Receptor-Defined Breast Cancer in Five East African Countries and Its Implications for Treatment: Systematic Review and Meta-Analysis.

PURPOSE: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) are determinants of treatment and mortality for patients with breast cancer (BC). In East Africa, the estimated 5-year survival (37.7%) is far lower than the US average (90%). This meta-analysis investigates BC receptor subtypes within five East African countries to ascertain cross-country patterns and prioritize treatment needs. METHODS: From a PubMed search, January 1, 1998-June 30, 2019, for all English-only BC articles for Ethiopia, Kenya, Rwanda, Tanzania, and Uganda, eligible studies had receptor distributions for female BC samples ≥ 30 patients. Outcomes were proportions of ER+, PR+, and HER2-positive (HER2+), and/or molecular subtypes. Data included study characteristics and mean or median patient age. Using metaprop, Stata 16, we estimated pooled proportions (ES) with 95% CIs and assessed heterogeneity. RESULTS: Among 36 BC studies with receptor data, 21 met criteria. Weighted mean age was 47.5 years and median, 48. Overall ES were as follows: 55% for ER-positive (ER+) (95% CI, 47 to 62), 23% for HER2+ (95% CI, 20 to 26), and 27% for triple-negative BC (TNBC) (95% CI, 23 to 32). CONCLUSION: We found differences between countries, for example, lower distribution of TNBC in Ethiopia (21%) compared with Uganda (35%). ER+, the dominant BC subtype overall at 55%, emphasizes the need to prioritize endocrine therapy. Overall proportions of HER2+ BC (with or without ER+ or PR+), 23%, approached proportions of TNBC, 27%, yet HER2 testing and treatment were infrequent. Testing and reporting of receptor subtypes would promote delivery of more effective treatment reducing the mortality disparity.

Prospective, population-based surveillance of the burden of Streptococcus pneumoniae in community-acquired pneumonia in older adults, Chrzanów County, Poland, 2010 to 2012.

INTRODUCTION: Community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae is a substantial cause of morbidity and mortality among older adults. This study estimated incidences of CAP, chest x-ray-confirmed CAP (CXR+CAP), S pneumonia- positive CAP, S pneumonia-positive CXR+CAP, and S. pneumoniae serotype distribution among 46,000 at-risk adults aged ≥ 50 years residing in Chrzanów County, Poland. MATERIAL AND METHODS: From January 2010 to January 2012, all facilities providing ambulatory and inpatient care enrolled all consenting resident patients with suspicion of CAP. Chest x-rays, urine, blood, and sputum samples were analyzed. Annualized incidence rates were determined. Presence of S pneumonia-positive CAP and/or S. pneumoniae serotype distribution was determined using the urine antigen detection assay (capable of detecting the serotypes in the 13-valent pneumococcal conjugate vaccine [PCV13]), BinaxNOW®, and/or microbiology cultures. RESULTS: Among 5055 enrolled patients, 1195 (23.7%) were diagnosed with CAP and 1166 (23.4%) had CXR+CAP. S. pneumoniae was detected in 144 (12.1%) and 131 (11.2%) patients from the CAP and CXR+CAP cohorts, respectively. Annualized incidence rates of CAP, CXR+CAP, S pneumonia-positive CAP, and S. pneumonia-positive CXR+CAP were 12.8, 12.5, 1.6, and 1.4 per 1000 residents, respectively. Among CXR+CAP patients, 39.7% were aged 50 to 64 years and 60.3% were aged ≥ 65 years. Incidence rates generally increased with age. The most common serotypes in S. pneumoniae-positive CXR+CAP patients were 3 (n = 15), 23F (n = 10), 18C (n = 9), and 9V (n = 6). CONCLUSIONS: CAP due to PCV13 serotypes is a source of morbidity among adults >50 years and may be reduced by greater access to pneumococcal vaccines.

[Clinical burden of multi-cause and pneumococcal pneumonia, meningitis, and septicemia in Hungary. Results of a retrospective study (2006-2011)]. / Pneumococcus, illetve bármely kórokú pneumonia, meningitis és septikaemia miatti hospitalizáció és halálozás Magyarországon. Egy retrospektív értékelés eredménye (2006-2011).

