Analyzing treatment aggressiveness and identifying high‐risk patients in diabetic foot ulcer return to care

Rates of diabetes and its associated comorbidities have been increasing in the United States, with diabetic foot ulcer treatment representing a large cost to the patient and healthcare system. These ulcers often result in multiple hospital admissions. This study examined readmissions following inpatient care for a diabetic foot ulcer and identified modifiable factors associated with all‐cause 30‐day readmissions to the inpatient or emergency department (ED) setting. We hypothesized that patients undergoing aggressive treatment would have lower 30‐day readmission rates. We identified patient discharge records containing International Classification of Disease ninth revision codes for both diabetes mellitus and distal foot ulcer in the State Inpatient and Emergency Department databases from the Agency for Healthcare Research and Quality, Healthcare Cost and Utilization Project in Florida and New York, 2011–2012. All‐cause 30‐day return to care visits (ED or inpatient) were analyzed. Patient demographics and treatment characteristics were evaluated using univariate and multivariable regression models. The cohort included 25,911 discharges, having a mean age of 63 and an average of 3.8 comorbidities. The overall rate of return to care was 30%, and 21% of subjects underwent a toe or midfoot amputation during their index stay. The most common diagnosis codes upon readmission were diabetes mellitus (19%) and infection (13%). Patients with a toe or midfoot amputation procedure were less likely to be readmitted within 30 days (odds ratio: 0.78; 95% confidence interval: 0.73, 0.84). Presence of comorbidities, black and Hispanic ethnicities, and Medicare and Medicaid payer status were also associated with higher odds of readmission following initial hospitalization (p < 0.05). The study suggests that there are many factors that affect readmission rates for diabetic foot ulcer patients. Understanding patients at high‐risk for readmission can improve counseling and treatment strategies for this fragile patient population.     

Aberrant gene methylation implicated in the progression of monoclonal gammopathy of undetermined significance to multiple myeloma

Malignant transformation is a multistep process that may involve dysregulation of oncogenes and tumour suppressor genes, and monoclonal gammopathy of undetermined significance (MGUS) is believed to be a precursor of multiple myeloma. To investigate whether aberrant promoter methylation might be involved in the evolution of MGUS to multiple myeloma, we examined the p16, protein tyrosine phosphatase, non-receptor type 6 (SHP1), death-associated protein (DAP) kinase, E-cadherin and oestrogen receptor genes, most being tumour suppressor genes, by methylation-specific polymerase chain reaction. In 32 cases of multiple myeloma and 19 cases of MGUS, significantly more frequent methylation of p16 (p = 0.001), SHP1 (p< or =0.001) and E-cadherin (p< or =0.001) genes was found in multiple myeloma than in MGUS. Methylation of DAP kinase and oestrogen receptor genes was comparable in multiple myeloma and MGUS. In conclusion, methylation of p16, SHP1 and E-cadherin genes might be involved in the progression of MGUS to multiple myeloma.     

Identification of neutralizing linear epitopes from the VP1 capsid protein of Enterovirus 71 using synthetic peptides

Enterovirus 71 (EV71) is the main causative agent of Hand, foot and mouth disease (HFMD) and has been associated with severe neurological diseases resulting in high mortalities. Currently, there is no vaccine available and treatment is limited to palliative care. In this study, antisera were raised in mice against 95 overlapping synthetic peptides spanning the VP1 capsid protein of EV71. Two peptides, SP55 and SP70, containing amino acid 163-177 and 208-222 of VP1, respectively, are capable of eliciting neutralizing antibodies against EV71 in the in vitro microneutralization assay. SP70 was identified to be particularly potent in eliciting a neutralizing antibody titer comparable to that obtained with a whole virion-immune serum. Immunization of mice with either SP55 or SP70 triggered an EV71-specific IgG response as high as that obtained with the whole virion as immunogen. The IgG sub-typing revealed that the neutralizing antibodies elicited by both synthetic peptides are likely belonging to the IgG1 sub-type. Alignment with databases showed that the amino acid residues of SP70 are highly conserved amongst the VP1 sequences of EV71 strains from various sub-genogroups. Altogether, these data indicate that SP70 represents a promising candidate for an effective synthetic peptide-based vaccine against EV71.     

TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions

TAR DNA-binding protein 43 (TDP-43) is a major pathological protein of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U) with or without motor neuron disease (MND). Thus, TDP-43 defines a novel class of neurodegenerative diseases called TDP-43 proteinopathies. We performed ubiquitin and TDP-43 immunohistochemistry on 193 cases of familial and sporadic FTLD with or without MND. On selected cases, immunoelectron microscopy and biochemistry were performed. Clinically defined frontotemporal dementias (FTDs) included four groups: 1) familial FTD with mutations in progranulin (n = 36), valosin-containing protein (n = 5), charged multivesicular body protein 2B (n = 4), and linked to chromosome 9p (n = 7); 2) familial cases of FTD with unknown gene association (n = 29); 3) sporadic FTD (n = 72); and 4) familial and sporadic FTD with MND (n = 40). Our studies confirm that the spectrum of TDP-43 proteinopathies includes most cases of sporadic and familial FTLD-U with and without MND and expand this disease spectrum to include reported families with FTD linked to chromosome 9p but not FTD with charged multivesicular body protein 2B mutations. Thus, despite significant clinical, genetic, and neuropathological heterogeneity of FTLD-U, TDP-43 is a common pathological substrate underlying a large subset of these disorders, thereby implicating TDP-43 in novel and unifying mechanisms of FTLD pathogenesis.     

Comparison of sonographic appearance of normal and postradiotherapy parotid glands: a preliminary study

This study was undertaken to evaluate and compare the grey-scale and Doppler sonographic features of postradiotherapy (RT) and normal parotid glands. A total of 10 patients with previous head and neck RT and with different degrees of xerostomia were included. Another 10 healthy subjects, who are age and gender-matched with the 10 patients, were also recruited. Grey-scale and Doppler ultrasound examinations of parotid glands were performed on both the patients and healthy subjects. The parotid glands were assessed for their size, echogenicity, echotexture, conspicuity of intraparotid ducts, blood flow velocity and vascular resistance. Results showed that post-RT parotid glands tended to be smaller than normal parotid glands with a significant difference in the transverse dimension (p < 0.05). Normal parotid glands appeared homogeneous, hyperechoic relative to the adjacent muscles and had marginally seen intraparotid ducts. Post-RT parotid glands were heterogeneous, isoechoic (50%) or hypoechoic (50%) relative to the adjacent muscles, and the intraparotid ducts were either marginally (50%) or obviously (50%) seen on ultrasound. The PSV, RI and PI of normal parotid glands were significantly higher than that of post-RT parotid glands (p < 0.05). However, the difference in EDV between normal and post-RT parotid glands was not significant (p > 0.05). In conclusion, ultrasound is useful in assessing parotid glands. To avoid image misinterpretation, post-RT changes in the sonographic appearance of parotid glands should be considered in examining patients with previous head and neck RT.     

Validation of the eleven-point pain scale in the measurement of migraine headache pain

The four-point pain scale (none, mild, moderate, severe) and the 11-point pain scale (0 = no pain, 10 = pain as bad as it could be) have been used in migraine studies to assess treatment efficacy. The primary objective of this study was to investigate the validity and responsiveness of the 11-point pain scale using the four-point pain scale as a benchmark. Using data from 95 migraine patients recruited from headache clinics, this study found that 11-point pain scale scores were highly correlated with four-point pain scores. The correlations between the pain scales were significantly higher than the correlations with quality of life measures such as functional ability and emotional feelings. The 11-point pain scale was 55% more sensitive than the four-point pain scale in detecting clinically important differences. The strong linear relationship between the two pain scales allowed researchers to transform four-point pain scores to 11-point pain scores using regression weights.     

Male Breast Cancer: A Population-Based Comparison with Female Breast Cancer in Hong Kong,Southern China: 1997–2006

Background

Male breast cancer (MBC) is uncommon. As a result, there is limited availability of studies and reviews and even fewer reports from Asia. This is the largest population-based study to compare Chinese MBC patients with female patients during a 10-year period in Hong Kong, Southern China.

Methods

A retrospective review of medical records of 132 male and 8,118 female breast cancer patients between year 1997 and 2006 in Hong Kong was performed. Each MBC patient was matched with three female breast cancer patients for further analysis. Different characteristics, overall, breast-cancer specific, and disease-free survivals (DFS) were compared.

Results

Mean age at diagnosis of male and female patients was 64.5 and 52.7 years respectively. Male patients showed lower histological grade, overall stage, smaller tumor size, and more positive sensitivity in hormone receptors. They were more likely to die of causes other than breast cancer. Matched analysis found that the 5-year overall survival (OS), breast-cancer–specific mortality, and DFS for male and female patients were 78.7, 90.5, 90.5, and 77.9, 86.4, and 81.4 % respectively. Male patients had poorer OS at early overall stage but better breast-cancer—specific mortality rates at any age (p < 0.01). Male patients had a significant risk of dying due to any cause in the presence of distant relapse and had less risk of dying when tumor was ER-positive and HER2-positive.

