Colonization With Antibiotic-Resistant Bacteria in a Hospital and Associated Communities in Guatemala: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: We estimated the prevalence of colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) from a hospital and associated communities in western Guatemala. METHODS: Randomly selected infants, children, and adults (<1, 1-17, and ≥18 years, respectively) were enrolled from the hospital (n = 641) during the coronavirus disease 2019 (COVID-19) pandemic, March to September 2021. Community participants were enrolled using a 3-stage cluster design between November 2019 and March 2020 (phase 1, n = 381) and between July 2020 and May 2021 (phase 2, with COVID-19 pandemic restrictions, n = 538). Stool samples were streaked onto selective chromogenic agar, and a Vitek 2 instrument was used to verify ESCrE or CRE classification. Prevalence estimates were weighted to account for sampling design. RESULTS: The prevalence of colonization with ESCrE and CRE was higher among hospital patients compared to community participants (ESCrE: 67% vs 46%, P < .01; CRE: 37% vs 1%, P < .01). Hospital ESCrE colonization was higher for adults (72%) compared with children (65%) and infants (60%) (P < .05). Colonization was higher for adults (50%) than children (40%) in the community (P < .05). There was no difference in ESCrE colonization between phase 1 and 2 (45% and 47%, respectively, P > .05), although reported use of antibiotics among households declined (23% and 7%, respectively, P < .001). CONCLUSIONS: While hospitals remain foci for ESCrE and CRE colonization, consistent with the need for infection control programs, community prevalence of ESCrE in this study was high, potentially adding to colonization pressure and transmission in healthcare settings. Better understanding of transmission dynamics and age-related factors is needed.

Ethics information retrieval in HTA: state of current practice.

OBJECTIVES: Though there have been longstanding discussions on the value of ethics in health technology assessment (HTA), less awareness exists on ethics information retrieval methods. This study aimed to scope available evidence and determine current practices for ethics information retrieval in HTA. METHODS: Literature searches were conducted in Ovid MEDLINE, LISTA, Scopus, and Google Scholar. Once a list of relevant articles was determined, citation tracking was conducted via Scopus. HTA agency websites were searched for published guidance on ethics searching, and for reports which included ethical analyses. Methods sections of each report were analyzed to determine the databases, subject headings, and keywords used in search strategies. The team also reached out to information specialists for insight into current search practices. RESULTS: Findings from this study indicate that there is still little published guidance from HTA agencies, few HTAs that contain substantial ethical analysis, and even less information on the methodology for ethics information retrieval. The researchers identified twenty-five relevant HTAs. Ten of these reports did not utilize subject-specific databases outside health sciences. Eight reports published ethics searches, with significant overlap in subject headings and text words. CONCLUSIONS: This scoping study of current practice in HTA ethics information retrieval highlights findings of previous studies-while ethics analysis plays a crucial role in HTA, methods for literature searching remain relatively unclear. These findings provide insight into the current state of ethics searching, and will inform continued work on filter development, database selection, and grey literature searching.

Excreted Antibiotics May Be Key to Emergence of Increasingly Efficient Antibiotic Resistance in Food Animal Production.

At a time when antibiotic resistance is seemingly ubiquitous worldwide, understanding the mechanisms responsible for successful emergence of new resistance genes may provide insights into the persistence and pathways of dissemination for antibiotic-resistant organisms in general. For example, Escherichia coli strains harboring a class A ß-lactamase-encoding gene (blaCTX-M-15) appear to be displacing strains that harbor a class C ß-lactamase gene (blaCMY-2) in Washington State dairy cattle. We cloned these genes with native promoters into low-copy-number plasmids that were then transformed into isogenic strains of E. coli, and growth curves were generated for two commonly administered antibiotics (ampicillin and ceftiofur). Both strains met the definition of resistance for ampicillin (≥32 µg/mL) and ceftiofur (≥16 µg/mL). Growth of the CMY-2-producing strain was compromised at 1,000 µg/mL ampicillin, whereas the CTX-M-15-producing strain was not inhibited in the presence of 3,000 µg/mL ampicillin or with most concentrations of ceftiofur, although there were mixed outcomes with ceftiofur metabolites. Consequently, in the absence of competing genes, E. coli harboring either gene would experience a selective advantage if exposed to these antibiotics. Successful emergence of CTX-M-15-producing strains where CMY-2-producing strains are already established, however, requires high concentrations of antibiotics that can only be found in the urine of treated animals (e.g., >2,000 µg/mL for ampicillin, based on literature). This ex vivo selection pressure may be important for the emergence of new and more efficient antibiotic resistance genes and likely for persistence of antibiotic-resistant bacteria in food animal populations. IMPORTANCE We studied the relative fitness benefits of a cephalosporin resistance enzyme (CTX-M-15) that is displacing a similar enzyme (CMY-2), which is extant in E. coli from dairy cattle in Washington State. In vitro experiments demonstrated that CTX-M-15 provides a significant fitness advantage, but only in the presence of very high concentrations of antibiotic that are only found when the antibiotic ampicillin, and to a lesser extent ceftiofur, is excreted in urine from treated animals. As such, the increasing prevalence of bacteria with blaCTX-M-15 is likely occurring ex vivo. Interventions should focus on controlling waste from treated animals and, when possible, selecting antibiotics that are less likely to impact the proximal environment of treated animals.