INTRODUCTION: Assessment of the impact of pneumococcal conjugate vaccines on the burden of pneumonia, meningitis, and septicemia in Hungary is limited. AIM: The aim of this retrospective study was to quantify rates of hospitalized multi-cause and pneumococcal pneumonia, meningitis, and septicemia in all age groups in Hungary between 2006 and 2011. METHOD: Aggregate data were obtained from the Hungarian National Healthcare Fund using pre-specified ICD-10 codes. Comparisons included average rates pre-vaccine (2006-2007) versus post-vaccine (2010-2011) using a χ2 test. RESULTS: Hospitalization rates among children aged 0-4 years significantly declined for multi-cause pneumonia and meningitis, but increased for septicemia. There were significant increases in multi-cause pneumonia and septicemia in other age groups. In-hospital mortality rates increased with age. Limited use of pneumococcal-specific codes led to inconclusive findings for pneumococcal diseases. CONCLUSIONS: Declines in multi-cause pneumonia and meningitis in children aged 0-4 years suggest direct effects of pneumococcal conjugate vaccination on hospitalization rates.

A retrospective study of hospitalized pneumonia in two Polish counties (2006-2008).

INTRODUCTION: In Poland, multi-cause pneumonia is not well characterized, and there is limited pneumococcal vaccination in the youngest and oldest age groups. The goal of this study was to assess hospitalized pneumonia across all age groups in two Polish counties. MATERIAL AND METHODS: Using electronic administrative databases, cases were identified as county residents hospitalized at Chrzanów and Inowroclaw County Hospitals from 2006-2008, assigned a diagnosis of pneumonia. Calculations by admission year, sex, and age category were: hospitalization rates per 1000 persons; in-hospital mortality rates per 100 persons; and median length of stay (LOS). RESULTS: There were 1444 and 2956 hospitalizations for new episodes of pneumonia with rates of 3.76 (95% confidence interval [CI] 3.57-3.96) and 5.99 (95% CI 5.77-6.21) per 1000 persons in Chrzanów and Inowroclaw counties, respectively. In combined data, the highest hospitalization rate was among patients aged 0-4 years (30.77; 95% CI 29.06-32.55) followed by those aged ≥ 75 years (25.39; 95% CI 24.01-26.83). In-hospital mortality rates increased with age at both sites. The median LOS was 8 days. CONCLUSIONS: Pneumonia hospitalizations were substantial, especially for the youngest and oldest age groups. Future public health interventions aimed at these age groups might improve disease outlook.

Postoperative outcomes associated with topical skin adhesives among women having hysterectomies.

BACKGROUND: Multiple options are available for closure of hysterectomy incisions. This study compared postoperative clinical and economic outcomes using topical skin adhesive (2-octyl cyanoacrylate; OCA) vs. conventional skin closure in women undergoing total abdominal hysterectomy. METHODS: A multi-hospital administrative database was used to identify women discharged in 2005 who had undergone total abdominal hysterectomy. Patients, classified by skin closure as suture (n = 21,201), staples (n = 23,441), OCA (n = 880), or staples + OCA (n = 489), were compared on length of inpatient stay (LOS), total inpatient cost, and non-prophylactic antibiotic treatment after day four. RESULTS: The unadjusted mean LOS was 3.9, 4.5, 3.7, and 5.2 days for suture, staples, OCA, and staples + OCA, respectively; and the percentages of patients having antibiotic treatment were 12.93, 17.51, 11.14, and 23.72. There were overall differences in adjusted mean LOS, mean total cost, and antibiotic treatment (p < 0.0001). Pairwise comparisons indicated no difference between sutures and OCA, whereas the outcomes for each of the non-staple groups were more favorable than those for the staple group (p < 0.01). Results were similar in adjusted comparisons, with pairwise comparisons between OCA and staples at or near the threshold for significance. CONCLUSIONS: 2-octyl cyanoacrylate appears to be a safe and cost-effective alternative to topical sutures for patients having total abdominal hysterectomy. There were less favorable outcomes in groups receiving staples.

Predicted risk of diabetes and coronary heart disease in patients with schizophrenia: aripiprazole versus standard of care.

