Antibiotic resistance of urinary tract infection recurrences in a large U.S. integrated health care system.

BACKGROUND: Data on antibiotic resistance of uropathogens for UTI recurrences are lacking. METHODS: In a retrospective cohort of adults at Kaiser Permanente Southern California with culture-confirmed index uncomplicated UTI (uUTI) between 01/2016 and 12/2020, we examined the number and characteristics of subsequent culture-confirmed UTIs through 2021. RESULTS: We identified 148,994 individuals with a culture-confirmed index uUTI (88% female, 44% Hispanic, mean age 51 years [s.d. 19]), of whom 19% developed a subsequent culture-confirmed UTI after a median 300 days (IQR: 126-627). The proportion of UTI due to E. coli was highest for index uUTI (79%) and decreased to 73% for sixth UTI (UTI 6) (p-for trend <0.001), while the proportion due to Klebsiella spp increased from index UTI (7%) to UTI 6 (11%) (p-for-trend <0.001). Non-susceptibility to ≥1 and ≥3 antibiotic classes was observed in 57% and 13% of index uUTIs, respectively, and was higher for subsequent UTIs (65% and 20%, respectively, for UTI 6). Most commonly observed antibiotic non-susceptibility patterns included penicillins alone (12%), and penicillins, trimethoprim-sulfamethoxazole plus ≥1 additional antibiotic class (9%). CONCLUSIONS: Antibiotic non-susceptibility is common in UTIs and increases with subsequent UTIs. Continuous monitoring of UTI recurrences and susceptibility patterns are needed to guide treatment decisions.

Effects of ketorolac on complications and postoperative pancreatic fistula in patients undergoing pancreatectomy.

BACKGROUND: There are conflicting data on the risk of postoperative pancreatic fistula (POPF) associated with postoperative NSAID use. The primary objective of this multi-center retrospective study was to assess the relationship between ketorolac use and POPF. The secondary objective was to assess for effect of ketorolac use on overall complication rate. METHODS: Retrospective chart review of patients undergoing pancreatectomy from January 1, 2005-January 1, 2016 was performed. Data on patient factors (age, sex, comorbidities, previous surgical history etc.), operative factors (surgical procedure, estimated blood loss, pathology etc.), and outcomes (morbidities, mortality, readmission, POPF) were collected. The cohort was compared based on ketorolac use. RESULTS: The study included 464 patients. Ninety-eight (21%) patients received ketorolac during the study period. Ninety-six (21%) patients were diagnosed with POPF within 30 days. There was a significant association between ketorolac use and clinically relevant POPF (21.4 vs. 12.7%) (p = 0.04, 95% CI [1.76, 1.04-2.97]). There was no significant difference in overall morbidity or mortality between the groups. DISCUSSION: Though there was no overall increase in morbidity, there was a significant association between POPF and ketorolac use. The use of ketorolac after pancreatectomy should be judicious.

Urinary Tract Infections After Urogynecologic Surgery: Risk Factors, Timeline, and Uropathogens.

