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Francisella tularensis is one of the most infectious human pathogens known. In the past, both the former Soviet Union and the US had programs to develop weapons containing the bacterium. We report the complete genome sequence of a highly virulent isolate of F. tularensis (1,892,819 bp). The sequence uncovers previously uncharacterized genes encoding type IV pili, a surface polysaccharide and iron-acquisition systems. Several virulence-associated genes were located in a putative pathogenicity island, which was duplicated in the genome. More than 10% of the putative coding sequences contained insertion-deletion or substitution mutations and seemed to be deteriorating. The genome is rich in IS elements, including IS630 Tc-1 mariner family transposons, which are not expected in a prokaryote. We used a computational method for predicting metabolic pathways and found an unexpectedly high proportion of disrupted pathways, explaining the fastidious nutritional requirements of the bacterium. The loss of biosynthetic pathways indicates that F. tularensis is an obligate host-dependent bacterium in its natural life cycle. Our results have implications for our understanding of how highly virulent human pathogens evolve and will expedite strategies to combat them.
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Francisella tularensis/genética , Genoma Bacteriano , Sequência de Bases , Elementos de DNA Transponíveis , Francisella tularensis/crescimento & desenvolvimento , Ilhas Genômicas , Ferro/metabolismo , Dados de Sequência Molecular , Mutação , Análise de Sequência de DNA , Virulência/genéticaRESUMO
Sexually transmitted infection (STI) prevalence and risks in a sample of rural Thai adolescents and young adults (14-29 years) were examined. Unprotected sex with a casual partner conferred the greatest risk for prevalent STIs, particularly for younger adolescents, and alcohol use increased the STI risk for women but not for men.
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População Rural/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/etiologia , Adolescente , Adulto , Distribuição por Idade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Prevalência , Fatores de Risco , Assunção de Riscos , Distribuição por Sexo , Comportamento Sexual/psicologia , Parceiros Sexuais/psicologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Infecções Sexualmente Transmissíveis/psicologia , Apoio Social , Inquéritos e Questionários , Tailândia/epidemiologiaRESUMO
Background: Significant morbidity and mortality can be associated with gastrostomy insertion, likely influenced by patient selection, indication and aftercare. We aimed to establish what current variation in practice exists and how this has improved by comparison to our previously published British Society of Gastroenterology survey of 2010. Methods: We approached all National Health Service (NHS) hospitals in England (n=198). Email and web-based questionnaires were circulated. These data were correlated with the National Endoscopy Database (NED). Results: The response rate was 69% (n=136/198). Estimated Percutaneous Endoscopic Gastrostomy (PEG) placements in the UK are currently 6500 vs 17 000 in 2010 (p<0.01). There is a dedicated PEG consultant involved in 59% of the centres versus 30% in 2010 (p<0.001). Multidisciplinary team meeting (MDT) discussion occurs in 66% versus 40% in 2010 (p<0.05). Formal aftercare provision occurs in 83% versus 64% in 2010 (p<0.001). 74/107 respondents (69%) reported feeling pressurised to authorise a gastrostomy. Conclusion: This national survey, validated by the results from NED, demonstrates a reduction of over 60% for PEG insertion rates compared with previous estimates. There has also been an increase in consultant involvement, MDT discussion and aftercare provision. However, two-third of responders described 'pressure' to insert a gastrostomy. Perhaps further efforts are needed to include and educate other specialty teams, patients and next of kin.
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BACKGROUND AND AIMS: Patients with intestinal failure requiring home parenteral nutrition are at risk of vitamin D and other micronutrient deficiencies. Conventional enteral replacement of Vitamin D may not be sufficient for this patient group. This study examines whether buccal Vitamin D provides an alternative, effective route for supplementing Vitamin D in patients with intestinal failure. METHODS: A retrospective review of patients who received buccal Vitamin D replacement between 1st January 2013 and 1st January 2020 at our hospital in Northern England was carried out. Demographics were recorded as were patients' daily intravenous fluid requirements using standard ESPEN definitions. Serum Vitamin D levels were recorded prior to buccal replacement and then at a minimum interval of 3 months after commencement. A cost comparison of a 6 month course of this preparation was also made with an equivalent duration of replacement using oral cholecalciferol capsules. RESULTS: 17 patients were identified. The mean level of Vitamin D prior to replacement was 28.4 nmol/l with 65% of patients classed as Vitamin D deficient (<25 nmol/l) prior to replacement. The average duration of buccal replacement prior to a repeat level was 5 months. Following buccal Vitamin D replacement no patients were classed as Vitamin D deficient with all levels ≥25 nmol/l and a mean of 62.3 nmol/l. There was a statistically significant increase in post buccal replacement serum Vitamin D concentrations (p = 0.001). Using costings from our hospital pharmacy a 6 month course of this buccal Vitamin D preparation was 38% less expensive than 6 months of replacement with oral cholecalciferol capsules. CONCLUSIONS: This study shows that in patients with intestinal failure on home parenteral nutrition, buccal Vitamin D is both a use and cost-effective method of replacement.
