Equivalent outcomes of ultra-congruent and standard cruciate-retaining inserts in total knee arthroplasty.

PURPOSE: No systematic review has compared the clinical outcome of anterior stabilized ultra-congruent and standard cruciate-retaining inserts in fixed-bearing primary total knee arthroplasty. This study aimed to compare the outcomes and establish the superiority or equivalence of these inserts. METHODS: Pubmed, EMBASE, Medline, AMED, ERIC, and Proquest databases were searched electronically. PRISMA guidelines were followed in the conduct of the study. The clinical outcomes compared in the meta-analysis were overall knee score, WOMAC, score for knee function, score for knee pain, SF-12 PCS, knee flexion, manipulation under anaesthesia for postoperative knee stiffness, revision total knee arthroplasty or change of polyethylene insert for post-operative instability (relative risk [RR]) and survivorship. Study quality was evaluated using the Newcastle Ottawa Scale and the Modified Jadad scale. RESULTS: Fourteen studies comprising 9989 knees (three RCTs and 11 comparative case-cohort studies) were included for qualitative and quantitative analysis. The pooled analysis of the ultracongruent insert and the standard cruciate retaining insert was based on a cohort of 2860 and 7129 TKA, respectively. Knee pain was significantly better in patients that had standard inserts (p = 0.02; 95% CI - 1.06 to - 0.10), and the physical component of health-related quality of life was also significantly better in patients that had standard inserts (p = 0.02; 95% CI - 6.43 to - 0.64). There was a 72% lesser chance of revision TKA or change of insert for postoperative instability in knees that had been implanted with ultracongruent inserts (RR = 0.28; p = 0.0002; 95% CI 0.15-0.55). There was no difference in the otheroutcome measures. There was no significant difference between the two inserts, considering the minimal clinically important difference or absolute ratio. CONCLUSION: Differences observed between the two types of inserts were not clinically significant. Therefore, based on current evidence, arthroplasty surgeons can use either of these inserts with cruciate-retaining knee prosthesis. LEVEL OF EVIDENCE: Therapeutic study, Level II.

Maternal opioid use disorder: Placental transcriptome analysis for neonatal opioid withdrawal syndrome.

Excessive prenatal opioid exposure may lead to the development of Neonatal Opioid Withdrawal Syndrome (NOWS). RNA-seq was done on 64 formalin-fixed paraffin-embedded placental tissue samples from 32 mothers with opioid use disorder, with newborns with NOWS that required treatment, and 32 prenatally unexposed controls. We identified 93 differentially expressed genes in the placentas of infants with NOWS compared to unexposed controls. There were 4 up- and 89 downregulated genes. Among these, 7 genes CYP1A1, APOB, RPH3A, NRXN1, LINC01206, AL157396.1, UNC80 achieved an FDR p-value of <0.01. The remaining 87 genes were significant with FDR p-value <0.05. The 4 upregulated, CYP1A1, FP671120.3, RAD1, RN7SL856P, and the 10 most significantly downregulated genes were RNA5SP364, GRIN2A, UNC5D, DMBT1P1, MIR3976HG, LINC02199, LINC02822, PANTR1, AC012178.1, CTNNA2. Ingenuity Pathway Analysis identified the 7 most likely to play an important role in the etiology of NOWS. Our study expands insights into the genetic mechanisms of NOWS development.

Placental DNA methylation profiles in opioid-exposed pregnancies and associations with the neonatal opioid withdrawal syndrome.

