Malaria infections are randomly distributed in diverse holoendemic areas of Papua New Guinea

Malaria is holoendemic in the lowlands of Papua New Guinea (PNG), and interactions among Plasmodium species may influence prevalence of mixed infections. Previously, field samples from a cross-sectional survey in Dreikikir, East Sepik Province, analyzed by blood smear and polymerase chain reaction (PCR), showed that mixed infections were common and randomly distributed in this malaria endemic region. To evaluate further whether Plasmodium species distribution is random, blood smear- and PCR/sequence-specific oligonucleotide probe hybridization-based analyses of cross-sectional survey samples were conducted in 2 additional malaria holoendemic regions of northern PNG. Despite ecologic, species prevalence, and transmission season differences in these new surveys, all 4 Plasmodium species were found to be randomly distributed in each area; random distribution patterns also were observed when study populations were divided into age groups. These findings provide consistent evidence that Plasmodium species infections occur independently of one another in PNG malaria holoendemic sites. This independent occurrence suggests that age-dependent, acquired malaria immunity has limited influence on the distribution pattern of Plasmodium species infections in endemic human populations; infection by 1 human malaria parasite species does not reduce susceptibility to infection by others; and malaria vaccines would exhibit limited protection against blood-stage infection by heterologous Plasmodium species.     

Risk Stratification for the In-Hospital Mortality in Subarachnoid Hemorrhage: The HAIR Score

Background

The intracerebral hemorrhage (ICH) score is a simple grading scale that can be used to stratify risk of 30 day mortality in ICH patients. A similar risk stratification scale for subarachnoid hemorrhage (SAH) is lacking. We sought to develop a risk stratification mortality score for SAH.

Methods

With approval from the Institutional Review Board, we retrospectively reviewed 400 consecutive SAH patients admitted to our institution from August 1, 2006 to March 1, 2011. The SAH score was developed from a multivariable logistic regression model which was validated with bootstrap method. A separate cohort of 302 SAH patients was used for evaluation of the score.

Results

Among 400 patients with SAH, the mean age was 56.9 ± 13.9 years (range, 21.5–96.2). Among the 366 patients with known causes of SAH, 292 (79.8 %) of patients had aneurysmal SAH, 65 (17.8 %) were angiogram negative, and 9 (2 %) were other vascular causes. The overall in-hospital mortality rate was 20 %. In multivariable analysis, the variables independently associated with the in-hospital mortality were Hunt and Hess score (HH) (p < 0.0001), age (p < 0.0001), intraventricular hemorrhage (IVH) (p = 0.049), and re-bleed (p = 0.01). The SAH score (0–8) was made by adding the following points: HH (HH1-3 = 0, HH4 = 1, HH5 = 4), age (<60 = 0, 60–80 = 1, ≥80 = 2), IVH (no = 0, yes = 1), and re-bleed within 24 h (no = 0, yes = 1). Using our model, the in-hospital mortality rates for patients with score of 0, 1, 2, 3, 4, 5, 6, and 7 were 0.9, 4.5, 9.1, 34.5, 52.9, 60, 82.1, and 83.3 % respectively. Validation analysis indicates good predictive performance of this model.

Conclusion

The SAH score allows a practical method of risk stratification of the in-hospital mortality. The in-hospital mortality increases with increasing SAH mortality score. Further investigation is warranted to validate these findings.     

Quantifying a Rare Disease in Administrative Data: The Example of Calciphylaxis

BACKGROUND

Calciphylaxis, a rare disease seen in chronic dialysis patients, is associated with significant morbidity and mortality. As is the case with other rare diseases, the precise epidemiology of calciphylaxis remains unknown. Absence of a unique International Classification of Diseases (ICD) code impedes its identification in large administrative databases such as the United States Renal Data System (USRDS) and hinders patient-oriented research. This study was designed to develop an algorithm to accurately identify cases of calciphylaxis and to examine its incidence and mortality.

DESIGN, PARTICIPANTS, AND MAIN MEASURES

Along with many other diagnoses, calciphylaxis is included in ICD-9 code 275.49, Other Disorders of Calcium Metabolism. Since calciphylaxis is the only disorder listed under this code that requires a skin biopsy for diagnosis, we theorized that simultaneous application of code 275.49 and skin biopsy procedure codes would accurately identify calciphylaxis cases. This novel algorithm was developed using the Partners Research Patient Data Registry (RPDR) (n?=?11,451 chronic hemodialysis patients over study period January 2002 to December 2011) using natural language processing and review of medical and pathology records (the gold-standard strategy). We then applied this algorithm to the USRDS to investigate calciphylaxis incidence and mortality.