IMPORTANCE: Urinary tract infection (UTI) is a common and potentially avoidable postoperative (PO) adverse event after urogynecologic surgery. Understanding pathophysiology will help prevent the associated morbidity of the disease and treatment of PO-UTI. OBJECTIVE: The objective of this study is to determine the following: (1) risk factors for both PO-UTI and PO recurrent UTI (RUTI) after urogynecologic surgery, (2) temporal distribution of UTI, and (3) uropathogen identification. STUDY DESIGN: Women undergoing urogynecologic surgery were retrospectively reviewed. Urinary tract infection was defined by culture or antibiotic prescription for symptoms. Recurrent UTI was defined as occurring outside a 6-week perioperative period. The χ 2 test or Fischer exact and Student t tests or Mann-Whitney U test were used as appropriate. Individual odds ratio (OR), 95% confidence interval [CI], and sequential multivariable logistic regression were calculated. Statistical significance was set at P < 0.05. RESULTS: The 6-week PO-UTI rate after 33,626 procedures was 12.9%. Recurrent UTI increased from 3.7% preoperatively to 4.4% postoperatively ( P < 0.001). A 6-week preoperative UTI and RUTI increased the risk of 6-week PO-UTI (OR, 1.65; 95% CI < 1.26-2.16; P = 0.001 and OR, 2.19; 95% CI, 1.84-2.62; P < 0.001, respectively) and PO-RUTI (OR, 2.95; 95% CI, 2.11-4.11; P < 0.001 and OR, 6.79; 95% CI, 5.61-8.23; P < 0.001, respectively). Compared with pelvic organ prolapse (POP) surgery only, stress urinary incontinence (SUI) surgery (OR 1.57[1.30-1.89]), and combined POP/SUI surgery (OR, 1.36; 95% CI, 1.13-1.63]) increased the risk of PO-RUTI ( P < 0.001). Urinary tract infection within 1 week preoperatively was protective against 6-week PO-UTI (OR, 0.68; 95% CI, 0.48-0.97; P = 0.035). No perioperative factors were protective of PO-RUTI. CONCLUSIONS: The PO-RUTI rate in the first year after urogynecologic surgery is low; however, SUI procedures may increase PO-RUTI risk. Potentially, modifiable risk factors for both PO-UTI and PO-RUTI include UTI diagnosis within 6 weeks preoperatively or preoperative RUTI diagnosis. Retesting women the week before surgery to ensure adequate treatment of preoperative UTI may reduce 6-week PO-UTI.

Prevention of Neisseria gonorrhoeae With Meningococcal B Vaccine: A Matched Cohort Study in Southern California.

BACKGROUND: Neisseria gonorrhoeae is acquiring increasing resistance to available oral antibiotics, and current screening and treatment approaches have not decreased gonorrhea incidence. Although a gonorrhea-specific vaccine does not exist, N. gonorrhoeae shares much of its genome with Neisseria meningitidis, notably critical antigenic determinants including outer membrane vesicles (OMV). Prior observational studies have suggested that OMV-based meningococcal serogroup B vaccines confer protection against gonorrhea. METHODS: We conducted a matched cohort study from 2016 to 2020 to examine the association of OMV-containing recombinant meningococcal serogroup B vaccine (4CMenB) with gonorrhea infection among teens and young adults at Kaiser Permanente Southern California. Recipients of 4CMenB were matched in a ratio of 1:4 to recipients of non-OMV-containing polysaccharide-conjugate vaccine targeting serotypes A, C, W, and Y (MenACWY) who had not received 4CMenB and were followed for incident gonorrhea. We used Cox proportional hazards regression to compare gonorrhea rates among recipients of 4CMenB vs MenACWY, adjusting for potential confounders. We conducted the same analysis with chlamydia as a negative control outcome. RESULTS: The study included 6641 recipients of 4CMenB matched to 26 471 recipients of MenACWY. During follow-up, gonorrhea incidence rates per 1000 person-years (95% confidence intervals [CIs]) were 2.0 (1.3-2.8) for recipients of 4CMenB and 5.2 (4.6-5.8) for recipients of MenACWY. In adjusted analyses, gonorrhea rates were 46% lower among recipients of 4CMenB vs MenACWY (hazard ratio [HR], 0.54; 95% CI, .34-.86), but chlamydia rates were similar between vaccine groups (HR, 0.98; 95% CI, .82-1.17). CONCLUSIONS: These results suggest cross-protection of 4CMenB against gonorrhea, supporting the potential for vaccination strategies to prevent gonorrhea.

The Influence of Medical Comorbidities on Survival Disparities in a Multiethnic Group of Patients with De Novo Metastatic Breast Cancer.

