Improving oral health and related health behaviours (substance use, smoking, diet) in people with severe and multiple disadvantage: A systematic review of effectiveness and cost-effectiveness of interventions.

BACKGROUND: People experiencing homelessness co-occurring with substance use or offending ('severe and multiple disadvantage' SMD) often have high levels of poor oral health and related health behaviours (particularly, substance use, smoking, poor diet). This systematic review aimed to assess the effectiveness and cost-effectiveness of interventions in adults experiencing SMD to improve oral health and related health behaviours. METHODS AND FINDINGS: From inception to February 2023, five bibliographic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, and Scopus) and grey literature were searched. Two researchers independently screened the search results. Randomized controlled trials (RCTs), comparative studies and economic evaluations were included that reported outcomes on oral health and the related health behaviours. Risk of bias was assessed and results narratively synthesized. Meta-analyses were performed where appropriate. This review was registered with PROSPERO (reg. no: CRD42020202416). Thirty-eight studies were included (published between 1991 and 2023) with 34 studies reporting about effectiveness. Most studies reported on substance use (n = 30). Interventions with a combination of housing support with substance use and mental health support such as contingent work therapy appeared to show some reduction in substance use in SMD groups. However, meta-analyses showed no statistically significant results. Most studies had short periods of follow-up and high attrition rates. Only one study reported on oral health; none reported on diet. Three RCTs reported on smoking, of which one comprising nicotine replacement with contingency management showed improved smoking abstinence at 4 weeks compared to control. Five studies with economic evaluations provided some evidence that interventions such as Housing First and enhanced support could be cost-effective in reducing substance use. CONCLUSION: This review found that services such as housing combined with other healthcare services could be effective in improving health behaviours, particularly substance use, among SMD groups. Gaps in evidence also remain on oral health improvement, smoking, and diet. High quality studies on effectiveness with adequate power and retention are needed to address these significant health challenges in SMD populations.

Factors influencing implementation and sustainability of interventions to improve oral health and related health behaviours in adults experiencing severe and multiple disadvantage: a mixed-methods systematic review.

OBJECTIVES: Among people experiencing severe and multiple disadvantage (SMD), poor oral health is common and linked to smoking, substance use and high sugar intake. Studies have explored interventions addressing oral health and related behaviours; however, factors related to the implementation of these interventions remain unclear. This mixed-methods systematic review aimed to synthesise evidence on the implementation and sustainability of interventions to improve oral health and related health behaviours among adults experiencing SMD. METHODS: Bibliographic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, EBSCO, Scopus) and grey literature were searched from inception to February 2023. Studies meeting the inclusion criteria were screened and extracted independently by two researchers. Quality appraisal was undertaken, and results were synthesised using narrative and thematic analyses. RESULTS: Seventeen papers were included (published between 1995 and 2022). Studies were mostly of moderate quality and included views from SMD groups and service providers. From the qualitative synthesis, most findings were related to aspects such as trust, resources and motivation levels of SMD groups and service providers. None of the studies reported on diet and none included repeated offending (one of the aspects of SMD). From the quantitative synthesis, no difference was observed in programme attendance between the interventions and usual care, although there was some indication of sustained improvements in participation in the intervention group. CONCLUSION: This review provides some evidence that trust, adequate resources and motivation levels are potentially important in implementing interventions to improve oral health and substance use among SMD groups. Further research is needed from high quality studies and focusing on diet in this population. PROSPERO REGISTRATION NUMBER: CRD42020202416.

Interventions to improve oral health and related health behaviours of substance use, smoking, and diet in people with severe and multiple disadvantage: a systematic review of effectiveness and cost-effectiveness.

