Using Nuclear Magnetic Resonance to Troubleshoot a Stability Issue in a Real-World Formulation Chassis-Application to Consumer Oral Healthcare.

With direct application to current and future consumer healthcare products, this research sheds light on the importance of packaging and its potential effects on both Active Pharmaceutical Ingredient (API) delivery and stability. Industrially sourced, proprietary experimental formulations (PEFs), specifically oral cleansers, based on salicylic acid and hydrogen peroxide, discolored over time at different rates, depending on packaging type used. This discoloration stemmed from an interplay of two factors, involving both spontaneous formulation degradation and the interaction of both degradants and salicylic acid with the internal surface of the packaging. This manuscript reports on the investigation to uncover the origins of discoloration. To investigate this real-world, industrial pipeline problem, we exploited the high dimensionality and simple sample preparation uniquely afforded by NMR. Using a combination of 1D/2D NMR and diffusion-ordered NMR spectroscopy (DOSY) to leverage molecular mass estimations from, we not only quickly confirmed the identities of these degradants, but also assessed their formation as a function of temperature and pH, providing insight into the mechanisms underlying their formation. We were able to identify catechol as the main source of discoloration over a period of several weeks, being formed at the ppm level. Furthermore, we evaluated the formulation-container interaction, employing NMR, ICP-MS, and ATR-IR. Despite this comprehensive analysis, the root causes of discoloration could only tentatively be assigned to a surface Ti complex of salicylic acid and other hydroxy carboxylic acids. Through the understanding of formulation degradation pathways, we were able to support further toxicology assessment, vital to both consumer safety and the manufacturer. This work underscores the invaluable role of NMR in the analysis of intricate proprietary mixtures with a consumer-centric purpose. Our findings demonstrate that conventional analytical techniques falter in the face of such complexity, requiring extensive preparation and pre-analytical processing, highlighting the novelty and crucial relevance of NMR research to manufacturers and consumers. Such an analysis is of value in the pursuit of materials within the consumer-healthcare space, which meet the requirements for successful recycling or re-use.

Rectum to Medulla Oblongata: Colorectal Cancer Metastasizing to the Brainstem.

Metastasis with colorectal cancer (CRC) is commonly seen in the liver, lungs and peritoneal cavity. Brainstem involvement with CRC is not studied with no prior reported cases. We report a case of CRC, admitted for apneic spells and dry cough and later found to have metastasis to the left anterolateral medulla oblongata. A 28-year-old male, with a past medical history of asthma, and colorectal adenocarcinoma metastatic to the brain, presented to the emergency department with complaints of a dry cough, altered mental status and shortness of breath. He was seen at urgent care before and was given a week of oral levofloxacin for presumptive pneumonia without any relief. Physical examination was concerning for stridor with clear lung fields. MRI brain showed previously noted post-operative right frontoparietal craniotomy changes and a new 9 x 8 x 8 mm ring-enhancing intra-axial lesion centered at the left anterolateral medulla oblongata indicative of brainstem metastatic disease. The patient was intubated for airway protection and underwent a suboccipital craniotomy for resection of the left pontomedullary mass, and histopathology was positive for metastatic adenocarcinoma, colorectal primary with hemorrhagic necrosis. He had a tracheostomy placed post multiple failed extubation trials and a gastrostomy tube for oral feeds. Goals of care were addressed with the patient and family, and a decision was made for home hospice.

Non-small cell lung cancer presenting as back cyst.

Cutaneous metastasis as the presenting sign of lung cancer is rare, with a poor prognosis and a life expectancy of 3 to 5 months. We present the complicated course of a 60-year-old woman with extensive metastatic non-small cell lung cancer that presented as a back cyst. Due to the benign appearance of the cyst and the difficulty discovering the location of the primary malignancy, diagnosis and treatment were delayed. Unfortunately, once aggressive treatment was initiated at the request of the patient, she died 2 weeks later. This case highlights the importance of recognizing cutaneous lesions as a sign of internal malignancy and emphasizes multidisciplinary discussion that focuses on the patient's quality of life.

The Assessment of Serum Fibronectin Levels as a Potential Biomarker for the Severity of Drug-Sensitive Pulmonary Tuberculosis: A Pilot Study.

