Harm Interventions Research Articles

Assessment of Acute Side Effects Among 3D-Concurrent Radiotherapy With Cisplatin-Treated Head and Neck Cancer Patients.

Three-dimensional conformal radiation therapy has become one of the basic components of multidisciplinary treatment for head and neck cancer. Generally, patients with squamous-cell carcinoma of the head and neck receive cisplatin-based chemoradiation. In the current project, the goal was to assess 3D-CRT with cisplatin-induced acute side effects (dermatitis plus xerostomia) among head and neck cancer patients. This descriptive case series was held at the Institute of Nuclear Medicine and Oncology, Lahore, Pakistan, with an enrollment of 106 head and neck cancer patients following the hospital's ethical approval. All patients received 3D-CRT with concurrent cisplatin chemotherapy according to the oncology treatment protocol at the Institute of Nuclear Medicine and Oncology. The evaluation of enrolled patients was done during treatment at a weekly interval and at one-month post-radiation. Stage 3 patients (17.9%) received chemo-radiation therapy with 40 mg/m2 cisplatin once weekly for seven weeks. All patients received 70 grays in 35 fractions with two grays per fraction over the course of seven weeks following a standard protocol. All enrolled cases had biopsy-proven squamous cell carcinoma of the head and neck. IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp. analyzed the data. Chi-square and Fisher's exact tests were applied, while a p-value ≤ 0.05 was taken as statistically significant. All patients developed acute skin changes (dermatitis plus xerostomia) as a side effect of radiation therapy, with cisplatin having different grades during treatment until seven weeks. However, these changes improved and became less severe in terms of grade after one month of post-treatment among all patients. It was concluded that 3D-CRT was associated with dermatitis and xerostomia during and immediately after follow-up, even though the treatment response was good. However, clinical signs and symptoms improved, indicating that radiation therapy is a relatively safe treatment modality among cancer patients. Moreover, 40 mg/m2 cisplatin once weekly for seven weeks resulted in better loco-regional control and survival among advanced-stage head and neck cancer patients as a part of treatment. Although, higher doses of cisplatin (100 mg/m2 ) every three weeks have more harmful acute side effects and delay treatment for patients due to poor compliance.

A study protocol for a European, mixed methods, prospective, cohort study of the effectiveness of naloxone administration by community members, in reversing opioid overdose: NalPORS

BackgroundWorldwide, opioid use causes more than 100,000 overdose deaths annually. Naloxone has proven efficacy in reversing opioid overdoses and is approved as an emergency antidote to opioid overdose. Take home naloxone (THN) programmes have been introduced to provide ‘community members’, who are likely to observe opioid overdoses, with naloxone kits and train them to recognise an overdose and administer naloxone. The acceptability and feasibility of THN programmes has been demonstrated, but the real-life effectiveness of naloxone administration by community members is not known. In recent years, the approval of several concentrated naloxone nasal-spray formulations (in addition to injectable formulations, eg.prenoxad) potentially increases acceptability and scope for wider provision. This study aims to determine the effectiveness of THN (all formulations) in real-world conditions.MethodsA European, multi-country, prospective cohort study, to assess the use of THN by community members to reverse opioid overdoses in a six-month, follow-up period. Participants provided with THN from participating harm reduction and drug treatment sites will be recruited to the study and followed-up for six months. We are particularly interested in the experiences of community members who have been provided with THN and have witnessed an opioid overdose. All participants who witness an opioid overdose during the six-month period (target approx. 600) will be asked to take part in a structured interview about this event. Of these, 60 will be invited to participate in a qualitative interview. A Post Authorisation Efficacy Study (PAES) for the concentrated nasal naloxone, Nyxoid, has been integrated into the study design.DiscussionThere are many challenges involved in evaluating the real-life effectiveness of THN. It is not possible to use a randomised trial design, recruitment of community members provided with THN will depend upon recruitment sites distributing THN kits, and the type of THN received by participants will depend on regulations and on local clinical and policy decision-makers. Following up this population, some of whom may be itinerant, over the 6-month study period will be challenging, but we plan to maintain contact with participants through regular text message reminders and staff contact.Trial registrationClinicalTrials.gov Identifier: NCT05072249. Date of Registration: 8.10.2021

Sociodemographic differences and experienced effects of young adults who use cannabis mainly for self-medication versus recreationally in Finland