BACKGROUND: Homelessness overlapping with substance use and offending is described as severe and multiple disadvantage (SMD). People experiencing SMD have poor oral health along with high levels of related behaviours such as substance use, smoking, and poor diet. Existing evidence largely describes the prevalence of oral health problems, substance use, and smoking in SMD groups. Little is known about interventions that can address these conditions in SMD groups. We aimed to review the effectiveness and cost-effectiveness of interventions on oral health and related health behaviours in adults experiencing SMD. METHODS: For this systematic review, we searched bibliographic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, EBSCO, Scopus) and grey literature for papers published from inception to February 2023. Two researchers independently reviewed the searches. Randomised controlled trials (RCTs), comparative studies and economic evaluations were included. Risk of bias was assessed. Population included adults experiencing SMD (including homelessness and substance use or repeat offending). Outcomes included oral health, and related behaviours (substance use, smoking, poor diet). Results were narratively synthesised. This review was registered with PROSPERO, CRD42020202416. FINDINGS: The review included 38 studies (published between 1991 and 2023), with 34 reporting effectiveness. These studies comprised of 23 RCTs and 11 quasi-experimental studies conducted in the USA (25 studies), Canada (seven studies), France (one study), and Spain (one study). The interventions involving multiple components, such as housing services with substance use and mental health support, effectively reduced substance use in SMD groups; these were mostly individual-level interventions. However, these studies had short follow-up periods and high attrition rates. Only one study addressed oral health outcomes, none focused on diet, and three RCTs covered smoking, with one intervention showing smoking abstinence at 4 weeks. Some limited evidence suggested cost-effectiveness of substance use interventions. INTERPRETATION: This review found that integrating services such as housing with other health-care services together could be effective in improving health behaviours, especially substance use among SMD groups. More evidence is needed specifically on oral health, smoking, and diet-related interventions. The generalisability of findings of this review is limited to high-income countries and shorter-term outcomes. FUNDING: National Institute for Health and Care Research (NIHR) Policy Research Programme.

Unique presentation of occipital condyle giant cell tumor as occipital condyle syndrome - A review.

Giant cell tumors (GCTs) of the skull are rare and only a few case series with limited number of cases have been reported till date. In the cranium, GCT usually occurs in the sphenoid and temporal bone, occipital condyle GCTs are very rare. We report a rare presentation of GCT of the occipital condyle manifested as occipital condyle syndrome. Despite gross total resection, they can recur aggressively; the presence of cortical breach might be an indicator of aggressiveness prompting early post-operative imaging and adjuvant therapy.

Clinical Reasoning: A Teenager With Chronic Meningitis-Does Occam's Razor Apply?

A 14-year-old girl presented with subacute onset headache, fever, and vomiting and was managed initially with antibiotics for suspected bacterial meningitis. Her symptoms further evolved over the next few weeks with systemic signs and symptoms favoring chronic meningitis with raised intracranial pressure. After the etiologic workup was unrevealing, she was started on empirical antituberculous therapy. After a period of partial improvement, symptoms recurred with a new-onset focal seizure. Her imaging findings evolved from features suggestive of focal leptomeningitis to multifocal heterogeneous enhancing cortical and subcortical lesions with hemorrhagic foci, leading to brain biopsy that confirmed diagnosis. Our case highlights the utility of diagnostic biopsy in patients with "chronic meningitis" in uncertain cases rather than confining the approach to the law of parsimony. The decision to initiate empirical therapy in chronic meningitis should be considered on a case-by-case basis and take into account factors, such as clinical examination findings, immune status, recent exposures, and potential risks of treatment. Atypical MRI features should lower the threshold for meningocortical biopsy when indicated.

Association between BMI and periodontitis in women living with or at risk for HIV.

AIMS: Currently, there is no data available assessing the association between body mass index (BMI) and periodontitis among women living with HIV (WLWH). This study aims to investigate this association among WLWH and women at risk for HIV (WRH) in the United States. METHODS AND RESULTS: Data from 351 WLWH and 52 WRH participants from the Women's Interagency HIV Study having pocket depths and clinical periodontal attachment loss assessments in 2003-2004 were included. Multinomial logistic regression analyses in the full sample assessed the relationship between BMI (underweight/normal, overweight, or obese) and periodontitis by severity (mild, moderate, severe), adjusting for study sites, age, education, annual household income, smoking, alcohol consumption, and diabetes. Overall, 75.2% women (76.0% WLWH; 69.0% WRH) had periodontitis. Moreover, 75.0% obese and 75.3% overweight women were affected by periodontitis. In the full sample, adjusted odds ratio (aOR) of having mild, moderate, and severe periodontitis in obese women were: 1.14 (95% confidence interval [CI]: 0.51-2.52), 1.02 (95% CI: 0.46-2.29), and 0.24 (95% CI: 0.06-1.07), respectively, and in overweight women: 0.70 (95% CI: 0.31-1.58), 0.85 (95% CI: 0.38-1.90), and 0.31 (95% CI: 0.08-1.15), respectively. CONCLUSIONS: Even with high prevalence of periodontitis among women with or without HIV infection in this cohort, this study does not provide evidence of an association between BMI and periodontitis.

