Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19.

BACKGROUND: Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials. METHODS: A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti-SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid antigen (viral Ag), and interleukin-6 (IL-6). Associations between factors and time to mortality by 90 days were assessed using univariate and multivariable Cox proportional hazards models. RESULTS: Viral Ag ≥4500 ng/L (vs <200 ng/L; adjusted hazard ratio [aHR], 2.07; 1.29-3.34), viral RNA (<35 000 copies/mL [aHR, 2.42; 1.09-5.34], ≥35 000 copies/mL [aHR, 2.84; 1.29-6.28], vs below detection), respiratory support (<4 L O2 [aHR, 1.84; 1.06-3.22]; ≥4 L O2 [aHR, 4.41; 2.63-7.39], or noninvasive ventilation/high-flow nasal cannula [aHR, 11.30; 6.46-19.75] vs no oxygen), renal impairment (aHR, 1.77; 1.29-2.42), and IL-6 >5.8 ng/L (aHR, 2.54 [1.74-3.70] vs ≤5.8 ng/L) were significantly associated with mortality risk in final adjusted analyses. Viral Ag, viral RNA, and IL-6 were not measured in real-time. CONCLUSIONS: Baseline virus-specific, clinical, and biological variables are strongly associated with mortality risk within 90 days, revealing potential pathogen and host-response therapeutic targets for acute COVID-19 disease.

Larvae of Spirocerca lupi and another spirurid species in the same dung beetles: notes on species identification.

Various dung beetle species of the family Scarabaeidae have been reported as intermediate hosts of Spirocerca lupi from different geographical locations, but there has been no data from south-east Asian countries. In the present study in Vietnam, by using morphological and molecular approaches, we identified the third-stage larvae of S. lupi for the first time in two dung beetle species, Catharsius molossus and Copris szechouanicus, adding them as new intermediate hosts of this nematode. In addition, both beetle species were infected with larvae of another spirurid nematode of Physocephalus sp. At large magnifications above 200×, these two spirurid larvae can be differentiated from each other by their body size (1880-2662 vs. 1417-1635 µm) and detailed morphological features of the anterior and posterior ends, such as the length of the buccal cavity, the position of the nerve ring and excretory pore, and tail characters. However, it is difficult to distinguish them at a lower magnification due to their minute size. Moreover, morphometric data of S. lupi larvae vary among reports and the body length may overlap with that of Physocephalus sp., thus, misidentification may occur, indicating the necessity of careful examination for accurate identification. The findings of the present study also supposed that larvae of S. lupi and more spirurid nematodes may be concurrently found in various dung beetle species, including C. molossus and C. szechouanicus, in other south-east Asian countries. Thus, more investigations in various countries should be conducted to identify spirurid larvae from dung beetles in order to fully understand their role as intermediate hosts of S. lupi and other spirurid nematodes.

Spreading of SARS-CoV-2 in West Africa and assessment of risk factors.

Although the African continent is, for the moment, less impacted than the rest of the world, it still faces the risk of a spread of COVID-19. In this study, we have conducted a systematic review of the information available in the literature in order to provide an overview of the epidemiological and clinical features of COVID-19 pandemic in West Africa and of the impact of risk factors such as comorbidities, climatic conditions and demography on the pandemic. Burkina Faso is used as a case study to better describe the situation in West Africa. The epidemiological situation of COVID-19 in West Africa is marked by a continuous increase in the numbers of confirmed cases. This geographic area had on 29 July 2020, 131 049 confirmed cases by polymerase chain reaction, 88 305 recoveries and 2102 deaths. Several factors may influence the SARS-CoV-2 circulation in Africa: (i) comorbidities: diabetes mellitus and high blood pressure could lead to an increase in the number of severe cases of SARS-CoV-2; (ii) climatic factors: the high temperatures could be a factor contributing to slow the spread of the virus and (iii) demography: the West Africa population is very young and this could be a factor limiting the occurrence of severe forms of SARS-CoV-2 infection. Although the spread of the SARS-CoV-2 epidemic in West Africa is relatively slow compared to European countries, vigilance must remain. Difficulties in access to diagnostic tests, lack of hospital equipment, but also the large number of people working in the informal sector (such as trading, businesses, transport and restoration) makes it difficult to apply preventive measures, namely physical distancing and containment.

