We retrospectively examined infant mortality and human immunodeficiency virus (HIV)-free survival among 211 infants who received a comprehensive package of health services, including breast milk substitution and clean water access, to prevent maternal-to-child transmission of HIV and improve child survival. The cumulative 12-month infant survival probability was 0.97 (95% confidence interval: 0.94-0.99). The cumulative 12- to 18-month HIV-free survival probability was 0.95 (confidence interval: 0.91-0.97).
Globally it is estimated that 273000 new cases of multidrug-resistant tuberculosis (MDR-TB, resistance to isoniazid and rifampicin) occurred in 2000. To address MDR-TB management in the context of the DOTS strategy, the World Health Organization and partners have been promoting an expanded treatment strategy called DOTS-Plus. However, standard definitions for MDR-TB patient registration and treatment outcomes do not exist.To propose a standardized set of case registration groups and treatment outcome definitions for MDR-TB and procedures for conducting cohort analyses under the DOTS-Plus strategy.Using published definitions for drug-susceptible TB as a guide, a 2-year-long series of meetings, conferences, and correspondence was undertaken to review published literature and country-specific program experience, and to develop international agreement.Definitions were designed for MDR-TB patient categorization, smear and culture conversion, and treatment outcomes (cure, treatment completion, death, default, failure, transfer out). Standards for conducting outcome analyses were developed to ensure comparability between programs.Optimal management strategies for MDR-TB have not been evaluated in controlled clinical trials. Standardized definitions and cohort analyses will facilitate assessment and comparison of program performance. These data will contribute to the evidence base to inform decision makers on approaches to MDR-TB control.
BACKGROUND: The WHO provides standardized outcome definitions for rifampicin-resistant (RR) and multidrug-resistant (MDR) TB. However, operationalizing these definitions can be challenging in some clinical settings, and incorrect classification may generate bias in reporting and research. Outcomes calculated by algorithms can increase standardization and be adapted to suit the research question. We evaluated concordance between clinician-assigned treatment outcomes and outcomes calculated based on one of two standardized algorithms, one which identified failure at its earliest possible recurrence (i.e., failure-dominant algorithm), and one which calculated the outcome based on culture results at the end of treatment, regardless of early occurrence of failure (i.e., success-dominant algorithm). METHODS: Among 2,525 patients enrolled in the multi-country endTB observational study, we calculated the frequencies of concordance using cross-tabulations of clinician-assigned and algorithm-assigned outcomes. We summarized the common discrepancies. RESULTS: Treatment success calculated by algorithms had high concordance with treatment success assigned by clinicians (95.8 and 97.7% for failure-dominant and success-dominant algorithms, respectively). The frequency and pattern of the most common discrepancies varied by country. CONCLUSION: High concordance was found between clinician-assigned and algorithm-assigned outcomes. Heterogeneity in discrepancies across settings suggests that using algorithms to calculate outcomes may minimize bias.
Malaria control is currently receiving significant international commitment. As part of this commitment, Rwanda has undertaken a two-pronged approach to combating malaria via mass distribution of long-lasting insecticidal-treated nets and distribution of antimalarial medications by community health workers. This study attempted to measure the impact of these interventions on paediatric hospitalizations for malaria and on laboratory markers of disease severity.A retrospective analysis of hospital records pre- and post-community-based malaria control interventions at a district hospital in rural Rwanda was performed. The interventions took place in August 2006 in the region served by the hospital and consisted of mass insecticide treated net distribution and community health workers antimalarial medication disbursement. The study periods consisted of the December-February high transmission seasons pre- and post-rollout. The record review examined a total of 551 paediatric admissions to identify 1) laboratory-confirmed malaria, defined by thick smear examination, 2) suspected malaria, defined as fever and symptoms consistent with malaria in the absence of an alternate cause, and 3) all-cause admissions. To define the impact of the intervention on clinical markers of malaria disease, trends in admission peripheral parasitaemia and haemoglobin were analyzed. To define accuracy of clinical diagnoses, trends in proportions of malaria admissions which were microscopy-confirmed before and after the intervention were examined. Finally, to assess overall management of febrile illnesses antibiotic use was described.Of the 551 total admissions, 268 (48.6%) and 437 (79.3%) were attributable to laboratory confirmed and suspected malaria, respectively. The absolute number of admissions due to suspected malaria was smaller during the post-intervention period (N = 150) relative to the pre-intervention period (N = 287), in spite of an increase in the absolute number of hospitalizations due to other causes during the post-intervention period. The percentage of suspected malaria admissions that were laboratory-confirmed was greater during the pre-intervention period (80.4%) relative to the post-intervention period (48.1%, prevalence ratio [PR]: 1.67; 95% CI: 1.39-2.02; chi-squared p-value < 0.0001). Among children admitted with laboratory-confirmed malaria, the risk of high parasitaemia was higher during the pre-intervention period relative to the post-intervention period (age-adjusted PR: 1.62; 95% CI: 1.11-2.38; chi-squared p-value = 0.004), and the risk of severe anaemia was more than twofold greater during the prei-ntervention period (age-adjusted PR: 2.47; 95% CI: 0.84-7.24; chi-squared p-value = 0.08). Antibiotic use was common, with 70.7% of all children with clinical malaria and 86.4% of children with slide-negative malaria receiving antibacterial therapy.This study suggests that both admissions for malaria and laboratory markers of clinical disease among children may be rapidly reduced following community-based malaria control efforts. Additionally, this study highlights the problem of over-diagnosis and over-treatment of malaria in malaria-endemic regions, especially as malaria prevalence falls. More accurate diagnosis and management of febrile illnesses is critically needed both now and as fever aetiologies change with further reductions in malaria.
