Wiley L.

The steadfast stars I expected to navigate this new course all scroll their screens instead,…

Abstract Background Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality. High HBV prevalence in immigrants and ethnic minorities and numerous barriers to healthcare access are associated with serious health disparities in the United States. Reportedly, self-awareness of HBV infection is low, suggesting a greater need for effective screening and education. Further, low levels of linkage to care (LTC) (completion of a first doctor’s visit after the diagnosis of chronic HBV infection) may be responsible for the lack of engagement over the continuum of care and for needed services. Methods Demographics and survey data were obtained from 97 Korean American adults chronically infected with HBV, initially identified through a series of community screening events in northern New Jersey between Dec. 2009 and June 2015. Eight year follow-up on these HBV-infected individuals was obtained to determine their access to care, and thus the efficacy of a campaign to improve LTC. The participants’ self-awareness of HBV infection and other factors for LTC were also evaluated. Results Of a total of 97 HBV-infected participants (age range 30 to 79), 74 were aware of their infections at screening. The remaining 23 had been unaware of their infections until screening. Eight years after the campaign, some 66 of these 97 individuals accessed care (LTC rate 68%). Health insurance status, presence or absence of symptoms and level of knowledge of CHB were among the most significant factors in LTC. Conclusion A community-based hepatitis B screening and education campaign can be instrumental in prompting HBV infected individuals to access care, as demonstrated in the cumulative increase in LTC in our cohort. Despite many years of awareness of HBV infection, many are not accessing care owing to a lack of health insurance, suggesting a pressing need for advocacy and health education to improve access to affordable coverage in the Asian American population. Community efforts and strategies similar to the ones employed in the current study may serve as a model to improve the engagement of HBV-infected individuals in high risk immigrant populations.…

Abstract Background Long-term outcome of DAAs therapy in kidney transplant recipients was unknown. Thus, we aimed to evaluate it in a Chinese cohort of HCV-infected kidney transplant recipients. Methods Single-center and retrospective study of HCV-infected kidney transplant recipients initiating an DAAs regimen between January 2015 and December 2017 was conducted. Totally 26 KTX recipients were divided into three groups, including KTX-HD Group, DAA-KTX Group and KTX-DAA Group. On-treatment response was defined as target not detected within 12 weeks. SVR 48, 96 were defined as HCV-RNA negativity 48, 96 weeks after treatment cessation, respectively. Results HCV genotype was predominantly 1b (80.8%), followed by 2a. All (100%) patients achieved on-treatment response. Time to first TnD was 1.9 ± 0.6 weeks, with no significant difference among the three groups. All patients achieved SVR, with an SVR rate of 100.0% (26/26) among the patients who were followed up over 48 weeks after treatment cessation, and the same SVR rate (24/24) among the patients who were followed up over 96 weeks. Trough levels of Tac remained stable under DAAs therapy, without any dose adjustment. Two patients with abnormal GFR before treatment experienced serum creatinine elevation. Other adverse events included nausea, diarrhea, acid regurgitation, bilirubin elevation and edema of lower limbs. All patients recovered after treatment cessation without reductions in dose, or withdrawal of DAAs or immunosuppressive agents. Conclusions HCV genotype 1b and 2a are the only genotypes and 1b is predominant in our center. Antiviral treatment with DAAs in HCV-infected kidney transplant recipients is persistently effective and well tolerated during long-term follow-up. A regular monitoring of renal function in patients who receive DAAs regimens with preexisting impaired renal function is strongly recommended. Furthermore, the trough CNIs levels were recommended to be frequently monitored.…

Nabatanzi R, Bayigga L, Cose S, et al.

AbstractBackgroundMonocyte dysfunction may persist during antiretroviral therapy (ART).MethodsFrozen peripheral blood mononuclear cells of 30 human immunodeficiency virus (HIV)-infected ART-treated adults with sustained viral suppression and CD4 counts ≥500 cells/µL were consecutively analyzed for monocyte phenotypes and function.ResultsNonclassical monocytes (CD14+, CD16++), interleukin (IL)-1β production, and expression of CD40 and CD86 were lower among ART-treated HIV-infected adults relative to age-matched HIV-negative adults (P = .01, P = .01, and P = .02, respectively). Intestinal fatty acid-binding protein, IL6, and soluble CD14 were higher among HIV-infected adults relative to HIV-negative adults (P = .0002, P = .04, and P = .0017, respectively).ConclusionsFurther investigation is required to understand drivers of persistent monocyte activation and dysfunction.

Venkatesan S, Myles P, Bolton K, et al.

AbstractBackgroundThe effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear.MethodsWe conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of

Lynch C, Green S, Lewis N, et al.

Abbasi J.

This Medical News article discusses how all physicians who treat seriously ill patients can integrate palliative care into their practices.