[Point of view of older adults on the potentially inappropriate medications prescribing in primary care facilities in Bobo-Dioulasso, Burkina Faso]. / Regard des personnes âgées sur la prescription des médicaments potentiellement inappropriés dans le premier niveau de soins à Bobo-Dioulasso, Burkina Faso.

BACKGROUND: Little is known about the organization of primary care facilities in sub-Saharan Africa that might lead to potentially inappropriate prescribing. The aim of this study was to analyze the factors that could lead to potentially inappropriate prescribing in primary care facilities in Bobo-Dioulasso (Burkina Faso), taking into consideration the patient's perspective. METHODS: A cross-sectional qualitative study was conducted in primary care facilities from November 2013 to February 2014. People aged 60 years or more with at least one chronic disease were included. Individual interviews were conducted. An analysis of the thematic content of the interviews was conducted. RESULTS: Our results showed that the patient referral system was insufficient. We also found many different prescribers for older people seeking care and poor communication between prescribers and patients. This caused some consequences such as the absence of review of drugs consumed before a new prescription, a lack of exchange on medication changes and repeated treatment change during hospitalization. Most of the persons who prescribed potentially inappropriate medications were nurses. CONCLUSION: The poor communication between prescribers and patients is a challenge for the prevention of prescribing potentially inappropriate medications. Teamwork is an important feature of the organizational care system, strengthening it could be a way to improve rational prescription.

Molecular identification of the trematode Paragonimus in faecal samples from the wild cat Prionailurus bengalensis in the Da Krong Nature Reserve, Vietnam.

Conventional identification of Paragonimus species and their natural definitive hosts is based on the morphological features of adult parasites isolated from the lungs of wild mammalian hosts. However, wild animals are protected by strict regulations and sampling is not always possible. Recently, molecular techniques have been developed to identify the internal transcribed spacer (ITS) sequences of Paragonimus eggs in faeces/sputum of human patients. Also, mammalian hosts can be identified using the D-loop sequence of mitochondrial DNA in faecal samples. In this study, we used molecular techniques on faeces from wild animals collected in Da Krong Nature Reserve, Quang Tri province, central Vietnam, where Paragonimus metacercariae are highly prevalent in mountain crabs, to identify Paragonimus species and their natural definitive hosts. The results indicated that wild cats, Prionailurus bengalensis, were infected with at least three different Paragonimus species, P. westermani, P. skrjabini and P. heterotremus. Because all of these species can infect humans in Asian countries, human paragonimiasis should be considered in this area.

Acute bacterial skin and skin structure infections (ABSSSI): practice guidelines for management and care transitions in the emergency department and hospital.

BACKGROUND: Acute bacterial skin and skin structure infections (ABSSSI), formally referred to as complicated skin and soft tissue infections, include infections with resistance to previously effective antimicrobials. Increasing dramatically in incidence, they have become a challenging medical problem associated with high direct and indirect costs to both the medical system and society. OBJECTIVES: To describe the burden of ABSSSI and to explore multidisciplinary approaches to its management and new treatments that can be initiated in the emergency department. DISCUSSION: We offer a best practice model aimed at providing risk-stratified and convenient care for ABSSSI at the lowest possible cost, while minimizing complications, readmissions, and inappropriate antibiotic use. In doing so, we focus on the care provided by emergency physicians and hospitalists and the transition of management between them for inpatient care, as well as the facilitation of observation or direct-to-outpatient care for suitable patients. CONCLUSIONS: A standard, consistent, and multidisciplinary approach to ABSSSI can streamline care, reduce admissions, support antimicrobial stewardship, and improve clinical and resource consumption outcomes.

Metacercarial polymorphism and genetic variation of Paragonimus heterotremus (Digenea: Paragonimidae), and a re-appraisal of the taxonomic status of Paragonimus pseudoheterotremus.

