Assessment of CT perfusion indices of the clinicoradiological response to anti-tubercular therapy in patients with intestinal tuberculosis.

AIM: To explore the possibility of using a novel technique, CT perfusion imaging, to monitor the response to anti-tubercular therapy (ATT) in patients with intestinal tuberculosis. MATERIALS AND METHODS: A prospective observational study was performed in adults with treatment naive-intestinal tuberculosis. Clinical, endoscopic, and conventional radiological findings of patients were compared at baseline and post-ATT. CT perfusion imaging was performed with recording of six perfusion parameters (blood flow, blood volume, mean transit time, time to peak, maximum peak intensity, and permeability/blood flow extraction). RESULTS: Twenty-two patients (13 women, 59%) with a median age of 25 years were recruited. The terminal ileum and ileocaecal junction were the most frequent sites of involvement (59%), with multiple segments of the intestine being involved in 16 patients (73%). Median duration of ATT was 6 months (range 6-10 months). Complete clinical response was observed in 22/22 (100%) patients, endoscopic response in 12/12 (100%) patients, and radiological response in 10/13 (76%) patients. There was a significant decrease in mean blood flow, blood volume, maximum peak intensity, and an increase in mean transit time and time to peak on follow-up CT perfusion imaging performed after 6 months of ATT. CONCLUSION: Significant alterations in CT perfusion parameters were demonstrated following treatment, consistent with a decline in inflammation and vascularity. CT perfusion imaging of the bowel is a novel means to assess the radiological response to ATT in intestinal tuberculosis, although at the cost of a higher dose of radiation exposure.

A Multicentre UK Study of Outcomes for Locally Advanced Sinonasal Squamous Cell Carcinoma Treated with Adjuvant or Definitive Intensity-modulated Radiotherapy.

AIMS: Sinonasal malignancies are rare; the most common histological subtype is squamous cell carcinoma (SCC). No randomised trial data exist to guide treatment decisions, with options including surgery, radiotherapy and chemotherapy. The role and sequence of a primary non-surgical approach in this disease remains uncertain. The aim of this study was to present treatment outcomes for a multicentre population of patients with locally advanced, stage IVa/b sinonasal SCC treated with radical-intent intensity-modulated radiotherapy, either definitively or postoperatively. MATERIALS AND METHODS: Consecutively treated patients with locally advanced, stage IVa/b sinonasal SCC at four UK oncology centres between January 2012 and December 2017 were retrospectively identified. Descriptive statistics and survival analyses were carried out. Univariable Cox regression analysis was carried out to evaluate the relationship between patient, disease and treatment factors and survival outcomes. RESULTS: In total, 56 patients with sinonasal SCC were included (70% maxillary sinus, 21% nasal cavity, 9% ethmoid/frontal sinus). Forty-one patients (73%) were treated by surgery/adjuvant (chemo)radiotherapy and 15 (27%) by definitive (chemo)radiotherapy. The median duration of follow-up was 3.8 years (interquartile range 2.0-4.7 years). Estimates for 5-year overall survival and progression-free survival were 30.2% and 24.2%, respectively. Local, regional and distant treatment failures were seen in 33%, 33% and 16% of patients, respectively. Univariable analysis revealed inferior progression-free survival for patients treated with neck dissection (hazard ratio 2.6, 95% confidence interval 1.2-6.1, P = 0.022) but no other significant association between the studied factors and survival outcomes. CONCLUSION: We show poor survival outcomes and high rates of locoregional treatment failure for patients with locally advanced stage IVa/b sinonasal SCC. There is a need to investigate improved treatments for this group of patients.

Dose-Volume Predictors for Patient-reported Late Diarrhoea, Faecal Incontinence and Urgency after Pelvic Radiotherapy.