Fractional-Dose Inactivated Poliovirus Vaccine Immunization Campaign - Telangana State, India, June 2016.

Wild poliovirus type 2 was declared eradicated in September 2015 (1). In April 2016, India, switched from use of trivalent oral poliovirus vaccine (tOPV; containing types 1, 2, and 3 polio vaccine viruses), to bivalent OPV (bOPV; containing types 1 and 3), as part of a globally synchronized initiative to withdraw Sabin poliovirus type 2 vaccine. Concurrently, inactivated poliovirus vaccine (IPV) was introduced into India's routine immunization program to maintain an immunity base that would mitigate the number of paralytic cases in the event of epidemic transmission of poliovirus type 2 (2,3). After cessation of use of type 2 Sabin vaccine, any reported isolation of vaccine-derived poliovirus type 2 (VDPV2) would be treated as a public health emergency and might need outbreak response with monovalent type 2 oral vaccine, IPV, or both (4). In response to identification of a VDPV2 isolate from a sewage sample collected in the southern state of Telangana in May 2016, India conducted a mass vaccination campaign in June 2016 using an intradermal fractional dose (0.1 ml) of IPV (fIPV). Because of a global IPV supply shortage, fIPV, which uses one fifth of regular intramuscular (IM) dose administered intradermally, has been recommended as a response strategy for VDPV2 (5). Clinical trials have demonstrated that fIPV is highly immunogenic (6,7). During the 6-day campaign, 311,064 children aged 6 weeks-3 years were vaccinated, achieving an estimated coverage of 94%. With appropriate preparation, an emergency fIPV response can be promptly and successfully implemented. Lessons learned from this campaign can be applied to successful implementation of future outbreak responses using fIPV.

Systematic review of biomarkers of brain injury in term neonatal encephalopathy.

Although neonatal hypoxic-ischemic encephalopathy is a common cause of childhood developmental disability, its timing, duration, and outcomes are poorly defined. Biomarkers serve as surrogates for disease injury, evolution, and outcome, but no tissue biomarker in routine clinical use can help predict outcomes in term newborn encephalopathy. We reviewed biomarkers in human term neonatal encephalopathy, to determine if current biomarkers are strong enough for clinical use as predictors of outcomes. A comprehensive search of databases identified 110 publications that met our inclusion criteria, i.e., (1) newborns at >36 weeks; (2) neonatal encephalopathy as defined by the American College of Obstetrics and Gynecology; (3) the use of a serum, urine, or cerebrospinal fluid biomarker; and (4) reported outcomes beyond age 12 months. Of those 110 publications, 22 reported outcomes beyond age 12 months. In single reports, urine lactate (P < 0.001), first urine S100 (P < 0.0001), cord-blood interleukin-6 (P = 0.02), serum nonprotein-bound iron (P < 0.001), serum CD14 cell NFkappaB activation (P = 0.014), serum interleukin-8 (P = 0.03), and serum ionized calcium (P = 0.001) were potential predictors of death or abnormal outcomes. A meta-analysis identified serum interleukin-1b (P = 0.04, n = 3), serum interleukin-6 (P = 0.04, n = 2), cerebrospinal fluid neuron-specific enolase (P = 0.03, n = 3), and cerebrospinal fluid interleukin-1b (P = 0.003, n = 2) as putative predictors of abnormal outcomes in survivors, when measured before age 96 hours. Several serum, urine, and cerebrospinal fluid biomarkers of term neonatal encephalopathy may provide important information regarding long-term outcomes. None, however, were studied extensively enough to warrant routine clinical use. Validation of these markers, either alone or in combination, is required in the development of viable therapeutic interventions.

Comparison of the effects of Hawley and perfector/spring aligner retainers on postorthodontic occlusion.