Abstract Non-typhoidal Salmonella (NTS) spp. causes about 40% of all infective aortitis and it is characterized by high morbidity and mortality. Human infection occurs by fecal–oral transmission through ingestion of contaminated food, milk, or water (inter-human or zoonotic transmission). Approximately 5% of patients with NTS gastroenteritis develop bacteremia and the incidence of extra-intestinal focal infection in NTS bacteremia is about 40%. The organism can reach an extra-intestinal focus through blood dissemination, direct extension from the surrounding organs and direct bacterial inoculation (e.g. invasive medical procedures). Medical and surgical interventions are both needed to successfully control the infection. Here, we report a case of abdominal sub-renal aortitis caused by Salmonella enterica serovar Enteritidis in an 80-year-old man.…

Abstract Background Given the widespread use of the Internet among men who have sex with men (MSM) and high risk of Internet-facilitated sexual behaviors, Internet-based interventions to reduce sexual risk are urgently needed. Methods We recruited 1,100 participants from online and randomly assigned to two groups. One group received online HIV intervention services. Online HIV intervention was developed through mix-method formative research, measures included scenarios experiencing intervention and HIV information dissemination. Self-reported condomless anal sex with a male in the past three months was measured to evaluate the intervention effect. Result Of the 1,100 participants, the majority were aged between 21 and 30 years old (62%), had a college degree or higher (80%), were single (88%), and self-identified as homosexual (78%). The estimated risk difference of condomless sex with a male in the past three months between groups was 9.3% (95% confidence interval (CI): 1.1, 17.5%). Using multiple imputations intention-to-treat, the estimated risk difference was 8.9% (95%CI: 1.2, 16.6%). Modification effects were found between intervention and characteristics including: educational attainment (p = 0.012), marital status (p = 0.005) and awareness of AIDS-related knowledge (p = 0.010). Conclusion Internet appears to be a promising approach to disseminate HIV prevention amongst MSM. Interactive online intervention appeals to MSM and poses a great potential for reducing HIV risky behavior. Trial registration ChiCTR1800014260 (retrospectively registered 2 Jan, 2018).…

Sundermann A, Babiker A, Marsh J, et al.

AbstractBackgroundVancomycin-resistant enterococci (VRE) are a major cause of hospital-acquired infections. The risk of infection from interventional radiology (IR) procedures is not well documented. Whole genome sequencing (WGS) surveillance of clinical bacterial isolates among hospitalized patients can identify previously-unrecognized outbreaks.MethodsWe analyzed WGS surveillance data from November 2016 to November 2017 for evidence of VRE transmission at our hospital. A previously-unrecognized cluster of ten genetically-related VRE (Enterococcus faecium) infections was discovered. Electronic health record review identified IR procedures as a potential transmission route. An outbreak investigation was conducted, which included a matched case-control study.ResultsOf the ten patient VRE infections, nine had undergone an IR procedure with intravenous (IV) contrast ≤22 days before infection. In the matched case-control study, preceding IR procedure and IR procedure with contrast were associated with VRE infection (matched odds ratio 16.72, 95% CI 2.01 to 138.73 and p=0.009; MOR=39.35, 95% CI 7.85 to infinity, p

Urwin JW, Emanuel EJ.

To the Editor In their study of overlapping surgery, Dr Sun and colleagues concluded that “among adults undergoing common operations, overlapping surgery was not significantly associated with differences in in-hospital mortality or postoperative complication rates but was significantly associated with increased surgery length.” However, their reported intraoperative times are consistently longer than empirical data, and the conclusions they draw do not seem warranted by their data.

Sun E, Kheterpal S, Jena AB.

In Reply Drs Urwin and Emanuel raise 2 concerns with our study on overlapping surgery. First, they note that the reported surgical times may not be representative, as the mean surgical times in the study are longer than times from other sources. These differences may stem from the fact that the institutions in our study were largely tertiary academic referral centers, where cases may take longer because of increased complexity and the presence of trainees. In this sense, our study may not be representative, as it did not include many relevant settings (ie, practice in community hospitals), but the magnitude of difference between the surgical times in our study and the times from these other sources (20 minutes) is consistent with the distribution of and variation in case times nationwide. For example, for THA, a large national study of 89 802 cases found a median time of 91 minutes with an interquartile range of 68-109 minutes and with a substantial proportion of cases taking 100 minutes or longer, and similar results were found in a large national study of patients undergoing TKA. In addition, the difference in times is not as large as the authors suggest when a true apples-to-apples comparison is made, because we reported mean times, whereas the studies cited by Urwin and Emanuel report median times. Because the distribution of surgical times tends to have a positive skew, a comparison of median times with mean times will tend to exaggerate differences across studies.

