Treatment regimens for rifampicin-resistant tuberculosis: highlighting a research gap

Treatment guidance for non-multidrug-resistant (MDR) rifampicin-resistant (RMP-R) tuberculosis (TB) is variable. We aimed to undertake a systematic review and meta-analysis of the randomised controlled trial (RCT) data behind such guidelines to identify the most efficacious treatment regimens. Ovid MEDLINE, the Web of Science and EMBASE were mined using search terms for TB, drug therapy and RCTs. Despite 12 604 records being retrieved, only three studies reported treatment outcomes by regimen for patients with non-MDR RMP-R disease, preventing meta-analysis. Our systematic review highlights a substantial gap in the literature regarding evidence-based treatment regimens for RMP-R TB

Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX-2) inhibitors

BACKGROUND: Epidemiologic and laboratory investigations suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive effects against breast cancer due to their activity against cyclooxygenase-2 (COX-2), the rate-limiting enzyme of the prostaglandin cascade. METHODS: We conducted a case control study of breast cancer designed to compare effects of selective and non-selective COX-2 inhibitors. A total of 323 incident breast cancer patients were ascertained from the James Cancer Hospital, Columbus, Ohio, during 2003–2004 and compared with 649 cancer free controls matched to the cases at a 2:1 ratio on age, race, and county of residence. Data on the past and current use of prescription and over the counter medications and breast cancer risk factors were ascertained using a standardized risk factor questionnaire. Effects of COX-2 inhibiting agents were quantified by calculating odds ratios (OR) and 95% confidence intervals. RESULTS: Results showed significant risk reductions for selective COX-2 inhibitors as a group (OR = 0.29, 95% CI = 0.14–0.59), regular aspirin (OR = 0.49, 95% CI = 0.26–0.94), and ibuprofen or naproxen (0.36, 95% CI = 0.18–0.72). Acetaminophen, a compound with negligible COX-2 activity and low dose aspirin (81 mg) produced no significant change in the risk of breast cancer. CONCLUSION: Selective COX-2 inhibitors (celecoxib and rofecoxib) were only recently approved for use in 1999, and rofecoxib (Vioxx) was withdrawn from the marketplace in 2004. Nevertheless, even in the short window of exposure to these compounds, the selective COX-2 inhibitors produced a significant (71%) reduction in the risk of breast cancer, underscoring their strong potential for breast cancer chemoprevention

Treatment regimens for rifampicin-resistant tuberculosis: highlighting a research gap.

Treatment guidance for non-multidrug-resistant (MDR) rifampicin-resistant (RMP-R) tuberculosis (TB) is variable. We aimed to undertake a systematic review and meta-analysis of the randomised controlled trial (RCT) data behind such guidelines to identify the most efficacious treatment regimens. Ovid MEDLINE, the Web of Science and EMBASE were mined using search terms for TB, drug therapy and RCTs. Despite 12 604 records being retrieved, only three studies reported treatment outcomes by regimen for patients with non-MDR RMP-R disease, preventing meta-analysis. Our systematic review highlights a substantial gap in the literature regarding evidence-based treatment regimens for RMP-R TB

Differential effects of tactile high- and low-frequency stimulation on tactile discrimination in human subjects

<p>Abstract</p> <p>Background</p> <p>Long-term potentiation (LTP) and long-term depression (LTD) play important roles in mediating activity-dependent changes in synaptic transmission and are believed to be crucial mechanisms underlying learning and cortical plasticity. In human subjects, however, the lack of adequate input stimuli for the induction of LTP and LTD makes it difficult to study directly the impact of such protocols on behavior.</p> <p>Results</p> <p>Using tactile high- and low-frequency stimulation protocols in humans, we explored the potential of such protocols for the induction of perceptual changes. We delivered tactile high-frequency and low-frequency stimuli (t-HFS, t-LFS) to skin sites of approximately 50 mm²on the tip of the index finger. As assessed by 2-point discrimination, we demonstrate that 20 minutes of t-HFS improved tactile discrimination, while t-LFS impaired performance. T-HFS-effects were stable for at least 24 hours whereas t-LFS-induced changes recovered faster. While t-HFS changes were spatially very specific with no changes on the neighboring fingers, impaired tactile performance after t-LFS was also observed on the right middle-finger. A central finding was that for both t-LFS and t-HFS perceptual changes were dependent on the size of the stimulated skin area. No changes were observed when the stimulated area was very small (< 1 mm²) indicating special requirements for spatial summation.</p> <p>Conclusion</p> <p>Our results demonstrate differential effects of such protocols in a frequency specific manner that might be related to LTP- and LTD-like changes in human subjects.</p