PurposeCannabis use continues to increase worldwide, and a number of nation states are changing their cannabis policies. Policy changes require research into key populations, namely, people who use cannabis. This study aims to examine sociodemographic differences of young Finns who reported using cannabis mainly for self-medication versus mainly recreationally, as well as their reported effects of cannabis use.Design/methodology/approachThe data come from an anonymous online survey (N = 247, 70.0% males, 25.9% females, 4.1% other) that was analysed using multiple logistic regression. The authors focused on whether various demographic indicators differed between those who reportedly used cannabis mainly for recreational purposes and mainly for self-medicinal purposes. The authors also qualitatively examined the respondents’ experienced effects of cannabis, both desired and undesired.FindingsBeing older and female, living in a smaller city and earlier age of initiation of cannabis use were statistically significant in predicting the medicinal use of cannabis. The majority of recreational effects were related to themes such as relaxation and pleasure, but many participants also reported desired medical effects. Similarly, many participants reported several undesired effects.Research limitations/implicationsUnderstanding especially young people’s motivations to use cannabis, which include using it for various medical effects, can improve the design of harm reduction and treatment programmes as well as enhance the well-being of people who use cannabis.Originality/valueThis study gives a nuanced account of sociodemographic factors and motivations of young people who use cannabis in Finland as well as the reported effects it has on them, which complements data from national drug surveys.

Unusual Cause of Recurrent Syncope in an Elderly Patient: Multiple System Atrophy

Abstract Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by various combinations of autonomic dysfunction, parkinsonism, and cerebellar dysfunction. Autonomic dysfunction has a debilitating course in patients of MSA, compared to other neurodegenerative disorders presenting with parkinsonism or ataxia. We report a case of MSA presenting with recurrent syncope due to orthostatic hypotension. We highlight that if not recognized, such patients may receive potentially harmful interventions.

Benign peripheral nerve sheath tumors: an interdisciplinary diagnostic and therapeutic challenge

A benign peripheral nerve sheath tumor (bPNST) is a rare lesion associated with peripheral nerval structures. Symptoms may be heterogeneous, complicating diagnosis finding. Additionally, management concepts of bPNST may vary. In some cases, initial misdiagnosis leads to mistreatment resulting in severe functional deficits and chronic pain syndromes. Therefore, we analyzed patients treated for bPNST in our specialized institution with a primary focus on prior misdiagnosis and possible mistreatment. Patients with bPNSTs (schwannomas, neurofibromas, hybrid nerve sheath tumors, and perineuriomas) treated at the Neurosurgical Department between January 1, 2015, and July 31, 2021, were included. Assessment of demographics, tumor entity, tumor location, symptoms, the interval between the onset of symptoms and surgery, involved medical specialties, and outpatients’ treatment, with particular focus on initial misdiagnosis and inappropriate medical treatment, was performed. Eighty-five patients were included in the final analysis with schwannoma being the most prevalent histopathological diagnosis (schwannoma (75.3%, n=64), neurofibroma (12.9%, n=11), hybrid nerve sheath tumor (5.9%, n=5), and perineurioma (5.9%, n=5)). An incorrect primary diagnosis was detected in 44.7% (n=38), leading to suboptimal or insufficient treatment in these cases. Of those, 28.9% (n=11/38) were treated suboptimal, while 18.5% (n=7/38) underwent unnecessary invasive diagnostics. Inappropriate surgery based on prior misdiagnosis, which led to severe neurological deficits in all these cases, was reported in 26.3% (n=10/38). For the first time, our data shows the quantity and impact of incorrect initial diagnosis in bPNST causing a delay in causative treatment or resulting in unnecessary or potentially harmful treatment.

