Mass Poisoning From Ethylene Glycol at a U.S. Military Base.

Ethylene glycol (EG) toxicity is an important cause of toxic alcohol poisoning in the USA with over 5,000 exposures reported annually. While classically characterized by solitary accidental or intentional ingestions, mass toxic alcohol poisoning outbreaks and more rarely collective consumptions (typically of methanol) have been described. We describe an ethylene glycol poisoning from collective ingestion that involved soldiers presenting at William Beaumont Army Medical Center in El Paso, Texas. Eleven soldiers presented to the emergency department over a 12-h period after ingestion of an unknown substance. The first two patients exhibited severe neurologic symptoms, while the remainder were asymptomatic. As serum EG levels were not immediately available, treatment decisions were based on surrogate laboratory values. Two patients received immediate hemodialysis, and fomepizole (FOM) because of severe acidosis with elevated anion and osmolal gaps. These patients developed acute kidney injury with renal recovery within a 3-week period. Two patients with elevated lactate received bicarbonate-based intravenous (IV) fluids and FOM. Two patients received IV fluids only and required prolonged observation for worsening acidosis and/or acute kidney injury. Five patients with normal laboratory values were treated with IV fluids and observation. All patients received cofactors including thiamine and pyridoxine. All patients survived. The outbreak occurred in the setting of limited dialysis resources, limited FOM availability, and in a resource-limited community. Additional guidelines are needed to determine allocation of limited resources, optimal dialysis and FOM treatment course, and comorbid conditions, which may prolong recovery.

Pertuzumab study in the neoadjuvant setting for HER2-positive nonmetastatic breast cancer in Australia (PeRSIA).

The pertuzumab study in the neoadjuvant setting for HER2+ nonmetastatic breast cancer in Australia (PeRSIA-ML39622) is an analysis of safety and effectiveness data from the pertuzumab patient registry. Although the prognosis of patients with early stage HER2+ breast cancer has been greatly improved by advances in chemotherapy approximately 25% to 30% of patients develop recurrent disease. Our study aimed to examine the effectiveness of neoadjuvant pertuzumab on surgical outcomes, describe the medium-term effectiveness outcomes of patients treated with pertuzumab, and describe the planned and actual anticancer treatment regimens that patients received. Deidentified data were collected from the patients' medical records and entered into REDCap, between March 2018 and July 2019 (n = 95). The adverse events (AEs) reported most frequently were diarrhea (20; 21.1%), rash (4; 4.2%), and LVSD (4; 4.2%; two patients during neoadjuvant treatment and two patients during adjuvant treatment). AEs, ≥Grade 3 were diarrhea (2; 2.1%) and LVSD (1; 1.1%). Following surgery, a breast pathological complete response (bpCR) was achieved in 65 patients (70.7%; 95% CI: 60.2%-79.7%) and total pathological complete response (tpCR) in 59 patients (64.1%; 95% CI: 53.4%-73.9%). All patients who did not achieve a tpCR obtained a partial response (33/92, 35.9%). Our study is the first to capture real-world data on the use of pertuzumab in the neoadjuvant setting in Australia. The effectiveness and safety data are consistent with those reported in clinical trials of pertuzumab in patients with HER2+ breast cancer, with no new safety concerns.

Improvements in Depression Outcomes Following a Digital Cognitive Behavioral Therapy Intervention in a Polychronic Population: Retrospective Study.