AIMS: Pelvic radiotherapy adds significantly to the curative treatment of many pelvic malignancies. However, this cure comes at a cost for many patients, where late bowel toxicities, such as faecal incontinence, urgency and diarrhoea, adversely affect quality of life. Despite the implementation of advanced radiotherapy techniques in many centres, there are deficiencies in our knowledge of how to make best use of these techniques to minimise these late toxicities, with dose-volume constraints specifically for late effects needing definition. The aims of this study were to establish dose-volume predictors for patient-reported late bowel toxicities and derive constraints for clinical use to reduce the risk of these toxicities. MATERIALS AND METHODS: All radiotherapy patients treated in our institution between 2012 and 2014 for gynaecological and urological cancers (bladder, prostate where pelvic nodes are treated) were identified. Patients were sent patient-reported toxicity questionnaires at 12 and 24 months after treatment. Planning computed tomography scans were retrospectively contoured with different definitions of bowel as organs at risk (OARs). Dose-volume data for each OAR were collected and predictors of these toxicities found using multivariate analysis. For those dose-volume predictors found to be significant on multivariate analysis, statistically significant and clinically relevant dose-volume constraints were derived. Furthermore, data collected were used to validate constraints from published studies. RESULTS: Faecal urgency, incontinence and diarrhoea rates were found in 52, 23.5 and 18.7% of the 203 patients included at 12 months following radiotherapy. Dose-volume parameters for sigmoid colon and large bowel were significant for these toxicities, and constraints for these OARs were derived, which are promising. A previously published constraint for bowel loops was validated with our data. CONCLUSIONS: The sigmoid colon and large bowel are important OARs for the development of faecal urgency, incontinence and diarrhoea. Promising constraints for these OARs were derived, which require further validation before prospective clinical use.

Scrub typhus in patients with acute febrile illness: a 5-year study from India.

BACKGROUND: Scrub typhus was once thought to be a disease of rural origin and was confined to specific pockets in South Asia. Early diagnosis and treatment is extremely important as it is associated with high mortality if left untreated. AIM: To delineate the clinical and molecular epidemiology of scrub typhus in patients presenting with acute febrile illness from various parts of India. METHODS: During the study period of 5 years (October 2013 to October 2018), a total of 1742 patients with acute febrile illness <15 days were enrolled after taking informed consent. Patients were diagnosed using IgM Enzyme-linked immunosorbent assay (ELISA) based on the pre-determined region specific cut offs. Patients with positive IgM ELISA were also subjected to IgM Immunofluorescence assay and nested polymerase chain reaction (PCR) assay. The demographic and relevant clinical details of the patients were documented and analyzed. RESULTS: A total of 210 (12.1%) patients were diagnosed with scrub typhus. Of these, nested PCR was positive in only 85 patients. Sequencing and phylogenetic analysis showed that the predominant circulating genotypes were Gilliam and Karp. On multivariate analysis, acute respiratory distress syndrome, myocarditis, encephalitis/encephalopathy, jaundice and splenomegaly were significantly more common in those patients who were diagnosed with scrub typhus. A total of 14 patients diagnosed with scrub typhus succumbed to the illness. CONCLUSION: Patients with fever, headache, pulmonary manifestations, CNS manifestations, myocarditis, transaminitis or thrombocytopenia presenting in the monsoon and post-monsoon season should be evaluated for scrub typhus irrespective of the geographical location in India.

Specificity of Incident Diagnostic Outcomes in Patients at Clinical High Risk for Psychosis.

It is not well established whether the incident outcomes of the clinical high-risk (CHR) syndrome for psychosis are diagnostically specific for psychosis or whether CHR patients also are at elevated risk for a variety of nonpsychotic disorders. We collected 2 samples (NAPLS-1, PREDICT) that contained CHR patients and a control group who responded to CHR recruitment efforts but did not meet CHR criteria on interview (help-seeking comparison patients [HSC]). Incident diagnostic outcomes were defined as the occurrence of a SIPS-defined psychosis or a structured interview diagnosis from 1 of 3 nonpsychotic Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) groups (anxiety, bipolar, or nonbipolar mood disorder), when no diagnosis in that group was present at baseline. Logistic regression revealed that the CHR vs HSC effect did not vary significantly across study for any emergent diagnostic outcome; data from the 2 studies were therefore combined. CHR (n = 271) vs HSC (n = 171) emergent outcomes were: psychosis 19.6% vs 1.8%, bipolar disorders 1.1% vs 1.2%, nonbipolar mood disorders 4.4% vs 5.3%, and anxiety disorders 5.2% vs 5.3%. The main effect of CHR vs HSC was statistically significant (OR = 13.8, 95% CI 4.2-45.0, df = 1, P < .001) for emergent psychosis but not for any emergent nonpsychotic disorder. Sensitivity analyses confirmed these findings. Within the CHR group emergent psychosis was significantly more likely than each nonpsychotic DSM-IV emergent disorder, and within the HSC group emergent psychosis was significantly less likely than most emergent nonpsychotic disorders. The CHR syndrome is specific as a marker for research on predictors and mechanisms of developing psychosis.