Opioid abuse during pregnancy can result in Neonatal Opioid Withdrawal Syndrome (NOWS). We investigated genome-wide methylation analyses of 96 placental tissue samples, including 32 prenatally opioid-exposed infants with NOWS who needed therapy (+Opioids/+NOWS), 32 prenatally opioid-exposed infants with NOWS who did not require treatment (+Opioids/-NOWS), and 32 prenatally unexposed controls (-Opioids/-NOWS, control). Statistics, bioinformatics, Artificial Intelligence (AI), including Deep Learning (DL), and Ingenuity Pathway Analyses (IPA) were performed. We identified 17 dysregulated pathways thought to be important in the pathophysiology of NOWS and reported accurate AI prediction of NOWS diagnoses. The DL had an AUC (95% CI) =0.98 (0.95-1.0) with a sensitivity and specificity of 100% for distinguishing NOWS from the +Opioids/-NOWS group and AUCs (95% CI) =1.00 (1.0-1.0) with a sensitivity and specificity of 100% for distinguishing NOWS versus control and + Opioids/-NOWS group versus controls. This study provides strong evidence of methylation dysregulation of placental tissue in NOWS development.

Evaluation of Acoustic Radiation Force Impulse Imaging in Differentiating Benign and Malignant Cervical Lymphadenopathy.

Background: The aim of this study was to assess the diagnostic role of acoustic radiation force impulse imaging (ARFI) in differentiating benign and malignant cervical nodes. Methods: This was a diagnostic accuracy cross-sectional study. All patients who underwent ultrasound-guided fine-needle aspiration cytology (FNAC) of cervical nodes were included. Patients without FNAC/biopsy and patients in whom cervical nodes were cystic or completely necrotic were excluded. FNAC was used as reference investigation to predict the diagnostic accuracy. In all cases, FNAC was carried out after the B-mode, color Doppler and the ARFI imaging. In patients with multiple cervical lymph nodes, the most suspicious node based on grayscale findings was chosen for ARFI. ARFI included Virtual Touch imaging (VTI), area ratio (AR), and shear wave velocity (SWV) for each node, and the results were compared with FNAC/biopsy. Results: The final analysis included 166 patients. Dark VTI elastograms had sensitivity and specificity of 86.2% and 72.1%, respectively, in identifying malignant nodes. Sensitivity and specificity of AR were 71.3% and 82.3%, respectively, for a cutoff of 1.155. Median SWV of benign and malignant nodes was 1.9 [95% confidence interval (CI), 1.56-2.55] m/s and 6.7 (95% CI, 2.87-9.10) m/s, respectively. SWV >2.68 m/s helped in identifying malignant nodes with 81% specificity, 81.6% sensitivity, and 81.3% accuracy. ARFI was found to be inaccurate in tuberculous and lymphomatous nodes. Conclusion: Malignant nodes had significantly darker elastograms, higher AR and SWV compared to benign nodes, and SWV was the most accurate parameter. ARFI accurately identifies malignant nodes, hence could potentially avoid unwarranted biopsy.

Multiple Psychiatric Morbidity and Continued Use of Naltrexone for Alcohol Use Disorder.

BACKGROUND AND OBJECTIVES: Despite substantial evidence of the efficacy of naltrexone in treating alcohol use disorder (AUD), naltrexone is used infrequently and often for short durations. Understanding factors related to the initiation and continued use of naltrexone could identify targets for improving its use in clinical practice. METHODS: We used the Fiscal year 2012 national data from the Veterans Health Administration to identify the proportion of veterans diagnosed with AUD who initiated and then continued to receive naltrexone for AUD over a 6-month period (N = 67,788). We further examined correlates of any use and continued use, and patterns of use in inpatient and outpatient mental health services and psychotropic prescription fills. Comparisons were made using bivariate analyses and multinomial logistic regression. RESULTS: Among the veterans diagnosed with AUD, 2.02% initiated treatment with naltrexone. Naltrexone initiation was associated with recent homelessness, concurrent psychiatric disorders, receipt of psychiatric outpatient services, psychotropic prescription fills, residential treatment, and psychiatric and medical-surgical hospitalization. Of the 1,366 patients initiating naltrexone, 43.2% (590) received 2 to 5 prescriptions and 16.3% (223) received more than 5 prescriptions for naltrexone. Use of naltrexone beyond one prescription was associated with homelessness, major depressive disorder, schizophrenia, psychotropic medication use, and psychiatric hospitalization. CONCLUSION: Veterans with AUD who used and continued naltrexone were primarily those with multimorbidity and extensive involvement in psychiatric treatment. SCIENTIFIC SIGNIFICANCE: Prior studies examined the correlates of initiation of naltrexone but retention in treatment has received less attention. This study identified the frequency and important patient and service correlates of continued use of naltrexone. (Am J Addict 2021;30:55-64).