Trends in Self-Reported Fentanyl and Other Illicit Substance Use in South Carolina Emergency Department Patients, 2020-2022

BackgroundOpioid-involved deaths are continuing to increase across the United States, exceeding 100,000 for the first time in 2021. Contamination with, and intentional use of, synthetic opioids such as fentanyl are a major driver of this increase. Utilizing self-report substance use data of patients being treated in the emergency department (ED) can be useful to determine which substances patients are intentionally seeking. Objectives1) Examine changes in self-reported illicit substance use (including fentanyl) over time; 2) Examine changes in the co-occurrence of self-reported fentanyl with other illicit substance use over time. MethodsAll patients presenting to the study EDs that answered anything other than “never” on the National Institute on Drug Abuse Quick Screen and were seen by a peer recovery specialist in the ED between July 1, 2020 and December 31, 2022 were included for analysis. The substance of use as reported by each patient was recorded by the peer recovery specialist. Differences in substance use by type over time were examined using chi-squared tests of proportions. ResultsThere were 7568 patients that met inclusion criteria. Self-reported fentanyl (1760%; p < 0.0001) and cocaine (82%; p = 0.034) use increased, whereas heroin use (16%; p < 0.0001) decreased. ConclusionsSelf-reported fentanyl and cocaine use has increased significantly in South Carolina ED patients between 2020 and 2022. Given the high morbidity and mortality associated with fentanyl and fentanyl analog use, further measures to identify these patients and provide harm reduction and treatment from the ED setting are warranted.

The impact of polysubstance use patterns on engagement of substance use disorder treatment among emergency department patients at high risk of opioid overdose

BackgroundSubstance use patterns are diverse, and multiple substances are often involved in fatal and nonfatal overdoses. Additionally, polysubstance use is associated with greater difficulty accessing and remaining in substance use disorder (SUD) treatment. The aim of this study was to identify substance use patterns and determine their association with SUD treatment engagement among emergency department (ED) patients at risk of opioid overdose. MethodsThis was a sub-analysis of a randomized controlled trial comparing two behavioral interventions for individuals at two EDs in Rhode Island from 2018 to 2021. Past six-month substance use frequency for eight substances plus injection drug use was self-reported at trial enrollment, and SUD treatment engagement within 90 days after enrollment was obtained using administrative data linkages. Latent class analysis identified substance use patterns and multivariable log-binomial models estimated the association with SUD treatment engagement. ResultsAmong 607 participants, there were four substance use patterns: 1) low reported use (n = 295), 2) frequent injection and heroin use (n = 131), 3) high frequency broad polysubstance use (n = 62), and 4) low frequency broad polysubstance use (n = 119). Compared to participants with the low reported use pattern, those with the frequent injection and heroin pattern had a greater likelihood of SUD treatment engagement (adjusted risk ratio = 1.28; 95% confidence interval = 1.02–1.61). ConclusionsDistinct and meaningful polysubstance use patterns showed differential SUD treatment engagement after ED discharge. Nuanced relationships between substance use patterns and treatment highlight the necessity for tailored harm reduction, treatment, and recovery services.

Case report: Ethylene glycol intoxication presenting as a mimic of acute stroke: a report of three cases

Stroke is a major cause of death and disability presenting with acute focal neurological symptoms of vascular origin. Several other disorders may cause symptoms similar to a stroke, referred to as stroke mimics. The misdiagnosis of stroke mimics may lead to potentially harmful treatments, including thrombolysis. Intoxication is a rare, but possible, cause of stroke mimic. We present three cases of ethylene glycol poisoning presenting as an acute stroke mimic within the time window of thrombolytic therapy. Two of three patients (a 54-year-old male and a 78-year-old male) had dysarthria, nystagmus, and truncal ataxia on admission. The third patient with a history of chronic alcoholism presented after an epileptic seizure with mixed aphasia and confusion. Non-contrast cerebral computed tomography and computed tomography angiography were negative in all three cases. As stroke could not be excluded in any of the patients, thrombolysis was performed. However, after some hours, two of the three patients developed agitation, somnolence, and hyperventilation. One patient's consciousness deteriorated rapidly, and he became comatose and tetraplegic. A blood gas analysis showed acidosis in two of the three patients, and toxicological screening revealed ethylene glycol intoxication in all three cases. Due to the appropriate treatment, two of the three patients became symptom-free; however, one of the three patients died. Our cases show that ethylene glycol intoxication in its early phase may mimic acute stroke, resulting in unnecessary thrombolytic therapy. Symptoms not characteristic of a stroke, such as hyperventilation, agitation, and disturbance of consciousness, may appear later and warn of intoxication. The final diagnosis of ethylene glycol intoxication can be established by severe metabolic acidosis and toxicological screening. Close monitoring of symptoms might contribute to the early recognition of ethylene glycol intoxication and its effective treatment.

