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21.

Objective

To determine whether differences in combination DTaP vaccine types at 2, 4 and 6?months of age were associated with mortality (all-cause or non-specific), within 30?days of vaccination.

Design

Observational nationwide cohort study.

Setting

Linked population data from the Australian Childhood Immunisation Register and National Death Index.

Participants

Australian infants administered a combination trivalent, quadrivalent or hexavalent DTaP vaccine (DTaP types) between January 1999 and December 2010 at 2, 4 and 6?months as part of the primary vaccination series. The study population included 2.9, 2.6, & 2.3?million children in the 2, 4 and 6?month vaccine cohorts, respectively.

Main outcome measures

Infants were evaluated for the primary outcome of all-cause mortality within 30?days. A secondary outcome was non-specific mortality (unknown cause of death) within 30?days of vaccination. Non-specific mortality was defined as underlying or other cause of death codes, R95 ‘Sudden infant death syndrome’, R96 ‘Other sudden death, cause unknown’, R98 ‘Unattended death’, R99 ‘Other ill-defined and unspecified cause of mortality’ or where no cause of death was recorded.

Results

The rate of 30?day all-cause mortality was low and declined from 127.4 to 59.3 deaths per 100,000 person-years between 2 and 6?month cohorts. When compared with trivalent DTaP vaccines, no elevated risk in all-cause or non-specific mortality was seen with any quadrivalent or hexavalent DTaP vaccines, for any cohort.

Conclusion

Use of routine DTaP combination vaccines with differing disease antigens administered during the first six months of life is not associated with infant mortality.  相似文献   
22.

Background

In a pooled analysis of the phase 3 Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT-I) and COMFORT-II clinical trials, adult patients with intermediate-2 or high-risk myelofibrosis who received oral ruxolitinib at randomization or after crossover from placebo or best available therapy (BAT) had improved overall survival (OS).

Methods

This post hoc analysis of pooled COMFORT data examined relevant disease outcomes based on the disease duration (≤12 or >12 months from diagnosis) before ruxolitinib initiation.

Results

The analysis included 525 patients (ruxolitinib: ≤12 months, n = 84; >12 months, n = 216; placebo/BAT: ≤12 months, n = 66; >12 months, n = 159); the median age was 65.0–70.0 years. Fewer thrombocytopenia and anemia events were observed among patients who initiated ruxolitinib treatment earlier. At Weeks 24 and 48, the spleen volume response (SVR) was higher for patients who initiated ruxolitinib earlier (47.6% vs. 32.9% at Week 24, p = .0610; 44.0% vs. 26.9% at Week 48, p = .0149). In a multivariable analysis of factors associated with spleen volume reduction, a logistic regression model that controlled for confounding factors found that a significantly greater binary reduction was observed among patients with shorter versus longer disease duration (p = .022). At Week 240, OS was significantly improved among patients who initiated ruxolitinib earlier (63% [95% CI, 51%‒73%] vs. 57% [95% CI, 49%‒64%]; hazard ratio, 1.53; 95% CI, 1.01‒2.31; p = .0430). Regardless of disease duration, a longer OS was observed for patients who received ruxolitinib versus those who received placebo/BAT.

Conclusions

These findings suggest that earlier ruxolitinib initiation for adult patients with intermediate-2 and high-risk myelofibrosis may improve clinical outcomes, including fewer cytopenia events, durable SVR, and prolonged OS.

Plain Language Summary

  • Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue.
  • Two large clinical trials showed that patients treated with the drug ruxolitinib lived longer and had improved symptoms compared to those treated with placebo or other standard treatments.
  • Here it was examined whether starting treatment with ruxolitinib earlier (i.e., within a year of diagnosis) provided benefits versus delaying treatment.
  • Patients who received ruxolitinib within a year of diagnosis lived longer and experienced fewer disease symptoms than those whose treatment was delayed.
  相似文献   
23.
In this review we summarize the impact of the various modalities of breast cancer therapy coupled with intrinsic patient factors on incidence of subsequent treatment-induced myelodysplasia and acute myelogenous leukemia (t-MDS/AML). It is clear that risk is increased for patients treated with radiation and chemotherapy at younger ages. Radiation is associated with modest risk, whereas chemotherapy, particularly the combination of an alkylating agent and an anthracycline, carries higher risk and radiation and chemotherapy combined increase the risk markedly. Recently, treatment with granulocyte colony-stimulating factor (G-CSF), but not pegylated G-CSF, has been identified as a factor associated with increased t-MDS/AML risk. Two newly identified associations may link homologous DNA repair gene deficiency and poly (ADP-ribose) polymerase inhibitor treatment to increased t-MDS/AML risk. When predisposing factors, such as young age, are combined with an increasing number of potentially leukemogenic treatments that may not confer large risk singly, the risk of t-MDS/AML appears to increase. Patient and treatment factors combine to form a biological cascade that can trigger a myelodysplastic event. Patients with breast cancer are often exposed to many of these risk factors in the course of their treatment, and triple-negative patients, who are often younger and/or BRCA positive, are often exposed to all of them. It is important going forward to identify effective therapies without these adverse associated effects and choose existing therapies that minimize the risk of t-MDS/AML without sacrificing therapeutic gain.