INTRODUCTION: The purpose of this study was to evaluate the short-term changes in posterior occlusion produced by perfector/spring aligner and Hawley retainers. METHODS: In this prospective clinical study, we randomly assigned 50 patients who had completed full orthodontic treatment to a Hawley retainer group or a perfector/spring aligner retainer group. Objective and subjective measures were collected when the retainers were delivered (T1) and approximately 2 months later (T2). Blu Mousse (Parkell Bio-Materials, Farmingdale, NY) was used to quantify posterior areas of contact (<50 microm) and near contact (50-350 microm). The patient's perception of occlusion was assessed by using a 7-item questionnaire. RESULTS: Areas of contact and near contact (ACNC) in the Hawley group increased significantly (P <0.05) from 6.71 mm(2) at T1 to 10.97 mm(2) at T2; ACNC in the perfector/spring aligner group increased from 8.44 mm(2) at T1 to 12.95 mm(2) at T2. There were no significant (P <0.05) differences in the increases of ACNC between the Hawley group (4.50 mm(2)) and the perfector/spring aligner group (3.26 mm(2)). Spearman correlations showed that ACNC at T1 were positively related with ACNC at T2 and negatively related with T2 to T1 ACNC changes. In comparison with the Hawley group, the patients wearing perfector/spring aligner retainers reported significantly greater improvements in how well their back teeth fit together, how well they could chew tough meats, and how much pain they felt when they bit down. CONCLUSIONS: ACNC increased substantially and similarly in patients wearing Hawley and perfector/spring aligner retainers. Changes over time were perceived to a greater extent by patients wearing perfector/spring aligner retainers.

Productivity cost due to postpartum ill health: A cross-sectional study in Sri Lanka.

OBJECTIVE: Even though postpartum morbidity continues to cause high disease burden in maternal morbidity and mortality across the globe, the literature pertaining to resultant productivity loss is scarce. Hence, the present study aimed at determining the productivity loss and associated cost of episodes of postpartum ill health. METHODS: A cross sectional study was conducted in two Medical Officer of Heath areas in the Anuradhapura district, Sri Lanka in 2011, among 407 women residing in Anuradhapura district with an infant aged between 8 to 24 weeks. Validated interviewer administered questionnaires, including the IMMPACT productivity cost tool, were used to collect data on self-reported episodes of postpartum ill health. The productivity loss was calculated as the sum of days lost due to partial and total incapacitation. The adjusted productivity loss for coping strategies was calculated. Productivity cost, both total and adjusted, were calculated based on the mean daily per capita income of the study sample. RESULTS: Of the 407 participants, 161(39.6%) reported at least one episode of postpartum illness. Hospitalisations were reported by 27 (16.8%) of all symptomatic postpartum women. Common symptoms of postpartum ill health were pain/infection at either episiotomy or surgical site (n = 44, 27.3%), lower abdominal pain (n = 40, 24.8%) and backache (n = 27, 16.8%). The mean productivity loss per episode of ill health was 15 days (SD = 7.8 days) and the mean productivity loss per episode after adjusting for coping strategies was 7.9 days (SD = 4.4 days). The mean productivity cost per an episode was US$ 34.2(95%CI US$ 26.7-41.6) and the mean productivity cost per an episode after adjusting for coping strategies was US$ 18.0 (95%CI US$ 14.1-22.0). CONCLUSIONS: The prevalence of self-reported postpartum ill health, associated productivity loss and cost were high in the study sample and the main contributors were preventable conditions including pain and infection. Thus, effective pain management and proper infection prevention and control measures are important in reducing the burden of postpartum illness and resultant productivity cost.

Cyclooxygenase-2 inhibition with celecoxib enhances antitumor efficacy and reduces diarrhea side effect of CPT-11.

Combining anticancer drugs with different mechanisms of action has the potential to enhance antitumor effect. CPT-11 (Camptosar, irinotecan), a topoisomerase I inhibitor, has been shown to be highly effective in the treatment of a variety of cancers. However, its clinical usage is often complicated by late diarrhea. A number of studies have shown that cyclooxygenase (COX)-2 is overexpressed in many forms of human tumors, suggesting that COX-2 inhibition may be useful in the treatment of cancer. In this study, we used two mouse tumor models (HT-29 and colon-26 cells) to evaluate the effect of combining CPT-11 with celecoxib on tumor growth. We also assessed the involvement of COX-2 in the pathogenesis of CPT-11-induced late diarrhea using a rat model. Results indicate that celecoxib enhances the antitumor effect of CPT-11 and reduces the severity of late diarrhea in a dose-dependent manner. The extended benefits of combining celecoxib with CPT-11 may significantly improve the outcome of cancer patients.

Abnormal vaginal discharge: what does and does not work in treating underlying causes.