BACKGROUND: Digital mental health interventions have shown promise in reducing barriers to effective care for depression. Depression and related mental disorders are known to be highly comorbid with common chronic physical conditions, such as obesity and type 2 diabetes. While some research has explored the interaction dynamics of treating populations living with both mental and physical disorders, very little is known about such dynamics in digital care. OBJECTIVE: We aimed to examine the effectiveness of a 12-week, therapist-supported, app-based cognitive behavioral therapy program in improving symptoms of depression and anxiety. The studied population included adults with a heavy burden of chronic physical disease, including obesity and type 2 diabetes. METHODS: A total of 1512 participants with at least moderate depression were enrolled. The treatment cohort consisted of 831 (54.96%) participants who completed a follow-up assessment. The program included structured lessons and tools (ie, exercises and practices) and offered one-on-one weekly video counseling sessions with a licensed therapist for 12 weeks and monthly sessions thereafter. The clinically validated 8-item Patient Health Questionnaire (PHQ-8) and the 7-item Generalized Anxiety Disorder scale (GAD-7) were used to assess depression and anxiety, respectively. Linear mixed-effects modeling was employed to examine changes in depression and anxiety over time. Given correlation among various measures of program usage, a composite variable for depth of usage was used to analyze the correlation between usage and changes in depressive symptoms. Body weight changes from baseline were assessed primarily with digitally connected scales. RESULTS: Out of 831 participants in the treatment cohort, 74.5% (n=619) showed a clinically significant reduction in depressive symptom severity after 12 weeks, where follow-up PHQ-8 scores had shifted downward by at least one diagnostic category. In total, 67.5% (n=561) of the participants showed a reliable improvement in PHQ-8 scores as measured by the reliable change index. There was an average reduction of 5.9 (SD 5.2) points (P<.001) between baseline and follow-up. Greater program usage was correlated with greater likelihood of reliable improvement in depressive symptoms (odds ratio 1.3, 95% CI 1.1-1.5; P=.002). An exploratory analysis of body weight changes with a multilevel, mixed-effect model suggested that reliable improvement in depressive symptoms at follow-up was associated with significantly greater weight loss at 9 months (ß=-1.11, P=.002). CONCLUSIONS: The results provide further support that digital interventions can support clinically meaningful improvements in depression. Some form of synergy in treatment of comorbid depression and obesity or diabetes could be studied in future research. The study was limited by postintervention participant attrition as well as the retrospective observational study design.

Dry eye signs and symptoms in patients on aromatase inhibitor therapy.

PURPOSE: The study aimed to test whether symptomatic dry eye in aromatase inhibitor (AI) patients is associated with the clinical features of evaporative dry eye. METHODS: A cross-sectional, observational study of postmenopausal women treated with AI was conducted. Clinical information was gathered from their treating clinician. Ocular and treatment symptoms were assessed using validated questionnaires. Clinical assessments were performed to assess for dry eye. The primary outcome measure for this study was dry eye symptoms measured via questionnaire. The secondary outcome measures were clinical signs of dry eye and hormone levels. RESULTS: A total of 25 women on AI were recruited. 64% of women reported symptoms of dry eye (ocular surface disease index ≥ 13). Higher tear osmolarity (323 vs 307 mOsm/L, p = 0.002) and increased meibomian gland dropout (4 vs 1, p = 0.002) were observed in patients with symptomatic dry eye when compared to asymptomatic patients. Multivariate logistic regression identified that longer duration of AI use and higher tear osmolarity increased the likelihood of a patient experiencing dry eye symptoms. CONCLUSION: Our study found increased tear osmolarity and meibomian gland drop out in women on AI with symptomatic dry eye. Longer duration of AI therapy and higher tear osmolarity may increase the risk of developing dry eye.

Focal Segmental Glomerulosclerosis, Risk Factors for End Stage Kidney Disease, and Response to Immunosuppression.