BACKGROUND: The influence of common medical comorbidities on mortality and racial/ethnic disparities in mortality among women with metastatic breast cancer remains largely unknown. METHODS: In this longitudinal study, women with newly diagnosed stage IV breast cancer were identified in a large, diverse, integrated healthcare delivery system from January 2009 to December 2017 (n = 995) and followed through December 31, 2018, for all-cause (overall) and breast cancer-specific mortality via electronic health records. We computed overall and breast cancer-specific mortality rates by race/ethnicity and Elixhauser comorbidity index (ECI). Multivariable-adjusted hazard ratios (HR) assessing the influence of race/ethnicity and comorbidity status on overall and breast cancer-specific mortality were estimated using proportional hazards regression adjusted for age, breast cancer subtype, geocoded income, and palliative cancer treatments. RESULTS: Nearly 17% of this cohort had diabetes and 45% had hypertension. Overall, 644 deaths occurred in the cohort (median follow-up time of 1.8 years), of which 88% were breast cancer related. The risk of overall mortality was increased in Asian/Pacific Islander (PI; adjusted HR = 1.45; 95% CI, 1.10-1.92) and African American/Black women (adjusted HR = 1.34; 95% CI, 1.02-1.76) when compared with white women. Women with more comorbidities (ECI ≥ 5) had more than 3-fold higher overall mortality rate than those without any comorbidities [602/1,000 person-year (PY) vs. 175/1,000 PY]. Similar associations were found for breast cancer-specific mortality. CONCLUSIONS: Medical comorbidities are associated with an increased risk of overall mortality among women with de novo metastatic disease and may influence racial/ethnic disparities in mortality. IMPACT: Optimizing the management of medical comorbidities in metastatic breast cancer patients may also help reduce disparities in breast cancer-related mortality.

Brief Report: COVID-19 Testing, Characteristics, and Outcomes Among People Living With HIV in an Integrated Health System.

BACKGROUND: Understanding the attributes of COVID-19 clinical severity among people living with HIV (PLWH) compared with those in HIV-uninfected patients is critical for risk stratification and treatment strategies. METHODS: We conducted a retrospective study at Kaiser Permanente Southern California among PLWH aged 18 years or older. We compared the incidence of SARS-CoV-2 molecular testing, COVID-19 diagnosis, and COVID-19 hospitalization among PLWH and HIV-uninfected adults. A chart review was conducted for PLWH with COVID-19 to examine viral suppression of HIV and most recent CD4+ counts in the year before COVID-19 diagnosis, known exposures to COVID-19, and clinical presentation. RESULTS: Between March 1, 2020, and May 31, 2020, the incidence of SARS-CoV-2 molecular testing, COVID-19 diagnosis, and COVID-19 hospitalization was 551.2, 57.0, and 9.3 per 10,000 PLWH, respectively, compared with 268.4, 34.6, and 5.3 per 10,000 HIV-uninfected individuals, respectively. Among those with COVID-19, the distribution of race/ethnicity, smoking status, and comorbidities was similar in PLWH and HIV-uninfected patients; however, PLWH were mostly men, younger, and less obese than HIV-uninfected individuals. Health care utilization regarding emergency care and hospitalizations in the year before COVID-19-related hospitalization was similar between the groups. Overall, HIV was virologically suppressed in >95% of PLWH with COVID-19, and HIV viral load and CD4+ status did not differ between hospitalized and nonhospitalized patients. CONCLUSIONS: In this population of patients with well-controlled HIV infection, the incidence of testing, diagnosis, and hospitalization for COVID-19 was higher in PLWH than that in HIV-uninfected patients.

Outcomes of adult patients in the intensive care unit with Pseudomonas aeruginosa pneumonia who received an active anti-pseudomonal ß-lactam: Does "S" equal success in the presence of resistance to other anti-pseudomonal ß-lactams?