Trends and psychosocial correlates of same day polysubstance use among people who inject drugs in Australia, 2012-2022.

Polysubstance use is associated with negative health and social outcomes among people who inject drugs. We aimed to describe trends in polysubstance use and identify psychosocial correlates and associated drug use risk behaviours. We defined polysubstance use as intentional same day use of more than one of three drug classes: opioids, other non-opioid depressants (hereafter 'depressants'), and stimulants. We used 10 years (2012-2022, excluding 2020) of data from annual surveys in Australian capital cities with people who inject drugs (N=5657) to construct five mutually exclusive polysubstance use profiles: opioid-depressant, opioid-stimulant, stimulant-depressant, opioid-stimulant-depressant, and single drug class use. We examined time trends using the Mann Kendall test and identified correlates using multinomial logistic regression. Same day polysubstance use was relatively common among this sample (43.6%). Opioid-depressant use was the most frequent polysubstance use profile, but this decreased over the study period (32.6% to 13.3%, p<0.001). This aligned with observed decreases in use of pharmaceutical opioids (p<0.001), opioid agonist treatment (p=0.007), and benzodiazepines (p=0.001). There was no evidence for any trend in the other polysubstance use profiles, although single drug class use increased (51.9% to 64.7%, p=0.031). The different polysubstance use profiles were variously associated with psychosocial factors, including unstable housing and very high psychological distress, and other drug use risk behaviours, including non-fatal overdose, receptive and/or distributive needle sharing, and reusing one's own needles. Same day polysubstance use has remained relatively common among this sample over time, although the typology has changed. Collectively, our findings point to diverse drug use patterns among people who inject drugs and reiterate the need for a range of harm reduction, treatment, and support options.

Perspectives of Cell Sensitivity/Resistance Assay in Soft Tissue Sarcomas Chemotherapy.

Treatment of highly malignant soft tissue sarcomas (STSs) requires multicomponent therapy including surgery, radiotherapy, and chemotherapy. Despite the advancements in targeted cancer therapies, cytostatic drug combinations remain the gold standard for STS chemotherapy. The lack of algorithms for personalized selection of STS chemotherapy leads to unhelpful treatment of chemoresistant tumors, causing severe side effects in patients. The goal of our study is to assess the applicability of in vitro chemosensitivity/resistance assays (CSRAs) in predicting STS chemoresistance. Primary cell cultures were obtained from 148 surgery samples using enzymatic and mechanical disaggregation. CSRA was performed using resazurin-based metabolic activity measurement in cells cultured with doxorubicin, ifosfamide, their combination and docetaxel, gemcitabine, and also their combination for 7 days. Both the clinical data of patients and the CSRA results demonstrated a higher resistance of some cancer histotypes to specific drugs and their combinations. The correlation between the CSRA results for doxorubicin and ifosfamide and clinical responses to the combination chemotherapy with these drugs was demonstrated via Spearman rank order correlation. Statistically significant differences in recurrence-free survival were also shown for the groups of patients formed, according to the CSRA results. Thus, CSRAs may help both practicing physicians to avoid harmful and useless treatment, and researchers to study new resistance markers and to develop new STS drugs.

Stroke mimics in a Brazilian stroke center: a retrospective cohort in a Brazilian stroke unit

This study assessed stroke patients in a Brazilian unit to describe the prevalence, clinical presentation, etiology, and treatment outcomes of cases initially diagnosed as stroke mimics (SM). SM refers to conditions that mimic stroke but are not caused by cerebrovascular events. Misdiagnosis can lead to unnecessary and potentially harmful treatments. The study examined patients admitted between October 2012 and September 2013. Among patients with symptoms onset within four hours, 7.1% (10 patients) were classified as SM. Six of these patients received intravenous thrombolysis, a treatment for acute ischemic stroke. The main clinical presentations among SM cases were motor symptoms (90%), dysarthria, and sensory symptoms (60%). The etiology of SM cases varied, with functional disorders being the most common (60%). The findings reveal a significant percentage of patients admitted to the stroke unit were ultimately diagnosed as SM, highlighting the need for improved diagnostic strategies to differentiate between stroke and SM. The study underscores the importance of developing well-defined guidelines to assess SM risk and utilize imaging methods for distinguishing between stroke and SM. Further research is necessary to address these issues and enhance stroke diagnosis accuracy.