Landmine injuries at the Emergency Management Center in Erbil, Iraq

<p>Abstract</p> <p>Background</p> <p>Landmines can cause death, injury and disability in addition to many indirect public health consequences. This study aimed at understanding the trends, demography and other epidemiological characteristics of hospitalized landmine injured patients in Erbil governorate.</p> <p>Methods</p> <p>The case records of landmine injured patients who had been admitted to the Emergency Management Centre in Erbil city from July 1998 to July 2007 were reviewed and descriptively analyzed.</p> <p>Results</p> <p>Two hundred eighty five landmine injured patients were admitted to the center, their mean ± SD age was 26.5 ± 13.2 years (range 6-71 years), 95.1% were males, nearly 50% were between 19 to 35 years of age and 96.8% were civilians. Around 72% of victims sustained limb amputations; 58.6% lower limb and 13.3% upper limb out of the total. The hospital mortality rate was 2.1%. The number of admissions for landmine injury was steadily decreasing between July 1998 and July 2001, followed by prominent increase between July 2002 and July 2003. The highest proportion of admissions occurred in summer (35.4%) and majority of incidents occurred along the borders with Iran and Turkey (61.8%).</p> <p>Conclusion</p> <p>Civilian male adolescents and young adults constituted the majority of hospitalized landmine victims in Erbil governorate. While a high proportion of victims sustained lower limb amputations, upper limb amputations particularly among children and injury to head and face were relatively common which might be attributed to handling explosives. This emphasizes the need to examine the reasons behind handling explosives.</p

A Longitudinal Study of Human Exposure to Potential Nuclear Power Plant Risk

This study constructs a potential risk index (PRI) for the 65 U.S.-based commercial nuclear power plant (NPP) sites in relation to their surrounding populations. Four risk levels are defined: low risk, moderate risk, high risk, and very high risk. Discrepancies that exist in the sociodemographic characteristics of the host communities’ populations are examined as sorted by risk-level category. It is found that a greater percentage of minority groups are exposed to the highest levels of risk. In addition, percent “Hispanic” and percent “Other,” a grouping that includes multiracial, mixed, interracial, as well as Hispanic and Latino groups (for example, Mexican, Puerto Rican, Cuban, or Spanish) are categories that show the greatest percent change in both the period 1990–2000 and 2000–2010

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Group formation under limited resources: narrow basin of equality

The formation of groups in competition and the aggressive interactions between them are ubiquitous phenomena in society. These include student activities in the classroom, election races between political parties, and intensifying trade wars between countries. Why do individuals form themselves into groups? What is the optimal size of groups? And how does the group size distribution affect resource allocations? These questions have been the subjects of intense research in economics, political science, sociology, and ethology. In this study, we explore the group-size effects on the formation of groups and resource allocations from an economic standpoint. While being in a large group is generally advantageous in competition, an increase in the management costs would set an upper bound to the individual benefit of members. Under such counteracting size effects, we consider the dynamics of group formation in which people seek a conservative measure to reduce their possible maximum loss. We are especially interested in the effects of group size on social inequalities at both group and individual level in resource allocation. Our findings show that the low positive size-effect and the high negative size-effect result in different types of social inequalities. We conclude, from the relation between the inequality measures and group distributions predicted within the model, that overall social equality only can be achieved within a narrow region where two counteracting size-effects are balanced

Task-evoked pupillary responses track precision-weighted prediction errors and learning rate during interceptive visuomotor actions.

This is the final version. Available from Nature Research via the DOI in this record.Data availability: All relevant data and code are available online from: https://osf.io/z96q8/.In this study, we examined the relationship between physiological encoding of surprise and the learning of anticipatory eye movements. Active inference portrays perception and action as interconnected inference processes, driven by the imperative to minimise the surprise of sensory observations. To examine this characterisation of oculomotor learning during a hand-eye coordination task, we tested whether anticipatory eye movements were updated in accordance with Bayesian principles and whether trial-by-trial learning rates tracked pupil dilation as a marker of 'surprise'. Forty-four participants completed an interception task in immersive virtual reality that required them to hit bouncing balls that had either expected or unexpected bounce profiles. We recorded anticipatory eye movements known to index participants' beliefs about likely ball bounce trajectories. By fitting a hierarchical Bayesian inference model to the trial-wise trajectories of these predictive eye movements, we were able to estimate each individual's expectations about bounce trajectories, rates of belief updating, and precision-weighted prediction errors. We found that the task-evoked pupil response tracked prediction errors and learning rates but not beliefs about ball bounciness or environmental volatility. These findings are partially consistent with active inference accounts and shed light on how encoding of surprise may shape the control of action.Leverhulme Trus