Paragonimus heterotremus, which is an important pathogen for human paragonimiasis in Asia, is recognized as having the smallest metacercariae (maximum diameter < 300 µm) of any previously reported Paragonimus species. Recently, P. pseudoheterotremus has been described from Thailand as a new species having metacercariae (about 200 µm) slightly smaller than those of Thai P. heterotremus. In fact, the small size of P. pseudoheterotremus metacercariae is compatible with those of P. heterotremus from India and China. In this study in Vietnam, we found variably sized small metacercariae which are expected to consist of both P. heterotremus and P. pseudoheterotremus. Contrary to expectation, the adult flukes obtained by separate infection of experimental cats with different sized metacercariae were all identified as P. heterotremus, using both morphological and molecular characteristics. The molecular analyses of an extensive collection of P. heterotremus/P. pseudoheterotremus isolates from Asian countries also indicated that genetic distances between different populations of P. heterotremus are even larger than that between P. pseudoheterotremus and P. heterotremus. The haplotype network showed that all P. heterotremus and P. pseudoheterotremus isolates formed a P. heterotremus complex consisting of three groups with strong geographical origins. In addition, the Indian P. heterotremus group is the root of the other P. heterotremus and P. pseudoheterotremus populations. Based on the observed metacercarial polymorphisms and genetic variation in P. heterotremus, P. pseudoheterotremus should be considered a geographically isolated population of the P. heterotremus complex.

[The unmet needs of the elderly living with functional disabilities in Bobo-Dioulasso (Burkina Faso)]. / Les besoins non couverts des personnes âgées en incapacités fonctionnelles à Bobo-Dioulasso (Burkina Faso).

BACKGROUND: In sub-Sahara Africa, the strong involvement of the family in multidimensional cares/supports of elderly is often presented like the family ensures almost everything to these people. Thus, few studies have focused on unmet needs of the elderly in their family or above. This study was conducted in Bobo-Dioulasso to identify those needs. METHODS: This is a longitudinal study including 58 people or 15 elderly and 43 caregivers from 15 families in Bobo-Dioulasso. In addition to regular observations of these families during 1 year, we conducted in-depth individual interview with each participant at the beginning and at the end of the study. The data were analyzed using QSR NVivo 8 software. RESULTS: A priori, respondents let believe that there is no unmet functional needs of the elderly in their family. However, the food, the first and main functional need of the elderly is not qualitatively satisfied by their family as well as other equipments or health needs. The quality of social cares/supports, biomedical cares and community supports are insufficient when these cares/supports are provided. The family demands many free or subsidized services to public or community structures then they are not currently available. DISCUSSION: In a context of widespread poverty, it is difficult for each actor of the social system of maintaining elderly in functional autonomy to provide services/supports of optimal quality. A synergy of action will reduce the unmet needs of the elderly in Bobo-Dioulasso.

Genetically variant populations of Paragonimus proliferus Hsia & Chen, 1964 from central Vietnam.

Among about 50 nominal Paragonimus species, Paragonimus proliferus is rather a rare species, found only in Yunnan province, China, until our recent discovery of this species in Lai Chau province, northern Vietnam close to Yunnan, China. Here we add Quang Binh province, central Vietnam as a new endemic area of P. proliferus. Large excysted metacercariae found in mountainous crabs, Potamiscus tannanti, were morphologically identified as P. proliferus, which was confirmed further by molecular analyses. Second internal transcribed spacer (ITS2) sequences of the P. proliferus population in Quang Binh province were completely (100%) identical with those of P. proliferus populations in Lai Chau province, northern Vietnam and Yunnan province, China. However, cytochrome oxidase subunit 1 (CO1) gene sequences of Quang Binh population were significantly different (5.6%) from that of previously reported northern Vietnam and Yunnan, China populations. A phylogenetic tree revealed that all CO1 sequences of P. proliferus Quang Binh population formed a distinct group, which was clustered with northern Vietnam and Yunnan, China populations with the bootstrap value of 75%. This is the first record of the genetically variant population of P. proliferus, distribution of which is geographically remote from the previously reported endemic areas in the border between northern Vietnam and Yunnan, China, suggesting that P. proliferus may be much more widely distributed in the Indochina peninsula (or South-East Asia) than expected.

Discovery of Paragonimus skrjabini in Vietnam and its phylogenetic status in the Paragonimus skrjabini complex.

Two members of the Paragonimus skrjabini complex, P. skrjabini and P. miyazakii, are now considered as two sub-species, P. skrjabini skrjabini and P. skrjabini miyazakii. They are well known as important pathogens for human paragonimiasis in China and Japan. Recently, members of this species complex have been reported from India. Here we report the first discovery of P. skrjabini from freshwater crab hosts in Thanh Hoa province, Vietnam. For morphological and molecular phylogenetic studies, adult worms were obtained by experimental infection in cats and dogs. Molecular analyses of metacercariae and adults revealed that the P. skrjabini population from Thanh Hoa, Vietnam was almost completely identical with that from Yunnan province, China. Those populations from Thanh Hoa, Vietnam and Yunnan, China and those from Manipur, India were significantly different from P. skrjabini populations reported from other localities of China in cytochrome oxidase subunit 1 (CO1) gene sequences, indicating considerable genetic variation within the P. skrjabini complex. Moreover, low bootstrap values in the CO1 tree suggested that more variant genotypes belonging to P. skrjabini complex may be found in other Asian countries in between Vietnam and India, such as Myanmar, Laos and Thailand. Since P. skrjabini is known as a pathogen for humans, paragonimiasis cases caused by P. skrjabini might be found in Vietnam and other Asian countries.