This Article explores what limits the Thirteenth Amendment’s prohibition on involuntary servitude places on the government’s use of informants in criminal investigations. Informants are a crucial part of all law enforcement efforts and a keystone in the investigation and prosecution of organized crime syndicates and “victimless” crimes, such as narcotics trafficking, prostitution, and gambling. While many informants merely provide previously-obtained information to the police, others take more active roles in assisting law enforcement, engaging in controlled drug buys, wearing wires, or infiltrating criminal organizations. This latter group of “active informants” is the most useful to law enforcement because they work under police direction to obtain hard evidence of criminal conduct. Though active informants cooperate for many reasons, most assist the police out of fear that if they refuse, they will be subject to criminal prosecution or more severe punishment. This Article argues that by compelling these “coerced informants” to work under such a threat, the government violates the Thirteenth Amendment’s prohibition on involuntary servitude.As a doctrinal matter, compelling coerced informants to serve under threat of criminal sanction fits the Thirteenth Amendment’s definition of involuntary servitude. Moreover, the use of coerced informants offends the free labor principles that animated the passage and ratification of the Thirteenth Amendment and underlie the Supreme Court’s Thirteenth Amendment jurisprudence. Though recognition that the use of coerced informants violates the Thirteenth Amendment may require significant changes to law enforcement practices, there are adequate alternatives to facilitate criminal cooperation that will not hamstring law enforcement efforts. In fact, these alternatives will ultimately strengthen other constitutional protections and ameliorate some of the negative societal effects on high-crime neighborhoods of the widespread use of informants.
Since 2000, the directly observed treatment, short-course (DOTS) strategy has been expanded in several countries to include treatment of multidrug-resistant tuberculosis (MDR-TB). This strategy is known as DOTS-Plus. Tuberculosis is a common cause of morbidity and mortality for children throughout the developing world. Children may also be infected with MDR-TB, yet most developing countries do not specifically address pediatric MDR-TB.To present the intermediate outcomes of the first 16 children enrolled in the Peruvian DOTS-Plus program and to demonstrate the tolerability of second-line anti-tuberculosis drugs.Three children completed therapy and are cured, one child had bacteriologic and clinical failure after 12 months of therapy and died of respiratory insufficiency, and 12 have intermediate outcomes demonstrating favorable clinical, bacteriologic, and radiographic evidence of improvement after 9-19 months of therapy.Of the 16 pediatric DOTS-Plus patients, 15 have tolerated therapy well and have had favorable clinical evolution. However, the diagnosis of pediatric MDR-TB is often extremely delayed due to reliance on the adult case definition and should be changed to prevent progressive, chronic illness in such children. Programmatic changes could facilitate earlier diagnosis and treatment of pediatric MDR-TB in Peru and in other DOTS-Plus programs.
Abstract Depression, low health-related quality of life, and low perceived social support have been shown to predict poor health outcomes, including HIV-related outcomes. Mental health morbidity and HIV are important public health concerns in Rwanda, where approximately half of the current population is estimated to have survived the genocide and 3% is living with HIV. We examined the reliability and construct validity of the Hopkins Symptom Checklist-15 (HSCL-15), the Medical Outcomes Study HIV Health Survey (MOS-HIV), and the Duke/UNC Functional Social Support Questionnaire (DUFSSQ), which were used to assess depression, health-related quality of life, and perceived social support, respectively, among HIV-infected adults in rural Rwanda. We also studied whether scale reliability differed by gender, literacy status, or antiretroviral therapy (ART) delivery strategy. The Kinyarwanda versions of the HSCL-15, MOS-HIV, and DUFSSQ performed well in the study population. Reliability was favorable (Cronbach's alpha coefficients ≥0.75 or above) for the scales overall and across subgroups of gender, literacy, and mode of ART delivery. The scales also demonstrated good convergent, discriminant, and known-group validity.