OBJECTIVE: Patients with schizophrenia are at increased risk of developing diabetes mellitus and cardiovascular disease. Furthermore, some atypical antipsychotics are associated with metabolic disturbances, which augment the risk for these comorbid conditions. In clinical trials, effects on metabolic parameters with aripiprazole are similar to those with placebo and superior to those with olanzapine, and the Schizophrenia Trial of Aripiprazole (STAR) demonstrated comparable efficacy of aripiprazole versus standard of care (SoC; physicians' selection of quetiapine, olanzapine, or risperidone). METHOD: In this post hoc analysis, data from STAR were used to assess the risks of diabetes and coronary heart disease (CHD) in patients with schizophrenia. The Stern (San Antonio Heart Disease Study) and Framingham models, with modifications, were used to predict the risk of diabetes at 7.5 years and CHD at 10 years, respectively. RESULTS: Aripiprazole-treated patients had more favorable changes in lipids, glucose, and body weight versus SoC. In a subsample of patients who had fasting lipid and glucose test results, the Stern model predicted 23.4 fewer incidences of new-onset diabetes with aripiprazole versus SoC in a hypothetical 1000-patient cohort. The number needed to treat with aripiprazole to avoid 1 adverse outcome expected with SoC was 43. In the same population, the Framingham model predicted 3.9 fewer CHD events, with a number needed to treat with aripiprazole of 256. CONCLUSION: Aripiprazole-treated patients had more favorable changes in metabolic parameters compared with SoC, leading to a reduced risk of diabetes and CHD, based on validated models.

Somnolence effects of antipsychotic medications and the risk of unintentional injury.

PURPOSE: This study examined the relationship between antipsychotic medications, categorized by published somnolence effects, and unintentional injury (UI). METHODS: The study population included patients of 18-64 years of age in a healthcare insurance database with claims from 2001 to 2004 and diagnoses of schizophrenia or affective disorder. A nested case-control design was used with cases defined by an E-code claim (a specified external cause of injury) for selected UIs. For cases, the index date referred to the first injury. For controls, the "control index date" was the date of claim if there was only a single medical claim; for patients with > or =2 claims, one was selected at random as the "control index date." Both groups had a prescription for a first-generation antipsychotic (FGA) or second-generation antipsychotic (SGA) overlapping the index date. Potential somnolence effects were defined as: low (referent)--aripiprazole/ziprasidone; medium--risperidone; high--olanzapine/quetiapine: or any single FGA. Logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) for UI, adjusted for gender, age, concomitant drug, and psychiatric diagnosis. RESULTS: Among 648 cases and 5214 controls, high-somnolence SGAs were associated with an OR of 1.41 95%CI (1.03-1.93) for risk of UI, while medium-somnolence SGAs, and FGAs had ORs of 1.17 95%CI (0.83-1.64) and 1.17 95%CI (0.79-1.74), respectively. When quetiapine and olanzapine were disaggregated, ORs were 1.61 95%CI (1.15-2.25) and 1.25 95%CI (0.89-1.74), respectively. CONCLUSIONS: High-somnolence SGAs may lead to UI among patients. When prescribing antipsychotics, clinicians should consider potential somnolence.

Risk of amputation in patients with diabetic foot ulcers: a claims-based study.

The objective of this study was to undertake a retrospective analysis of claims data of diabetic foot ulcer (DFU) patients to determine the rates of amputation and identify the risk and protective factors. Rates of amputation were calculated in patients diagnosed with DFU in the MEDSTAT Marketscan database between January 2000 and December 2002, who had prediagnosis coverage of 90 days. A nested case-control study was conducted using a 1 : 10 ratio of amputee cases to randomly selected nonamputee controls matched on follow-up days. The association of co-morbid conditions, demographic factors, and severity (5+ outpatient claims for DFU) on amputation was estimated by adjusted odds ratios (AOR) with 95% confidence intervals (CIs). The 5911 eligible patients yielded an incidence density rate of 2.30 amputations per 100 person years (95% CI = 1.91, 2.77). The 116 cases and 1153 controls averaged 307.3 and 308.5 observation days, respectively. Amputation was significantly increased by male gender (AOR 1.98), Charlson co-morbidity scores of 4-5 and 6+ (AOR = 2.89 and 5.36, respectively), renal disease (AOR = 2.11), peripheral vascular disease (AOR = 2.67), and 5+ outpatient DFU services (AOR = 2.17). Practitioners may consider more aggressive care and earlier referral to specialists for DFU patients who fit risk profiles for amputation, which include peripheral vascular disease, multiple co-morbid conditions, and repeated outpatient DFU services.