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Nutrição Parenteral no Domicílio , Deficiência de Vitamina D , Humanos , Estudos Retrospectivos , Vitamina D , Deficiência de Vitamina D/tratamento farmacológico , VitaminasRESUMO
Home parenteral nutrition (HPN) is necessary for patients with prolonged intestinal failure which can be secondary to a variety of pathophysiological mechanisms or surgical resection. HPN is needed to supply micronutrients, macronutrients and water to reduce morbidity and mortality and to maximise the patient's quality of life. HPN requires close monitoring by a dedicated multidisciplinary team and is vital to minimise complications; both catheter related and metabolic. A regular comprehensive review is required including history, examination including anthropometry and blood testing. The focus of this review is on the monitoring of haematological and biochemical parameters. There is a paucity of evidence-based literature on the biochemical monitoring of HPN and existing guidance is sourced mostly on expert opinion and lower grade studies. Sources offering guidance on the frequency of biochemical monitoring for the stable adult HPN patient are the British Association for Parenteral and Enteral Nutrition, the European Society for Parenteral and Enteral Nutrition, the National Institute for Health and Care Excellence and the Australasian Society of Parenteral and Enteral Nutrition (AuSPEN). The aim of this work is to review and collate this existing guidance into one clear and concise review. It is recommended that biochemical parameters are checked at baseline, thereafter more frequently if concerns arise and less frequently when the patient's condition is stable, as assessed by the multidisciplinary team with expertise in HPN.
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BACKGROUND: Manganese toxicity can occur as a complication of home parenteral nutrition (HPN). Patients can present with Parkinson disease-like symptoms. Preparations of trace elements (TEs) in parenteral nutrition (PN) generally provide amounts in excess of requirements. Our previous review observed 60% of adult HPN patients had high whole-blood manganese levels. Multi-TE (MTE) solutions were subsequently removed from all HPN formulations in January 2015. The aim of this evaluation was to determine whole-blood concentrations of manganese in adult patients receiving HPN to establish whether levels are now maintained within the normal reference range. METHODS: A retrospective review of whole-blood manganese levels in all patients receiving HPN between January 2018 and January 2019 from 1 hospital site was carried out. RESULTS: 100 patients were included in the review (59 female and 41 male). Normal whole-blood manganese levels (73-219 nmol/L) were observed in 70% of patients and elevated levels (>219 nmol/L) in 30% of patients. In the patients with elevated levels, 57% had not received manganese supplementation for at least 1 year prior to manganese being measured. Markers of cholestasis were similar between the 2 groups. CONCLUSIONS: Incidence of elevated whole-blood manganese concentrations in patients receiving HPN decreased from 60% to 30% upon discontinued use of an MTE solution. Elevated levels remain a concern despite patients being prescribed "manganese-free" PN. Patients receive this TE in amounts adequate to meet requirements through contamination and dietary intake alone, suggesting additional parenteral supplementation of manganese is not required.
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Manganês , Nutrição Parenteral no Domicílio , Oligoelementos , Adulto , Feminino , Humanos , Masculino , Manganês/sangue , Nutrição Parenteral Total , Estudos RetrospectivosRESUMO
OBJECTIVE: To determine whether development of localised protocol could reduce the number of non-targeted gastric biopsies taken at endoscopy, without risking harm from non-detection of malignant conditions. DESIGN: Retrospective analysis of patient records over a 3-month period in 2013, repeated in 2015 following intervention. SETTING: Two UK teaching hospitals. PATIENTS: Patient record data on indication for endoscopy, endoscopy findings, histopathology results and patient outcome. INTERVENTIONS: Guidance on upper gastrointestinal biopsy in the form of a new trust-wide protocol, as well as lecture-based education. MAIN OUTCOME MEASURES: Rates of non-targeted and targeted biopsies before and after intervention, and differences between grade of endoscopist. RESULTS: Between 2013 and 2015, there was a 36% reduction in non-targeted biopsies (10.4% vs 6.7%, p=0.001), predominantly within registrar and nurse endoscopist groups, with reduction in non-targeted biopsies of 9.5% and 64%, respectively. Percentage of targeted biopsies remained relatively static, 7.9% and 8.2%. In 2013, 92% of non-targeted biopsies had no management change based on histology; in 2015 this was 90%. Of patients with alteration to management, only 0.4% and 0.7% were due to malignancy, in known high-risk patients. Reduction in non-targeted biopsies resulted in estimated annual savings in this trust of £36,000. CONCLUSION: Development of local protocol reduces the numbers of non-targeted biopsies taken, without risk of harm from non-detection of malignant conditions, enabling a significant reduction in workload within busy histopathology services, with significant cost savings. Localised protocols are adaptable to local population demographics.