Implications for Practice

Breast cancer is far more curable than in the past but requires multimodality treatment. Great care must be taken to use the least leukemogenic treatment programs that do not sacrifice efficacy. Elimination of radiation and anthracycline/alkylating agent regimens will be helpful where possible, particularly in younger patients and possibly those with homologous repair deficiency (HRD). Use of colony-stimulating factors should be limited to those who truly require them for safe chemotherapy administration. Further study of a possible leukemogenic association with HRD and the various forms of colony-stimulating factors is badly needed.
  相似文献   
24.
ABSTRACT

Abortion is legal in South Africa, but negative abortion attitudes remain common and are poorly understood. We used nationally representative South African Social Attitudes Survey data to analyze abortion attitudes in the case of fetal anomaly and in the case of poverty from 2007 to 2016 (n = 20,711; ages = 16+). We measured correlations between abortion attitudes and these important predictors: religiosity, attitudes about premarital sex, attitudes about preferential hiring and promotion of women, and attitudes toward family gender roles. Abortion acceptability for poverty increased over time (b = 0.05, p < .001), but not for fetal anomaly (b = ?0.008, p = .284). Highly religious South Africans reported lower abortion acceptability in both cases (Odds Ratio (OR)anomaly = 0.85, p = .015; ORpoverty = 0.84, p = .02). Premarital sex acceptability strongly and positively predicted abortion acceptability (ORanomaly = 2.63, p < .001; ORpoverty = 2.46, p < .001). Attitudes about preferential hiring and promotion of women were not associated with abortion attitudes, but favorable attitudes about working mothers were positively associated with abortion acceptability for fetal anomaly ((ORanomaly = 1.09, p = .01; ORpoverty = 1.02, p = .641)). Results suggest negative abortion attitudes remain common in South Africa and are closely tied to religiosity, traditional ideologies about sexuality, and gender role expectations about motherhood.  相似文献   
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Background

Nursing Home Compare (NHC) ratings, created and maintained by Medicare, are used by both hospitals and consumers to aid in the skilled nursing facility (SNF) selection process. To date, no studies have linked NHC ratings to actual episode-based outcomes. The purpose of this study was to evaluate whether NHC ratings are valid predictors of 90-day complications, readmission, and bundle costs for patients discharged to an SNF after primary total joint arthroplasty (TJA).

Methods

All SNF-discharged primary TJA cases in 2017 at a multihospital academic health system were queried. Demographic, psychosocial, and clinical variables were manually extracted from the health record. Medicare NHC ratings were then collected for each SNF. For patients in the Medicare bundle, postacute and total bundle cost was extracted from claims.

Results

Four hundred eighty-eight patients were discharged to a total of 105 unique SNFs. In multivariate analysis, overall NHC rating was not predictive of 90-day readmission/major complications, >75th percentile postacute cost, or 90-day bundle cost exceeding the target price. SNF health inspection and quality measure ratings were also not predictive of 90-day readmission/major complications or bundle performance. A higher SNF staffing rating was independently associated with a decreased odds for >75th percentile 90-day postacute spend (odds ratio, 0.58; P = .01) and a 90-day bundle cost exceeding the target price (odds ratio = 0.69; P = .02) but was similarly not predictive of 90-day readmission/complications.

Conclusion

Results of our study suggest that Medicare's NHC tool is not a useful predictor of 90-day costs, complications, or readmissions for SNFs within our health system.  相似文献   
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