Afshar, Majid; Arain, Erum; Ye, Chen; Gilbert, Emily; Xie, Meng; Lee, Josh; Churpek, Matthew M.; Durazo-Arvizu, Ramon; Markossian, Talar; Joyce, Cara

Objectives: Assess patient outcomes in patients with suspected infection and the cost-effectiveness of implementing a quality improvement program. Design, Setting, and Participants: We conducted an observational single-center study of 13,877 adults with suspected infection between March 1, 2014, and July 31, 2017. The 18-month period before and after the effective date for mandated reporting of the sepsis bundle was examined. The Sequential Organ Failure Assessment score and culture and antibiotic orders were used to identify patients meeting Sepsis-3 criteria from the electronic health record. Interventions: The following interventions were performed as follows: 1) multidisciplinary sepsis committee with sepsis coordinator and data abstractor; 2) education campaign; 3) electronic health record tools; and 4) a Modified Early Warning System. Main Outcomes and Measures: Primary health outcomes were in-hospital death and length of stay. The incremental cost-effectiveness ratio was calculated and the empirical 95% CI for the incremental cost-effectiveness ratio was estimated from 5,000 bootstrap samples. Results: In multivariable analysis, the odds ratio for in-hospital death in the post- versus pre-implementation periods was 0.70 (95% CI, 0.57–0.86) in those with suspected infection, and the hazard ratio for time to discharge was 1.25 (95% CI, 1.20–1.29). Similarly, a decrease in the odds for in-hospital death and an increase in the speed to discharge was observed for the subset that met Sepsis-3 criteria. The program was cost saving in patients with suspected infection (–$272,645.7; 95% CI, –$757,970.3 to –$79,667.7). Cost savings were also observed in the Sepsis-3 group. Conclusions and Relevance: Our health system’s program designed to adhere to the sepsis bundle metrics led to decreased mortality and length of stay in a cost-effective manner in a much larger catchment than just the cohort meeting the Centers for Medicare and Medicaid Services measures. Our single-center model of interventions may serve as a practice-based benchmark for hospitalized patients with suspected infection. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Afshar received funding from the National Institute of Health (NIH)/National Institute of Alcoholism and Alcohol Abuse (K23 AA024503). Dr. Churpek received funding from the NIH/National Institute of General Medical Sciences (R01 GM 123193), NIH/National Heart, Lung, and Blood Institute (K08 HL121080), American Thoracic Society Foundation: Recognition Award for Early Career Investigators, and from a patent pending (ARCD. P0535US.P2). He received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Majid.afshar@lumc.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Mayer C.

Antibiotic resistanceAmpC-type beta-lactamaseantipseudomonal weaponspeptidoglycan recyclingadjuvant strategyin-vivo virulence and resistancevalidation of drug target…

N. A. Chow et al.

Poland GA, Tilburt JC, Marcuse EK.

This Viewpoint calls out the threat to vaccine policy posed by a very small number of antivaccine (“antivax”) advocates who disrupt attempts to engage vaccine-hesitant persons in public hearings about risks and benefits of vaccination and, acknowledging the concerns of a skeptical public, calls for a renewed commitment to civility in discussing public health policy.

Abstract Background The importance of submicroscopic malaria infections in high-transmission areas could contribute to maintain the parasite cycle. Regarding non-endemic areas, its importance remains barely understood because parasitaemia in these afebrile patients is usually below the detection limits for microscopy, hence molecular techniques are often needed for its diagnosis. In addition to this, the lack of standardized protocols for the screening of submicroscopic malaria in immigrants from endemic areas may underestimate the infection with Plasmodium spp. The aim of this study was to assess the prevalence of submicroscopic malaria in afebrile immigrants living in a non-endemic area. Methods A prospective, observational, multicentre study was conducted. Afebrile immigrants were included, microscopic observation of Giemsa-stained thin and thick blood smears, and two different molecular techniques detecting Plasmodium spp. were performed. Patients with submicroscopic malaria were defined as patients with negative blood smears and detection of DNA of Plasmodium spp. with one or both molecular techniques. Demographic, clinical, analytical and microbiological features were recorded and univariate analysis by subgroups was carried out with STATA v15. Results A total of 244 afebrile immigrants were included in the study. Of them, 14 had a submicroscopic malaria infection, yielding a prevalence of 5.7% (95% confidence interval 3.45–9.40). In 71.4% of the positive PCR/negative microscopy cases, Plasmodium falciparum alone was the main detected species (10 out of the 14 patients) and in 4 cases (28.6%) Plasmodium vivax or Plasmodium ovale were detected. One patient had a mixed infection including three different species. Conclusions The prevalence of submicroscopic malaria in afebrile immigrants was similar to that previously described in Spain. Plasmodium vivax and P. ovale were detected in almost a third of the submicroscopic infections. Screening protocols for afebrile immigrants with molecular techniques could be useful for a proper management of these patients.…