Background: FSGS is a heterogeneic glomerular disease. Risk factors for kidney disease ESKD and the effect of immunosuppression treatment (IST) has varied in previously published cohorts. These cohorts were limited by relatively small case numbers, short follow-up, lack of racial/ethnic diversity, a mix of adult and pediatric patients, lack of renin-angiotensin-aldosterone system (RAAS) inhibition, or lack of subgroup analysis of IST. Methods: We compared demographics, clinical characteristics, histopathology, and IST to long-term renal survival in a large, ethnically diverse, adult cohort of 338 patients with biopsy-proven FSGS with long-term follow-up in the era of RAAS inhibition using data from the US Department of Defense health care network. Results: Multivariate analysis showed that nephrotic-range proteinuria (NRP), eGFR <60 ml/min per 1.73 m2, hypoalbuminemia, interstitial fibrosis and tubular atrophy, and interstitial inflammation at diagnosis and the absence of remission were all associated with worse long-term renal survival. IgM, C3, and a combination of IgM/C3 immunofluorescence staining were not associated with reduced renal survival. IST was not associated with improved renal survival in the whole cohort, or in a subgroup with NRP. However, IST was associated with better renal survival in a subgroup of patients with FSGS with both NRP and hypoalbuminemia and hypoalbuminemia alone. Conclusions: Our study suggests that IST should be reserved for patients with FSGS and nephrotic syndrome. It also introduces interstitial inflammation as a potential risk factor for ESKD and does not support the proposed pathogenicity of IgM and complement activation.

Learning to be well in the health workplace: an integrated model.

This article was migrated. The article was marked as recommended. Introduction: Problems with the well-being of workers in health is a crisis that directly impacts on health care workers themselves and on the quality of care provided. Academic inquiry has utilised a broad diversity of perspectives. There is an urgent need for theory that guides interventions and mediates between the perspectives taken. Methods: An initial model was generated by mapping concepts from a meta-synthesis of systematic reviews of resilience, burnout, well- being and compassion fatigue. An iterative process identifying and critically applying additional literature refined the model. Results: The final model addressed positive /negative; individual/organisational and focal or global perspectives. It was structured on the Job-demands resources model with stressors mediated by cognitive appraisal, and organisational climate. A cycle of learning in practice was identified as the key to adaptation. The relevant educational domains include learning to be, believe, feel, do, Interact and adapt to maximise well-being. Discussion: An integrated, evidence based learning model of well-being in the health workplace has been developed which may act as a guide for both individuals and organisation to maximise well-being. Implications of the model have been discussed.

Delayed stabilisation of dynamically unstable syndesmotic injuries results in worse functional outcomes.

PURPOSE: Patients with primarily ligamentous injuries of the distal tibiofibular joint comprise up to 12% of all ankle sprains. Patients frequently present late after a syndesmosis injury and delayed treatment potentially leads to pain, prolonged disability and arthritis in the long term. This study aimed to assess clinical outcomes in patients who required syndesmosis fixation in the presence of arthroscopically proven instability, the hypothesis being that a delay to treatment would be associated with worse function. METHOD: A retrospective cohort study was performed of patients with dynamic instability requiring fixation between the years of 2010-2016. The procedures were performed by two foot and ankle fellowship trained orthopaedic surgeons, over three hospital sites. Patients were classified into three groups based on the time since injury to surgery, acute syndesmotic injury (< 6 weeks), sub-acute (6 weeks-6 months) and chronic syndesmotic injury (> 6 months). Functional scores were retrospectively collected using the Foot and Ankle Outcome Score (FAOS). RESULTS: Compared to patients with acute injuries, those with chronic injuries had significantly lower FAOS subscales (p < 0.001), with the greatest difference in quality of life (- 20.7, 95% CI - 31.6 to - 9.8, p = 0.012). There was a mean follow-up of 4.3 years. Although the average FAOS subscales in those with sub-acute injuries were lower than in those with acute injuries, the difference was not statistically significant. CONCLUSION: The results of this study suggest that delayed surgical stabilisation (> 6 months) is associated with significantly worse clinical function, and thus timely identification and early referral of those patients with potentially unstable syndesmotic injuries is recommended. LEVEL OF EVIDENCE: Level III.

MRI for high ankle sprains with an unstable syndesmosis: posterior malleolus bone oedema is common and time to scan matters.