MutT Homolog1 has multifaceted role in glioma and is under the apparent orchestration by Hypoxia Inducible factor1 alpha.

AIMS: The study focused on the expression and role of a recent potential cancer therapeutic target protein, MutT Homolog1 (MTH1). MTH1 gets activated in an increased reactive oxygen species (ROS) environment and removes the oxidized nucleotides from the cell. The study aimed to check the role of MTH1 in DNA damage and apoptosis, migration and angiogenesis and also to examine its regulation in glioma. MAIN METHODS: The experiments were carried out in human glioma tissue samples and brain tissues of epilepsy patients (non-tumor control). We used two human glioblastomas cell lines, U87MG and U251MG cells. In order to study the role of MTH1 in glioma and to analyze the relation of MTH1 with Hif1α, we have used MTH1 siRNA and Hif1α siRNA respectively. KEY FINDINGS: We found an increased expression of MTH1 in glioma tissues compared to the non-tumor brain tissues. Correlation analysis revealed that those samples showing reduced expression of MTH1 also had high levels of DNA damage and apoptotic markers, while diminished expression of angiogenesis regulators and levels of migration. MTH1 knockdown in vitro by siRNA in tumor cell lines corroborates the above observation. This justifies the emergence of MTH1 inhibitors as potential first-in-class drugs. Mechanistically, our observations suggest that Hif1α may modulate MTH1 expression. SIGNIFICANCE: We found elevated MTH1 expression in glioma irrespective of their grades, while its inhibition affects multiple tumor progression pathways, and that targeting Hif1α could simulate the same.

Anticholinergic, anti-depressant and other medication use is associated with clinically relevant oesophageal manometric abnormalities.

BACKGROUND: Medications can affect gastrointestinal tract motility. However, their effects on oesophageal motility in particular are often not as widely known or may be underestimated. AIM: To review the effect of existing medication use on high-resolution oesophageal manometry (HRM) in a 'real-world' setting. METHODS: Adult patients with upper gut symptoms and normal endoscopy or imaging who had HRM over a 22-month period were analysed. Achalasia and major disorders of peristalsis were excluded. All medications taken within 24 hours of the procedure were prospectively recorded and compared with HRM results, controlling for age, gender and proton pump inhibitor use. RESULTS: A total of 502 patients (323 female, mean age 51) were recruited. Of these, 41.2% had normal oesophageal HRM, while 41.4% had ineffective oesophageal motility (IOM) and 7.6% had oesophagogastric junction outflow obstruction (OGJOO). Serotonin/norepinephrine reuptake inhibitors (SNRI) and opioids were associated with significantly higher resting lower oesophageal sphincter pressure. Benzodiazepines and opioids were associated with elevated integrated relaxation pressure. SNRI and inhaled beta-agonists were associated with increased distal contractile index, whereas calcium channel blockers were associated with a lower distal contractile index. Odds ratio of being on anticholinergics was higher in IOM patients vs normal (3.6, CI 1.2-10.8). Odds ratio for anticholinergics, inhaled beta-agonists, anticonvulsants, SNRIs and opioids (trend) were all > 3 for OGJOO patients vs normal. CONCLUSION: Many medication classes are associated with abnormal HRM variables and diagnoses such as OGJOO and IOM; some of these associations are probably causal. These possible links should be taken into consideration during manometry interpretation.

To be Wild or Mutant: Role of Isocitrate Dehydrogenase 1 (IDH1) and 2-Hydroxy Glutarate (2-HG) in Gliomagenesis and Treatment Outcome in Glioma.