Rehabilitation of Severe Atrophic Ridges with Zygomatic Implant and/or All-on-4 Treatment Concepts-A Case Series.

Rehabilitation of completely edentulous patients with implant-supported prosthesis (ISP) is the need of the day, but in many patients, the routine ISP is not possible due to the severe atrophic residual ridges. The present case series describes three cases with atrophic ridges rehabilitated using zygomatic implants and/or All-on-4 treatment concepts. In case 1 and case 3, in maxillary arch, there was not enough bone in Zone 3 to rehabilitate the patient with routine protocol followed for the All-on-4 treatment concept, so in these two cases, zygomatic implants were placed. Case 1 and case 2 were rehabilitated with Malo Bridge and case 3 with acrylic teeth-hybrid prosthesis using a computerized milling procedure to obtain improved fit, function, esthetics, and ease of retrievability whenever required.

Effects of Alcohol Cue Reactivity on Subsequent Treatment Outcomes Among Treatment-Seeking Individuals with Alcohol Use Disorder: A Multisite Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Varenicline.

BACKGROUND: The alcohol cue reactivity paradigm is increasingly used to screen medications for the treatment of alcohol use disorder (AUD) and other substance use disorders. Yet, its prospective association with craving and naturalistic drinking outcomes in clinical trials remains unknown. This study embedded repeated human laboratory assessments of alcohol cue reactivity within the context of a randomized controlled trial to examine the effects of varenicline tartrate (Chantix® ), a partial agonist of α4ß2 nicotinic acetylcholine receptors, on alcohol craving among treatment-seeking heavy drinkers with AUD. Our main objectives were to test whether varenicline, as compared to placebo, blunts alcohol cue-elicited craving and test whether alcohol cue reactivity observed in the human laboratory predicts subsequent alcohol craving and use during the remainder of the trial. DESIGN AND METHODS: This double-blind, randomized, 2-site study compared the effects of varenicline (up to 2 mg/d) and placebo on responses to in vivo alcohol cue and affective picture cue exposure in the human laboratory. Forty-seven volunteers (18 females, 29 males), ages 23 to 67 years (M = 43.7, SD = 11.5), were recruited from the community via advertisements to participate in a clinical trial designed to study the effects of varenicline on alcohol use. Participants were randomized to either varenicline or placebo for 6 weeks. RESULTS: Varenicline did not attenuate cue-induced alcohol craving relative to placebo, but craving captured during the cue reactivity paradigm significantly predicted subsequent alcohol use in real-world settings during the clinical trial. Higher craving predicted heavier alcohol use. CONCLUSIONS: Our results are among the first to show alcohol cue-induced craving captured during a human laboratory paradigm predicts drinking outcomes in the context of a clinical trial.

Clinical features and haematological parameters among malaria patients in Mangaluru city area in the southwestern coastal region of India.