BACKGROUND: Tuberculosis (TB) is a global health burden caused by Mycobacterium tuberculosis (Mtb) infection. Fibronectin (Fn) facilitates Mtb attachment to host cells. We studied the Fn levels in smear-positive TB patients to assess its correlation with disease severity based on sputum smears and chest X-rays. METHODS: Newly detected consecutive sputum AFB-positive pulmonary TB patients (n = 78) and healthy control subjects (n = 11) were included. The mycobacterial load in the sputum smear was assessed by IUATLD classification, ranging from 0 to 3. The severity of pulmonary involvement was assessed radiologically in terms of both the number of zones involved (0-6) and as localized (up to 2 zones), moderate (3-4 zones), or extensive (5-6 zones). The serum human fibronectin levels were measured by using a commercially available enzyme-linked immunosorbent assay (ELISA) kit (Catalogue No: CK-bio-11486, Shanghai Coon Koon Biotech Co., Ltd., Shanghai, China). RESULTS: The PTB patients showed lower Fn levels (102.4 ± 26.7) compared with the controls (108.8 ± 6.8), but they were not statistically significant. Higher AFB smear grades had lower Fn levels. The chest X-ray zones involved were inversely correlated with Fn levels. The Fn levels, adjusted for age and gender, decreased with increased mycobacterial load and the number of chest radiograph zones affected. A Fn level <109.39 g/mL predicted greater TB severity (sensitivity of 67.57% and specificity of 90.38%), while a level <99.32 pg/mL predicted severity based on the chest radiology (sensitivity of 84.21% and specificity of 100%). CONCLUSIONS: The Fn levels are lower in tuberculosis patients and are negatively correlated with severity based on sputum mycobacterial load and chest radiographs. The Fn levels may serve as a potential biomarker for assessing TB severity, which could have implications for early diagnosis and treatment monitoring.

A Complex Case of Lemierre's Syndrome With Facial Vein Involvement.

Lemierre's syndrome is a rare disease that generally occurs in young, healthy individuals, where an index of suspicion for something so serious is often low. There is no standardized definition of Lemierre's syndrome, which has led to a dilemma if Lemierre's can be diagnosed without internal jugular vein (IJV) thrombophlebitis. We highlight a complex case of Lemierre's syndrome that deviates from the classical presentation of the disease. A 31-year-old male presented to the hospital with "throat swelling" and difficulty swallowing. He was in severe sepsis with end-organ damage. The patient developed severe pneumonia with pleural/pericardial effusions and bilateral nodular necrosed lesions during hospitalization. A facial vein thrombus was diagnosed, but the absence of internal jugular vein involvement initially delayed Lemierre's diagnosis. However, blood culture speciation revealed Fusobacterium necrophorum, which supported the suspected diagnosis. Persistent fevers and leukocytosis complicated the hospital course despite appropriate antibiotic coverage. The patient ultimately required bilateral thoracotomy and a pericardial window. He made a full recovery.

Paradoxical Arthralgia Secondary to Anti-Tumor-Necrosis-Factor Alpha Therapy in Crohn's Disease.

The current treatment of choice for polyarthralgia in Crohn's disease consists of disease-modifying agents and anti-inflammatory therapy, such as anti-tumor-necrosis-factor alpha inhibitors like infliximab. However, here we report the case of a patient with longstanding Crohn's disease, who developed polyarthritis after receiving only one dose of infliximab. A 57-year-old male with a past medical history of Crohn's disease and stage 1 colon cancer was admitted to our hospital with complaints of polyarticular polyarthralgia, stiffness, and restriction of movements at the joints that started one day prior to admission. It initially began in bilateral wrists, impairing him to hold objects, then spread to bilateral ankles, causing him to fall, and finally affected his jaw, leading to inability to chew or articulate. He received the first dose of infliximab infusion 10 days prior to admission. Labs revealed elevated anti-infliximab antibody levels with low infliximab drug levels. He was treated with steroids, azathioprine, and non-steroidal anti-inflammatory drugs with discontinuation of infliximab. On follow-up, he was initiated on vedolizumab for maintenance of Crohn's disease and did not develop similar complaints again. Our patient had neither had pre-medication antibodies and positive anti-nuclear antibody, nor received the medication for a long duration as proposed in various studies. He developed severe symptoms affecting the majority of axial skeleton from face to feet just after receiving one dose of infliximab. This suggests that further studies in regard to pathophysiological mechanisms and the dose and duration in correlation to symptoms need to be performed for a better understanding of this disease entity.