Abstract Background The diagnoses of active smear negative PTB, remains difficult. As a result, treatment is often carried out empirically relaying on clinical criteria. The distribution and magnitude of smear negative PTB, smear negative MDR-TB and associated factors in the same day diagnosis strategy are not clearly known in the study area. Therefore, this study aimed to determine the prevalence of TB, MDR-TB and associated risk factors among presumptive smear negative pulmonary tuberculosis patients in Addis Ababa, Ethiopia. Methods Analytic cross sectional study design was used. A total of 418 smear negative presumptive pulmonary TB patients were enrolled from selected health facilities since August 01, 2017 to January 5, 2018. Sputum samples were examined by Ziehl Neelsen microscopy, Xpert MTB/RIF assay and Culture. Drug susceptibility testing was performed by line probe assay and BACTEC MGIT 960 system. These laboratory tests were performed in Ethiopian Public Health Institute, National TB Reference Laboratory. Data was analyzed by SPSS Ver.20. Results From the total of 418 enrolled patients, 27 (6.5%) were Xpert MTB/ RIF and 26 (6.4%) were culture confirmed smear negative PTB patients. The positivity rate among male and female was 10.2 and 3.5% (p = 0.005) respectively. From 26 culture positive isolates 3 (11.54%) were MDR TB; from MDR-TB confirmed isolates 2/23 (8.7%) were among new and 1/3 (33.3%) was among retreatment smear negative presumptive pulmonary TB patients. All Rifampicin resistant smear negative pulmonary TB isolates by Xpert MTB/ RIF assay were found to be MDR TB and 7/26 (26.9%) isolates were INH mono resistant. History of migration found to be a potential factor for developing smear negative pulmonary TB. Conclusion In this study a significant proportion of smear negative pulmonary TB was diagnosed. Furthermore, a high smear negative multi drug resistant (MDR) TB and other mono drug resistant TB prevalence was confirmed. Due to the limitations of smear microscopy which is used as a primary diagnostic tool, these TB strains are missed to be diagnosed and transmission continues in the community.…

Hwang TJ, Dusetzina SB, Feng J, et al.

This study characterizes price increases exceeding inflation between 2012 and 2017 for protected-class drugs (antineoplastics, antiretrovirals, antidepressants, antipsychotics, anticonvulsants, and immunosuppressants for transplant patients) that would lead to their exclusion from Medicare Part D coverage based on excessive cost under a 2018 CMS rule intended to facilitate more effective price negotiations.

Rose L, Muttalib F, Adhikari NJ.

For most patients and their families, admission to the intensive care unit (ICU) is an unanticipated event that causes substantial psychological distress. For patients, short- and long-term consequences include delirium, anxiety, depression, and acute and posttraumatic stress disorder (PTSD). Psychological consequences may be exacerbated by delusions experienced during delirium, which is common among critically ill patients and has adverse effects on physical and cognitive function and leads to increased health care use and costs. For families, anxiety and acute stress arise from concern and uncertainty regarding the prognosis of their family member. Long-term psychological effects in family members appear similar to those experienced by patients. Mitigating these effects is increasingly recognized as a core objective of critical care, along with managing and preventing organ failure and providing timely prognostic information and compassionate end-of-life care when appropriate.

Abstract Background Rat bite fever (RBF), a severe infectious disease, can result from transmission of the pathogen Streptobacillus moniliformis (S. moniliformis) by rat bite. RBF diagnosis can be overlooked. Case presentation We present a case of RBF in a Chinese patient who was infected with S. moniliformis in mainland China. Meta-next generation sequencing (mNGS) was used to identify potential pathogens and detected S. moniliformis genome sequences in the pustular sample in less than 72 h. Then the diagnosis was validated by polymerase chain reaction analysis. Despite having severe RBF with complications, this 54-year-old male patient was successfully cured with penicillin as a result of timely pathogen-based diagnosis. Conclusions Physicians should inquire about recent rat exposure and consider the possibility of RBF when a patient develops unexplained fever and rashes. mNGS is a new diagnostic technology and may identify RBF pathogens even when blood culture results are negative.…

Abstract Background Candida arthritis is extremely rare and also represents a major challenge of diagnosis and treatment. Here we reported a rare case of recurrent arthritis caused by Candida parapsilosis. Case presentation A 56-year-old Chinese male suffered from recurrent pain and swelling in his right knee after several times of “small needle-knife” acupuncture and corticosteroid injection of the joint. Candida parapsilosis was cultured in his synovial fluid and identified by sequencing of its Internal Transcribed Spacer (ITS) gene. Here we present the radiological characteristics, arthroscopic pictures, and synovium pathology of this patient. Also, blood test and chemical analysis of his synovial fluid were listed as well as the ITS sequence of this Candida species identified. The patient underwent thorough arthroscopic debridement and then set on fluconazole 400 mg daily for 12 months. His symptoms resolved and no relapse was observed on the last follow-up. Additionally, a brief but comprehensive review of C. parapsilosis arthritis episodes from past to now were studied. Conclusion With the detailed clinical information reported in this case and our literature review, we hope they would add to our knowledge of C. parapsilosis arthritis - its clinical settings, laboratory features, radiological characteristics, arthroscopic findings and experience of management.…

Kuehn B.

A combination of increased cervical cancer screening, better coverage with the human papillomavirus (HPV) vaccine, and better access to radiotherapy will be needed to cut global cervical cancer incidence and deaths, according to a pair of studies in The Lancet Oncology.