A systematic review of organ motion and image-guided strategies in external beam radiotherapy for cervical cancer.

Advanced radiotherapy techniques, such as intensity-modulated radiotherapy (IMRT), may significantly benefit cervical cancer patients, in terms of reducing late toxicity and potentiating dose escalation. Given the steep dose gradients around the planning target volume (PTV) with IMRT planning, internal movement of organs during treatment may cause geographical miss of the target and unnecessary organs at risk (OAR) inclusion into high dose regions. It is therefore important to consider the extent and patterns of organ motion and to investigate potential image-guided radiotherapy (IGRT) solutions before implementing IMRT for cervical cancer. A systematic literature search was carried out using Medline, Embase, Cochrane Library, Web of Science, Cinahl and Pubmed. Database-appropriate search strategies were developed based upon terms for uterine neoplasms, IGRT, organ motion and target volume. In total, 448 studies were identified and screened to find 39 relevant studies, 12 of which were abstracts. These studies show that within the target volume for cervical cancer radiotherapy, uterine motion is greater than cervical. Uterine motion is predominantly influenced by bladder filling, cervical motion by rectal filling. Organ motion patterns are patient specific, with some having very little (5 mm) and others having much larger shifts (40 mm) of the target volume. Population-based clinical target volume (CTV)-PTV margins would be large (up to 4 cm around the uterus), resulting in unnecessary OAR inclusion within the PTV, reducing the benefits of IMRT. Potential solutions include anisotropic margins with increased margins in the anteroposterior and superoinferior directions, or greater PTV margins around the uterine fundus than the cervix. As pelvic organ motion seems to be patient specific, individualised PTV margins and adaptive IGRT strategies have also been recommended to ensure target volume coverage while increasing OAR sparing. Although these strategies are promising, they need significant validation before they can be adopted into clinical practice.

Association of aphthous ulcers with self-reported symptoms of depression in a sample of smartphone users.

BACKGROUND: Our goal is to examine the association of recurrent aphthous stomatitis (RAS) with symptoms of depression using a smartphone-based questionnaire survey. METHODS: An electronic survey was administered through a smartphone app asking respondents about current depressive symptoms using the Quick Inventory of Depressive Symptoms (QIDS), and asking whether they had ever or recently experienced RAS. Multivariate logistic regression analysis was used to determine associations. RESULTS: A total of 478 individuals completed the survey, with 64% reporting a lifetime prevalence of RAS, and 21% experiencing an aphthous ulcer within the last month. RAS was significantly associated with increased sleep, decreased appetite, low energy, and feeling sluggish. RAS was not associated with overall depression severity as measured by total QIDS score, or with cardinal features of depression such as sadness, insomnia, impaired concentration, self-blame, thoughts of death, or anhedonia. Prevalence of RAS did not differ by age, sex, or smoking status, but was less likely in blacks and Asians compared with whites. CONCLUSIONS: RAS was a common phenomenon in this sample of mostly depressed individuals, and was associated with some neurovegetative symptoms of depression, but not depression severity.

Prevalence of vitreous floaters in a community sample of smartphone users.

AIM: To estimate the prevalence and risk factors for vitreous floaters in the general population. METHODS: An electronic survey was administered through a smartphone app asking various demographic and health questions, including whether users experience floaters in their field of vision. Multivariate logistic regression analysis was used to determine risk factors. RESULTS: A total of 603 individuals completed the survey, with 76% reporting that they see floaters, and 33% reporting that floaters caused noticeable impairment in vision. Myopes were 3.5 times more likely (P=0.0004), and hyperopes 4.4 times more likely (P=0.0069) to report moderate to severe floaters compared to those with normal vision. Floater prevalence was not significantly affected by respondent age, race, gender, and eye color. CONCLUSION: Vitreous floaters were found to be a very common phenomenon in this non-clinical general population sample, and more likely to be impairing in myopes and hyperopes.