PURPOSE: Early clinical examination combined with MRI allows accurate diagnosis of syndesmosis instability after a high ankle sprain. However, patients often present late. The aims of the current study were to describe MRI characteristics associated with syndesmosis instability and to test the hypothesis that MRI patterns would differ according to time from injury. METHODS: Over a 5-year period, 164 consecutive patients who had arthroscopically proven syndesmosis instability requiring fixation were retrospectively studied. Patients with distal fibula fractures were not included. Injuries were classified as acute in 108 patients (< 6 weeks), intermediate in 32 (6-12 weeks) and chronic in 24 patients (> 12 weeks). RESULTS: Posterior malleolus bone oedema was noted in 65 (60.2%), and posterior malleolus fracture in 17 (15.7%) of acute patients, respectively, which did not significantly differ over time. According to MRI, reported rates of posterior syndesmosis disruption significantly differed over time, observed in 101 (93.5%), 28 (87.5%) and 13 (54.2%) of acute, intermediate and chronic patients, respectively (p < 0.001). Apparent rates of PITFL injury significantly reduced with time (p < 0.001). CONCLUSIONS: MRI detected a posterior syndesmosis injury in 93.5% of patients acutely but became less reliable with time. The clinical relevance of this study is that posterior malleolus bone oedema may be the only marker of a complete syndesmosis injury and can help clinically identify those injuries which require arthroscopic assessment for instability. If suspicious of a high ankle sprain, we advocate early MRI assessment to help determine stable versus unstable injuries as MRI becomes less reliable after 12 weeks. LEVEL OF EVIDENCE: III.

Minimally Invasive Tendon Release for Symptomatic Accessory Soleus Muscle in an Athlete: A Case Report.

The accessory soleus muscle can pose a diagnostic dilemma for exertional ankle pain, especially in athletes. Once diagnosed, the current treatment options require an extensile approach and can be associated with substantial risk and a slow recovery. We describe a minimally invasive, safe method that has proved successful in our practice.

A Case Report of Acute Renal Failure as a Result of Light-Chain-Mediated Acute Tubular Interstitial Nephritis in a 30-Year-Old Combat Veteran.

We present a 30-year-old combat veteran with an unclear exposure history, with multiple deployments who was later diagnosed with acute renal failure as a result of light-chain deposition disease. Despite a drastic decline in kappa light chains following chemotherapy; his renal function worsened, and he progressed to end-stage renal disease, requiring hemodialysis. Light-chain-mediated acute tubular interstitial nephritis is an uncommon type of monoclonal gammopathy of renal significance presenting with acute renal failure without significant glomerular disease. Our case illustrates that light-chain-mediated acute tubular interstitial nephritis may present clinically like acute interstitial nephritis and that renal biopsy is critical for diagnosis. We also explore possible links between various environmental and occupational exposures that could have precipitated his disease process at such a young age.

Psychiatry trainees' views and educational needs regarding the care of patients with a life-limiting illness.

OBJECTIVE: People with a life-limiting physical illness experience high rates of significant psychological and psychiatric morbidity. Nevertheless, psychiatrists often report feeling ill-equipped to respond to the psychiatric needs of this population. Our aim was to explore psychiatry trainees' views and educational needs regarding the care of patients with a life-limiting physical illness. METHOD: Using semistructured interviews, participants' opinions were sought on the role of psychiatrists in the care of patients with a life-limiting illness and their caregivers, the challenges faced within the role, and the educational needs involved in providing care for these patients. Interviews were audiotaped, fully transcribed, and then subjected to thematic analysis. RESULTS: A total of 17 psychiatry trainees were recruited through two large psychiatry training networks in New South Wales, Australia. There were contrasting views on the role of psychiatry in life-limiting illness. Some reported that a humanistic, supportive approach including elements of psychotherapy was helpful, even in the absence of a recognizable mental disorder. Those who reported a more biological and clinical stance (with a reliance on pharmacotherapy) tended to have a nihilistic view of psychiatric intervention in this setting. Trainees generally felt ill-prepared to talk to dying patients and felt there was an educational "famine" in this area of psychiatry. They expressed a desire for more training and thought that increased mentorship and case-based learning, including input from palliative care clinicians, would be most helpful. SIGNIFICANCE OF RESULTS: Participants generally feel unprepared to care for patients with a life-limiting physical illness and have contrasting views on the role of psychiatry in this setting. Targeted education is required for psychiatry trainees in order to equip them to care for these patients.