The aim of this study was to assess the clinical profile, severity and complications of patients suffering from malaria in Mangaluru, a southwestern coastal city in India. A total of 579 patients, who were treated at the District Wenlock Hospital, Mangaluru, and 168 healthy controls were recruited in this study. The clinical profile, haematological and biochemical parameters, and disease complications were assessed. The majority of patients were treated as outpatients and patients who had severe clinical conditions were admitted to the hospital for treatment and supportive care. Among the total 579 patients recruited in this study, the distribution of P. vivax, P. falciparum and mixed infections were 364 (62.9%), 150 (25.9%) and 65 (11.2%), respectively. Among these, 506 (87.4%) had mild malaria, whereas 73 (12.6%) had severe malaria. Overall, the clinical features and severity of malaria in P. vivax and mixed infection patients were comparable to P. falciparum patients, albeit with some significant differences. The clinical complications in severe malaria cases included thrombocytopenia (50.7%), metabolic acidosis (30.1%), severe anaemia (26.0%), jaundice (21.9%), hepatic dysfunction (15.1%), acute renal failure (6.8%), haematuria (8.2%), hypotension (9.6%), cerebral malaria (1.4%) and acute respiratory distress syndrome (1.4%). All the patients with severe malaria recruited in our study were successfully treated and discharged. Majority of patients had mild malaria, likely due to seeking treatment soon after experiencing symptoms and/or having preexisting immune protection. However, a significant number of patients had severe malaria and required hospital admission indicating that there is a substantial need for creating awareness among vulnerable immigrant population. Implementing effective surveillance and vector control measures in malaria hotspot locations in the city and educating people about preventive measures are likely to reduce the malaria burden in this endemic region.

Stitching a solution to the addiction epidemic: A longitudinal addiction curricular thread across four years of medical training.

BACKGROUND: Despite the enormous burden and public health impact, addiction continues to be one of the most under-treated chronic diseases primarily because of the lack of adequately trained work force of medical providers. To address this issue, medical schools should greatly expand education on addiction. Methods: The six-step Kern model of curriculum development was used as a framework to create an addiction curriculum which includes didactic activities, workshop exercises, practice-based learning activities, clinical simulations, and clinical experiences. Results: The authors and other members of the addiction thread committee conducted a comprehensive needs assessment, developed curriculum goals and objectives, and worked with course and clerkship directors to develop and enhance educational strategies and implement a longitudinal curricular thread woven across all four years of medical school curriculum. Conclusion: Development and implementation of a comprehensive addiction curriculum is feasible, and this model could lay the ground work for implementation at other institutions.

Paraquat Poisoning: A Retrospective Study of 55 Patients From a Tertiary Care Center in Southern India.

BACKGROUND: In India the data on paraquat (PQ) poisoning are limited to case reports and small case series. Hence, this study was carried out to understand the clinical features and outcomes of PQ poisoning. We also briefly report the relevant Indian studies on PQ poisoning. MATERIALS AND METHODS: This was a retrospective case record-based study of PQ poisoning victims admitted over a period of 5 years. RESULTS: Of the 55 patients included in this study, the in-hospital mortality rate was 72.7%. Acute kidney injury was the most common manifestation. The use of cyclophosphamide did not affect the clinical outcome. Hemoperfusion (HP) was not done for any patient. Pulmonary edema and acute tubular necrosis were the most common histopathological findings. CONCLUSION: In India, this is one of the most comprehensive studies of PQ toxicity. Hence, we hope that this information would be of use to clinicians who deal with PQ poisoning. HOW TO CITE THIS ARTICLE: Ravichandran R, Amalnath D, Shaha KK, Srinivas BH. Paraquat Poisoning: A Retrospective Study of 55 Patients from a Tertiary Care Center in Southern India. Indian J Crit Care Med 2020;24(3):155-159.

Malaria prevalence in Mangaluru city area in the southwestern coastal region of India.