Challenges for accurate and prompt molecular diagnosis of clades of highly pathogenic avian influenza H5N1 viruses emerging in Vietnam.

Forty-six chickens and 48 ducks were sampled from four Vietnamese poultry premises in 2009 infected with H5N1 highly pathogenic avian influenza (HPAI) clade 2.3.2 and 2.3.4 viruses, which also differed by cleavage site (CS) sequences in their haemagglutinin (HA) genes. All clinical specimens (n=282), namely tracheal and cloacal swabs plus feathers, were tested by five Eurasian reverse-transcriptase AI RealTime polymerase chain reaction (RRT-PCR) methods. Bayesian modelling showed similar high sensitivity for the validated H5 HA2 RRT-PCR and a new modified M-gene RRT-PCR that utilizes lyophilized reagents. Both were more sensitive than the validated "wet" M-gene RRT-PCR. Another RRT-PCR, which targeted the H5-gene CS region, was effective for clade 2.3.4 detection, but severely compromised for clade 2.3.2 viruses. Reduced sensitivity of the H5 CS and "wet" M-gene RRT-PCRs correlated with mismatches between the target and the primer and/or probe sequences. However, the H5 HA2 RRT-PCR sensitively detected both clade 2.3.2 and 2.3.4 viruses, and agreed with N1 RRT-PCR results. Feather testing from diseased chicken and duck flocks by AI RRT-PCRs resulted in the most sensitive identification of H5N1 HPAI-infected birds. Evolution of new H5N1 HPAI clades remains a concern for currently affected Asian countries, but also for more distant regions where it is important to be prepared for new incursions of H5N1 HPAI viruses. Genetic evidence for adamantane resistance and sensitivity was also observed in isolates from both clades.

Investigation of nosocomial SARS-CoV-2 transmission from two patients to healthcare workers identifies close contact but not airborne transmission events.

OBJECTIVE: To describe the pattern of transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) during 2 nosocomial outbreaks of coronavirus disease 2019 (COVID-19) with regard to the possibility of airborne transmission. DESIGN: Contact investigations with active case finding were used to assess the pattern of spread from 2 COVID-19 index patients. SETTING: A community hospital and university medical center in the United States, in February and March, 2020, early in the COVID-19 pandemic. PATIENTS: Two index patients and 421 exposed healthcare workers. METHODS: Exposed healthcare workers (HCWs) were identified by analyzing the electronic medical record (EMR) and conducting active case finding in combination with structured interviews. Healthcare coworkers (HCWs) were tested for COVID-19 by obtaining oropharyngeal/nasopharyngeal specimens, and RT-PCR testing was used to detect SARS-CoV-2. RESULTS: Two separate index patients were admitted in February and March 2020, without initial suspicion for COVID-19 and without contact or droplet precautions in place; both patients underwent several aerosol-generating procedures in this context. In total, 421 HCWs were exposed in total, and the results of the case contact investigations identified 8 secondary infections in HCWs. In all 8 cases, the HCWs had close contact with the index patients without sufficient personal protective equipment. Importantly, despite multiple aerosol-generating procedures, there was no evidence of airborne transmission. CONCLUSION: These observations suggest that, at least in a healthcare setting, most SARS-CoV-2 transmission is likely to take place during close contact with infected patients through respiratory droplets, rather than by long-distance airborne transmission.

Hospitalist to home: outpatient parenteral antimicrobial therapy at an academic center.

The cost of health care in the United States continues to increase as an aging population places increasing demands on institutions providing health care. Moreover, despite increases in the complexity and cost of health care, reimbursement for some services has been reduced or denied. Thus, the current challenge at many hospitals throughout the United States is to deliver high-quality health care while maximizing resource use and reducing costs without compromising clinical outcomes. We describe an answer to the challenge that combines 2 emerging treatment models in an academic setting: hospital-based physicians and outpatient parenteral antimicrobial therapy.

