Katharine A. Kirby

Traumatic brain injury and risk of dementia in older veterans

Objectives: Traumatic brain injury (TBI) is common in military personnel, and there is growing concern about the long-term effects of TBI on the brain; however, few studies have examined the association between TBI and risk of dementia in veterans. Methods: We performed a retrospective cohort study of 188,764 US veterans aged 55 years or older who had at least one inpatient or outpatient visit during both the baseline (2000–2003) and follow-up (2003–2012) periods and did not have a dementia diagnosis at baseline. TBI and dementia diagnoses were determined using ICD-9 codes in electronic medical records. Fine-Gray proportional hazards models were used to determine whether TBI was associated with greater risk of incident dementia, accounting for the competing risk of death and adjusting for demographics, medical comorbidities, and psychiatric disorders. Results: Veterans were a mean age of 68 years at baseline. During the 9-year follow-up period, 16% of those with TBI developed dementia compared with 10% of those without TBI (adjusted hazard ratio, 1.57; 95% confidence interval: 1.35–1.83). There was evidence of an additive association between TBI and other conditions on risk of dementia. Conclusions: TBI in older veterans was associated with a 60% increase in the risk of developing dementia over 9 years after accounting for competing risks and potential confounders. Our results suggest that TBI in older veterans may predispose toward development of symptomatic dementia and raise concern about the potential long-term consequences of TBI in younger veterans and civilians.

A Clinical Index to Stratify Hospitalized Older Adults According to Risk for New-Onset Disability

BACKGROUND: Many older adults who are independent prior to hospitalization develop a new disability by hospital discharge. Early risk stratification for new‐onset disability may improve care. Thus, this studys objective was to develop and validate a clinical index to determine, at admission, risk for new‐onset disability among older, hospitalized adults at discharge.

Lack of Follow-up After Fecal Occult Blood Testing in Older Adults: Inappropriate Screening or Failure to Follow Up?

BACKGROUND It is unclear whether lack of follow-up after screening fecal occult blood testing (FOBT) in older adults is due to screening patients whose comorbidity or preferences do not permit follow-up vs failure to complete follow-up in healthy patients. METHODS A prospective cohort study of 2410 patients 70 years or older screened with FOBT was conducted at 4 Veteran Affairs (VA) medical centers from January 1 to December 31, 2001. The main outcome measure was receipt of follow-up within 1 year of FOBT based on national VA and Medicare data. For patients with positive FOBT results, age and Charlson comorbidity scores were evaluated as potential predictors of receiving a complete colon evaluation (colonoscopy or sigmoidoscopy plus barium enema), and medical records were reviewed to determine reasons for lack of follow-up. RESULTS A total of 212 patients (9%) had positive FOBT results; 42% received a complete colon evaluation within 1 year. Age and comorbidity were not associated with receipt of a complete follow-up, which was similar among patients 70 to 74 years old with a Charlson score of 0 compared with patients 80 years or older with a Charlson score of 1 or higher (48% vs 41%; P=.28). The VA site, number of positive FOBT cards, and number of VA outpatient visits were predictors. Of 122 patients who did not receive a complete follow-up within 1 year, 38% had documentation that comorbidity or preferences did not permit follow-up, and over the next 5 years 76% never received a complete follow-up. CONCLUSIONS While follow-up after positive FOBT results was low regardless of age or comorbidity, screening patients in whom complete evaluation would not be pursued substantially contributes to lack of follow-up. Efforts to improve follow-up should address the full chain of decision making, including decisions to screen and decisions to follow up.

Long-term Outcomes Following Positive Fecal Occult Blood Test Results in Older Adults: Benefits and Burdens

BACKGROUND In the United States, older adults have low rates of follow-up colonoscopy after a positive fecal occult blood test (FOBT) result. The long-term outcomes of these real world practices and their associated benefits and burdens are unknown. METHODS Longitudinal cohort study of 212 patients 70 years or older with a positive FOBT result at 4 Veteran Affairs (VA) facilities in 2001 and followed up through 2008. We determined the frequency of downstream outcomes during the 7 years of follow-up, including procedures, colonoscopic findings, outcomes of treatment, complications, and mortality based on chart review and national VA and Medicare data. Net burden or benefit from screening and follow-up was determined according to each patients life expectancy. Life expectancy was classified into 3 categories: best (age, 70-79 years and Charlson-Deyo comorbidity index [CCI], 0), average, and worst (age, 70-84 years and CCI, ≥4 or age, ≥85 years and CCI, ≥1). RESULTS Fifty-six percent of patients received follow-up colonoscopy (118 of 212), which found 34 significant adenomas and 6 cancers. Ten percent experienced complications from colonoscopy or cancer treatment (12 of 118). Forty-six percent of those without follow-up colonoscopy died of other causes within 5 years of FOBT (43 of 94), while 3 died of colorectal cancer within 5 years. Eighty-seven percent of patients with worst life expectancy experienced a net burden from screening (26 of 30) as did 70% with average life expectancy (92 of 131) and 65% with best life expectancy (35 of 51) (P = .048 for trend). CONCLUSIONS Over a 7-year period, older adults with best life expectancy were less likely to experience a net burden from current screening and follow-up practices than are those with worst life expectancy. The net burden could be decreased by better targeting FOBT screening and follow-up to healthy older adults.

