Decline in Pneumococcal Disease Attenuated in Older Adults and Those With Comorbidities Following Universal Childhood PCV13 Immunization.

BACKGROUND: Following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in the United States, epidemiology of pneumococcal disease shifted such that disease incidence in the elderly exceeded that in children. We evaluated the impact of replacing PCV7 with PCV13 on disease burden in adults and identified age/risk-specific subgroups with the highest remaining disease burden. METHODS: A retrospective design and data from two US healthcare claims repositories were used. Study population included adults aged ≥18 years and was stratified by age (18-49, 50-64, 65-74, ≥75) and risk profile (healthy, at-risk, high-risk). Rate ratios comparing invasive pneumococcal disease (IPD), all-cause hospitalized pneumonia (ACHP), and pneumococcal pneumonia requiring hospitalization among at-risk and high-risk adults vs healthy counterparts were estimated for 2007-2010 (pre-PCV13), 2011-2012 (peri-PCV13), and 2013-2015 (post-PCV13). RESULTS: Across study periods, IPD and ACHP rates increased with age (2-27 times higher in persons ≥75 vs 18-49) and comorbidity (4-20 times higher in high-risk vs healthy). From pre- to post-PCV13 period, IPD rates declined 5%-48% and ACHP rates declined 4%-19% across age and risk groups (ACHP did not decline in persons ≥75). Decline in IPD and ACHP was attenuated among older adults and those with comorbidities. Accordingly, rate ratios among at-risk and high-risk persons (vs healthy counterparts) increased during the peri- and post-PCV13 periods compared with the pre-PCV13 period. CONCLUSIONS: The switch to PCV13 was associated with large declines in pneumococcal disease among US adults. However, the decline was attenuated with increasing age (and, for ACHP, was absent in persons ≥75) and in those with comorbidities.

Use and effectiveness of pegfilgrastim prophylaxis in US clinical practice:a retrospective observational study.

BACKGROUND: Febrile neutropenia (FN) is a serious complication of myelosuppressive chemotherapy. Clinical practice guidelines recommend routine prophylactic coverage with granulocyte colony-stimulating factor (G-CSF)-such as pegfilgrastim-for most patients receiving chemotherapy with an intermediate to high risk for FN. Patterns of pegfilgrastim prophylaxis during the chemotherapy course and associated FN risks in US clinical practice have not been well characterized. METHODS: A retrospective cohort design and data from two commercial healthcare claims repositories (01/2010-03/2016) and Medicare Claims Research Identifiable Files (01/2007-09/2015) were employed. Study population included patients who had non-metastatic breast cancer or non-Hodgkin's lymphoma and received intermediate/high-risk regimens. Pegfilgrastim prophylaxis use and FN incidence were ascertained in each chemotherapy cycle, and all cycles were pooled for analyses. Adjusted odds ratios for FN were estimated for patients who did versus did not receive pegfilgrastim prophylaxis in that cycle. RESULTS: Study population included 50,778 commercial patients who received 190,622 cycles of chemotherapy and 71,037 Medicare patients who received 271,944 cycles. In cycle 1, 33% of commercial patients and 28% of Medicare patients did not receive pegfilgrastim prophylaxis, and adjusted odds of FN were 2.6 (95% CI 2.3-2.8) and 1.6 (1.5-1.7), respectively, versus those who received pegfilgrastim prophylaxis. In cycle 2, 28% (commercial) and 26% (Medicare) did not receive pegfilgrastim prophylaxis; corresponding adjusted FN odds were comparably elevated (1.9 [1.6-2.2] and 1.6 [1.5-1.8]). Results in subsequent cycles were similar. Across all cycles, 15% of commercial patients and 23% of Medicare patients did not receive pegfilgrastim prophylaxis despite having FN in a prior cycle, and prior FN increased odds of subsequent FN by 2.1-2.4 times. CONCLUSIONS: Notwithstanding clinical practice guidelines, a large minority of patients did not receive G-CSF prophylaxis, and FN incidence was substantially higher among this subset of the population. Appropriate use of pegfilgrastim prophylaxis may reduce patient exposure to this potentially fatal but largely preventable complication of myelosuppressive chemotherapy.