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OBJECTIVES: Parenteral nutrition (PN) is widely used to provide nutritional support to patients with inaccessible or inadequate length of gut or non-functioning gut. The objective was to compare practice in PN administration to results of the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report, 'A Mixed Bag', and to establish whether good practice was being followed within this part of the UK. SETTING: Using the Northern Nutrition Network (NNN), we examined the care of adult patients receiving PN in all 10 secondary care hospitals in our region. PARTICIPANTS: All patients receiving PN were included with no exclusions. Data were collected on 192 patients (51% females, median age 65â years (range 18-96)). OUTCOME MEASURES: A data collection tool was designed based on the recommendations of the NCEPOD report. RESULTS: PN was used for a median of 7â days with a 30-day mortality rate of 8%. Metabolic complications occurred in 34%, of which only 13% were avoidable. The catheter sepsis rate was 1.5 per 1000 PN days. The audit suggests that nutrition team input improves patient assessment prior to starting PN and review once PN is established. Risk of refeeding syndrome was identified in 75%. Areas for improvement are documentation of treatment goal (39%), review of PN constitution (38%), ensuring patients are weighed regularly (56%) and documentation of line-tip position (52%). CONCLUSIONS: This region-wide prospective audit suggests improved practice within the UK compared to the NCEPOD audit with lower mortality and line sepsis rates. However, documentation remains suboptimal. This work strengthens the case for introducing nutrition teams in hospitals without this service. These findings are likely to be reproduced across the UK and in other healthcare settings. We provide a template for similar audits of clinical practice.
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Fidelidade a Diretrizes , Nutrição Parenteral , Equipe de Assistência ao Paciente/normas , Qualidade da Assistência à Saúde/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo , Inglaterra/epidemiologia , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Estado Nutricional , Nutrição Parenteral/normas , Nutrição Parenteral/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
We report a case of ileo-colonic Histoplasmosis without apparent respiratory involvement in a patient who had previously undergone an orthotopic liver transplant (OLT) for primary biliary cholangitis 15 years earlier. The recipient lived in the United Kingdom, a non-endemic region for Histoplasmosis. However, she had previously lived in rural southern Africa prior to her OLT. The patient presented with iron deficiency anaemia, diarrhoea, abdominal pain and progressive weight loss. She reported no previous foreign travel, however, it later became known that following her OLT she had been on holiday to rural southern Africa. On investigation, a mild granulomatous colitis primarily affecting the right colon was identified, that initially improved with mesalazine. Her symptoms worsened after 18 mo with progressive ulceration of her distal small bowel and right colon. Mycobacterial, Yersinia, cytomegalovirus and human immunodeficiency virus infections were excluded and the patient was treated with prednisolone for a working diagnosis of Crohn's disease. Despite some early symptom improvement following steroids, there was subsequent deterioration with the patient developing gram-negative sepsis and multi-organ failure, leading to her death. Post-mortem examination revealed that her ileo-colonic inflammation was caused by Histoplasmosis.