Challenges of caring for older patients with multimorbidity including cancer

IntroductionAs the population is ageing, the number of older patients with multimorbidity including cancer continues to increase. To improve care for these patients, the European Union-funded project “Streamlined Geriatric and Oncological evaluation based on IC Technology” (GERONTE) was initiated to develop a new, patient-centred, holistic care pathway. The aim of this paper is to analyse what challenges are encountered in everyday clinical practice according to patients, their informal caregivers, and healthcare professionals as a starting point for the development of the care pathway. Materials and MethodsAn expert panel of cancer and geriatrics specialists participated in an online survey to answer what challenges they experience in caring for older patients with multimorbidity including cancer and what treatment outcomes could be improved. Furthermore, in-depth interviews with older patients and their informal caregivers were organised to assess what challenges they experience. ResultsHealthcare professionals (n = 36) most frequently mentioned the challenge of choosing the best treatment in light of the lack of evidence in this population and how to handle interactions between the (cancer) treatment and multimorbidities. Twelve patients and caregivers participated, and they most frequently mentioned challenges related to treatment outcomes, such as how to deal with symptoms of disease or treatment and how to maintain quality of life. From the challenges, five main themes emerged that should be taken into account when developing a new care pathway for older patients with multimorbidity including cancer. Two themes focus on decision making aspects such as personalized treatment recommendations and inclusion of non-oncologic information, two focus on patient support and monitoring to maintain quality of life and functioning, and one overarching theme addresses care coordination to prevent fragmentation of care. DiscussionIn conclusion, the management of older patients with multimorbidity including cancer is complex and although progress has been made on improving aspects of their care, challenges remain and patients are at risk of receiving inappropriate, unnecessary, and potentially harmful treatment. A patient-centred care pathway that integrates solutions to the five main themes and that moves away from a single-disease centred approach is needed.

Assay interference as a cause of false positive troponin T elevation in emergency department patients

BackgroundTroponin assays are used in the diagnosis of myocardial injury and may show elevated results for a variety of reasons. However it is increasingly recognised that cardiac troponin elevation may in some cases be due to assay interference. This is of significant importance as a misdiagnosis of myocardial injury may lead to unnecessary and potentially harmful investigation and treatment for patients. We sought to confirm the accuracy of cardiac high sensitivity troponin T (chsTnT) elevation in an unselected group of patients presenting to the emergency department, by using a second confirmatory cardiac high sensitivity troponin I (chsTnI) assay. MethodsWe identified patients presenting to two local emergency departments over a five-day period who had chsTnT levels measured as part of routine clinical care. All samples with elevated chsTnT levels (above the 99% centile URL) were retested for chsTnI in order to confirm true myocardial injury. ResultsA total of 74 samples from 54 patients were analysed for chsTnT and chsTnI. 7 samples (9.5%) had chsTnI levels < 5 ng/L suggesting assay interference as the cause of chsTnT elevation. ConclusionsAssay interference leading to false positive troponin elevation may be more common than many physicians appreciate and can potentially lead to harmful investigation and treatment for patients. In cases where the diagnosis of myocardial injury is uncertain, a second alternative troponin assay should be performed to confirm true myocardial injury.

Exploring experiences of vaccine-related and alternative treatments for individuals with autism: A qualitative study

Some alternative treatments wrongly suggest that routine childhood vaccines cause autism resulting in vaccine skepticism and false claims about curing autism. In the present study we explore the experiences of vaccine-related and alternative treatments of autistic individuals. Semi-structured interviews were conducted with autistic adults (n = 3), parents of autistic children (n = 5) and parents of autistic adults (n = 5). Thematic analysis showed five themes: (1) reasons for choosing alternative treatment, (2) treatment content, (3) experiences with alternative care, (4) outcomes of the vaccine-related treatment and (5) future directions for treating autism. Both positive (holistic approach, time and attention) and negative aspects (false claims about vaccines and curability of autism) were found. Improved support and guidelines could reduce ineffective and harmful alternative treatments for autism.