Occurrence of phlebitis related to peripheral venous catheterization in the emergency services of the Souro Sanou National Teaching Hospital in Burkina Faso.

Patients must receive high-quality and safe health care. Peripheral venous catheterization (PVC) exposes patients to complications, mostly phlebitis. This study investigated the incidence of phlebitis and its PVC-related risk factors among patients in the medical and surgical emergency departments of the Souro Sanou University Hospital Center (CHUSS) in Bobo Dioulasso, Burkina Faso. This prospective cross-sectional study took place from July 4 to August 3, 2018. The incidence of PVC-related phlebitis was calculated and its risk factors were identified by logistic regression, with SPSS software version 20 (entry option), with significance set at 5%. The 511 patients included in the study had a mean age of 44.7 (95% CI 43.1-46.3) years. The mean duration of PVC was 3.1 days. Of these patients, 149 developed phlebitis, for an incidence of 29.2% (95% CI 25.0%-33.0%). There was no statistically significant difference between the two emergency (medical and surgical) departments. Second-degree phlebitis accounted for slightly more than half the cases (53%). Risk factors associated with the occurrence of PVC-related phlebitis were female gender, catheterization duration more than 3 days, small size of the catheter, and the healthcare worker's failure to use friction in washing with a hydroalcoholic hand solution. Preventive measures are essential.

Nonmonotonic Pathway Gene Expression Analysis Reveals Oncogenic Role of p27/Kip1 at Intermediate Dose.

The mechanistic basis by which the level of p27Kip1 expression influences tumor aggressiveness and patient mortality remains unclear. To elucidate the competing tumor-suppressing and oncogenic effects of p27Kip1 on gene expression in tumors, we analyzed the transcriptomes of squamous cell papilloma derived from Cdkn1b nullizygous, heterozygous, and wild-type mice. We developed a novel functional pathway analysis method capable of testing directional and nonmonotonic dose response. This analysis can reveal potential causal relationships that might have been missed by other nondirectional pathway analysis methods. Applying this method to capture dose-response curves in papilloma gene expression data, we show that several known cancer pathways are dominated by low-high-low gene expression responses to increasing p27 gene doses. The oncogene cyclin D1, whose expression is elevated at an intermediate p27 dose, is the most responsive gene shared by these cancer pathways. Therefore, intermediate levels of p27 may promote cellular processes favoring tumorigenesis-strikingly consistent with the dominance of heterozygous mutations in CDKN1B seen in human cancers. Our findings shed new light on regulatory mechanisms for both pro- and anti-tumorigenic roles of p27Kip1. Functional pathway dose-response analysis provides a unique opportunity to uncover nonmonotonic patterns in biological systems.

Advantages and disadvantages of using the PRISMA7 to determine the elderly subjects for whom the SMAF is useful for assessing functional status in Bobo-Dioulasso (Burkina Faso).

One of the difficulties faced by African actors working with the elderly is the lack of appropriate tools for the identification and/or diagnosis of functional disabilities among older people in this limited-resource (material, human, and financial) setting. This study sought to assess the advantages and disadvantages of the combined use of two tools, PRISMA7 (for identifying older individuals at risk of functional disabilities and loss of autonomy) and SMAF (to evaluate the functional status of the elderly) in Bobo-Dioulasso (Burkina Faso). PRISMA7 and SMAF were administered to a representative sample of elderly people who lived at home. Data analysis was performed with Stata. The results show that the combination of PRISMA7 and SMAF made it possible to avoid unncessary administration of the SMAF to all subjects, reducing the number of questionnaires to photocopy by 48 % and the working time by 45 %. The prevalence of moderate to severe functional disabilities was 32 % according to the SMAF alone and 25 % when PRISMA7 was administered first and determined whether the SMAF would be used. The 7 % rate of loss to follow-up shows a need for monitoring or help, generally in instrumental activities. In a limited-resource setting, this combination is a good strategy for identifying and evaluating functional disabilities in the elderly. This strategy allows the development of work plans tailored to individual functional needs.

Discerning mechanistically rewired biological pathways by cumulative interaction heterogeneity statistics.