BACKGROUND: Malaria is highly prevalent in many parts of India and the Indian subcontinent. Mangaluru, a city in the southwest coastal region of Karnataka state in India, and surrounding areas are malaria endemic with 10-12 annual parasite index. Despite high endemicity, to-date, very little has been reported on the epidemiology and burden of malaria in this area. METHODS: A cross-sectional surveillance of malaria cases was performed among 900 febrile symptomatic native people (long-time residents) and immigrant labourers (temporary residents) living in Mangaluru city area. During each of dry, rainy, and end of rainy season, blood samples from a group of 300 randomly selected symptomatic people were screened for malaria infection. Data on socio-demographic, literacy, knowledge of malaria, and treatment-seeking behaviour were collected to understand the socio-demographic contributions to malaria menace in this region. RESULTS: Malaria is prevalent in Mangaluru region throughout the year and Plasmodium vivax is predominant species compared to Plasmodium falciparum. The infection frequency was found to be high during rainy season. Infections were markedly higher in males than females, and in adults aged 16-45 years than both younger and older age groups. Also, malaria incidence was high among immigrants compared to native population. In both groups, infection rate was directly correlated with their literacy level, knowledge on malaria, dwelling environment, and protective measures used. There was also a significant difference in treatment-seeking behaviour between these two groups. CONCLUSIONS: Malaria incidences in Mangaluru region are predominantly localized to certain hotspot areas within the city, where socioeconomically underprivileged and immigrant labourers are densely populated. These areas have inadequate sanitation and constant water stagnation, harbouring high vector density and contributing to high infection incidences. Additionally, people in these areas seldom practice preventive measures such as using bed nets. The high incidences of malaria in adults are due to minimal cloth wearing, and long working hours stretching to late evenings in places with high vector density. Instituting heightened preventive public measures by governments and creating awareness on using preventive protective and environmental hygienic measures through educational programmes may substantially reduce the risk of contracting infections in these areas and spreading to other areas.

Matrix-Assisted Ionization on a Portable Mass Spectrometer: Analysis Directly from Biological and Synthetic Materials.

Matrix-assisted ionization (MAI)-mass spectrometry (MS) eliminates the need for high voltage, a heat source, lasers, and compressed gases in the ionization process and uses minimal solvents in sample preparation, thus making MAI ideal for field-portable mass spectrometers. The broad applicability of MAI is demonstrated by simple, rapid, and robust positive and negative detection mode analyses of low and high mass compounds including some pesticides, dyes, drugs, lipids, and proteins (186 Da to 8.5 kDa) from various materials including urine, biological tissue sections, paper, and plant material on a low pumping capacity, single-quadrupole mass spectrometer. Different sample introduction methods are applicable, including the use of a pipet tip or glass melting point tube, allowing integration of sample preparation with sample introduction for increased analytical utility and ease of operation, even when sampling directly from surfaces.

Acute Interstitial Nephritis Following Snake Envenomation: A Single-Center Experience.

OBJECTIVES: To identify the clinical and histopathological characteristics of patients who develop acute interstitial nephritis (AIN) following snake envenomation. METHODS: A retrospective analysis of patients diagnosed with snake envenomation-induced AIN from October 2013 to November 2014. RESULTS: After snake envenomation, 88 patients developed acute kidney injury (AKI). Biopsies were performed on 7 patients due to nonrecovery of kidney function. Among these, 5 patients had AIN. Thus, AIN accounted for 5.7% of snakebite-related acute kidney injury. All patients had severe envenomation at presentation and had prolonged renal failure. Kidney biopsy found a mixed infiltrate composed of predominantly lymphocytes, with variable proportions of other cells including eosinophils neutrophils and plasma cells. The response rate to corticosteroids was 80%. CONCLUSIONS: AIN after snake bite is not uncommon. AIN needs to be considered in patients with persistent renal failure after snake envenomation. Identifying this complication is of utmost importance because of the potentially reversible nature.

An Innovative Use of Case Conference to Teach Future Educators in Addiction Psychiatry.

Objective An innovative course was developed for fellows enrolled in the Yale School of Medicine Addiction Psychiatry program to educate them in key principles of adult learning, apply these principles in a case conference presentation, and to improve skills in providing and receiving feedback. Methods An initial training module on educational skills was followed by individual mentorship to prepare a case presentation. A feedback module provided space to learn and practice skills in feedback delivery. Results The program showed positive results and improved confidence levels of the participants in presenting and providing/receiving feedback. Conclusions Implementing a course designed to improve teaching and feedback skills is feasible in a 1-year Addiction Psychiatry fellowship.

High-throughput characterization of small and large molecules using only a matrix and the vacuum of a mass spectrometer.

