Interrupted time series design is the strongest, quasi-experimental approach for evaluating longitudinal effects of interventions. Segmented regression analysis is a powerful statistical method for estimating intervention effects in interrupted time series studies. In this paper, we show how segmented regression analysis can be used to evaluate policy and educational interventions intended to improve the quality of medication use and/or contain costs.

Segmented regression analysis of interrupted time series studies in medication use research

Bacteria belonging to the genus Klebsiella frequently cause human nosocomial infections. In particular, the medically most important Klebsiella species, Klebsiella pneumoniae, accounts for a significant proportion of hospital-acquired urinary tract infections, pneumonia, septicemias, and soft tissue infections. The principal pathogenic reservoirs for transmission of Klebsiella are the gastrointestinal tract and the hands of hospital personnel. Because of their ability to spread rapidly in the hospital environment, these bacteria tend to cause nosocomial outbreaks. Hospital outbreaks of multidrug-resistant Klebsiella spp., especially those in neonatal wards, are often caused by new types of strains, the so-called extended-spectrum-β-lactamase (ESBL) producers. The incidence of ESBL-producing strains among clinical Klebsiella isolates has been steadily increasing over the past years. The resulting limitations on the therapeutic options demand new measures for the management of Klebsiella hospital infections. While the different typing methods are useful epidemiological tools for infection control, recent findings about Klebsiella virulence factors have provided new insights into the pathogenic strategies of these bacteria. Klebsiella pathogenicity factors such as capsules or lipopolysaccharides are presently considered to be promising candidates for vaccination efforts that may serve as immunological infection control measures.

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Klebsiella spp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors

ContextClinical practice guidelines (CPGs) have been developed to improve the
quality of health care for many chronic conditions. Pay-for-performance initiatives
assess physician adherence to interventions that may reflect CPG recommendations.ObjectiveTo evaluate the applicability of CPGs to the care of older individuals
with several comorbid diseases.Data SourcesThe National Health Interview Survey and a nationally representative
sample of Medicare beneficiaries (to identify the most prevalent chronic diseases
in this population); the National Guideline Clearinghouse (for locating evidence-based
CPGs for each chronic disease).Study SelectionOf the 15 most common chronic diseases, we selected hypertension, chronic
heart failure, stable angina, atrial fibrillation, hypercholesterolemia, diabetes
mellitus, osteoarthritis, chronic obstructive pulmonary disease, and osteoporosis,
which are usually managed in primary care, choosing CPGs promulgated by national
and international medical organizations for each.Data ExtractionTwo investigators independently assessed whether each CPG addressed
older patients with multiple comorbid diseases, goals of treatment, interactions
between recommendations, burden to patients and caregivers, patient preferences,
life expectancy, and quality of life. Differences were resolved by consensus.
For a hypothetical 79-year-old woman with chronic obstructive pulmonary disease,
type 2 diabetes, osteoporosis, hypertension, and osteoarthritis, we aggregated
the recommendations from the relevant CPGs.Data SynthesisMost CPGs did not modify or discuss the applicability of their recommendations
for older patients with multiple comorbidities. Most also did not comment
on burden, short- and long-term goals, and the quality of the underlying scientific
evidence, nor give guidance for incorporating patient preferences into treatment
plans. If the relevant CPGs were followed, the hypothetical patient would
be prescribed 12 medications (costing her $406 per month) and a complicated
nonpharmacological regimen. Adverse interactions between drugs and diseases
could result.ConclusionsThis review suggests that adhering to current CPGs in caring for an
older person with several comorbidities may have undesirable effects. Basing
standards for quality of care and pay for performance on existing CPGs could
lead to inappropriate judgment of the care provided to older individuals with
complex comorbidities and could create perverse incentives that emphasize
the wrong aspects of care for this population and diminish the quality of
their care. Developing measures of the quality of the care needed by older
patients with complex comorbidities is critical to improving their care.