STUDY OBJECTIVES: The most commonly prescribed antibiotics for patients with hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) due to Pseudomonas aeruginosa are the conventional anti-pseudomonal ß-lactams (APBLs) (ie, ceftazidime, cefepime, meropenem, or piperacillin-tazobactam). Similar resistance mechanisms in P. aeruginosa affect the APBLs, and it is unclear if resistance to one APBL can affect the effectiveness of other APBLs. This exploratory, hypothesis-generating analysis evaluates the impact of APBL resistance among patients in the intensive care unit (ICU) with P. aeruginosa HABP/VABP who initially receive a microbiologically active APBL. DESIGN: A retrospective cohort [GJ1] [LT2] study. SETTING: Kaiser Permanente Southern California members (01/01/2011-12/31/2017). PATIENTS: The study included adult patients admitted to the ICU with a monomicrobial P. aeruginosa HABP/VABP who received a microbiologically active APBL within 2 days of index P. aeruginosa respiratory culture. INTERVENTION: Patients were stratified by presence of resistance to APBL on index P. aeruginosa (0 vs. ≥1 resistant APBL). MEASUREMENTS: Primary outcomes were 30-day mortality and discharge to home. MAIN RESULTS: Overall, 553 patients were included. Thirty-day mortality was 28%, and 32% of patients were discharged home. Eighty-eight patients (16%) had a P. aeruginosa HABP/VABP that was resistant to ≥1 APBL (other than active empiric treatment). Relative to patients with no APBL resistance, patients with resistance to ≥1 APBL had a higher 30-day mortality (adjusted odds ratio (aOR) [95% confidence interval (CI)]: 1.65 [1.02-2.66]) and were less likely to be discharged home (adjusted hazard ratio (aHR) [95% CI]: 0.50 [0.29-0.85]). CONCLUSION: Further study is needed, but this exploratory analysis suggests that the full APBL susceptibility profile should be considered when selecting therapy for patients with P. aeruginosa HABP/VABP.

Adverse Reactions Associated with Penicillins, Carbapenems, Monobactams, and Clindamycin: A Retrospective Population-based Study.

BACKGROUND: Limited population-based data on penicillin-, carbapenem-, monobactam-, and clindamycin-associated reported adverse reactions exist. OBJECTIVE: To collect data on penicillin, carbapenem, monobactam, and clindamycin usage and associated adverse reactions. METHODS: Data from January 1, 2009, to December 31, 2017, in Kaiser Permanente Southern California were collected. RESULTS: There were 6,144,422 unique individuals, mean age 33.6 ± 21.1 years, 52.2% females, with at least 1 health care visit during the 9-year study interval, for a total of 37,387,313 patient-years of follow-up. This population was exposed to 5,617,402 courses of oral penicillins, 370,478 courses of parenteral penicillins, 59,645 courses of parenteral carbapenems or monobactams, 817,232 courses of oral clindamycin, and 215,880 courses of parenteral clindamycin. New penicillin allergies were reported more commonly after parenteral (0.85%) compared with oral (0.74%) exposures (P < .0001). There were 22 cases (1 in 255,320) of oral penicillin-associated anaphylaxis and 3 cases (1 in 123,792) of parenteral penicillin-associated anaphylaxis (P < .001). There were 2 clindamycin-associated anaphylaxis cases, 1 (1 in 817,232) oral and 1 (1 in 215,880) parenteral. There were 2 (1 in 2,993,940) penicillin-associated serious cutaneous adverse reaction (SCAR) cases, but both also had co-trimoxazole coexposure within 45 days. There was 1 (1 in 1,033,112) clindamycin-associated SCAR. Clostridioides difficile infection was more common after parenteral exposures, and with extended-spectrum penicillins, beta-lactamase combinations, carbapenems, monobactam, and clindamycin exposures compared with oral penicillins or clindamycin. CONCLUSIONS: Only 1 of 1543 (0.065%) oral and 1 of 1030 (0.097%) parenteral penicillin-associated allergy reports were confirmed to be anaphylaxis. C. difficile was more common after parenteral versus oral penicillin, carbapenem, monobactam, and clindamycin exposures, and with broader spectrum antibiotic exposures.

The prevalence of MS in the United States: A population-based estimate using health claims data.

OBJECTIVE: To generate a national multiple sclerosis (MS) prevalence estimate for the United States by applying a validated algorithm to multiple administrative health claims (AHC) datasets. METHODS: A validated algorithm was applied to private, military, and public AHC datasets to identify adult cases of MS between 2008 and 2010. In each dataset, we determined the 3-year cumulative prevalence overall and stratified by age, sex, and census region. We applied insurance-specific and stratum-specific estimates to the 2010 US Census data and pooled the findings to calculate the 2010 prevalence of MS in the United States cumulated over 3 years. We also estimated the 2010 prevalence cumulated over 10 years using 2 models and extrapolated our estimate to 2017. RESULTS: The estimated 2010 prevalence of MS in the US adult population cumulated over 10 years was 309.2 per 100,000 (95% confidence interval [CI] 308.1-310.1), representing 727,344 cases. During the same time period, the MS prevalence was 450.1 per 100,000 (95% CI 448.1-451.6) for women and 159.7 (95% CI 158.7-160.6) for men (female:male ratio 2.8). The estimated 2010 prevalence of MS was highest in the 55- to 64-year age group. A US north-south decreasing prevalence gradient was identified. The estimated MS prevalence is also presented for 2017. CONCLUSION: The estimated US national MS prevalence for 2010 is the highest reported to date and provides evidence that the north-south gradient persists. Our rigorous algorithm-based approach to estimating prevalence is efficient and has the potential to be used for other chronic neurologic conditions.

