Oxygenation Status in Chronic Leg Ulcer After Topical Hemoglobin Application May Act as a Surrogate Marker to Find the Best Treatment Strategy and to Avoid Ineffective Conservative Long-term Therapy

Purpose

Chronic leg ulcers can be a challenge to treat and long-term therapy a significant cost factor in western public health budgets. Objective wound assessment assays enabling selection of appropriate wound therapy regimes would be desirable. Oxygenation status in ulcer tissue has obtained increased attention as a relevant factor in wound healing. To increase oxygenation in wounds, a topical hemoglobin spray was developed. Although favorable results have been noted, the link between clinical efficacy and the mode of action has not been demonstrated. The aims were to determine if changes in tissue oxygenation can be measured after topical application of hemoglobin on chronic wounds and to evaluate the findings in terms of therapy strategies.

Procedures

Photoacoustic imaging was used to measure the local oxygen saturation (StO₂) in leg ulcers before and after hemoglobin spray treatment. Sclerosis of the leg ulcers was histopathologically graded and the change in wound size was documented in a follow-up examination.

Results

Measuring 49 patients, an increase in StO₂ after topical hemoglobin application from on average 66.1 to 71 % (p = 0.017) after 20 min was observed. Depending on the increase in StO₂ (>10 % or <10 %) patients were stratified into a Responder and a Non-Responder group. Wound size significantly decreased in the Responder Group (p = 0.001), while no significant difference in the Non-Responder group (p = 0.950) was noted.

Conclusion

Our findings suggest that the likelihood of wound healing under conservative therapy can be predicted by measuring changes in StO₂ after topical hemoglobin application. This assay may reduce treatment time and costs by avoiding ineffective conservative long-term therapy.

Trial Registration

German Clinical Trials Register: DRKS00005993

     

Flu and Finances: Influenza Outbreaks and Loan Defaults in US Cities, 2004–2012

Objectives. We examined the association between influenza outbreaks in 83 metropolitan areas and credit card and mortgage defaults, as measured in quarterly zip code–level credit data over the period of 2004 to 2012.Methods. We used ordinary least squares, fixed effects, and 2-stage least squares instrumental variables regression strategies to examine the relationship between influenza-related Google searches and 30-, 60-, and 90-day credit card and mortgage delinquency rates.Results. We found that a proxy for influenza outbreaks is associated with a small but statistically significant increase in credit card and mortgage default rates, net of other factors. These effects are largest for 90-day defaults, suggesting that influenza outbreaks have a disproportionate impact on vulnerable borrowers who are already behind on their payments.Conclusions. Overall, it appears there is a relationship between exogenous health shocks (such as influenza) and credit default. The results suggest that consumer finances could benefit from policies that aim to reduce the financial shocks of illness, particularly for vulnerable borrowers.Seasonal influenza is a viral airborne disease that generally spreads each fall and winter, causing an estimated 1.5 million people to get sick and 200 000 to be hospitalized in a typical year in the United States.1,2 Symptoms can range from mild and hardly distinguishable from a common cold to severe and life-threatening. Influenza accounts for at least 500 000 deaths in the United States in the past 3 decades.3For employed individuals, influenza can make attending work difficult, because of either personal illness or caring for sick household members. This generates significant costs to employers and employees. Estimates from 2007 suggest that annual influenza outbreaks lead to $16.3 billion in lost productivity and wages, and $10.4 billion in medical costs,4 although these costs vary considerably across place.5Although there is a robust literature on the economic costs of influenza, we know little about how such unexpected health shocks are associated with other aspects of the economy, such as loan defaults. We built on existing knowledge of the economic costs of influenza by examining how influenza outbreaks influence credit card and mortgage default rates in US cities.In the wake of the Great Recession, loan defaults have increased, with negative financial consequences for families.6 For loans due on a monthly basis, such as mortgages and credit cards, past-due balances and late fees accumulate each month. Three missed payments (90-day delinquent) is a signal of a loan at high risk for failure and in most states triggers legal collections processes.7In the microeconomic literature, illness is seen as a shock—an unexpected event—that can affect household income and expenses. If the shock results in a disruption to income, households will respond with shifts in consumption and expenditure patterns.8 We contend that influenza, as a health shock, has the potential to trigger loan default by constraining a family’s budget because of personal illness or caretaking burdens. Influenza may also trigger inattention to household financial management and a lack of planning for future bill payments.9–11 This may be especially problematic for borrowers who are already behind on their payments, whom we define as vulnerable borrowers. For these borrowers, who also tend to be economically vulnerable and disadvantaged in other ways,12,13 an influenza outbreak could increase the likelihood of further missed payments. A recent study supports this notion, and shows that economically vulnerable households are more likely to borrow and borrow more in the event of a health shock than less vulnerable households.14 However, this study did not examine credit default.A growing literature examines the complex and potentially multidirectional relationship between health and default.15–19 Most research examines whether defaults influence health,15,19,20 and less examines how health may have an impact on default risk.21 However, a key problem inherent in this literature is that health status is endogenous, and it is difficult if not impossible to disentangle processes of causation, selection, and reverse causation with survey data.Our interest in influenza provides us with a unique opportunity to improve causal estimates of health shocks on default. Influenza occurs to varying degrees in every city and year in the United States, and the intensity of the outbreak is an ostensibly exogenous health shock for communities. Thus, influenza outbreaks provide a natural experiment in which we use variation in influenza severity across time and place to identify the effects of a particular health shock on default. Specifically, we ask whether influenza outbreaks in US metropolitan statistical areas (MSAs) are associated with defaults from the first quarter (March) of 2004 (Q1 2004) to the second quarter (June) of 2012 (Q2 2012).We make 3 contributions with this study. First, we extended the literature on the economic costs of influenza. Second, we contributed to the literature on health shocks and default by providing a stronger test of the potential causal impacts of health shocks on loan default. Third, we considered whether effects vary across types of default, including 30-, 60-, and 90-day defaults. We predicted that influenza may have the greatest effect on borrowers who are already in default, such that the association between influenza and default should be stronger for borrowers who are farther behind.     