Molecular and clinical research based on isocitrate dehydrogenase (IDH) mutations is much sought after in glioma research since a decade of its discovery in 2008. IDH enzyme normally catalyzes isocitrate to α-keto-glutarate (α-KG), but once the gene is mutated it produces an 'oncometabolite', 2-hydroxyglutarate (2-HG). 2-HG is proposed to inhibit α-KG-dependent dioxygenases and also blocks cellular differentiation. Here, we discuss the role of the IDH1 mutation in gliomagenesis. The review also focuses on the effect of 2-HG on glioma epigenetics, the cellular signaling involved in IDH1 mutant glioma cells and the therapeutic response seen in mutant IDH1(mIDH1) harboring glioma patients in comparison to the patients with wild-type IDH1. The review encompasses the debatable impacts of the mutation on immune microenvironment a propos of various mIDH1 inhibitors in practice or in trials. Recent studies revealing the relation of IDH mutation with the immune microenvironment and inflammatory status in untreated versus treated glioblastoma patients are highlighted with respect to prospective therapeutic targets. Also at the molecular level, the association of mIDH1/2-HG with the intracellular components such as mitochondria and other neighboring cells is discussed.

The HSP90 inhibitor, 17AAG, protects the intestinal stem cell niche and inhibits graft versus host disease development.

Graft versus host disease (GvHD), which is the primary complication of allogeneic bone marrow transplantation, can alter the intestinal barrier targeted by activated donor T-cells. Chemical inhibition of the stress protein HSP90 was demonstrated in vitro to inhibit T-cell activation and to modulate endoplasmic reticulum (ER) stress to which intestinal cells are highly susceptible. Since the HSP90 inhibitor 17-allylamino-demethoxygeldanamycin (17AAG) is developed in clinics, we explored here its ability to control intestinal acute GvHD in vivo in two mouse GvHD models (C57BL/6BALB/c and FVB/NLgr5-eGFP), ex vivo in intestine organoids and in vitro in intestinal epithelial cultures. We show that 17AAG decreases GvHD-associated mortality without impairing graft versus leukemia effect. While 17AAG effect in T-cell activation is just moderate at the dose used in vivo, we observe a striking intestinal integrity protection. At the intestine level, the drug promotes the splicing of the transcription factor X-box binding protein 1 (XBP1), which is a key component of the ER stress. This effect is associated with a decrease in intestinal damage and an increase in Lgr5(+) stem cells, Paneth cells and defensins production. The importance of XBP1 splicing control is further confirmed in cultured cells and organoids of primary intestinal epithelium where XBP1 is either shRNA depleted or inhibited with toyocamycin. In conclusion, 17AAG has a protective effect on the epithelial intestinal barrier in mouse models of acute GvHD. This compound deserves to be tested in the therapeutic control of acute GvHD.

Single institutional experience of prevalence and risk factors of thromboembolic events in children with solid tumors.

Children with cancer are long-term survivors and sequelae from thromboembolic events (TEEs) that include postthrombotic syndrome can cause significant morbidity. Prevalence and risk factors in children with solid tumors are not well described despite some recent studies. If risk factors were better defined, it may be possible to institute appropriate strategies to prevent TEEs and sequelae. A single institution study was performed to investigate the prevalence and risk factors of TEEs in pediatric solid tumors; this included a retrospective analysis of children with central nervous system (CNS) and non-CNS solid tumors with and without TEEs. TEEs were observed in 7.16% of analyzed tumors, higher in the non-CNS (10.6%) than in the CNS tumor category (1.9% P <0.0066). Factors associated with significant risk of TEEs are as follows: presence of a mediastinal mass (P = 0.0005), metastatic disease (P = 0.0086), infection (0.0120), central venous access device (CVAD) (P = 0.0167), and steroids as chemotherapy (P = 0.01). In patients with CVADs, a mediastinal mass (P = 0.0024) and the type of CVAD (peripherally inserted central catheters were more significant risk factors compared with Mediport; P < 0.0001) were significant risk factors. There was a 3.5-fold increased risk of TEEs in patients with CVADs with an underlying diagnosis of lymphoma vs. CNS tumors. Patients with non-CNS solid tumors had increased prevalence of TEEs in our study. Risk factors included metastatic disease, presence of a mediastinal mass, CVAD use, infection, and the use of steroids. Our study underscores the need to conduct a prospective study to formulate the use of prophylactic anticoagulation in patients with identified risk factors to prevent TEEs.