KEY RESULTS

Comparison of our novel research strategy against the gold standard yielded: sensitivity 89.2 %, specificity 99.9 %, positive likelihood ratio 3,382.3, negative likelihood ratio 0.11, and area under the curve 0.96. Application of the algorithm to the USRDS identified 649 incident calciphylaxis cases over the study period. Although calciphylaxis is rare, its incidence has been increasing, with a major inflection point during 2006–2007, which corresponded with specific addition of calciphylaxis under code 275.49 in October 2006. Calciphylaxis incidence continued to rise even after limiting the study period to 2007 onwards (from 3.7 to 5.7 per 10,000 chronic hemodialysis patients; r?=?0.91, p?=?0.02). Mortality rates among calciphylaxis patients were noted to be 2.5–3 times higher than average mortality rates for chronic hemodialysis patients.

CONCLUSIONS

By developing and successfully applying a novel algorithm, we observed a significant increase in calciphylaxis incidence. Because calciphylaxis is associated with extremely high mortality, our study provides valuable information for future patient-oriented calciphylaxis research, and also serves as a template for investigating other rare diseases.

     

RSSDI-ESI Clinical Practice Recommendations for the Management of Type 2 Diabetes Mellitus 2020

International Journal of Diabetes in Developing Countries -     

Determination and Method Validation of Metamitron in Soil by RP-HPLC

A simple, rapid and economical method was developed and validated for the determination of metamitron using UV detector with RP-HPLC. Study of metamitron in soil was carried out. The compound was extracted from soil by methanol and clean-up was done on C-18 SPE column. Recovery ranged from 90.75 % to 94.05 % within 0.1–2.0 μg g^?1 and RSD 1.80 %. Retention time was 3.8 min and limit of detection and limit of quantification were 0.001 and 0.008 μg g^?1. The results indicated that the reported method could meet the requirement for the analysis of metamitron in trace amounts.     

Dietary supplementation of milk fermented with probiotic Lactobacillus fermentum enhances systemic immune response and antioxidant capacity in aging mice

Although probiotics are known to enhance the host immune response, their roles in modulating immunosenescence, resisting infection, and improving redox homeostasis during aging remain unclear. Therefore, the present study was devised in aging mice to assess the antiimmunosenescence potential from the consumption of milk that is fermented with probiotic Lactobacillus fermentum MTCC 5898 (LF). We hypothesized that probiotic supplementation would boost immunity, improve antioxidant capacity, and resist severity of pathogenic infection in aging mice. To test this hypothesis, during a trial period of 2 months, 16-month-old male Swiss mice were kept on 3 experimental diets: basal diet (BD), BD supplemented with skim milk, and BD supplemented with probiotic LF-fermented milk. A concurrent analysis of several immunosenescence markers that include neutrophil functions, interleukins profile, inflammation and antibody responses in the intestine as well as analysis of antioxidant enzymes in the liver and red blood cells was performed. Neutrophil respiratory burst enzymes and phagocytosis increased significantly in probiotic LF-fed groups, whereas no exacerbation in plasma levels of monocyte chemotactic protein 1 and tumor necrosis factor α was observed. Splenocytes registered increased interferon-γ but decreased interleukin 4 and interleukin 10 production, whereas humoral antibodies registered decreases in immunoglobulin G1 (IgG1)/IgG2a ratio and IgE levels in the probiotic-fed groups. Antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in LF-fed groups showed increased activities, which were more pronounced in the liver than in red blood cell. An Escherichia coli–based infection model in aging mice was also designed to validate the protective attributes of LF. Administration of probiotic LF significantly reduced E coli population in organs (intestine, liver, spleen, and peritoneal fluid), as compared with control groups, by enhancing E coli–specific antibodies and inflammatory proteins. Based on these results, it appears that LF supplementation alleviated immunosenescence, enhanced antioxidant enzyme activities, and resisted E coli infection in aging mice; thereby, signifying its potential in augmenting healthy aging.     

Convalescent plasma treatment for COVID-19: Tempering expectations with the influenza experience

The COVID-19 pandemic caused by the zoonotic coronavirus, SARS-CoV-2 has swept the world in 5 months. A proportion of cases develop severe respiratory tract infections progressing to acute respiratory distress syndrome and a diverse set of complications involving different organ systems. Faced with a lack of coronavirus-specific antiviral drugs and vaccines, hundreds of clinical trials have been undertaken to evaluate repurposed drugs. Convalescent plasma from recovered patients is an attractive option because antibodies can have direct or indirect antiviral activity and immunotherapy works well in principle, in animal models, and in anecdotal reports. However, the benefits of convalescent plasma treatment can only be clearly established through carefully designed randomized clinical trials. The experience from investigations of convalescent plasma products for severe influenza offers a cautionary tale. Despite promising pilot studies, large multicenter randomized controlled trials failed to show a benefit of convalescent plasma or hyperimmune intravenous globulin for the treatment of severe influenza A virus infection. These studies provide important lessons that should inform the planning of adequately powered randomized controlled trials to evaluate the promise of convalescent plasma therapy in COVID-19 patients.