Prisoner of war status, posttraumatic stress disorder, and dementia in older veterans

It is not known whether prisoners of war (POWs) are more likely to develop dementia independently of the effects of posttraumatic stress disorder (PTSD).

Five-year downstream outcomes following prostate-specific antigen screening in older men.

IMPORTANCE Despite ongoing controversies surrounding prostate-specific antigen (PSA) screening, many men 65 years or older undergo screening. However, few data exist that quantify the chain of events following screening in clinical practice to better inform decisions. OBJECTIVE To quantify 5-year downstream outcomes following a PSA screening result exceeding 4.0 ng/mL in older men. DESIGN AND SETTING Longitudinal cohort study in the national Veterans Affairs health care system. PARTICIPANTS In total, 295,645 men 65 years or older who underwent PSA screening in the Veterans Affairs health care system in 2003 and were followed up for 5 years using national Veterans Affairs and Medicare data. MAIN OUTCOME MEASURES Among men whose index screening PSA level exceeded 4.0 ng/mL, we determined the number who underwent prostate biopsy, were diagnosed as having prostate cancer, were treated for prostate cancer, and were treated for prostate cancer and were alive at 5 years according to baseline characteristics. Biopsy and treatment complications were also assessed. RESULTS In total, 25,208 men (8.5%) had an index PSA level exceeding 4.0 ng/mL. During the 5-year follow-up period, 8313 men (33.0%) underwent at least 1 prostate biopsy, and 5220 men (62.8%) who underwent prostate biopsy were diagnosed as having prostate cancer, of whom 4284 (82.1%) were treated for prostate cancer. Performance of prostate biopsy decreased with advancing age and worsening comorbidity (P < .001), whereas the percentage treated for biopsy-detected cancer exceeded 75% even among men 85 years or older, those with a Charlson-Deyo Comorbidity Index of 3 or higher, and those having low-risk cancer. Among men with biopsy-detected cancer, the risk of death from non-prostate cancer causes increased with advancing age and worsening comorbidity (P < .001). In total, 468 men (5.6%) had complications within 7 days after prostate biopsy. Complications of prostate cancer treatment included new urinary incontinence in 584 men (13.6%) and new erectile dysfunction 588 men (13.7%). CONCLUSIONS AND RELEVANCE Performance of prostate biopsy is uncommon in older men with abnormal screening PSA levels and decreases with advancing age and worsening comorbidity. However, once cancer is detected on biopsy, most men undergo immediate treatment regardless of advancing age, worsening comorbidity, or low-risk cancer. Understanding downstream outcomes in clinical practice should better inform individualized decisions among older men considering PSA screening.

Coreactivation of human herpesvirus 6 and cytomegalovirus is associated with worse clinical outcome in critically ill adults

Objectives:Human herpesvirus 6 is associated with a variety of complications in immunocompromised patients, but no studies have systematically and comprehensively assessed the impact of human herpesvirus 6 reactivation, and its interaction with cytomegalovirus, in ICU patients. Design:We prospectively assessed human herpesvirus 6 and cytomegalovirus viremia by twice-weekly plasma polymerase chain reaction in a longitudinal cohort study of 115 adult, immunocompetent ICU patients. The association of human herpesvirus 6 and cytomegalovirus reactivation with death or continued hospitalization by day 30 (primary endpoint) was assessed by multivariable logistic regression analyses. Setting:This study was performed in trauma, medical, surgical, and cardiac ICUs at two separate hospitals of a large tertiary care academic medical center. Patients:A total of 115 cytomegalovirus seropositive, immunocompetent adults with critical illness were enrolled in this study. Interventions:None. Measurements and Main Results:Human herpesvirus 6 viremia occurred in 23% of patients at a median of 10 days. Human herpesvirus 6B was the species detected in eight samples available for testing. Most patients with human herpesvirus 6 reactivation also reactivated cytomegalovirus (70%). Severity of illness was not associated with viral reactivation. Mechanical ventilation, burn ICU, major infection, human herpesvirus 6 reactivation, and cytomegalovirus reactivation were associated with the primary endpoint in unadjusted analyses. In a multivariable model adjusting for mechanical ventilation and ICU type, only coreactivation of human herpesvirus 6 and cytomegalovirus was significantly associated with the primary endpoint (adjusted odds ratio, 7.5; 95% CI, 1.9–29.9; p = 0.005) compared to patients with only human herpesvirus 6, only cytomegalovirus, or no viral reactivation. Conclusions:Coreactivation of both human herpesvirus 6 and cytomegalovirus in ICU patients is associated with worse outcome than reactivation of either virus alone. Future studies should define the underlying mechanism(s) and determine whether prevention or treatment of viral reactivation improves clinical outcome.