Characteristics of Chronic Pain among Head and Neck Cancer Patients Treated with Radiation Therapy: A Retrospective Study.

Pain is common among patients with head and neck cancer (HNC). However, there are very limited data on chronic pain among HNC patients treated with radiation therapy (XRT). In this retrospective study, we focused on the characteristics of chronic post-XRT pain in such patients. Post-XRT pain is common among HNC patients; however, we found discrepancy between frequency of treatment and frequency of chronic pain, suggesting poor documentation of pain in the medical records. Among patients who reported to have chronic post-XRT pain, most of them described having severe pain and used descriptors of neuropathic pain. Pharynx was the commonest site of cancer as well as the commonest site of cancer-related chronic pain; squamous cell carcinoma was the most frequent histological pattern, and opioids were used most often to treat such chronic pain. There was a significant association between chronic pain and number of sites of pain, and chronic pain was also associated with use of opioids.

Severe metabolic alkalosis-a diagnostic dilemma.

BACKGROUND: Cushing's syndrome due to ectopic ACTH secretion has been associated with many cancers; most commonly small cell carcinoma of the lung and bronchial carcinoid tumors. Usually, patients who confer this diagnosis have poor prognosis. CASE PRESENTATION: A 66-year-old female presented with worsening shortness of breath and weakness over three days. Initial laboratory derangements included severe hypokalemia and metabolic alkalosis. Treatment included high amounts of potassium chloride and acetazolamide. Imaging studies revealed anterior medial right upper lobe lung mass as well as suspicion for many liver metastases. Liver biopsy was sought and was positive for small cell carcinoma. CONCLUSION: We describe a case of severe metabolic alkalosis and hypokalemia in a patient with Cushing's syndrome due to ectopic ACTH secretion from small cell lung cancer. To our knowledge, this is the first case identified which exhibited such significant metabolic derangements in the form of serum and arterial blood bicarbonate. As prognosis is quite poor, we recommend swift diagnosis and management.

Quality improvement of delirium status communication and documentation for intensive care unit patients during daily multidisciplinary rounds.

Delirium is a key quality metric identified by The Society of Critical Care Medicine for intensive care unit (ICU) patients. If not recognised early, delirium can lead to increased length of stay, hospital and societal costs, ventilator days and risk of mortality. Clinical practice guidelines recommend ICU patients be assessed for delirium at least once per shift. An initial audit at our urban tertiary care hospital in Illinois, USA determined that delirium assessments were only being performed 31% of the time. Nurses completed simulation based education and were trained using delirium screening videos. After the educational sessions, delirium documentation increased from 40% (12/30) to 69% (41/59) (two-proportion test, p<0.01) for dayshift nurses and from 27% (8/30) to 61% (36/59) (two-proportion test, p<0.01) during the nightshift. To further increase the frequency of delirium assessments, the delirium screening tool was standardised and a critical care progress note was implemented that included a section on delirium status, management strategy and discussion on rounds. After the documentation changes were implemented, delirium screening during dayshift increased to 93% (75/81) (two-proportion test, p<0.01). Prior to this project, physicians were not required to document delirium screening. After the standardised critical care note was implemented, documentation by physicians was 95% (106/111). Standardising delirium documentation, communication of delirium status on rounds, in addition to education, improved delirium screening compliance for ICU patients.

Durapain in symptomatic treatment of severe acute pain: a post-marketing, prospective, multicenter, observational study - PRIME study.