Prevalence of stimulant use in a sample of US medical students.

BACKGROUND: Stimulant use for academic performance is widespread among college students, but less is known about use among students obtaining advanced degrees. METHODS: In this cross-sectional survey, we measured the prevalence and demographic correlates of prescription stimulant use among a sample of US medical students. RESULTS: The lifetime prevalence of stimulant use in this sample of 144 medical students was 20%, and prevalence of use during medical school was 15%. More white students (32%) than Asian students (7%) had used stimulants. Nine percent of respondents reported an attention-deficit/hyperactivity disorder (ADHD) diagnosis, and those diagnosed were more than 30 times more likely to have used stimulants compared with those without a diagnosis. Of those who had taken stimulants, 83% reported using them specifically for cognitive performance enhancement such as studying better and staying awake longer while on clinical duties. CONCLUSIONS: This study suggests a high prevalence of stimulant use among medical students compared with the general population. Personal experience with these medications as medical students could impact physician attitudes and prescribing patterns toward patients seeking help for ADHD-related symptoms.

Contemplating cognitive enhancement in medical students and residents.

Medical school and residency can be stressful times, involving years of intensive academic study and pressure to earn high grades. Students and residents must learn to care for the sick, a task requiring long work hours and sleep deprivation. In such an environment, it is important to monitor the mental health of trainees and the factors that influence it. This essay examines a relatively unexplored facet of physician mental health: the use of pharmacological stimulants by students and residents to study better, earn higher grades, stay awake longer, and take better care of patients. Practical and ethical considerations of stimulant use in the medical profession, along with future directions for medical student mental health, are discussed.

Prevalence of aerobic and anaerobic uterine bacteria during peripartum period in normal and dystocia-affected buffaloes.

Parturition complications predispose establishment of uterine infections, which in turn affect subsequent fertility. The aim of present study was to characterize and compare the type of bacterial flora prevalent within the uterine lumen of dystocia-affected buffaloes and compare them with the normally calving buffaloes. The study was conducted on 40 buffaloes; of which 10 calved normally (Group I) and 30 were treated for dystocia (Group II). Bacteriological examination was performed using uterine swabs, which were collected before delivery, immediately after delivery and day's 24-60 postpartum. A total of 30 uterine swabs from Group I and 79 swabs from Group II were collected, of which 19 (63.3%) and 71 (89.9%) yielded significant bacterial growth, respectively. A total of 205 isolates belonging to 10 different genera of bacteria were identified, 8 facultative anaerobes and 2 obligate anaerobes. In Group II, 91.6% of the bacteria positive swabs (n = 71) yielded mixed cultures, whereas the remainder being pure cultures. In contrast, 89.5% of the bacteria positive swabs of Group I (n = 19) yielded pure cultures. Mixed infections comprised mostly Arcanobacter (Actinomyces) pyogenes together with obligate anaerobes, Fusobacterium spp. and Bacteroides spp. In Group II, the frequency of incidental and coliform group bacteria was highest at the time of parturition, i.e., before and immediately after delivery, and decreased to nil during the 24-60-day postpartum period. However, in Group I, the incidental and coliform group of bacteria present at the time of parturition apparently persisted beyond the period when uterine involution is complete. The frequency of obligate anaerobes and A. pyogenes at the time of parturition was nil in the Group I while they predominated in dystocia-affected buffaloes (Group II). During the postpartum period of 24-60 days, the frequency of both obligate anaerobes and A. pyogenes increased significantly in Group II, whereas in Group I, only occasional isolates were obtained. To conclude, at the time of calving the prevalence of obligate anaerobes and A. pyogenes occurring in combination was highest in dystocia-affected buffaloes, and further increased in the postpartum period suggesting that these infections act synergistically.