Perk-dependent repression of miR-106b-25 cluster is required for ER stress-induced apoptosis.

Activation of the unfolded protein response sensor PKR-like endoplasmic reticulum kinase (Perk) attenuates endoplasmic reticulum (ER) stress levels. Conversantly, if the damage is too severe and ER function cannot be restored, this signaling branch triggers apoptosis. Bcl-2 homology 3-only family member Bim is essential for ER stress-induced apoptosis. However, the regulatory mechanisms controlling Bim activation under ER stress conditions are not well understood. Here, we show that downregulation of the miR-106b-25 cluster contributes to ER stress-induced apoptosis and the upregulation of Bim. Hypericin-mediated photo-oxidative ER damage induced Perk-dependent cell death and led to a significant decrease in the levels of miRNAs belonging to miR-106b-25 cluster in wild-type (WT) but not in Perk⁻/⁻ MEFs. Further, we show that expression of miR-106b-25 and Mcm-7 (host gene of miR-106b-25) is co-regulated through the transcription factors Atf4 (activating transcription factor 4) and Nrf2 (nuclear factor-erythroid-2-related factor 2). ER stress increased the activity of WT Bim 3'UTR (untranslated region) construct but not the miR-106b-25 recognition site-mutated Bim 3'UTR construct. Overexpression of miR-106b-25 cluster inhibits ER stress-induced cell death in WT but did not confer any further protection in Bim-knockdown cells. Further, we show downregulation in the levels of miR-106b-25 cluster in the symptomatic SOD1(G86R) transgenic mice. Our results suggest a molecular mechanism whereby repression of miR-106b-25 cluster has an important role in ER stress-mediated increase in Bim and apoptosis.

Renal cell carcinoma associated with granulomatous reaction.

Granulomatous inflammation is a distinctive pattern of chronic inflammatory reaction characterized by accumulation of epithelioid histiocytes and multinucleate giant cells. The cause of granulomas can be infectious or non-infectious. Granulomas have been described within the stroma of malignancies like carcinomas of the breast and colon, seminoma and Hodgkin's lymphoma, where they represent T-cell-mediated reaction of the tumor stroma to antigens expressed by the tumor. Granulomatous reaction in association with renal cell carcinoma (RCC) is uncommon, with only few published reports in the literature. We describe three cases of conventional (clear cell) RCC associated with epithelioid granulomas within the tumor parenchyma.

NK/T-cell lymphoma in a renal transplant recipient and review of literature.

T-cell lymphomas, particularly NK/T-cell lymphomas are rare post transplantation malignancies. Only a few cases have been described. These tumors behave aggressively and the outcome is poor. We present here a case of NK/T-cell lymphoma who presented to us with an orbital swelling 9 years after renal transplantation, along with the review of literature. To the best of our knowledge, this is the first case of NK/T-cell lymphoma post-renal transplantation reported from India.

Pediatric tumors of the central nervous system: a retrospective study of 1,043 cases from a tertiary care center in South India.

OBJECTIVE: The objective of this study is to describe the age, sex, location, and histopathology of pediatric tumors of the central nervous system diagnosed at a tertiary care center in South India. PATIENTS AND METHODS: One thousand forty-three tumors that occurred in children between 0 and 18 years of age diagnosed between 1 January 1990 and 31 December 2004 were reclassified according to the WHO 2007 classification, and the clinical data were analyzed. RESULTS: The mean age at diagnosis was 10.9 years with a male/female ratio of 1.7:1 with a male preponderance in most tumors. The five most frequent tumors were: astrocytoma (47.3%), medulloblastoma (11.4%), craniopharyngioma (9.7%), ependymal tumors (4.8%), and nerve sheath tumors (4.1%). Of these, 53.3% of the tumors were supratentorial, 40.6% were infratentorial, and 6.1% occurred in the spinal cord. Although the number of patients treated annually steadily increased over the study period, there was no relative increase in pediatric neoplasms compared to adults. CONCLUSIONS: The majority of tumors showed a male preponderance with astrocytoma being the most common tumor type. Although the cerebellum was the most frequent single site of occurrence, tumors involved the supraratentorial compartment more often than the infratentorial compartment.