Abstract Background Lassa fever virus has been enlisted as a priority pathogen of epidemic potential by the World Health organization Research and Development (WHO R & D) Blueprint. Diagnostics play a crucial role in epidemic preparedness. This systematic review was conducted to determine the sensitivity and specificity of Lassa fever diagnostic tests for humans. Methods We searched OVID Medline, OVID Embase, Scopus and Web of Science for laboratory based and field studies that reported the performance of diagnostic tests for Lassa fever in humans from 1 January 1990 to 25 January 2019. Two reviewers independently screened all the studies and included only studies that involved the evaluation of a Lassa fever diagnostic test and provided data on the sensitivity and specificity. The quality of the studies was assessed using the QUADAS-2 criteria. Data on the study location, study design, type of sample, index test, reference tests and diagnostic performance were extracted from the studies. Results Out of a total of 1947 records identified, 1245 non-duplicate citations were obtained. Twenty-six (26) full-text articles examined which identified 08 studies meeting pre-defined criteria. Only one study was a field evaluation study. The sensitivity and specificity of the point of care (RDT) against the Nikisins qPCR were 91.2%(95% CI:75.2–97.7) and 86%(95% CI: 71.4–94.2) at temperatures 18–30 °C, while the sensitivity and specificity of the single IgM ELISA assay against standard RT-PCR were 31.1%(95%CI: 25.6–37) and 95.7%(95%CI:92.8–97.7). The sensitivity of the combined ELISA Antigen/IgM assay(against virus isolation), the recombinant IgM/IgG ELISA(against standard RT-PCR), and the IgM/IgG immunoblot(against IFA) were 88%(95%CI:77–95), 25.9%(95%CI:20.8–31.6), and 90.7%(95%CI:84.13–97.27) respectively. The specificity of the combined ELISA Antigen/IgM assay(against virus isolation), the recombinant IgM/IgG ELISA(against standard RT-PCR), and the IgM/IgG immunoblot(against IFA) were 90%(95%CI:88–91), 100%(95%CI:98.2–100), and 96.3%(95%CI:92.2–100) respectively. Conclusion Lassa fever has assays for antigenaemia, IgM, IgG and PCR detection. The RDT reportedly performed well but more data are needed from other countries and at temperatures above 30 °C. Most combined immunoassays perform better than the single IgM. Multiplex and pan-Lassa assays are needed. More well conducted field studies are needed. Trial registration Prospero registration number: CRD42018091585.…

Abstract Background Varicella-zoster virus (VZV) infection in children is an important public health problem in China. We performed the current study to explore the seroprevalence of VZV infection in Chinese children in order to provide more information for improvement of varicella vaccination in China. Methods Three thousand fourteen children were recruited from Chinese kindergarten students aged from four to six years. Anti-VZV IgG and IgM were assayed using enzyme-linked immunosorbent assay. Both ORF22 and ORF62 of VZV were amplified, sequenced, and analyzed by nested PCR. Results Among 3014 children, 43.9% of boys and 46.3% of girls were vaccinated with varicella vaccine, respectively. The seroprevalence of anti-VZV IgG was 54.4% in the children with varicella vaccination, which was significantly higher than those in unvaccinated children (49.2%) (χ2 = 8.206, P = 0.004). Among of the vaccinated children, the detection rates of VZV IgG antibody increased with age, with 49.4, 50.9 and 58.9% in 4, 5 and 6-year groups, respectively (Trend χ2 = 17.202, P = 0.002). However, there was no difference in anti-VZV IgG detection rates among those unvaccinated children in different age groups (Trend χ2 = 8.681, P = 0.070). In addition, 13 boys and 13 girls were positive for anti-VZV IgM, respectively. Among of them, eight children (0.6%) have received varicella vaccination, which was similar to those in unvaccinated children (1.1%). However, only one ORF22 sequence was isolated from an unvaccinated 5-year boy. Compared to the reference VZV sequences, the nucleotide homology was estimated to be 99.7% with genotype J. Conclusions Our study indicated that about half of Chinese children aged four to six years have a high risk of VZV infection. It should be helpful for the evaluation on the necessity of varicella immunization in China.…

Abstract Background We describe a case of severe Guillain-Barre syndrome (GBS) associated with chronic active hepatitis C and mixed cryoglobulinemia (MC). To our knowledge, this association between GBS and hepatitis C virus (HCV) infection has been rarely reported. Case presentation A 56-year-old man developed symmetrical muscle weakness in all extremities, areflexia and sensorial disorder followed by acute respiratory failure associated with chronic active hepatitis C, which was confirmed by the presence of anti-HCV antibodies in the serum and persistence of HCV RNA viral load for more than 6 months. Chronic hepatitis C was further complicated by type 3 MC. Electromyography showed peripheral nerve injury (mainly in axon). A severe acute motor sensory axonal neuropathy (AMSAN) was diagnosed. After treatment with intravenous immunoglobulin and plasma exchange followed by antiviral therapy by direct-acting antiviral agent, patient showed progressive recovery and was transferred 3 months after his first admission to a rehabilitation center. Conclusions Our case reported a severe GBS associated with HCV infection and MC. EMG classified for the first time the subtype of GBS (severe AMSAN) correlated with severe clinical form. HCV infection should be screened in high-risk patients to prevent silent progression of the chronic hepatitis C and its potentially severe extra-hepatic manifestations.…