Use of colony-stimulating factor primary prophylaxis and incidence of febrile neutropenia from 2010 to 2016: a longitudinal assessment.

BACKGROUND: Guidelines recommend primary prophylactic use of colony-stimulating factor (PP-CSF) when risk of febrile neutropenia (FN) - based on chemotherapy and patient risk factors - is high. Whether and how PP-CSF use may have changed over time (e.g. due to guideline revisions, increasing use of myelosuppressive regimens, controversy regarding inappropriate CSF use), and whether there has been a concomitant change in the incidence of FN, is unknown. METHODS: A retrospective cohort design and data from two US healthcare claims repositories were employed. The study population included patients who had non-metastatic cancer of the breast, colon/rectum, lung or ovaries, or non-Hodgkin's lymphoma (NHL), and who received myelosuppressive chemotherapy regimens with an intermediate/high risk for FN. For each patient, the first cycle of the first course was characterized in terms of PP-CSF use and FN episodes. Crude incidence proportions for PP-CSF and FN during the first cycle were estimated by calendar quarter (2010-2016); multivariable logistic regression models were used to estimate quarter-specific adjusted mean probabilities of FN by PP-CSF use. RESULTS: The study population totaled 142,730 patients with breast cancer (61%), colorectal cancer (14%), NHL (11%), ovarian cancer (10%) or lung cancer (5%). PP-CSF use increased from 52% in 1Q2010 to 58% in 4Q2016; pegfilgrastim was the most commonly used agent (>96% across quarters). PP-CSF administration on the same day as chemotherapy ranged from 8 to 11% until 1Q2015, and increased to 64% by 4Q2016. Adjusted incidence proportions for FN in the first chemotherapy cycle ranged from 2.7% (95% CI: 2.3-3.0) to 3.7% (95% CI: 3.1-4.3) among those who did not receive PP-CSF, and was 2.6% (95% CI: 2.5-2.7) across quarters among those who received PP-CSF. CONCLUSIONS: Although the use of PP-CSF is commonplace in current US clinical practice, underutilization in cancer patients receiving chemotherapy regimens with an intermediate/high risk for FN may still be an issue. Use of same-day PP-CSF increased markedly from the end of 2015, although this finding reflects (at least in part) increased uptake of pegfilgrastim delivered via an on-body injector as well as the recent change in clinical practice guidelines. Overall, patients receiving PP-CSF appear to have a lower risk of FN during the first cycle of chemotherapy.

Mean arterial pressure and mortality in patients with distributive shock: a retrospective analysis of the MIMIC-III database.

BACKGROUND: Maintenance of mean arterial pressure (MAP) at levels sufficient to avoid tissue hypoperfusion is a key tenet in the management of distributive shock. We hypothesized that patients with distributive shock sometimes have a MAP below that typically recommended and that such hypotension is associated with increased mortality. METHODS: In this retrospective analysis of the Medical Information Mart for Intensive Care (MIMIC-III) database from Beth Israel Deaconess Medical Center, Boston, USA, we included all intensive care unit (ICU) admissions between 2001 and 2012 with distributive shock, defined as continuous vasopressor support for ≥ 6 h and no evidence of low cardiac output shock. Hypotension was evaluated using five MAP thresholds: 80, 75, 65, 60 and 55 mmHg. We evaluated the longest continuous episode below each threshold during vasopressor therapy. The primary outcome was ICU mortality. RESULTS: Of 5347 patients with distributive shock, 95.7%, 91.0%, 62.0%, 36.0% and 17.2%, respectively, had MAP < 80, < 75, < 65, < 60 and < 55 mmHg for more than two consecutive hours. On average, ICU mortality increased by 1.3, 1.8, 5.1, 7.9 and 14.4 percentage points for each additional 2 h with MAP < 80, < 75, < 65, < 60 and < 55 mmHg, respectively. Multivariable logistic modeling showed that, compared to patients in whom MAP was never < 65 mmHg, ICU mortality increased as duration of hypotension < 65 mmHg increased [for > 0 to < 2 h, odds ratio (OR) 1.76, p = 0.005; ≥ 6 to < 8 h, OR 2.90, p < 0.0001; ≥ 20 h, OR 7.10, p < 0.0001]. When hypotension was defined as MAP < 60 or < 55 mmHg, the associations between duration and mortality were generally stronger than when hypotension was defined as MAP < 65 mmHg. There was no association between hypotension and mortality when hypotension was defined as MAP < 80 mmHg. CONCLUSIONS: Within the limitations due to the nature of the study, most patients with distributive shock experienced at least one episode with MAP < 65 mmHg lasting > 2 h. Episodes of prolonged hypotension were associated with higher mortality.