OBJECTIVE: To assess the effectiveness, overall tolerability, and gastrointestinal (GI) tolerability of Durapain (fixed dose combination of tramadol hydrochloride immediate release [50 mg] and diclofenac sodium sustained release [75 mg]) in symptomatic treatment of severe acute pain in physician's routine clinical practice. MATERIALS AND METHODS: In this prospective, multicenter, observational, post-marketing study, adult patients (aged 18-60 years) with severe acute pain were treated with tramadol hydrochloride/diclofenac sodium as per approved prescribing information. Evaluation was done at base-line, day 2, and day 5. Primary end point was pain intensity difference from baseline to day 5. RESULTS: A total of 351 patients (mean age 44.2 years; male 43%; female 57%) were included. The mean pain score was reduced from 9.2±1.09 at baseline to 2.8±1.73 at day 5 (p<0.0001). The number of patients with severe intensity of pain reduced from 100% at baseline to 18.3% at day 2 and 6.96% at day 5. According to the patient assessment, 68.36% of patients reported tolerability as "very good to good", whereas according to physician's assessment, "very good to good" tolerability was reported in 68.27% of patients. Five (1.43 %) patients discontinued the study because of adverse drug reaction. Five patients developed nine GI-related events of moderate intensity. Two patients developed three adverse reactions (burning sensation in urine, giddiness, and urine retention) other than GI events. No serious adverse drug reactions were reported during the study period. CONCLUSION: Tramadol hydrochloride/diclofenac sodium is an effective and well-tolerated treatment in Indian patients with severe acute pain. Treatment with tramadol hydrochloride/diclofenac sodium provides significant pain relief on day 2 and maintained until day 5 without any serious adverse reactions.

Evaluation of a Model of Integrated Care for Patients With Chronic Medical and Psychiatric Illness.

BACKGROUND: Chronic illnesses are prevalent in general medical and psychiatric practices, causing significant disease burden to care givers and providers. Systems of care that treat individuals with mental illness are often separate from general medical systems of care. OBJECTIVE: This study sought to compare the quality of life, satisfaction with care, and utilization of care in patients with comorbid chronic medical and mental illnesses. METHODS: A total of 64 participants from an integrated medicine and psychiatry clinic (med/psych), were compared with 52 patients from separate internal medicine and psychiatry clinics (within the same institution) for quality of life, satisfaction with care, and utilization of care. RESULT: Patients receiving integrated care reported being more satisfied with care compared with patients treated separately. There were no differences in quality of life between the groups. A nonsignificant trend toward fewer emergency room visits and fewer hospital stays for the integrated care group compared with the separate care group was observed. CONCLUSION: This study demonstrated that integrated care for psychiatric and medical disorders improved the patients׳ experience of care and therefore may have positively affected the outcome of care. Further work is needed to compare medical and psychiatric comorbidities and costs of care and quality measures in these 2 groups.

R-134a (1,1,1,2-Tetrafluoroethane) Inhalation Induced Reactive Airways Dysfunction Syndrome.

R-134a (1,1,1,2-tetrafluoroethane) is widely used as a refrigerant and as an aerosol propellant. Inhalation of R-134a can lead to asphyxia, transient confusion, and cardiac arrhythmias. We report a case of reactive airways dysfunction syndrome secondary to R-134a inhalation. A 60-year-old nonsmoking man without a history of lung disease was exposed to an air conditioner refrigerant spill while performing repairs beneath a school bus. Afterward, he experienced worsening shortness of breath with minimal exertion, a productive cough, and wheezing. He was also hypoxic. He was admitted to the hospital for further evaluation. Spirometry showed airflow obstruction with an FEV1 1.97 L (45% predicted). His respiratory status improved with bronchodilators and oral steroids. A repeat spirometry 2 weeks later showed improvement with an FEV1 2.5 L (60% predicted). Six months after the incident, his symptoms had improved, but he was still having shortness of breath on exertion and occasional cough.

A Case of Lung Cancer Originating from Cavitary Mycobacterium xenopi Infection.

Coexistence of Mycobacterium xenopi with lung cancer has been reported. However, lung cancer originating within a pre-existing cavity caused by M. xenopi has not. A 55-y-old woman with a history of smoking presented with complaints of chronic dry cough, night sweats, and weight loss for several months. Computed tomography (CT) scanning revealed a 3.5-cm irregular thick-walled cavity in the right lung apex. Cultures obtained from a CT-guided biopsy grew M. xenopi. The patient received standard treatment, and her clinical symptoms improved, and the radiographic lesion stabilized. However, 2 y later, a repeat chest x-ray showed the original right upper lobe cavity with an interval development of a mass adjoining the cavity. A CT-guided needle biopsy of the new mass demonstrated squamous cell carcinoma. Whenever there is a change in the radiological appearance of a cavity, a repeat biopsy should be performed to exclude lung cancer.

Abnormalities of the corpus callosum in non-psychotic high-risk offspring of schizophrenia patients.