Clinicians' Perspectives on Managing Symptom Clusters in Advanced Cancer: A Semistructured Interview Study.

CONTEXT: Managing symptom clusters or multiple concurrent symptoms in patients with advanced cancer remains a clinical challenge. The optimal processes constituting effective management of symptom clusters remain uncertain. OBJECTIVES: To describe the attitudes and strategies of clinicians in managing multiple co-occurring symptoms in patients with advanced cancer. METHODS: Semistructured interviews were conducted with 48 clinicians (palliative care physicians [n = 10], oncologists [n = 6], general practitioners [n = 6], nurses [n = 12], and allied health providers [n = 14]), purposively recruited from two acute hospitals, two palliative care centers, and four community general practices in Sydney, Australia. Transcripts were analyzed using thematic analysis and adapted grounded theory. RESULTS: Six themes were identified: uncertainty in decision making (inadequacy of scientific evidence, relying on experiential knowledge, and pressure to optimize care); attunement to patient and family (sensitivity to multiple cues, prioritizing individual preferences, addressing psychosocial and physical interactions, and opening Pandora's box); deciphering cause to guide intervention (disaggregating symptoms and interactions, flexibility in assessment, and curtailing investigative intrusiveness); balancing complexities in medical management (trading off side effects, minimizing mismatched goals, and urgency in resolving severe symptoms); fostering hope and empowerment (allaying fear of the unknown, encouraging meaning making, championing patient empowerment, and truth telling); and depending on multidisciplinary expertise (maximizing knowledge exchange, sharing management responsibility, contending with hierarchical tensions, and isolation and discontinuity of care). CONCLUSION: Management of symptom clusters, as both an art and a science, is currently fraught with uncertainty in decision making. Strengthening multidisciplinary collaboration, continuity of care, more pragmatic planning of clinical trials to address more than one symptom, and training in symptom cluster management are required.

Patients' experiences and perspectives of multiple concurrent symptoms in advanced cancer: a semi-structured interview study.

PURPOSE: Patients with advanced cancer typically experience multiple concurrent symptoms, which have a detrimental impact on patient outcomes. No studies to date have qualitatively explored advanced cancer patients' perceptions of multiple symptoms in oncology and palliative care settings. Understanding the experience of multiple symptoms can inform integrated clinical pathways for treating, assessing and reducing symptom burden. This study aims to describe the beliefs, attitudes and experiences of patients with multiple symptoms in advanced cancer. METHODS: Semi-structured interviews were conducted with 58 advanced cancer patients (23 inpatients and 35 outpatients), recruited purposively from two palliative care centres and two hospital-based oncology departments in Sydney, Australia. Transcripts were analysed thematically. RESULTS: Six major themes were identified: imminence of death and deterioration (impending death, anticipatory fear); overwhelming loss of control (symptom volatility, debilitating exhaustion, demoralisation, isolation); impinging on autonomy and identity (losing independence, refusal to a diminished self, self-advocacy, reluctance to burden others); psychological adaptation (accepting the impossibility of recovery, seeking distractions, maintaining hope, mindfulness, accommodating self-limitations), burden of self-management responsibility (perpetual self-monitoring, ambiguity in self-report, urgency of decision making, optimising management); and valuing security and empowerment (safety in coordinated care, compassionate care, fear of medical abandonment, dependence on social support). Patients transitioning from oncology to palliative care settings were more vulnerable to self-management burden. CONCLUSION: Multiple symptoms have a profound impact on patients' autonomy, function and psychological state. Multiple symptom management and integrated care is needed to empower advanced cancer patients and reduce their struggles with self-management burden, hopelessness, isolation, fear of abandonment and mortality anxieties.