Validation of an algorithm for identifying MS cases in administrative health claims datasets.

OBJECTIVE: To develop a valid algorithm for identifying multiple sclerosis (MS) cases in administrative health claims (AHC) datasets. METHODS: We used 4 AHC datasets from the Veterans Administration (VA), Kaiser Permanente Southern California (KPSC), Manitoba (Canada), and Saskatchewan (Canada). In the VA, KPSC, and Manitoba, we tested the performance of candidate algorithms based on inpatient, outpatient, and disease-modifying therapy (DMT) claims compared to medical records review using sensitivity, specificity, positive and negative predictive values, and interrater reliability (Youden J statistic) both overall and stratified by sex and age. In Saskatchewan, we tested the algorithms in a cohort randomly selected from the general population. RESULTS: The preferred algorithm required ≥3 MS-related claims from any combination of inpatient, outpatient, or DMT claims within a 1-year time period; a 2-year time period provided little gain in performance. Algorithms including DMT claims performed better than those that did not. Sensitivity (86.6%-96.0%), specificity (66.7%-99.0%), positive predictive value (95.4%-99.0%), and interrater reliability (Youden J = 0.60-0.92) were generally stable across datasets and across strata. Some variation in performance in the stratified analyses was observed but largely reflected changes in the composition of the strata. In Saskatchewan, the preferred algorithm had a sensitivity of 96%, specificity of 99%, positive predictive value of 99%, and negative predictive value of 96%. CONCLUSIONS: The performance of each algorithm was remarkably consistent across datasets. The preferred algorithm required ≥3 MS-related claims from any combination of inpatient, outpatient, or DMT use within 1 year. We recommend this algorithm as the standard AHC case definition for MS.

Value of incorporating newly identified risk factors into risk prediction for chemotherapy-induced febrile neutropenia.

Several comorbidities have recently been shown to affect risk of chemotherapy-induced febrile neutropenia (FN). Here, we evaluated the added predictive value of these comorbidities beyond established FN risk factors. A retrospective cohort study was conducted among adult patients diagnosed with cancer and treated with chemotherapy at Kaiser Permanente Southern California between 2000 and 2009. The study cohort was equally split into training and validation datasets to develop and evaluate the performance of FN risk prediction models in the first chemotherapy cycle. A reference model was developed based on the model proposed by Lyman et al (Cancer 2011;117:1917). A new model was developed by incorporating the newly identified comorbidities such as rheumatoid conditions and thyroid disorders into the reference model. Area under the receiver operating characteristic curve (AUROCC), risk reclassification, and integrated discrimination improvement (IDI) were used to evaluate the potential improvement of FN risk prediction by incorporating comorbidities. A total of 15 279 patients were included; 4.2% experienced FN in the first chemotherapy cycle. Including comorbidities in FN risk prediction did not improve AUROCC (reference model 0.71 vs new model 0.72). A significant improvement in individual-level FN risk prediction was indicated by IDI (P = .02). However, significant improvement in risk reclassification was not observed overall (although 6% of all patients were more accurately classified for their FN risk level, 5% were less accurately classified) or when examining predicted FN risk among patients who did and did not develop FN. Incorporating several new comorbidities into FN prediction led to improved FN risk prediction in the first chemotherapy cycle, although the observed improvements were small and might not be clinically relevant.

MS Sunshine Study: Sun Exposure But Not Vitamin D Is Associated with Multiple Sclerosis Risk in Blacks and Hispanics.