Conclusions

Chinese male breast cancer patients tend to have poorer OS but better breast-cancer—specific survival compared with their female counterparts.     

Hospital Costs Associated With Laparoscopic and Open Inguinal Herniorrhaphy

Purpose:

The purpose of this study was to compare the total hospital costs associated with elective laparoscopic and open inguinal herniorrhaphy.

Methods:

A prospectively maintained database was used to identify patients who underwent elective inguinal herniorrhaphy from April 2009 to March 2011. A retrospective review of electronic patient records was performed along with a standardized case-costing analysis using data from the Ontario Case Costing Initiative. The main outcomes were operating room (OR) and total hospital costs.

Results:

Two hundred eleven patients underwent elective unilateral inguinal herniorrhaphy (117 open and 94 laparoscopic), and 33 patients underwent elective bilateral inguinal herniorrhaphy (9 open and 24 laparoscopic). OR and total hospital costs for open unilateral inguinal hernia repair were significantly lower than for the laparoscopic approach (median total cost, $3207.15 vs $3723.66; P < .001). OR and total hospital costs for repair of elective bilateral inguinal hernias were similar between the open and laparoscopic approaches (median total cost, $4574.02 vs $4662.89; P = .827).

Conclusions:

In the setting of a Canadian academic hospital, when considering the repair of an elective unilateral inguinal hernia, the OR and total hospital costs of open surgery were significantly lower than for the laparoscopic techniques. There was no statistical difference between OR and total hospital costs when comparing open surgery and laparoscopic techniques for the repair of bilateral inguinal hernias. Given the perioperative benefits of laparoscopy, further studies incorporating hernia-specific outcomes are necessary to determine the cost-effectiveness of each approach and to define the optimal treatment strategy.     

Epidemiology and potential risk factors of drug-related problems in Hong Kong paediatric wards

Aims

A drug-related problem (DRP) is ‘an event or circumstance involving drug therapy that actually or potentially interferes with the desired health outcome’. The extent and characteristics of DRPs in children in Hong Kong are unknown. The aim of this study was to determine the epidemiology of and identify risk factors for DRPs in hospitalized children in Hong Kong.

Methods

This was a prospective cohort study in children aged 0–18 years who were admitted to a medical ward, paediatric intensive care unit or neonatal intensive care unit of seven Hong Kong hospitals, during a 3 month period. Patients'' charts, medical records and laboratory data were reviewed daily to identify DRPs; their preventability and severity were assessed. Logistic regression was used to analyse potential risk factors associated with the incidence of DRPs.

Results

Three hundred and twenty-nine children (median age, 2 years; interquartile range, 0 months to 9 years) were included. In total, 82 DRPs were experienced by 69 patients. The overall incidence of DRPs was 21.0% (95% confidence interval, 16.7–25.8%). The incidence was higher in neonatal and paediatric intensive care units than medical wards. Dosing problems were the most frequently reported DRPs (n = 35; 42.7%), followed by drug choice problems (n = 19; 23.2%) and adverse drug reactions (n = 11; 13.4%). Sixty-seven (81.7%) DRP cases were assessed as preventable, 42 (51.2%) as minor and 40 (48.8%) as moderate. The number of prescribed drugs and ‘certain infectious and parasitic diseases’ were potential risk factors for occurrence of DRPs.

Conclusions

Drug-related problems were common in hospitalized children in this study in Hong Kong; the most frequent were dosing and drug choice problems, and the majority of them were preventable. Polypharmacy and ‘certain infectious and parasitic diseases’ were potential risk factors.     

The Economic Burden of Ischemic Stroke and Major Hemorrhage in Medicare Beneficiaries with Nonvalvular Atrial Fibrillation: A Retrospective Claims Analysis

Background

Understanding the economic implications of oral anticoagulation therapy requires careful consideration of the risks and costs of stroke and major hemorrhage. The majority of patients with atrial fibrillation (AF) are aged ≥65 years, so focusing on the Medicare population is reasonable when discussing the risk for stroke.

Objective

To examine the relative economic burden associated with stroke and major hemorrhage among Medicare beneficiaries who are newly diagnosed with nonvalvular atrial fibrillation (NVAF).