/pdf/clinical-practice-guidelines-and-quality-of-care-for-older-4dkwbw3b1x.pdf

Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance.

https://journal.chestnet.org/article/S0012-3692(08)60117-8/pdf

Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

Oral Anticoagulants: Mechanism of Action, Clinical Effectiveness, and Optimal Therapeutic Range

Objective. —To determine the effect of regular intake of cranberry juice beverage on bacteriuria and pyuria in elderly women. Design. —Randomized, double-blind, placebo-controlled trial. Subjects. —Volunteer sample of 153 elderly women (mean age, 78.5 years). Intervention. —Subjects were randomly assigned to consume 300 mL per day of a commercially available standard cranberry beverage or a specially prepared synthetic placebo drink that was indistinguishable in taste, appearance, and vitamin C content but lacked cranberry content. Outcome Measures. —A baseline urine sample and six clean-voided study urine samples were collected at approximately 1-month intervals and tested quantitatively for bacteriuria and the presence of white blood cells. Results. —Subjects randomized to the cranberry beverage had odds of bacteriuria (defined as organisms numbering ≥105/mL) with pyuria that were only 42% of the odds in the control group (P=.004). Their odds of remaining bacteriuric-pyuric, given that they were bacteriuric-pyuric in the previous month, were only 27% of the odds in the control group (P=.006). Conclusions. —These findings suggest that use of a cranberry beverage reduces the frequency of bacteriuria with pyuria in older women. Prevalent beliefs about the effects of cranberry juice on the urinary tract may have microbiologic justification. (JAMA. 1994;271:751-754)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=JAMA&articleId=366888&pdfFileName=jama_271_10_031.pdf

Reduction of bacteriuria and pyuria after ingestion of cranberry juice.

Background. Many state Medicaid programs limit the number of reimbursable medications that a patient can receive. We hypothesized that such limitations may lead to exacerbations of illness or to admissions to institutions where there are no caps on drug reimbursements. Methods. We analyzed 36 months of Medicaid claims data from New Hampshire, which had a three-drug limit per patient for 11 of those months, and from New Jersey, which did not. The study patients in New Hampshire (n = 411) and a matched comparison cohort in New Jersey (n = 1375) were Medicaid recipients 60 years of age or older who in a base-line year had been taking three or more medications per month, including at least one maintenance drug for certain chronic diseases. Survival (defined as remaining in the community) and time-series analyses were conducted to determine the effect of the reimbursement cap on admissions to hospitals and nursing homes. Results. The base-line demographic characteristics of the cohorts were nearly ide...

/pdf/effects-of-medicaid-drug-payment-limits-on-admission-to-1ysdo510tr.pdf

Effects of Medicaid drug-payment limits on admission to hospitals and nursing homes.

Objective To assess the effect of aging on the anticoagulant response to warfarin. Design Retrospective cohort study. Setting A university hospital outpatient anticoagulation clinic. Patients All patients (n = 530) monitored in the anticoagulation clinic over a 10-year period (1980 to 1990). The 530 study patients had a mean age of 61.5 (+/- 14.7) years (age range, 12 to 90 years). The patients were stratified into four age groups: younger than 50 years (n = 97); 50 to 59 years (n = 107); 60 to 69 years (n = 149); and 70 years or older (n = 177). Measurements For each patient, a dose-adjusted mean prothrombin time ratio was calculated by dividing the mean prothrombin time ratio by the mean daily warfarin dose. Results Older patients were more likely to be female (P less than 0.001), to have more medical problems (P less than 0.001), to be taking more medications (P less than 0.001), and to weigh less than younger patients (P less than 0.001). Across age groups, there were no significant differences in the use of medications that potentiated or inhibited the anticoagulant effects of warfarin. The prothrombin time ratio, when adjusted for dose, was significantly increased in older patients (P less than 0.001). The increased anticoagulant response to warfarin seen with increasing patient age persisted even after simultaneously controlling for relevant demographic and clinical variables in a multivariate model. Other factors significantly associated with an increased sensitivity to warfarin included use of a medication with a potentiating interactive effect with warfarin, female gender, and overall medication use. Increased body weight and duration of warfarin use exceeding 6 months were found to be inversely related to anticoagulant response. Conclusion The anticoagulant response to warfarin is exaggerated with advancing age. This finding emphasizes the need for close monitoring of older patients treated with warfarin therapy.