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Histoplasma/isolamento & purificação , Histoplasmose/diagnóstico , Imunossupressores/efeitos adversos , Transplante de Fígado/efeitos adversos , Doença Relacionada a Viagens , Dor Abdominal/sangue , Dor Abdominal/diagnóstico , Dor Abdominal/microbiologia , África Austral , Idoso , Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/microbiologia , Colangite Esclerosante/cirurgia , Doença de Crohn/diagnóstico , Diagnóstico Diferencial , Diarreia/sangue , Diarreia/diagnóstico , Diarreia/microbiologia , Evolução Fatal , Feminino , Histoplasmose/sangue , Histoplasmose/microbiologia , Humanos , Hospedeiro Imunocomprometido , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/microbiologia , Fatores de Tempo , Redução de PesoRESUMO
AIM: To discover the causes of markedly raised ferritin levels in patients seen at a teaching hospital in Newcastle Upon Tyne, United Kingdom. METHODS: Demographic and medical data were collected for all patients over 18 years who had a serum ferritin levels recorded as >=1500 microg/L during the period January to September 2002. The cause or causes for their hyperferritinaemia were identified from their medical notes. Patients from a defined local population were identified. RESULTS: A total of 19583 measurements were provided of which 406 from 199 patients were >=1500 microg/L. An annual incidence for the local population was determined to be 0.44/1000. 150/199 medical notes were scrutinised and 81 patients were identified as having a single cause for their raised ferritin level. The most common single cause was alcoholic liver disease in the local population and renal failure was the most common single cause in the overall population. Confirmed hereditary haemochromatosis was the 10th most common cause. Liver disease contributed to hyperferritinaemia in 44% of the patients. Weight loss may have contributed to hyperferritinaemia in up to 11%. CONCLUSION: Alcohol related liver disease, haemat-ological disease, renal failure and neoplasia are much more common causes of marked hyperferritinaemia than haemochromatosis. The role of weight loss in hyperferritinaemia may warrant further investigation.
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Ferritinas/sangue , Distúrbios do Metabolismo do Ferro/epidemiologia , Distúrbios do Metabolismo do Ferro/etiologia , Feminino , Doenças Hematológicas/complicações , Doenças Hematológicas/epidemiologia , Hemocromatose/complicações , Hemocromatose/epidemiologia , Humanos , Incidência , Distúrbios do Metabolismo do Ferro/sangue , Cirrose Hepática Alcoólica/complicações , Cirrose Hepática Alcoólica/epidemiologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/complicações , Insuficiência Renal/epidemiologia , Reino Unido , Redução de Peso/fisiologiaRESUMO
AIM: To determine the prevalence of osteoporosis in a cohort of patients with Crohn's disease (CD) and to identify the relative significance of risk factors for osteoporosis. METHODS: Two hundred and fifty-eight unselected patients (92 M, 166 F) with CD were studied. Bone mineral density (BMD) was measured at the lumbar spine and hip by dual X-ray absorptiometry. Bone formation was assessed by measuring bone specific alkaline phosphatase (BSAP) and bone resorption by measuring urinary excretion of deoxypyridinoline (DPD) and N-telopeptide (NTX). RESULTS: Between 11.6%-13.6% patients were osteoporotic (T score < -2.5) at the lumbar spine and/or hip. NTX levels were significantly higher in the patients with osteoporosis (P < 0.05) but BSAP and DPD levels were not significantly different. Independent risk factors for osteoporosis at either the lumbar spine or hip were a low body mass index (P < 0.001), increasing corticosteroid use (P < 0.005), and male sex (P < 0.01). These factors combined accounted for 23% and 37% of the reduction in BMD at the lumbar spine and hip respectively. CONCLUSION: Our results confirm that osteoporosis is common in patients with CD and suggest that increased bone resorption is the mechanism responsible for the bone loss. However, less than half of the reduction in BMD can be attributed to risk factors such as corticosteroid use and low BMI and therefore remains unexplained.
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Densidade Óssea/fisiologia , Reabsorção Óssea/fisiopatologia , Doença de Crohn/complicações , Doença de Crohn/fisiopatologia , Osteoporose/etiologia , Osteoporose/fisiopatologia , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Idoso , Fosfatase Alcalina/metabolismo , Aminoácidos/urina , Índice de Massa Corporal , Reabsorção Óssea/etiologia , Reabsorção Óssea/metabolismo , Estudos de Coortes , Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Estudos Transversais , Feminino , Fraturas Ósseas/etiologia , Fraturas Ósseas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteoporose/metabolismo , Fatores de RiscoRESUMO
This study aimed to establish prevalence of malnutrition in older adult care home residents and investigate whether a nutritional screening and intervention program could improve nutritional and clinical outcomes. A community-based cohort study was conducted in five Newcastle care homes. 205 participants entered; 175 were followed up. Residents already taking oral nutritional supplements (ONS) were excluded from interventions. Those with Malnutrition Universal Screening Tool (MUST) score of 1 received dietetic advice and ≥2 received dietetic advice and were prescribed ONS (220 ml, 1.5 kcal/ml) twice daily for 12 weeks. Body mass index (BMI), MUST, mini nutritional assessment score (MNA)®, mid upper arm muscle circumference (MAMC), and Geriatric Depression Scale (GDS) were recorded at baseline and 12 weeks. Malnutrition prevalence was 36.6% ± 6.6 (95% CI). A higher MUST was associated with greater mortality (p = 0.004). Type of intervention received was significantly associated with change in MUST score (p < 0.001); dietetic advice resulting in the greatest improvement. There were no significant changes in BMI (p = 0.445), MAMC (p = 0.256), or GDS (p = 0.385) following the interventions. Dietitian advice may slow the progression of nutritional decline. In this study oral nutritional supplements over a 3-month period did not significantly improve nutritional status in malnourished care home residents.