Abstract Background Tak Province, at the Thai–Myanmar border, is one of three high malaria incidence areas in Thailand. This study aimed to describe and identify possible factors driving the spatiotemporal trends of disease incidence from 2012 to 2015. Methods Climate variables and forest cover were correlated with malaria incidence using Pearson’s r. Statistically significant clusters of high (hot spots) and low (cold spots) annual parasite incidence per 1000 population (API) were identified using Getis-Ord Gi* statistic. Results The total number of confirmed cases declined by 76% from 2012 to 2015 (Plasmodium falciparum by 81%, Plasmodium vivax by 73%). Incidence was highly seasonal with two main annual peaks. Most cases were male (62.75%), ≥ 15 years (56.07%), and of Myanmar (56.64%) or Thai (39.25%) nationality. Median temperature (1- and 2-month lags), average temperature (1- and 2-month lags) and average relative humidity (2- and 3-month lags) correlated positively with monthly total, P. falciparum and P. vivax API. Total rainfall in the same month correlated with API for total cases and P. vivax but not P. falciparum. At sub-district level, percentage forest cover had a low positive correlation with P. falciparum, P. vivax, and total API in most years. There was a decrease in API in most sub-districts for both P. falciparum and P. vivax. Sub-districts with the highest API were in the Tha Song Yang and Umphang Districts along the Thai–Myanmar border. Annual hot spots were mostly in the extreme north and south of the province. Conclusions There has been a large decline in reported clinical malaria from 2012 to 2015 in Tak Province. API was correlated with monthly climate and annual forest cover but these did not account for the trends over time. Ongoing elimination interventions on one or both sides of the border are more likely to have been the cause but it was not possible to assess this due to a lack of suitable data. Two main hot spot areas were identified that could be targeted for intensified elimination activities.…

Sen AP, Willink A, Anderson GF.

This Viewpoint proposes an array of approaches state governments might take to lower health care prices paid by private insurance, including rate setting using reference pricing; scrutiny of hospital mergers; expanding scope-of-practice laws to increase workforce; and investing in alternative payment models.

Grennan D, Wang S.

This JAMA Patient Page describes use of steroid medications and the side effects that can result.

Abstract Background The Plasmodium falciparum reticulocyte binding protein homolog 2b (PfRh2b) is an important P. falciparum merozoite ligand that mediates invasion of erythrocytes by interacting with a chymotrypsin-sensitive “receptor Z”. A large deletion polymorphism is found in the c-terminal ectodomain of this protein in many countries around the world, resulting in a truncated, but expressed protein. The varying frequencies by region suggest that there could be region specific immune selection at this locus. Therefore, this study was designed to determine temporal changes in the PfRh2b deletion polymorphism in infected individuals from Thiès (Senegal) and Western Gambia (The Gambia). It was also sought to determine the selective pressures acting at this locus and whether prevalence of the deletion in isolates genotyped by a 24-SNP molecular barcode is linked to background genotype or whether there might be independent selection acting at this locus. Methods Infected blood samples were sourced from archives of previous studies conducted between 2007 and 2013 at SLAP clinic in Thiès and from 1984 to 2013 in Western Gambia by MRC Unit at LSHTM, The Gambia. A total of 1380 samples were screened for the dimorphic alleles of the PfRh2b using semi-nested Polymerase Chain Reaction PCR. Samples from Thiès were previously barcoded. Results In Thiès, a consistent trend of decreasing prevalence of the PfRh2b deletion over time was observed: from 66.54% in 2007 and to 38.1% in 2013. In contrast, in Western Gambia, the frequency of the deletion fluctuated over time; it increased between 1984 and 2005 from (58.04%) to (69.33%) and decreased to 47.47% in 2007. Between 2007 and 2012, the prevalence of this deletion increased significantly from 47.47 to 83.02% and finally declined significantly to 57.94% in 2013. Association between the presence of this deletion and age was found in Thiès, however, not in Western Gambia. For the majority of isolates, the PfRh2b alleles could be tracked with specific 24-SNP barcoded genotype, indicating a lack of independent selection at this locus. Conclusion PfRh2b deletion was found in the two countries with varying prevalence during the study period. However, these temporal and spatial variations could be an obstacle to the implementation of this protein as a potential vaccine candidate.…

Khullar D, Frakt AB, Burke LG.

This Viewpoint reviews evidence about the outcomes and costs of health care at teaching vs nonteaching hospitals in an attempt to answer the question of whether the costs of academic medical centers are defensible and whether they deliver value for their price.

Uehara T, Hayden F, Kawaguchi K, et al.