The Prevalence of Vibrio cholerae and Vibrio parahaemolyticus Virulence Genes and Multiple Antibiotics Resistant (MAR) Assessment from Local Shrimp Farm in Sarawak

Excessive and improper antibiotic use in animals raised for human consumption can increase the risk of antibiotic-resistant infections, causing more harm and higher treatment costs. This study examined the virulence genes and antibiotic susceptibility of Vibrio cholerae and V. parahaemolyticus, two bacteria that can affect public health. A total of 32 water samples were collected from August to December 2021 from a shrimp farm in Sarawak. Ten (n = 10) V. cholerae and ten (n = 10) V. parahaemolyticus presumptive isolates were identified and purified using selective agar and duplex-PCR method. The results showed that 70% of V. cholerae isolates contained rtxA and 90% of V. cholerae isolates contained rtxC while tdh and trh were not found in V. parahaemolyticus isolates. Antibiotic susceptibility testing showed that all V. cholerae and V. parahaemolyticus isolates were resistant to at least one antibiotic with the mean Multiple Antibiotic Resistance (MAR) indices of 0.34 for V. cholerae and 0.24 for V. parahaemolyticus. The MAR index of 0.20 and greater indicates that antibiotics are heavily contaminating the shrimp farm water. This study highlights the need for the proper administration of antibiotics in shrimp farming environments to reduce the risk of antibiotic-resistant infections caused by V. cholerae and V. parahaemolyticus. Water treatment should also be implemented before being released back to the environment to lessen the negative impact brought by the rearing of shrimp from a highly contaminated source.&#x0D;

Size matters: characterizing penile augmentation content from the 100 most popular YouTube videos.

Aesthetic penile augmentation is considered investigational and not shown to be safe or efficacious. This study sought to characterize the quality and reliability of YouTube videos on the topic of penile augmentation. A systematic search identifying the 100 most viewed YouTube videos on penile augmentation was conducted. The videos were then evaluated by two independent urologists for reliability and quality using a modified DISCERN scoring system and Global Quality Scale (GQS). The median total views were 530,612 (range 123,478-32,914,713). The median DISCERN and GQS scores for all 100 videos were generally poor at 1.75 (IQR 1-2.63) and 2.5 (IQR 1.5-3.5), respectively. A little under half of the videos had a physician present (44.7%). DISCERN and GQS scores were significantly higher in videos with physicians compared to those without one (p < 0.001 for both). The majority of videos discussed nonsurgical methods of penile augmentation (65.1%) with penile traction devices being the most frequently discussed (19.2%). Urologists and medical organizations should strive to have more of a presence in this space to ensure patients are appropriately educated and counseled before pursuing potentially ineffective or harmful treatments.

CD14 Mouth ulcer mayhem secondary to dental fillings

Abstract Dental amalgam contains mercury, which may cause an uncommon lichenoid allergic contact dermatitis (ACD) affecting the oral mucosa in direct contact with the amalgam filling. Distinguishing a lichenoid amalgam reaction from oral lichen planus is challenging, both clinically and histopathologically. This case illustrates the important role that patch testing to dental materials can play in providing a simple answer in the management of resistant cases of mouth ulceration, protecting patients from exposure to potentially toxic immunosuppressive treatments. A 64-year-old woman presented with a 5-year history of oral ulceration affecting the buccal mucosa and tongue bilaterally. These ulcers were persistent, very painful and bled intermittently, causing a significant adverse effect on her quality of life. She worked as a manager at a local wildlife sanctuary, and hobbies included walking, writing and artwork. An incisional biopsy taken from an ulcer in the left buccal mucosa demonstrated a dense lichenoid inflammatory cell infiltrate. The oral surgical team treated her for presumed ulcerative oral lichen planus with multiple treatments, including topical steroids, high doses of oral prednisolone, hydroxychloroquine, mycophenolate mofetil and azathioprine. She gained only very minimal benefit. The oral surgeons then requested dermatological advice for the next potential treatment option, which was suggested to be rituximab. At this point, the surgeons noticed that the ulcers seemed to be most prominent at sites of the patient’s longstanding amalgam fillings and she was referred for patch testing. Patch tests were performed to the British Standard series, medicaments series and oral and dental series. Positive reactions were noted to both amalgam (D2+/D4+) and mercury (D2+/D4+). The patient had her amalgam fillings replaced with white acrylate fillings, and her oral ulceration completely healed without the need for any further immunosuppression. Clinically and histologically, lichenoid ACD secondary to dental fillings can be indistinguishable from idiopathic oral erosive lichen planus. However, the proximity of ulceration to dental filling materials should always raise the possibility of a lichenoid ACD and trigger referral for patch testing, preferably prior to systemic medications being tried. This case highlights the importance of patch testing in patients with localized, asymmetrical, difficult-to-treat oral ulcers adjacent to amalgam fillings, which could spare the patient from exposure to potentially harmful immunosuppressive treatments.