Multiple sclerosis (MS) incidence and serum 25-hydroxyvitamin D (25OHD) levels vary by race/ethnicity. We examined the consistency of beneficial effects of 25OHD and/or sun exposure for MS risk across multiple racial/ethnic groups. We recruited incident MS cases and controls (blacks 116 cases/131 controls; Hispanics 183/197; whites 247/267) from the membership of Kaiser Permanente Southern California into the MS Sunshine Study to simultaneously examine sun exposure and 25OHD, accounting for genetic ancestry and other factors. Higher lifetime ultraviolet radiation exposure (a rigorous measure of sun exposure) was associated with a lower risk of MS independent of serum 25OHD levels in blacks (adjusted OR = 0.53, 95% CI = 0.31-0.83; p = 0.007) and whites (OR = 0.68, 95% CI = 0.48-0.94; p = 0.020) with a similar magnitude of effect that did not reach statistical significance in Hispanics (OR = 0.66, 95% CI = 0.42-1.04; p = 0.071). Higher serum 25OHD levels were associated with a lower risk of MS only in whites. No association was found in Hispanics or blacks regardless of how 25OHD was modeled. Lifetime sun exposure appears to reduce the risk of MS regardless of race/ethnicity. In contrast, serum 25OHD levels are not associated with MS risk in blacks or Hispanics. Our findings challenge the biological plausibility of vitamin D deficiency as causal for MS and call into question the targeting of specific serum 25OHD levels to achieve health benefits, particularly in blacks and Hispanics.

Vitamin D-Binding Protein Polymorphisms, 25-Hydroxyvitamin D, Sunshine and Multiple Sclerosis.

Blacks have different dominant polymorphisms in the vitamin D-binding protein (DBP) gene that result in higher bioavailable vitamin D than whites. This study tested whether the lack of association between 25-hydroxyvitamin D (25OHD) and multiple sclerosis (MS) risk in blacks and Hispanics is due to differences in these common polymorphisms (rs7041, rs4588). We recruited incident MS cases and controls (blacks 116 cases/131 controls; Hispanics 183/197; whites 247/267) from Kaiser Permanente Southern California. AA is the dominant rs7041 genotype in blacks (70.0%) whereas C is the dominant allele in whites (79.0% AC/CC) and Hispanics (77.1%). Higher 25OHD levels were associated with a lower risk of MS in whites who carried at least one copy of the C allele but not AA carriers. No association was found in Hispanics or blacks regardless of genotype. Higher ultraviolet radiation exposure was associated with a lower risk of MS in blacks (OR = 0.06), Hispanics and whites who carried at least one copy of the C allele but not in others. Racial/ethnic variations in bioavailable vitamin D do not explain the lack of association between 25OHD and MS in blacks and Hispanics. These findings further challenge the biological plausibility of vitamin D deficiency as causal for MS.

Development and Assessment of Risk Scores for Carbapenem and Extensive ß-Lactam Resistance Among Adult Hospitalized Patients With Pseudomonas aeruginosa Infection.