AbstractBackgroundSingle-dose baloxavir rapidly reduces influenza virus titers and symptoms in patients with uncomplicated influenza, but viruses with reduced in vitro susceptibility due to amino acid substitutions at position 38 of polymerase acidic protein (PA/I38X) sometimes emerge.MethodsWe evaluated the kinetics, risk factors, and effects on clinical and virologic outcomes of emergence of PA/I38X-substituted viruses.ResultsViruses containing PA/I38X substitutions were identified 3–9 days after baloxavir treatment in 9.7% (36/370) of patients, of whom 85.3% had transient virus titer rises. Median time to sustained cessation of infectious virus detection was 192, 48, and 96 hours in the baloxavir recipients with PA/I38X-substituted viruses, without PA/I38X-substituted viruses, and placebo recipients, respectively. The corresponding median times to alleviation of symptoms were 63.1, 51.0, and 80.2 hours, respectively. After day 5, symptom increases occurred in 11.5%, 8.0%, and 13.0%, respectively, and in 8.9% of oseltamivir recipients. Variant virus emergence was associated with lower baseline neutralizing antibody titers.ConclusionsThe emergence of viruses with PA/I38X substitutions following baloxavir treatment was associated with transient rises in infectious virus titers, prolongation of virus detectability, initial delay in symptom alleviation, and uncommonly with symptom rebound. The potential transmissibility of PA/I38X-substituted viruses requires careful study.Clinical Trial RegistrationNCT02954354.

Abstract Background Group A Streptococcal (GAS) infections cause the autoimmune disease acute rheumatic fever (ARF), which can progress to chronic rheumatic heart disease (RHD). Treating pharyngitis caused by GAS with antibiotics is important in preventing ARF. However, it is difficult to distinguish these infections from GAS carriers. There is growing evidence for GAS skin infections as a cause of ARF. This study will identify the incidence of true GAS pharyngitis and serological responses to GAS skin infections. The effectiveness of antibiotics for these conditions will be explored, and modifiable risk factors. Serum antibody titres indicating the upper limits of normal (ULN for ASO/ADB antibodies) will be established alongside carriage rates in asymptomatic children. Methods This is a prospective disease incidence study, with an associated case-control study. The study population includes 1000 children (5–14 years) from Auckland, New Zealand, 800 of whom have visited their healthcare professional, resulting in a throat or skin swab for GAS, and 200 who are asymptomatic. The conditions of interest are GAS throat swab positive pharyngitis (n = 200); GAS carriage (n = 200); GAS negative throat swab (n = 200); GAS skin infections (n = 200); and asymptomatic controls (n = 200). All participants, except asymptomatic controls, will have acute and convalescent serological testing for ASO/ADB titres (collected

Ryom L, Lundgren J, Reiss P, et al.

AbstractBackgroundIt is unclear if use of contemporary protease inhibitors (PIs) pose a similar chronic kidney disease (CKD) risk as older PIs.MethodsD:A:D participants were followed to CKD, last visit or 2016. Adjusted Poisson regression assessed associations between CKD and boosted atazanavir (ATV/r) and darunavir (DRV/r).ResultsCKD incidence (10.0/1000 PYFU [95%CI 9.5-10.4]) increased gradually with increasing exposure to ATV/r, but less clearly for DRV/r. After adjustment, only exposure to ATV/r (1.4 [1.2-1.6]), but not DRV/r (1.0 [0.8-1.3]) remained significantly associated with CKD.ConclusionWhile DRV/r use was not significantly associated with CKD an increasing incidence with longer ATV/r use was confirmed.

Abstract Background Hepatitis B virus (HBV) testing in oral fluid samples may provide advantages in diagnosis, screening or prevalence studies, especially among individuals with venous access difficulties. This study aims to optimize one commercially available assay for detecting total anti-HBc marker in oral fluid samples and to evaluate its utility under real life conditions in different settings for the purposes of prevalence and diagnostic studies. Methods Oral fluid was collected using a Salivette device and some parameters were initially evaluated: type of elution buffer and sample volume. Thereafter, the utility of oral fluid samples for detection of anti-HBc was evaluated in real life conditions in which, 1296 individuals gave serum and oral fluid samples. All serum samples were submitted to commercial EIAs to detect total anti-HBc, according to the manufacturer’s instructions and oral fluid samples according to previous optimization. Results In optimization evaluation, PBS/BSA 0.5% and 100 μL of oral fluid (volume was two-fold increased compared to serum in EIA) were chosen as transport buffer and sample volume. In the field study, anti-HBc was detected in 211 out of 1296 serum samples giving overall oral fluid sensitivity of 52.6% and specificity of 96%. Concordance was higher in ambulatory setting (67.7) compared to general population (31.8). Mean ± standard deviation values of optical density/cutoff (OD/CO) in serum samples were higher in false-negative oral fluid samples than those seen in true positive samples. Sensitivity was higher in those presenting active infection compared to anti-HBc isolate and past infection. Sensitivity also increased in the ambulatory group when HCV individuals were excluded. Conclusions It was possible to optimize a commercial EIA for detecting anti-HBc in oral fluid samples and where the highest concordance was found in ambulatory settings and among individuals with active infection.…