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Instituição de Longa Permanência para Idosos , Desnutrição/dietoterapia , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Coortes , Depressão/epidemiologia , Suplementos Nutricionais , Feminino , Avaliação Geriátrica , Humanos , Masculino , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Avaliação Nutricional , Estado Nutricional , Resultado do TratamentoRESUMO
Carcinoma is a recognized but rare complication of small bowel Crohn's disease. This case series emphasizes the importance of considering this diagnosis in patients with small bowel Crohn's disease. We report three cases in which patients were treated for presumed exacerbations of Crohn's, but were subsequently found to have underlying small bowel adenocarcinoma. This case series will demonstrate the need for the surgical assessment of patients with long-standing symptomatic Crohn's disease that fails to settle with conservative management.
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Adenocarcinoma/etiologia , Doença de Crohn/complicações , Neoplasias do Íleo/etiologia , Neoplasias do Jejuno/etiologia , Adenocarcinoma/diagnóstico por imagem , Adulto , Evolução Fatal , Humanos , Neoplasias do Íleo/diagnóstico por imagem , Obstrução Intestinal/etiologia , Neoplasias do Jejuno/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
We present a case of a 62-year-old man with known coeliac disease who was admitted for investigation of abdominal pain and weight loss. He underwent multiple biochemical, haematological, radiological and endoscopic investigations (which were all normal) and also had a normal laparoscopy. Abdominal computerized tomography angiography, however, suggested significant mesenteric stenosis. Mesenteric angiography confirmed superior mesenteric artery stenosis and reproduced the patient's abdominal pain when the catheter crossed the lesion. Balloon angioplasty successfully dilated the stenosis, and since then the patient has gained 19 kg in weight (returning his body mass index from 17 to 23) and has been symptom free. Symptomatic single vessel mesenteric ischaemia (other than coeliac artery stenosis in median arcuate syndrome) is not previously well described. The symptom reproduction on catheterization highlights how useful angiography can be in diagnosis of disease significance. Symptom resolution after angioplasty demonstrated clearly how even single vessel disease can cause significant compromise to the mesenteric circulation.
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Isquemia/etiologia , Oclusão Vascular Mesentérica/complicações , Dor Abdominal/etiologia , Angioplastia com Balão/métodos , Constrição Patológica/complicações , Constrição Patológica/cirurgia , Humanos , Isquemia/cirurgia , Masculino , Artéria Mesentérica Superior/patologia , Oclusão Vascular Mesentérica/cirurgia , Mesentério/irrigação sanguínea , Pessoa de Meia-Idade , Resultado do Tratamento , Redução de PesoAssuntos
Ingestão de Energia/fisiologia , Pessoal de Saúde , Necessidades Nutricionais , Feminino , Humanos , Masculino , Reino UnidoRESUMO
PURPOSE: Methamphetamine (MA) has become the leading drug of abuse in northern Thailand over the past several years, particularly among youth. The current qualitative study examines factors associated with initiation of MA use. METHODS: Between March 2002 and January 2003, 48 in-depth interviews with young MA users were conducted in advance of a randomized, MA harm reduction, peer outreach intervention trial. The interviews were conducted in the city of Chiang Mai and the surrounding district. Data were inductively analyzed using the constant comparative method common to grounded theory methods. Atlas-ti was used for data management. RESULTS: Participants were 57% male and had a median age of 20 years (range 15-31 years). A culture of MA ubiquity characterized participants' initiation stories. Drug ubiquity encompassed three elements: the extent of MA use within peer networks; the availability of MA; and exposure to MA before initiation. All participants were introduced to MA by people close to them, most often by their friends. Internal reasons for trying MA were curiosity, a way to lose weight or to enhance hard work, and a way to "forget life's problems." With the prevalence of MA use among participants' peers, initiation seemed inevitable. CONCLUSIONS: Initiation was characterized as ubiquitous in terms of peer networks' use and availability. Because of the prevalent norm of MA use, these data indicate that interventions targeting social networks and young Thais before MA initiation are needed.