Importance: Treatment of patients with infections due to Pseudomonas aeruginosa has been complicated by increased antibiotic resistance rates, which contribute to delayed appropriate treatment and deleterious outcomes. Objective: To develop 2 clinical risk scores based on variables available at clinical presentation to estimate the risk of carbapenem resistance (CR) or extensive ß-lactam resistance (EBR) among hospitalized, adult patients with P aeruginosa infections. Design, Setting, and Participants: This retrospective cohort study included adult (age, ≥18 years) members of Kaiser Permanente Southern California (KPSC) with a P aeruginosa infection during hospitalization from September 1, 2011, through August 31, 2016, who received antibiotic therapy within 2 days of the culture date. Data were analyzed from July 2, 2017, through August 15, 2018. Exposures: Demographic, clinical, and laboratory covariates 1 year before the index culture date were evaluated. Main Outcomes and Measures: Pseudomonas aeruginosa was categorized as antibiotic susceptible, CR, or EBR (nonsusceptibility to carbapenems, ceftazidime, and combined piperacillin sodium and tazobactam sodium). Patients were randomly split (1:1) into training and validation data sets. The training data set was used to develop 2 prediction models using high-performance logistic regression with variable selection by Schwarz-Bayesian criterion. The models were translated into risk scores, with risk score points equaling the weighted sums of regression coefficients from the prediction model. The patient's risk was estimated as the inverse logit of the risk score. Results: Of the 7775 patients with 11 502 P aeruginosa infections included in the analysis, most were male (4308 [55.4%]) and non-Hispanic white (3927 [50.5%]). The mean (SD) age was 70.3 (15.5) years. Among 11 502 P aeruginosa infections, 2324 (20.2%) were CR, 9178 (79.8%) were non-CR, 1033 (9.0%) were EBR, and 10 469 were non-EBR (91.0%). The strongest predictors of resistance in the CR and EBR models were history of CR P aeruginosa infection (odds ratios [ORs], 8.80 [95% CI, 6.74-11.49] and 5.04 [95% CI, 3.88-6.54], respectively), tracheostomy (ORs, 3.49 [95% CI, 2.92-4.16] and 3.13 [95% CI, 2.50-3.91], respectively), and carbapenem use in the prior 30 days (ORs, 4.18 [95% CI, 3.29-5.31] and 2.26 [95% CI, 1.74-2.93], respectively). The models for CR and EBR performed well, with areas under the receiver operating characteristics curve of 0.81 or greater for the training and validation data sets. Conclusions and Relevance: The findings of this study suggest that parsimonious risk scores can aid physicians in appropriate treatment selection during the critical period when P aeruginosa infection is suspected but antibiotic susceptibility results are not yet available.

Care in the Final Month of Life among Adolescent and Young Adult Cancer Patients in Kaiser Permanente Southern California.

BACKGROUND: Little is known about the care that adolescent and young adult (AYA) patients with cancer receive at the end of life (EOL). OBJECTIVE: To examine care in the last month of life among AYA patients with cancer. DESIGN: Medical record review of the last 30 days of life. SETTING/SUBJECTS: One hundred eleven AYA patients aged 15-39 years at death with either stage I-III cancer and evidence of cancer recurrence or stage IV cancer at diagnosis. Patients received care in Kaiser Permanente Southern California, an integrated healthcare delivery system, and died from 2007 to 2010. MEASUREMENTS: Use of intensive measures, including chemotherapy in the last 14 days of life and emergency room visits, hospitalizations, and intensive care unit admissions in the last 30 days; documented care preferences; symptom prevalence and treatment; advance care planning; hospice use; and location of death. RESULTS: One hundred seven patients (96%) had documented care preferences in the last month of life. At first documentation, 72% of patients wished for life-prolonging care, 20% wished for care focused on comfort, and 8% were undecided. Forty-seven percent of patients had documented changes in preferences in the last month, with 40% wishing for life-prolonging care when preferences were last noted before death, 56% preferring comfort, and 4% undecided. Seventy-eight percent of patients received at least one form of intensive EOL care, including 75% of those who preferred comfort measures at last documentation. CONCLUSIONS: Many AYA patients enter the last month of life wishing for life-prolonging care. While most ultimately wish for comfort, intensive care is prevalent even among such patients.

Oral Contraceptives and Multiple Sclerosis/Clinically Isolated Syndrome Susceptibility.

BACKGROUND: The incidence of multiple sclerosis (MS) is rising in women. OBJECTIVE: To determine whether the use of combined oral contraceptives (COCs) are associated with MS risk and whether this varies by progestin content. METHODS: We conducted a nested case-control study of females ages 14-48 years with incident MS or clinically isolated syndrome (CIS) 2008-2011 from the membership of Kaiser Permanente Southern California. Controls were matched on age, race/ethnicity and membership characteristics. COC use up to ten years prior to symptom onset was obtained from the complete electronic health record. RESULTS: We identified 400 women with incident MS/CIS and 3904 matched controls. Forty- percent of cases and 32% of controls had used COCs prior to symptom onset. The use of COCs was associated with a slightly increased risk of MS/CIS (adjusted OR = 1.52, 95%CI = 1.21-1.91; p<0.001). This risk did not vary by duration of COC use. The association varied by progestin content being more pronounced for levenorgestrol (adjusted OR = 1.75, 95%CI = 1.29-2.37; p<0.001) than norethindrone (adjusted OR = 1.57, 95%CI = 1.16-2.12; p = 0.003) and absent for the newest progestin, drospirenone (p = 0.95). CONCLUSIONS: Our findings should be interpreted cautiously. While the use of some combination oral contraceptives may contribute to the rising incidence of MS in women, an unmeasured confounder associated with the modern woman's lifestyle is a more likely explanation for this weak association.