Abstract Background Systemic Inflammatory Response Syndrome (SIRS) criteria are often used to evaluate the risk of sepsis and to identify in-hospital mortality among patients with suspected infection. However, utilization of the SIRS criteria in mortality prediction among geriatric patients with influenza in the emergency department (ED) remains unclear. Therefore, we conducted a research to delineate this issue. Methods This is a retrospective case–control study including geriatric patients (age ≥ 65 years) with influenza, who presented to the ED of a medical center between January 1, 2010 and December 31, 2015. Vital signs, past history, subtype of influenza, demographic data, and outcomes were collected from all patients and analyzed. We calculated the accuracy for predicting 30-days mortality using the SIRS criteria. We also performed covariate adjustment of the area under the receiver operating characteristic curve (AUROC) via regression modeling. Results We recruited a total of 409 geriatric patients in the ED, with mean age 79.5 years and an equal sex ratio. The mean SIRS criteria score was 1.9 ± 1.1. The result of a Hosmer–Lemeshow goodness-of-fit test was 0.34 for SIRS criteria. SIRS criteria score ≥ 3 showed better mortality prediction, with odds ratio (OR) 3.37 (95% confidence interval (CI), 1.05–10.73); SIRS score ≥ 2 showed no statistical significance, with p = 0.85 (OR, 1.15; 95% CI, 0.28–4.69). SIRS score ≥ 3 had acceptable 30-days mortality discrimination, with AUROC 0.77 (95% CI, 0.68–0.87) after adjustment. SIRS score ≥ 3 also had a notable negative predictive value of 0.97 (95% CI, 0.94–0.99). Conclusion The presence of a higher number of SIRS criteria (≥ 3) showed greater accuracy for predicting mortality among geriatric patients with influenza.…

Abstract Background Nosocomial infections and persistence of multidrug resistant biofilm forming Acinetobacter baumannii in hospitals has made it as a serious problem in healthcare settings worldwide. Methods A total of 100 A. baumannii clinical isolates from immunocompromised patients hospitalized in ICU were investigated for biofilm formation, the presence of biofilm related genes (bap, ompA, csuE, fimH, epsA, blaPER-1, bfmS, ptk, pgaB, csgA, kpsMII), integron characterization and molecular typing based on REP-PCR. Results All isolates were resistant to three or more categories of antibiotics and considered as multidrug resistant (MDR). A total of 32 isolates were resistant to all tested antibiotics and 91% were extensively drug-resistance (XDR). All isolates were able to produce biofilm and 58% of isolates showed strong ability to biofilm formation. All strong biofilm forming A. baumannii isolates were XDR. All A. baumannii isolates carried at least one biofilm related gene. The most prevalent gene was csuE (100%), followed by pgaB (98%), epsA and ptk (95%), bfmS (92%) and ompA (81%). 98% of isolates carried more than 4 biofilm related genes, simultaneously. Class I integron (67%) was more frequent in comparison with class II (10%) (P 

Abstract Background In light of increasing complexity of identifying and treating malaria cases in low transmission settings, operational solutions are needed to increase effective delivery of interventions. Community engagement (CE) is at the forefront of this conversation given the shift toward creating local and site-specific solutions. Malaria programmes often confuse CE with providing information to the community or implementing community-based interventions. This study seeks to expand on CE approaches for malaria by looking to a variety of health and development programmes for lessons that can be applied to malaria elimination. Methods Qualitative data was collected from key informant interviews and community-based focus group discussions. Manual analysis was conducted with a focus on key principles, programme successes and challenges, the operational framework, and any applicable results. Results Ten programmes were included in the analysis: Ebola, HIV/Hepatitis C, Guinea worm, malaria, nutrition, and water, sanitation and hygiene. Seven focus group discussions (FGDs) with 69 participants, 49 key informant (KI) interviews with programme staff, and 7 KI interviews with thought leaders were conducted between October–April 2018. Participants discussed the critical role that village leaders and community health workers play in CE. Many programmes stated understanding community priorities is key for CE and that CE should be proactive and iterative. A major theme was prioritizing bi-directional interpersonal communication led by local community health workers. Programmes reported that measuring CE is difficult, particularly since CE is ongoing and fluid. Conclusions Results overwhelmingly suggest that CE must be an iterative process that relies on early involvement, frequent feedback and active community participation to be successful. Empowering districts and communities in planning and executing community-based interventions is necessary. Communities affected by the disease will ultimately achieve malaria elimination. For this to happen, the community itself must define, believe in, and commit to strategies to interrupt transmission.…

Lukela J.

In this narrative medicine essay, an associate director of an internal medicine residency program describes when a student addressed her in an email by her first name but at the same time the student addressed a male colleague as “Doctor” and explains how she decided to handle the discrepancy.

Y. Romer et al.