Antifungal medications for intravaginal use have been available in the United States for more than a decade. Women may be inclined to self-diagnose yeast infections with any vaginal discharge or other vulvovaginal symptoms that they deem abnormal. As we saw in the first part of this article, "Abnormal vaginal discharge: Using office diagnostic testing more effectively" (J Fam Pract 2004; 53[10]:805-814), abnormal discharge is more likely to be bacterial vaginosis or no pathogen at all. Potential delay in diagnosis and treatment of a sexually transmitted disease is also a concern. Increasing resistance of Candida sp. to imidazoles is associated with indiscriminate use of over-the-counter products.

Responding to abuse: Children's experiences of child protection in a central district, Uganda.

Part of a comprehensive response to violence against children involves child protection systems, but there are few data available on such systems in low-income countries. This study describes the characteristics and help seeking behavior of children referred to local child protection services and the quality of the first-line response in one district in Uganda. Participants included 3,706 children from 42 primary schools who participated in a baseline survey on violence as part of the Good Schools Study (NCT01678846, clinicaltrial.gov). Children who disclosed violence were referred according to predefined criteria based on the type, severity, and timeframe of their experiences. Children were followed up to 4 months after the study ended. First-line responses by receiving agencies were classified into 3 categories: plan for action only, some action taken, and no plan and no action taken. Appropriateness of responses was based on which agency responded, timeliness of the response, quality of the documentation, and final status of the case. From the baseline survey, 529 children (14%) were referred. Girls were more likely to be referred and to meet the criteria for a serious case (9% girls, 4% boys). In total, 104 referrals (20%) had some kind of concrete action taken, but only 20 (3.8%) cases met all criteria for having received an adequate response. Nearly half (43%) of referred children had ever sought help by disclosing their experiences of violence prior to the baseline survey. In our study areas, the first-line response to children's reports of abuse was poor even though some referral structures are in place.

Minor ailments in pregnancy are not a minor concern for pregnant women: a morbidity assessment survey in rural Sri Lanka.

BACKGROUND: Although maternal mortality has become a major focus on global public health agenda, maternal morbidity is a neglected area of research. The purpose of this paper is to present the burden of acute maternal illness during pregnancy. METHODS: A cross sectional study was carried out in Anuradhapura district, Sri Lanka. Pregnant women residing in the Anuradhapura district with a gestational age more than 24 weeks through 36 weeks were recruited to the study using a two-stage cluster sampling technique. All pregnant women who consented participated in a detailed interview using a structured questionnaire. Self reported episodes of acute illness during pregnancy were the main outcome measures. Secondary outcomes were utilization of medical services and frequency of hospitalizations. RESULTS: Nausea and vomiting during pregnancy (NVP) was experienced by 325 (69.7%) of the 466 pregnant women studied. Other common symptoms were backache (152, 32.6%), dizziness (112, 24.0%) and heartburn/regurgitation (107, 23.0%). Of the 421 pregnant women who reported ill health conditions 260 (61.8%) women sought medical treatment for these illnesses. Total number of episodes that needed treatment seeking were 373. Hospitalizations were reported by 83 (17.8%) pregnant women and the total number of hospitalizations was 109. The leading cause of hospitalization was NVP which accounted for 43.1% of total admissions and 49.1% of total days spent in hospitals. CONCLUSIONS: Minor maternal ill health conditions affecting day-to-day life have a major burden on pregnancy period. Evidence based management guidelines and health promotion strategies are needed to control and prevent these conditions, in order to provide comprehensive, good quality maternal health care.

Systematic review data extraction: cross-sectional study showed that experience did not increase accuracy.

OBJECTIVE: This study assessed the impact of systematic review and data extraction experience on the accuracy and efficiency of data extraction in systematic reviews. STUDY DESIGN AND SETTING: We conducted a prospective cross-sectional study from October to December 2006. Participants were classified as having minimal, moderate, or substantial experience in systematic reviews and data extraction. Three studies on insomnia treatment were extracted. Our primary outcome was the accuracy of data extraction. Data sets of each experience level were analyzed for errors in data extraction and results of meta-analyses. Additionally, the time required for completion of data extraction was compared. RESULTS: Error rates were similar across the various levels of experience and ranged from 28.3% to 31.2%. Mean rates for errors of omission (11.3-16.4%) were generally lower than those for errors of inaccuracy (13.9-17.9%). There were no significant differences in error rates or accuracy of meta-analysis results between groups. Time required approached significance, with minimally experienced participants requiring the most time. CONCLUSION: Overall, there were high error rates by participants at all experience levels; however, time required for extraction tended to decrease with experience. These results illustrate the need to develop strategies aimed at mastery of data extraction, rather than reliance on previous data extraction experience alone.