Without informants, policing would grind to a halt. The majority of drug and organized crime prosecutions hinge on the assistance of confidential informants, and white collar prosecutions and anti-terrorism investigations increasingly depend on them. Yet society by and large hates informants. The epithets used to describe them – “snitch,” “rat,” and “weasel,” among others – suggest the reason: the informant, by assisting the police, is guilty of betrayal. And betrayal is, in the words of George Fletcher, “one of the basic sins of our civilization.” But identifying disloyalty as the reason for society’s disdain raises more questions than it answers. Are all informants disloyal, or are only some? Are there governing principles to distinguish those informants who are disloyal from those who are not? To whom are these informants disloyal? What import does an informant’s disloyalty have beyond the social stigma on the informant? These questions matter because informants are crucial cogs in the law enforcement machine, but they have largely escaped the attention of legal scholars. This Article seeks to remedy this oversight. First, it explores how disloyalty functions in today’s society by looking to the observations of philosophers and legal scholars who have considered the nature of loyalty and disloyalty as moral constructs. The Article then examines three scenarios that suggest insights into when and why informants are considered disloyal. The first is the case of an accomplice-informant who assists police in apprehending and prosecuting her partners in crime. The second scenario is that of a community with particularized norms against cooperating with the police, with a particular focus on the “Stop Snitching” movement that has become increasingly influential in high-crime communities. The third scenario looks at informants in the rest of society, where particularized norms against assisting the police do not govern. The analysis of these scenarios reveals that issues of disloyalty arising from the use of informants intersect with and inform sociological research on the marginalization of communities and the impact of police legitimacy on civilian cooperation and compliance with the law, as well as scholarly concerns about overcriminalization. The Article then makes three policy proposals that aim to enhance civilian cooperation with law enforcement without undermining police effectiveness. First, it is proposed that police and prosecutors amend their informant screening guidelines to explicitly and publicly require consideration of loyalty issues arising from the use of a given informant. Public acknowledgement in this manner that law enforcement officials share important community values would encourage voluntary cooperation with police and compliance with the law. Second, law enforcement policymakers should curtail informant recruitment in marginalized communities that are home to anti-cooperation norms in favor of alternative policing strategies, as current policies that encourage the widespread use of informants undermine police-community relations in these communities. Finally, lawmakers should limit the use of initiatives, derogatorily called “snitch lines,” that encourage civilian to report minor crimes and non-criminal suspicious behavior and consider decriminalizing some minor regulatory-type offenses. Mainstream society’s dissatisfaction with these programs, expressed in the harsh language of disloyalty, suggests discomfort with the “snitch lines” themselves, as well as the criminalization of the relatively minor offenses that they target.
Treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation. Novel combinations of newer and repurposed drugs bring hope in the fight against MDR/RR-TB, but their use has not been optimized in all-oral, shorter regimens. This has greatly limited their impact on the burden of disease. There is, therefore, dire need for high-quality evidence on the performance of new, shortened, injectable-sparing regimens for MDR-TB which can be adapted to individual patients and different settings.endTB is a phase III, pragmatic, multi-country, adaptive, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of shorter treatment regimens containing new drugs for patients with fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Study participants are randomized to either the control arm, based on the current standard of care for MDR/RR-TB, or to one of five 39-week multi-drug regimens containing newly approved and repurposed drugs. Study participation in all arms lasts at least 73 and up to 104 weeks post-randomization. Randomization is response-adapted using interim Bayesian analysis of efficacy endpoints. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 750 patients across 6 arms affords at least 80% power to detect the non-inferiority of at least 1 (and up to 3) experimental regimens, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per protocol populations.The lack of a safe and effective regimen that can be used in all patients is a major obstacle to delivering appropriate treatment to all patients with active MDR/RR-TB. Identifying multiple shorter, safe, and effective regimens has the potential to greatly reduce the burden of this deadly disease worldwide.ClinicalTrials.gov Identifier NCT02754765. Registered on 28 April 2016; the record was last updated for study protocol version 3.3, on 27 August 2019.
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