Individualizing life expectancy estimates for older adults using the Gompertz Law of Human Mortality.

Background Guidelines recommend incorporating life expectancy (LE) into clinical decision-making for preventive interventions such as cancer screening. Previous research focused on mortality risk (e.g. 28% at 4 years) which is more difficult to interpret than LE (e.g. 7.3 years) for both patients and clinicians. Our objective was to utilize the Gompertz Law of Human Mortality which states that mortality risk doubles in a fixed time interval to transform the Lee mortality index into a LE calculator. Methods We examined community-dwelling older adults age 50 and over enrolled in the nationally representative 1998 wave of the Health and Retirement Study or HRS (response rate 81%), dividing study respondents into development (n = 11701) and validation (n = 8009) cohorts. In the development cohort, we fit proportional hazards Gompertz survival functions for each of the risk groups defined by the Lee mortality index. We validated our LE estimates by comparing our predicted LE with observed survival in the HRS validation cohort and an external validation cohort from the 2004 wave of the English Longitudinal Study on Ageing or ELSA (n = 7042). Results The ELSA cohort had a lower 8-year mortality risk (14%) compared to our HRS development (23%) and validation cohorts (25%). Our model had good discrimination in the validation cohorts (Harrell’s c 0.78 in HRS and 0.80 in the ELSA). Our predicted LE’s were similar to observed survival in the HRS validation cohort without evidence of miscalibration (Hosmer-Lemeshow, p = 0.2 at 8 years). However, our predicted LE’s were longer than observed survival in the ELSA cohort with evidence of miscalibration (Hosmer-Lemeshow, p<0.001 at 8 years) reflecting the lower mortality rate in ELSA. Conclusion We transformed a previously validated mortality index into a LE calculator that incorporated patient-level risk factors. Our LE calculator may help clinicians determine which preventive interventions are most appropriate for older US adults.

Medical center characteristics associated with PSA screening in elderly veterans with limited life expectancy.

ABSTRACTBACKGROUNDAlthough guidelines recommend against prostate-specific antigen (PSA) screening in elderly men with limited life expectancy, screening is common.OBJECTIVEWe sought to identify medical center characteristics associated with screening in this population.DESIGN/PARTICIPANTSWe conducted a prospective study of 622,262 screen-eligible men aged 70+ seen at 104 VA medical centers in 2003.MAIN MEASURESPrimary outcome was the percentage of men at each center who received PSA screening in 2003, based on VA data and Medicare claims. Men were stratified into life expectancy groups ranging from favorable (age 70–79 with Charlson score = 0) to limited (age 85+ with Charlson score ≥1 or age 70+ with Charlson score ≥4). Medical center characteristics were obtained from the 1999–2000 VA Survey of Primary Care Practices and publicly available VA data sources.KEY RESULTSAmong 123,223 (20%) men with limited life expectancy, 45% received PSA screening in 2003. Across 104 VAs, the PSA screening rate among men with limited life expectancy ranged from 25-79% (median 43%). Higher screening was associated with the following center characteristics: no academic affiliation (50% vs. 43%, adjusted RR = 1.14, 95% CI 1.04–1.25), a ratio of midlevel providers to physicians ≥3:4 (55% vs. 45%, adjusted RR = 1.20, 95% CI 1.09–1.32) and location in the South (49% vs. 39% in the West, adjusted RR = 1.25, 95% CI 1.12–1.40). Use of incentives and high scores on performance measures were not independently associated with screening. Within centers, the percentages of men screened with limited and favorable life expectancies were highly correlated (r = 0.90).CONCLUSIONSSubstantial practice variation exists for PSA screening in older men with limited life expectancy across VAs. The high center-specific correlation of screening among men with limited and favorable life expectancies indicates that PSA screening is poorly targeted according to life expectancy.

Depressive symptoms after hospitalization in older adults: function and mortality outcomes.

To determine the relationship between depressive symptoms after hospitalization and survival and functional outcomes.