Matrix assisted ionization vacuum (MAIV) rapidly generates gas-phase analyte ions from subliming solid-phase matrix:analyte crystals for analysis by mass spectrometry (MS). Ionization from the solid-phase allows the use of a variety of surfaces for introducing matrix:analyte samples to the vacuum of a mass spectrometer, including common laboratory materials, such as disposable pipet tips, filter paper, tooth picks, and nylon mesh. MAIV is shown here to be capable of analyses as fast as 3 s per sample with achievable sensitivities in the low femtomole range. MAIV-MS coupled with ion mobility spectrometry (IMS)-MS and tandem mass spectrometry (MS/MS) is shown to be especially powerful for analysis and characterization of a wide range of molecules ranging from small molecules such as drugs and metabolites (∼300 Da) to intact proteins (25.6 kDa). Automated sample introduction is demonstrated on two different commercial mass spectrometers using a programmable XYZ stage. A MAIV high-throughput nontargeted MS(E) approach is also demonstrated utilizing IMS for rapid characterization of small molecules and peptides from standard solutions, as well as drug spiked human urine.

Reproducibility and quantification of illicit drugs using matrix-assisted ionization (MAI) mass spectrometry.

Matrix-assisted ionization (MAI) mass spectrometry (MS) is a simple and sensitive method for analysis of low- and high-mass compounds, requiring only that the analyte in a suitable matrix be exposed to the inlet aperture of an atmospheric pressure ionization mass spectrometer. Here, we evaluate the reproducibility of MAI and its potential for quantification using six drug standards. Factors influencing reproducibility include the matrix compound used, temperature, and the method of sample introduction. The relative standard deviation (RSD) using MAI for a mixture of morphine, codeine, oxymorphone, oxycodone, clozapine, and buspirone and their deuterated internal standards using the matrix 3-nitrobenzonitrile is less than 10% with either a Waters SYNAPT G2 or a Thermo LTQ Velos mass spectrometer. The RSD values obtained using MAI are comparable to those using ESI or MALDI on these instruments. The day-to-day reproducibility of MAI determined for five consecutive days with internal standards was better than 20% using manual sample introduction. The reproducibility improved to better than 5% using a mechanically assisted sample introduction method. Hydrocodone, present in a sample of undiluted infant urine, was quantified with MAI using the standard addition method.

Pulmonary-renal syndromes: Experience from an Indian Intensive Care Unit.

BACKGROUND: The etiology of patients presenting with pulmonary-renal syndrome (PRS) to Intensive Care Units (ICUs) in India is not previously reported. AIMS: The aim was to describe the prevalence, etiology, clinical manifestations, and outcomes of PRS in an Indian ICU and identify variables that differentiate immunologic causes of PRS from tropical syndromes presenting with PRS. MATERIALS AND METHODS: We conducted a prospective observational study of all patients presenting with PRS over 1-year. Clinical characteristics of patients with "definite PRS" were compared with those with "PRS mimics". RESULTS: We saw 27 patients with "provisional PRS" over the said duration; this included 13 patients with "definite PRS" and 14 with "PRS mimics". The clinical symptoms were similar, but patients with PRS were younger and presented with longer symptom duration. Ninety-two percent of the PRS cohort required mechanical ventilation, 77% required vasopressors and 61.5% required dialysis within 48 h of ICU admission. The etiologic diagnosis of PRS was made after ICU admission in 61.5%. Systemic lupus erythrematosus (54%) was the most common diagnosis. A combination of biopsy and serology was needed in the majority (69%, 9/13). Pulse methylprednisolone (92%) and cyclophosphamide (61.5%) was the most common protocol employed. Patients with PRS had more alveolar hemorrhage, hypoxemia and higher mortality (69%) when compared to "PRS mimics". CONCLUSION: The spectrum of PRS is different in the tropics and tropical syndromes presenting with PRS are not uncommon. Multicentric studies are needed to further characterize the burden, etiology, treatment protocols, and outcomes of PRS in India.