Changes in response of a biological pathway could be a consequence of either pathway rewiring, changed input, or a combination of both. Most pathway analysis methods are not designed for mechanistic rewiring such as regulatory element variations. This limits our understanding of biological pathway evolution. Here we present a Q-method to discern whether changed pathway response is caused by mechanistic rewiring of pathways due to evolution. The main innovation is a cumulative pathway interaction heterogeneity statistic accounting for rewiring-specific effects on the rate of change of each molecular variable across conditions. The Q-method remarkably outperformed differential-correlation based approaches on data from diverse biological processes. Strikingly, it also worked well in differentiating rewired chaotic systems, whose dynamics are notoriously difficult to predict. Applying the Q-method on transcriptome data of four yeasts, we show that pathway interaction heterogeneity for known metabolic and signaling pathways is indeed a predictor of interspecies genetic rewiring due to unbalanced TATA box-containing genes among the yeasts. The demonstrated effectiveness of the Q-method paves the way to understanding network evolution at the resolution of functional biological pathways.

Overdiagnosis of Clostridium difficile Infection in the Molecular Test Era.

IMPORTANCE: Clostridium difficile is a major cause of health care-associated infection, but disagreement between diagnostic tests is an ongoing barrier to clinical decision making and public health reporting. Molecular tests are increasingly used to diagnose C difficile infection (CDI), but many molecular test-positive patients lack toxins that historically defined disease, making it unclear if they need treatment. OBJECTIVE: To determine the natural history and need for treatment of patients who are toxin immunoassay negative and polymerase chain reaction (PCR) positive (Tox-/PCR+) for CDI. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study at a single academic medical center among 1416 hospitalized adults tested for C difficile toxins 72 hours or longer after admission between December 1, 2010, and October 20, 2012. The analysis was conducted in stages with revisions from April 27, 2013, to January 13, 2015. MAIN OUTCOMES AND MEASURES: Patients undergoing C difficile testing were grouped by US Food and Drug Administration-approved toxin and PCR tests as Tox+/PCR+, Tox-/PCR+, or Tox-/PCR-. Toxin results were reported clinically. Polymerase chain reaction results were not reported. The main study outcomes were duration of diarrhea during up to 14 days of treatment, rate of CDI-related complications (ie, colectomy, megacolon, or intensive care unit care) and CDI-related death within 30 days. RESULTS: Twenty-one percent (293 of 1416) of hospitalized adults tested for C difficile were positive by PCR, but 44.7% (131 of 293) had toxins detected by the clinical toxin test. At baseline, Tox-/PCR+ patients had lower C difficile bacterial load and less antibiotic exposure, fecal inflammation, and diarrhea than Tox+/PCR+ patients (P < .001 for all). The median duration of diarrhea was shorter in Tox-/PCR+ patients (2 days; interquartile range, 1-4 days) than in Tox+/PCR+ patients (3 days; interquartile range, 1-6 days) (P = .003) and was similar to that in Tox-/PCR- patients (2 days; interquartile range, 1-3 days), despite minimal empirical treatment of Tox-/PCR+ patients. No CDI-related complications occurred in Tox-/PCR+ patients vs 10 complications in Tox+/PCR+ patients (0% vs 7.6%, P < .001). One Tox-/PCR+ patient had recurrent CDI as a contributing factor to death within 30 days vs 11 CDI-related deaths in Tox+/PCR+ patients (0.6% vs 8.4%, P = .001). CONCLUSIONS AND RELEVANCE: Among hospitalized adults with suspected CDI, virtually all CDI-related complications and deaths occurred in patients with positive toxin immunoassay test results. Patients with a positive molecular test result and a negative toxin immunoassay test result had outcomes that were comparable to patients without C difficile by either method. Exclusive reliance on molecular tests for CDI diagnosis without tests for toxins or host response is likely to result in overdiagnosis, overtreatment, and increased health care costs.

Treatments for hepatitis B.

New optimism surrounds treatments for chronic hepatitis B (CHB). Interferon- alpha , lamivudine, and adefovir dipivoxil are currently approved by the United States Food and Drug Administration for the treatment of CHB. All 3 treatments possess unique characteristics with respect to their side effect profiles, potencies, and treatment niches within the spectrum of CHB. New agents, which are in various stages of clinical development, represent potential improvements within existing, as well as novel, classes of antiviral therapy, and they offer significant promise of a cure for the many patients with chronic and progressive hepatitis B. However, there remain many challenges in understanding the implications of drug resistance, the role of combination therapy, and how to define the response to therapy within subsets of patients with hepatitis B.