Methods

This study was a retrospective analysis of a 5% sample of Medicare claims data for patients with NVAF from 2006 to 2008. Patients with NVAF without any claims of AF during the 12 months before the first (index) claim for AF in 2007 (baseline period) were identified and were classified into 4 cohorts during a 12-month follow-up period after the index date. These cohorts included (1) no claims for ischemic stroke or major hemorrhage (without stroke or hemorrhage); (2) no claims for ischemic stroke and ≥1 claims for major hemorrhage (hemorrhage only); (3) ≥1 claims for ischemic stroke and no major hemorrhage claims (stroke only); and (4) ≥1 claims each for ischemic stroke and for major hemorrhage (stroke and hemorrhage). The 1-year mean postindex total all-cause healthcare costs adjusted by the Centers for Medicare & Medicaid Services Hierarchical Condition Categories (HCC) score were compared among the study cohorts. Results: Of the 9455 eligible patients included in this study, 3% (N = 261) of the patients had ischemic stroke claims only, 3% (N = 276) had hemorrhage claims only, and <1% (N = 13) had both during the follow-up period. The unadjusted follow-up healthcare costs were $63,781 and $64,596 per patient for the ischemic stroke only and the hemorrhage only cohorts, respectively, compared with $35,474 per patient for those without hemorrhage or stroke claims. After adjustment for HCC risk score, the mean incremental costs for patients with stroke claims only and hemorrhage claims only, relative to those without stroke or hemorrhage claims, were $26,776 (95% confidence interval [CI], $20,785-$32,767; P <.001) and $26,168 (95% CI, $20,375-$31,961; P <.001), respectively.

Conclusion

The economic burden of managing patients with NVAF who experience ischemic stroke and hemorrhage were similarly significant during the first year after a diagnosis of NVAF. The burden of major bleeding complications on patients, clinicians, and payers should not be overlooked, and these complications should be considered in conjunction with the cost-savings associated with ischemic stroke risk reduction in future cost-benefit evaluations of oral anticoagulation therapy.Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia.1,2 The most recent estimates (published in 2013) of the prevalence of AF in the United States are for 2010 and range from 2.7 million to 6.1 million.3,4 The prevalence of AF doubles with each decade of life after the age of 60 years and occurs in approximately 10% of the US population aged ≥80 years.5–7 A recent study estimates that the number of patients with AF in the United States could potentially reach 12.1 million by 20303; other estimates range from 5.6 million to 12 million patients with AF by 2050.4Patients with AF have an approximate 5-fold increased risk for stroke compared with patients in normal sinus rhythm.4 Furthermore, the percentage of strokes that can be attributed to AF increases steeply with age, with rates of 1.5% in patients aged 50 to 59 years and 23.5% in those aged 80 to 89 years.4 The term “nonvalvular atrial fibrillation” (NVAF) is used to describe cases of AF that occur in the absence of rheumatic mitral valve disease, mitral valve repair, or a prosthetic heart valve.8 NVAF affects approximately 85% of the overall population with AF and is a substantial medical burden for Medicare beneficiaries (aged ≥65 years) in the United States.9,10The current evidence-based clinical guidelines recommend the use of oral anticoagulation in patients with NVAF who are at an intermediate to high risk for stroke.8,11 Although the efficacy of oral anticoagulation therapy to prevent stroke in patients with NVAF is well-established, it is also associated with a risk of bleeding.12–15 Understanding the relative economic burdens of stroke and major hemorrhage is important when considering the costs and benefits of anticoagulation therapy.Several studies have reported the incremental costs associated with stroke alone or with hemorrhage alone using different NVAF payer populations (ie, commercial or Medicare), and a few recent studies have provided incremental cost data for stroke and hemorrhage for the Medicare population, reporting significant incremental costs in the year after the stroke or hemorrhage index dates.7,16–20 Other studies have analyzed the incremental costs associated with stroke alone or with hemorrhage alone, or have analyzed these costs for a commercial population with NVAF.21–24 Most of these studies were done in separate patient populations and different time periods, making assessment of the relative economic burden of stroke versus bleeding difficult. By contrast, our study provides the cost estimates for these 2 conditions simultaneously based on the same patient population, which allows a more appropriate comparison of the economic implication of these 2 major consequences of oral anticoagulation therapy for the prevention of stroke among patients with NVAF.The prespecified objective in our study was to assess the relative economic burden (including Medicare Part D costs) associated with ischemic stroke and with major hemorrhagic events (ie, intracranial and gastrointestinal [GI] bleeding) among Medicare beneficiaries with newly diagnosed NVAF in the 12 months after the NVAF index diagnosis.