Adrenal function in HIV infected patients

Since anatomopathological lesions of the adrenal gland have been frequently observed at autopsy in AIDS, we investigated the glucocorticoid function in 63 patients (51 men, 12 women) infected by the human immunodeficiency virus (HIV) in order to determine the incidence and the nature of any adrenocortical abnormalities at various stages of HIV infection. The patients were classified according to the Centers for Disease Control (CDC) recommendations into group II (asymptomatic; N = 13), group III (lymphadenopathy; N = 27) and group IV (clinical manifestations; N = 23). Plasma ACTH and cortisol before and after an exogenous ACTH stimulation test were measured in patients as in 30 age-matched controls. Plasma renin activity and plasma aldosterone before and after ACTH stimulation were also measured in 31 patients (group II: 12; group III: 10; group IV: 9). Compared with controls patients from group II-III had higher levels of ACTH (39.11 +/- 17.01 vs 29.73 +/- 8.53 ng/l; p = 0.003) and basal cortisol (232 +/- 91.2 vs 184.3 +/- 30.9 micrograms/l; p = 0.03). No significant differences were noted between group IV patients and controls as to ACTH and basal and stimulated cortisol levels. Among the 63 patients, only one from group IV had a blunted cortisol response after ACTH stimulation test. Plasma renin activity, and basal and stimulated aldosterone levels in the 3 groups of patients were not different from control values. In conclusion: 1. Adrenal insufficiency does not seem very frequent in group IV patients and is likely to be a late complication in AIDS. 2. The increased ACTH and basal cortisol levels found in group II and group III patients argue for an early dysregulation of the adrenocortical axis in HIV infection. The exact physiopathological mechanism is not yet known, but an enhanced CRH production by interleukin 1 and/or a direct role of the HIV envelope glycoprotein (gp 120) may explain the high ACTH level in HIV patients.     

Hair analysis of antidepressants and antipsychotics—Overview of quantitative data

Antidepressant and antipsychotic drugs are regularly encountered in different aspects of forensic toxicology, and some cases require the examination of hair samples. In this study, common antidepressant and antipsychotic drugs regarding hair concentrations over the past decades were reviewed. Although numerous publications around method validations, case reports, or controlled dose studies were found, apparently there is a lack of comprehensive data for many substances. Information on the hair length and dosage across the publications varied largely, and case numbers were generally low except for several retrospective controlled dose studies. Many substances were described only in method validations or case reports, and data were obtained from small case numbers. On the contrary, clozapine, haloperidol, amitriptyline, nortriptyline, risperidone and its metabolite, methylphenidate, citalopram, chlorpromazine, chlorprothixene, and quetiapine had a well‐founded database as these substances were investigated in controlled dose studies with higher case numbers. Given the advancements made in analytical techniques over the past years, gas chromatography–mass spectrometry and liquid chromatography with tandem mass spectrometry techniques were the methods of choice and allowed the detection of chemical compounds at low concentrations. The controversy around a potential use of hair analysis to estimate the dosage remains as dose‐concentration studies provided divergent results. A harmonization on the investigated hair length as well as on the extraction protocol would be of favor to achieve better comparability. Although hair analysis research focused mainly on drug abuse, availability of more data on antidepressants and antipsychotics would help to gain better knowledge and assist other forensic investigators.     

The emerging role of microRNAs in regulating immune and inflammatory responses in the lung

Chronic inflammatory diseases of the lung are leading causes of morbidity and mortality worldwide. Many of these disorders can be attributed to abnormal immune responses to environmental stimuli and infections. As such, understanding the innate host defense pathways and their regulatory systems will be critical to developing new approaches to treatment. In this regard, there is increasing interest in the role of microRNAs (miRNAs) in the regulation of pulmonary innate host defense responses and the inflammatory sequelae in respiratory disease. In this review, we discuss recent findings that indicate an important role for miRNAs in the regulation in mouse models of various respiratory diseases and in host defense against bacterial and viral infection. We also discuss the potential utility and limitations of targeting these molecules as anti-inflammatory strategies and also as a means to improve pathogen clearance from the lung.