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis based on real-world data from 2010 to 2015.

OBJECTIVE: Evidence suggests that not all cancer chemotherapy patients who receive first-cycle pegfilgrastim prophylaxis (PP) continue to receive it in later cycles, and that these patients may be subsequently at higher risk of febrile neutropenia (FN). Available evidence, however, may not be reflective of current clinical practice. We undertook an evaluation to estimate the odds of FN, beginning with second chemotherapy cycle, among patients who received PP in that cycle and all previous cycles versus those who received PP in all previous cycles only, using recent real-world data. METHODS: A matched-cohort design and data from two US healthcare claims repositories (2010-2015) were employed. The source population comprised cancer patients who received intermediate/high-risk chemotherapy and first-cycle PP. From the source population, beginning with the second cycle, all patients who received PP in all previous cycles were identified. From this subset, patients who did not receive PP in the cycle of interest ("comparison patients") were matched to those who received PP in that cycle ("PP patients"); the same process was repeated for subsequent cycles. Odds ratios (ORs) for FN (broad and narrow definitions) were estimated using generalized estimating equations. RESULTS: Among 47,254 patients in the source population, 9% did not receive second-cycle PP and were matched to those who did. FN odds in cycle 2 were significantly higher among comparison patients versus PP patients (OR [broad definition]: 1.7, p < .001); OR [narrow definition]: 4.3, p < .001). Results for subsequent cycles and for the last cycle, respectively, were comparable (OR [range, broad definition]: 1.6 to 3.1, p < .001 for all; OR [range, narrow definition]: 2.7 to 11.8, p < .001 for all). CONCLUSIONS: In this real-world evaluation of cancer chemotherapy patients who received first-cycle PP, FN risk was substantially higher among patients who did not receive PP in subsequent cycles versus those who continued PP.

Risk of chemotherapy-induced febrile neutropenia by day of pegfilgrastim prophylaxis in US clinical practice from 2010 to 2015.

OBJECTIVE: Pegfilgrastim prophylaxis (PP) is recommended 1-3 days following administration of chemotherapy during the cycle. Some patients, however, receive PP before or after the recommended timing. While evidence suggests that risk of febrile neutropenia (FN) may be lower when PP is administered per recommendation, such evidence is based on older data. We undertook a new study to compare FN risk between patients who received PP on the last day of chemotherapy ("day 0") or 4-5 days following chemotherapy ("days 4-5"), versus 1-3 days following chemotherapy ("days 1-3"), using recent data from US clinical practice. METHODS: A retrospective cohort design and data from two US private healthcare claims repositories (2010-2016) were employed. Patients received intermediate/high-risk chemotherapy regimens for solid tumors or non-Hodgkin's lymphoma, and PP in ≥1 cycle; all cycles with PP were pooled for analyses. Adjusted odds ratios (OR) for FN during the cycle were estimated for patients who received PP on day 0 or days 4-5, vs. days 1-3, using generalized estimating equations. RESULTS: The study population included 53,814 patients who received PP in 217,273 cycles; in 9% of cycles, patients received PP on day 0 (8%) or days 4-5 (<1%). Odds of FN in cycle 1 were significantly higher among patients receiving PP on day 0 (OR: 1.4 [95% CI: 1.2-1.7]) or days 4-5 (1.9 [1.2-3.0]), vs. days 1-3, in that cycle. Results for subsequent cycles of chemotherapy were comparable to those for the first cycle. CONCLUSIONS: In this large-scale retrospective evaluation of cancer chemotherapy patients receiving PP in recent US clinical practice, PP was administered before or after the recommended timing in 9% of cycles. FN incidence was significantly higher in these cycles providing additional real-world evidence that PP should be administered the day after chemotherapy in alignment with recently updated US practice guidelines.