Aging and the anticoagulant response to warfarin therapy.

Background: Since the introduction of exogenous factor VIII therapy, several studies have explored the clinical benefits of prophylactic use of factor VIII. Little research, though, has focused on the economic aspects of this regimen. We conducted a cost analysis using data from the Orthopedic Outcomes Study, a prospective, cross-national study of the clinical outcomes associated with different patterns of factor VIII utilization to examine the health care costs incurred and expen-ditures averted in patients receiving on-demand versus prophylactic use of factor VIII in hemophilia. Methods and Analysis: 831 patients with severe hemophilia aged 1 to 31 years, from 19 centers around the world were included in the cost analysis. Patients were categorized into three groups according to the number of weeks during the study years in which they received prophylactic regimens of factor VIII. For each subject, we estimated the costs of hospitalization, surgery, days lost from school or work, and factor VIII utilization. Costs were then stratified by age and by joint score to assess confounding, and a multivariate model developed to determine the relationship between use of factor VIII prophylaxis and total costs, while controlling for potential confounders. Results: Patients who received factor VIII episodically incurred substantially greater disability-related costs (days lost from school or work, days hospitalized due to hemophilia, surgery) than patients who received factor VIII prophylactically for some or all of the study period. For all treatment regimens, most disability-related costs were accounted for by hospitalization for hemophilia-related conditions. The cost of factor VIII itself was substantial in all treatment categories but was highest among patients who received year-round prophylaxis, exceeding the savings resulting from reduced disability and other health care expenditures. Conclusions: Reductions in non-factor health care costs and disability associated with prophylactic use of factor VIII in hemophilia were substantial and helped somewhat to offset the much higher costs of this regimen. For certain subgroups, frequent episodic treatment may be more expensive than full-time prophylaxis. However, because of the very high cost of year-round prophylactic use of factor VIII, total health care expenditures were highest among patients receiving this therapetic regimen. However, because prophylaxis clearly offers important clinical benefits, this approach may be warranted on medical rather than economic grounds.

Prophylactic Use of Factor VIII: an Economic Evaluation

OBJECTIVES: To examine prescribing and utilization patterns of laxatives, stool softeners, and enemas in a large, long-term care facility, to compare self-reports of constipation with specific, bowel-related symptoms in residents of this facility, and to examine concordance between bowel symptoms reported by residents and the assessments of the nursing staff.



DESIGN: Cross-sectional study.



SETTING AND SUBJECTS: All individuals residing in an academically oriented long-term care facility in the United States for at least 1 month (n = 694).



MEASUREMENTS: Clinical, functional, and medication data were abstracted from the medical and nursing records. Individual interviews regarding bowel-related symptoms were conducted with all able participants (n = 456 (66%)) and their respective primary nurses, and concordance was determined. The study definition of symptom-specific constipation was no more than 2 bowel movements per week and/or straining on more than 1 in 4 bowel movements.



RESULTS: Fifty percent (n = 367) of all residents used at least 1 daily laxative, stool softener or enema during a 1-month study period. Over half of all laxative users (n = 200) took more than 60 doses per month. Stool softeners were most commonly prescribed, followed by saline laxatives, stimulant laxatives, hyperosmolar laxatives, and bulk laxatives. Forty-seven percent (n = 213) of the 456 interview responders reported constipation (“self-reporters”), but only 62% of self-reporters met the study criteria for symptom-specific constipation. Concordance between resident's and nurse's report regarding specific bowel symptoms was only fair to slight (kappa 0.12–0.38). Self-reporters of constipation took almost twice as many laxatives, stool softeners, and enemas as residents who did not report constipation.



CONCLUSION: Our findings emphasize the need for a more systematic approach to the assessment of constipation in the long-term care setting, particularly when pharmacologic treatment is being considered.

Igor Choodnovskiy

Papers

Reduction of bacteriuria and pyuria after ingestion of cranberry juice.

Effects of Medicaid drug-payment limits on admission to hospitals and nursing homes.

Aging and the anticoagulant response to warfarin therapy.

Prophylactic Use of Factor VIII: an Economic Evaluation

Constipation: assessment and management in an institutionalized elderly population.