Alterations in the structure of the corpus callosum (CC) have been observed in schizophrenia. Offspring of schizophrenia parents have 10-15 times higher risk for developing schizophrenia. We examined CC volume in offspring at genetic high-risk (HR) subjects. Since the sub-regions of the CC are topographically mapped to cortical brain regions, we hypothesized that HR subjects may show a decrement in total volume and differential volume decreases in sub-regions of the CC. The offspring of schizophrenia parents (HR; n=70; 36 males) and healthy volunteers with no family or personal history of psychotic disorders (healthy controls (HC); n=73; 37 males) matched for age, gender and education were selected for the study. Magnetic resonance images were collected using a GE 1.5 T scanner and processed using FreeSurfer image analysis software. The CC was divided into five neuroanatomically based partitions. The volume of total CC and the five sub-regions were measured blind to clinical information. With covariation for intracranial volume, HR subjects had significantly reduced total CC, more prominently observed in the anterior splenium. An age-related increase in CC volume was found in the anterior and posterior splenium of healthy controls but not in HR subjects. The volume reduction was greater in male than female HR subjects. The volume reduction in the CC may reflect a reduction in axonal fibers crossing the hemispheres and/or myelination between the left and right temporo-parietal cortices. The absence of an age-related volume increase suggests an abnormal developmental trajectory that may underlie susceptibility to schizophrenia.

Premorbid cognitive deficits in young relatives of schizophrenia patients.

Neurocognitive deficits in schizophrenia (SZ) are thought to be stable trait markers that predate the illness and manifest in relatives of patients. Adolescence is the age of maximum vulnerability to the onset of SZ and may be an opportune "window" to observe neurocognitive impairments close to but prior to the onset of psychosis. We reviewed the extant studies assessing neurocognitive deficits in young relatives at high risk (HR) for SZ and their relation to brain structural alterations. We also provide some additional data pertaining to the relation of these deficits to psychopathology and brain structural alterations from the Pittsburgh Risk Evaluation Program (PREP). Cognitive deficits are noted in the HR population, which are more severe in first-degree relatives compared to second-degree relatives and primarily involve psychomotor speed, memory, attention, reasoning, and social-cognition. Reduced general intelligence is also noted, although its relationship to these specific domains is underexplored. Premorbid cognitive deficits may be related to brain structural and functional abnormalities, underlining the neurobiological basis of this illness. Cognitive impairments might predict later emergence of psychopathology in at-risk subjects and may be targets of early remediation and preventive strategies. Although evidence for neurocognitive deficits in young relatives abounds, further studies on their structural underpinnings and on their candidate status as endophenotypes are needed.

Verbal fluency deficits and altered lateralization of language brain areas in individuals genetically predisposed to schizophrenia.

Alterations of verbal fluency may correlate with deficits of gray matter volume and hemispheric lateralization of language brain regions like the pars triangularis (PT) in schizophrenia. Examining non-psychotic individuals at high genetic risk (HR) for schizophrenia may clarify if these deficits represent heritable trait markers or state dependent phenomena. We assessed adolescent and young adult HR subjects (N=60) and healthy controls (HC; N=42) using verbal fluency tests and Freesurfer to process T1-MRI scans. We hypothesized volumetric and lateralization alterations of the PT and their correlation with verbal fluency deficits. HR subjects had letter verbal fluency deficits (controlling for IQ), left PT deficits (p=.00), (controlling ICV) and reversal of the L>R PT asymmetry noted in HC. Right Heschl's (p=.00), left supramarginal (p=.00) and right angular gyrii (p=.02) were also reduced in HR subjects. The L>R asymmetry of the Heschl's gyrus seen in HC was exaggerated and asymmetries of L>R of supramarginal and R>L of angular gyri, seen in HC were attenuated in HR subjects. L>R asymmetry of the PT predicted better verbal fluency across the pooled HR and HC groups. Young relatives of schizophrenia patients have verbal fluency deficits, gray matter volume deficits and reversed asymmetry of the pars triangularis. A reversed structural asymmetry of the PT in HR subjects may impair expressive language abilities leading to verbal fluency deficits. Volumetric deficits and altered asymmetry in inferior parietal and Heschl's gyrii may accompany genetic liability to schizophrenia.