Health-related quality of life for caregivers of patients with Alzheimer disease.

We investigated the relationship of caregivers' health-related quality of life (HRQOL) to the burden of caring for patients with Alzheimer disease (AD) and resource utilization. Caregiver HRQOL was assessed using the SF-12 Mental and Physical Summary scores. Compared with a normative, age-adjusted sample, the 2477 caregivers had lower mental and physical scores (for the latter, only those <54 years of age). Increased caregiver mental functioning was associated with caregiver support and perceived quality of patient medical care, fewer hours of caregiving, and fewer patient behavioral symptoms. The burden of caregiving has substantial effects on HRQOL. Interventions that improve AD status and reduce caregiving hours have the potential to improve caregivers' HRQOL.

Sleep-related outcomes in persons with mild to moderate Alzheimer disease in a placebo-controlled trial of galantamine.

STUDY OBJECTIVES: To recognize the potential effect of acetylcholinesterase-inhibiting medications on sleep quality when used for the treatment of mild to moderate Alzheimer disease and describe sleep outcomes for patients treated with galantamine. DESIGN: This study examined sleep quality among individuals with mild to moderate Alzheimer disease using data from a 3-month, double-blind, flexible-dose trial of galantamine. The hypothesis was no difference in sleep quality between galantamine- and placebo-treated subjects. PATIENTS: 136 patients treated with galantamine 24 mg per day and 125 patients treated with placebo. MEASUREMENTS: Based on caregiver reports, the sleep-related outcome measures were the Pittsburgh Sleep Quality Index and the sleep disorders item from the Neuropsychiatric Inventory. Using a P-value of 0.05 (2-tailed), analysis of covariance was used to compare treatments on mean change from baseline to month 3 (Pittsburgh Sleep Quality Index) or mean score at month 3 (Neuropsychiatric Inventory), adjusted for baseline score and investigator. RESULTS: Both patient groups had an average age of 75 years and a mean Mini-Mental Status Examination score of 20. There were no significant differences between groups on the Pittsburgh Sleep Quality Index total (P=0.59) or subscales. For galantamine and placebo, the mean adjusted changes from baseline on the total Pittsburgh Sleep Quality Index were 0.01 and -0.17, respectively. There also was no difference on the Neuropsychiatric Inventory sleep score at month 3 (P=0.51). CONCLUSIONS: Medications to treat Alzheimer disease should maintain sleep quality and have a neutral effect on sleep. These results further confirm the lack of sleep problems associated with galantamine treatment.

Co-use of donepezil and hypnotics among Alzheimer's disease patients living in the community.

BACKGROUND: In clinical trials, sleep problems have been identified as side effects of donepezil, an acetylcholinesterase (AChE)-inhibiting medication for the treatment of Alzheimer's disease (AD). Poor sleep quality can exacerbate behavior problems among patients and add to the burden experienced by their caregivers. We examined the relationship between co-use of donepezil and hypnotics in a large sample of persons with AD living in the community. METHOD: This secondary data analysis used cross-sectional subjects from a multiwave, consumer-based survey of AD caregivers conducted in 1997 and 1998. Rates of hypnotic use among users and non-users of donepezil were compared using chi-square analysis for independent samples, and multivariate logistic regression was used to identify significant independent correlates of hypnotic use. RESULTS: A total of 2638 caregivers completed at least 1 study wave. Use of hypnotics was higher in the donepezil subgroup (9.78%) compared with subjects not taking this medication (3.93%). Multivariate analysis demonstrated that donepezil use was independently linked to increased hypnotic use after controlling for the potential confounding effects of disruptive behavior and depressive symptoms (adjusted odds ratio = 3.34, p <.001). CONCLUSION: In this large community sample, donepezil use was statistically linked to increased hypnotic use. Because sleep quality may be a critical issue for persons with AD and their caregivers, more rigorous evaluation of sleep problems linked to AChE-inhibitor treatment is indicated.