End-of-Life Care Intensity Among Adolescent and Young Adult Patients With Cancer in Kaiser Permanente Southern California.

IMPORTANCE: Cancer is the leading disease-related cause of death among adolescents and young adults (AYAs), but little is known about the care that AYA patients with cancer receive at the end of life (EOL). OBJECTIVE: To evaluate the intensity of EOL care among AYA patients with cancer. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of Kaiser Permanente Southern California (KSPC) cancer registry data and electronic health records for 663 AYA patients with either stage I to III cancer and evidence of cancer recurrence or stage IV cancer at diagnosis. All patients were treated within KSPC, an integrated health care delivery system, and died between 2001 and 2010 before age 40 years (age range at time of death, 15-39 years). MAIN OUTCOMES AND MEASURES: (1) Chemotherapy use in the last 14 days of life; (2) intensive care unit (ICU) care in the last 30 days of life; (3) more than 1 emergency department (ED) visit in the last 30 days of life; (4) hospitalization in the last 30 days of life; and (5) a composite measure of medically intensive EOL care including any of the aforementioned measures. RESULTS: Eleven percent of patients (72 of 663) received chemotherapy within 14 days of death. In the last 30 days of life, 22% of patients (144 of 663) were admitted to the ICU; 22% (147 of 663) had more than 1 ED visit; and 62% (413 of 663) were hospitalized. Overall, 68% of patients (449 of 663) received at least 1 medically intensive EOL care measure. CONCLUSIONS AND RELEVANCE: Most AYA patients received at least 1 form of medically intensive EOL care. These findings suggest the need to better understand EOL care preferences and decision making in this young population.

Outcomes of root canal treatment and restoration, implant-supported single crowns, fixed partial dentures, and extraction without replacement: a systematic review.

STATEMENT OF PROBLEM: Dentists and patients are regularly confronted by a difficult treatment question: should a tooth be saved through root canal treatment and restoration (RCT), be extracted without any tooth replacement, be replaced with a fixed partial denture (FPD) or an implant-supported single crown (ISC)? PURPOSE: The purpose of this systematic review was to compare the outcomes, benefits, and harms of endodontic care and restoration compared to extraction and placement of ISCs, FPDs, or extraction without tooth replacement. MATERIAL AND METHODS: Searches performed in MEDLINE, Cochrane, and EMBASE databases were enriched by hand searches, citation mining, and expert recommendation. Evidence tables were developed following quality and inclusion criteria assessment. Pooled and weighted mean success and survival rates, with associated confidence intervals, were calculated for single implant crowns, fixed partial dentures, and initial nonsurgical root canal treatments. Data related to extraction without tooth replacement and psychosocial outcomes were evaluated by a narrative review due to literature limitations. RESULTS: The 143 selected studies varied considerably in design, success definition, assessment methods, operator type, and sample size. Direct comparison of treatment types was extremely rare. Limited psychosocial data revealed the traumatic effect of loss of visible teeth. Economic data were largely absent. Success rates for ISCs were higher than for RCTs and FPDs, respectively; however, success criteria differed greatly among treatment types, rendering direct comparison of success rates futile. Long-term survival rates for ISCs and RCTs were similar and superior to those for FPDs. CONCLUSIONS: Lack of comparative studies with similar outcomes criteria with comparable time intervals limited comparison of these treatments. ISC and RCT treatments resulted in superior long-term survival, compared to FPDs. Limited data suggested that extraction without replacement resulted in inferior psychosocial outcomes compared to alternatives. Long-term, prospective clinical trials with large sample sizes and clearly defined outcomes criteria are needed.