Transmorphic phage-guided systemic delivery of TNFα gene for the treatment of human pediatric medulloblastoma.

Medulloblastoma is the most common childhood brain tumor with an unfavorable prognosis and limited options of harmful treatments that are associated with devastating long-term side effects. Therefore, the development of safe, noninvasive, and effective therapeutic approaches is required to save the quality of life of young medulloblastoma survivors. We postulated that therapeutic targeting is a solution. Thus, we used a recently designed tumor-targeted bacteriophage (phage)-derived particle, named transmorphic phage/AAV, TPA, to deliver a transgene expressing the tumor necrosis factor-alpha (TNFα) for targeted systemic therapy of medulloblastoma. This vector was engineered to display the double-cyclic RGD4C ligand to selectively target tumors after intravenous administration. Furthermore, the lack of native phage tropism in mammalian cells warrants safe and selective systemic delivery to the tumor microenvironment. In vitro RGD4C.TPA.TNFα treatment of human medulloblastoma cells generated efficient and selective TNFα expression, subsequently triggering cell death. Combination with the chemotherapeutic drug cisplatin used clinically against medulloblastoma resulted in augmented effect through the enhancement of TNFα gene expression. Systemic administration of RGD4C.TPA.TNFα to mice-bearing subcutaneous medulloblastoma xenografts resulted in selective tumor homing of these particles and consequently, targeted tumor expression of TNFα, apoptosis, and destruction of the tumor vasculature. Thus, our RGD4C.TPA.TNFα particle provides selective and efficient systemic delivery of TNFα to medulloblastoma, yielding a potential TNFα anti-medulloblastoma therapy while sparing healthy tissues from the systemic toxicity of this cytokine.

Advanced perception and control method of harmful gas during construction period of coal tunnel based on DeepAR

Effective real-time treatment and control of harmful gases are key to ensuring the safety of tunnel construction workers. Currently, the monitoring ability of harmful gases is insufficient to match the processing needs, which poses significant risks to the safety of tunnel construction workers. This paper proposes an advanced perception and treatment method for harmful gases during tunnel construction, utilizing the DeepAR algorithm. Real-time monitoring of the concentration and diffusion of harmful gases is conducted, and a harmful gas concentration prediction model is established using the DeepAR algorithm, achieving advanced perception of harmful gases during tunnel construction. The harmful gas treatment plan is developed in advance, and the effectiveness of the proposed method is demonstrated by simulation testing under realistic field scenarios and comparing with other prediction models. The method was applied in a coal mine tunnel in Qinghai Province, achieving an accuracy rate of 94.3%, which is higher compared to those obtained using RNN and LSTM algorithms. Moreover, the computational time is less than 60 s. The method provides timely perception of the concentration distribution of harmful gases in the tunnel and proposes targeted treatment measures, verifying the effectiveness of the prediction model from the perspective of practical engineering application.

Addressing stigma within the dissemination of research products to improve quality of care for pregnant and parenting people affected by substance use disorder.

Substance use disorders are a common and treatable condition among pregnant and parenting people. Social, self, and structural stigma experienced by this group represent a barrier to harm reduction, treatment utilization, and quality of care. We examine features of research dissemination that may generate or uphold stigmatization at every level for pregnant and parenting individuals affected by substance use disorder and their children. We explore stigma reduction practices within the research community that can increase uptake of evidence-based treatment programs and prevent potential harm related to substance use in pregnant and parenting people. The strategies we propose include: (1) address researcher stereotypes, prejudice, and misconceptions about pregnant and parenting people with substance use disorder; (2) engage in interdisciplinary and transdisciplinary collaborations that engage with researchers who have lived experience in substance use; (3) use community-based approaches and engage community partners, (4) address stigmatizing language in science communication; (5) provide contextualizing information about the social and environmental factors that influence substance use among pregnant and parenting people; and (6) advocate for stigma-reducing policies in research articles and other scholarly products.