kidney Allograft Rejection: Where Are We?

The observation decades ago that inflammatory injuries because of an alloimmune response might be present even in the absence of concomitant clinical impairment in allograft function conduced to the later definition of subclinical rejection. Many studies have investigated the different subclinical rejections defined according to the Banff classification (subclinical T cell-mediated rejection and antibody-mediated rejection), overall concluding that these episodes worsened long-term allograft function and survival. These observations led several transplant teams to perform systematic protocolar biopsies to anticipate treatment of rejection episodes and possibly prevent allograft loss. Paradoxically, the invasive characteristics and associated logistics of such procedures paved the way to investigate noninvasive biomarkers (urine and blood) of subclinical rejection. Among them, several research teams proposed a blood gene signature developed from cohort studies, most of which achieved excellent predictive values for the occurrence of subclinical rejection, mainly antibody-mediated rejection. Interestingly, although all identified genes relate to immune subsets and pathways involved in rejection pathophysiology, very few transcripts are shared among these sets of genes, highlighting the heterogenicity of such episodes and the difficult but mandatory need for external validation of such tools. Beyond this, their application and value in clinical practice remain to be definitively demonstrated in both biopsy avoidance and prevention of clinical rejection episodes. Their combination with other biomarkers, either epidemiological or biological, could contribute to a more accurate picture of a patient's risk of rejection and guide clinicians in the follow-up of kidney transplant recipients.

Hepatitis C (HCV) Reinfection and Risk Factors among Clients of a Low-Threshold Primary Healthcare Service for People Who Inject Drugs in Sydney, Australia.

Hepatitis C (HCV) reinfection studies have not focused on primary healthcare services in Australia, where priority populations including people who inject drugs (PWID) typically engage in healthcare. We aimed to describe the incidence of HCV reinfection and associated risk factors in a cohort of people most at risk of reinfection in a real-world community setting. We conducted a secondary analysis of routinely collected HCV testing and treatment data from treatment episodes initiated with direct-acting antiviral (DAA) therapy between October 2015 and June 2021. The overall proportion of clients (N = 413) reinfected was 9% (N = 37), and the overall incidence rate of HCV reinfection was 9.5/100PY (95% CI: 6.3-14.3). Reinfection incidence rates varied by sub-group and were highest for Aboriginal and/or Torres Strait Islander people (20.4/100PY; 95% CI: 12.1-34.4). Among PWID (N= 321), only Aboriginality was significantly associated with reinfection (AOR: 2.73, 95% CI: 1.33-5.60, p = 0.006). High rates of HCV reinfection in populations with multiple vulnerabilities and continued drug use, especially among Aboriginal and Torres Strait Islander people, highlight the need for ongoing regular HCV testing and retreatment in order to achieve HCV elimination. A priority is resourcing testing and treatment for Aboriginal and/or Torres Strait Islander people. Our findings support the need for novel and holistic healthcare strategies for PWID and the upscaling of Indigenous cultural approaches and interventions.

Risk of drug-related death associated with co-prescribing of gabapentinoids and Z-drugs among people receiving opioid-agonist treatment: A national retrospective cohort study

BackgroundPrescribing of gabapentinoids and Z-drug-hypnotics has increased in the population and among people receiving opioid-agonist treatment (OAT) for opioid dependence. Evidence is mixed on whether co-prescribing of sedatives such as gabapentinoids and Z-drugs during OAT increases risk of drug-related death (DRD). MethodsWe conducted a retrospective cohort study of individuals prescribed OAT between 2011 and 2020 in Scotland. Prescribing records were linked to mortality data and other healthcare datasets (sociodemographic, comorbidity). We identified episodes of treatment with gabapentinoids/Z-drugs and used multivariable quasi-Poisson regression to model associations between co-prescription and DRD risk. ResultsAmong 46,602 individuals with 304,783 person-years of follow-up, we found that co-prescription was common, with 25 % and 34 % ever being co-prescribed gabapentinoids and Z-drugs, respectively. Gabapentinoid exposure was strongly associated (adjusted hazard ratio (aHR)=2·18, 95 % CI=1·92, 2·46) and Z-drug exposure moderately associated (aHR=1·39, 95 % CI=1·15, 1·66) with elevated risk of DRD. Gabapentinoid exposure was associated with DRD risk on and off OAT; Z-drug exposure was less strongly associated with DRD risk when on OAT. ConclusionsCo-prescription of gabapentinoids and Z-drugs is common among OAT patients. However, co-prescription is associated with increased risk of DRD. Alternatives to prescribing sedative medications to OAT patients and/or greater monitoring – if prescribed – are needed.