Protein interaction networks at the host-microbe interface in Diaphorina citri, the insect vector of the citrus greening pathogen.

The Asian citrus psyllid (Diaphorina citri) is the insect vector responsible for the worldwide spread of 'Candidatus Liberibacter asiaticus' (CLas), the bacterial pathogen associated with citrus greening disease. Developmental changes in the insect vector impact pathogen transmission, such that D. citri transmission of CLas is more efficient when bacteria are acquired by nymphs when compared with adults. We hypothesize that expression changes in the D. citri immune system and commensal microbiota occur during development and regulate vector competency. In support of this hypothesis, more proteins, with greater fold changes, were differentially expressed in response to CLas in adults when compared with nymphs, including insect proteins involved in bacterial adhesion and immunity. Compared with nymphs, adult insects had a higher titre of CLas and the bacterial endosymbionts Wolbachia, Profftella and Carsonella. All Wolbachia and Profftella proteins differentially expressed between nymphs and adults are upregulated in adults, while most differentially expressed Carsonella proteins are upregulated in nymphs. Discovery of protein interaction networks has broad applicability to the study of host-microbe relationships. Using protein interaction reporter technology, a D. citri haemocyanin protein highly upregulated in response to CLas was found to physically interact with the CLas coenzyme A (CoA) biosynthesis enzyme phosphopantothenoylcysteine synthetase/decarboxylase. CLas pantothenate kinase, which catalyses the rate-limiting step of CoA biosynthesis, was found to interact with a D. citri myosin protein. Two Carsonella enzymes involved in histidine and tryptophan biosynthesis were found to physically interact with D. citri proteins. These co-evolved protein interaction networks at the host-microbe interface are highly specific targets for controlling the insect vector responsible for the spread of citrus greening.

Medication adherence in elderly patients receiving home health services following hospital discharge.

OBJECTIVE: To assess prevalence and risk factors for medication under- and overadherence in a two-week period following hospital discharge in adults > or = 65 years. DESIGN: Prospective, cohort study. SETTING: Three home healthcare agencies in Madison, Wisconsin, and surrounding vicinity. PARTICIPANTS: One hundred forty-seven older participants taking three or more medications who were hospitalized for medical illness, received home nursing after discharge, and completed the two-week interview. MEASUREMENTS: The main outcome measures were having at least one medication with less than 70% adherence (underadherence) and having at least one medication with more than 120% adherence (overadherence) based on pill counts. RESULTS: Forty-five (30.6%) participants were underadherent and 27 (18.4%) participants were overadherent with at least one medication> In a multivariate model, underadherence was predicted by poor cognition (OR 2.5; 95% CI 1.02 to 6.10) and higher medication use (OR 1.16; 95% CI 1.03 to 1.31, for each 1-unit increase in number of medications). Both poor cognition and low education were significantly associated with overadherence in univariate analysis; however, neither variable was significant once included in the multivariate model. CONCLUSIONS: Under- and overadherence to medications is common after hospital discharge. Poor cognition and a greater number of medications were associated with underadherence. Poor and lower education were markers for overadherence; however, further study is needed to determined whether these are independent predictors. Patients who have impaired cognition or are taking a greater number of medications after hospitalization may benefit from targeted interventions to monitor and improve medication compliance.

Increased prevalence and analysis of risk factors for indinavir nephrolithiasis.

PURPOSE: Indinavir is a protease inhibitor used for treating HIV-1. The drug is lithogenic and was thought to cause a 3% incidence of kidney stones. We evaluated a cohort of patients positive for HIV on indinavir to determine the incidence of indinavir nephrolithiasis and identify risk factors for indinavir stone formation. MATERIALS AND METHODS: Our cohort study of the prevalence of indinavir nephrolithiasis included 155 patients with HIV for 5,732 patient-weeks. The same cohort was then used for a retrospective chart review to assess patient age, weight, duration of drug use, time to stone formation, CD4 count, creatinine, alanine transaminase, and urinary pH and specific gravity as risk factors for stone formation. RESULTS: We estimated the cumulative incidence of indinavir stone formation by the Kaplan-Meier product limit estimator method. At 78 weeks 43.2% of patients had stones (95% confidence interval [CI] 0.292 to 0.543). Increasing age was the only variable that was a statistically significant predictor of indinavair urolithiasis (relative risk 0.955, 95% CI 0.918 to 0.993, p = 0.0159). The mean duration plus or minus standard deviation of indinavir use was statistically the same in each group (42.5 +/- 27. 2 and 40.3 +/- 27.1 weeks in those without and with stones, respectively) despite the observed mean time to stone formation of 23.0 +/- 19.8 weeks. CONCLUSIONS: The clinical prevalence of indinavir nephrolithiasis is much greater than initially reported. Nephrolithiasis during indinavir use does not appear to induce patients to withdraw from the drug.

Temporal association between hospitalization and rate of falls after discharge.

BACKGROUND: Evidence suggests that acute illness and hospitalization may increase the risk for falls. OBJECTIVE: To evaluate the rate of falls, and associated risk factors, for 90 days following hospital discharge. METHODS: We consecutively enrolled 311 patients, aged 65 years and older, discharged from the hospital after an acute medical illness and receiving home-nursing services. Patients were assessed within 5 days of discharge for prehospital and current functioning by self-report, and balance, vision, cognition, and delirium by objective measures. Patients were followed up weekly for 13 weeks for falls, injuries, and health care use. RESULTS: The rate of falls was significantly higher in the first 2 weeks after hospitalization (8.0 per 1000 person-days) compared with 3 months later (1.7 per 1000 person-days) (P =.002). Fall-related injuries accounted for 15% of all hospitalizations in the first month after discharge. Independent prehospital risk factors significantly associated with falls included dependency in activities of daily living, use of a standard walker, 2 or more falls, and more hospitalizations in the year prior. Posthospital risk factors included use of a tertiary amine tricyclic antidepressant, probable delirium, and poorer balance, while use of a cane was protective. CONCLUSIONS: The rate of falls is substantially increased in the first month after medical hospitalization, and is an important cause of injury and morbidity. Posthospital risk factors may be potentially modifiable. Efforts to assess and modify risk factors should be integral to the hospital and posthospital care of older adults (those aged >/=65 years).

Problems of older adults living alone after hospitalization.

OBJECTIVE: To describe functional deficits among older adults living alone and receiving home nursing following medical hospitalization, and the association of living alone with lack of functional improvement and nursing home utilization 1 month after hospitalization. DESIGN: Secondary analysis of a prospective cohort study. PARTICIPANTS: Consecutive sample of patients age 65 and over receiving home nursing following medical hospitalization. Patients were excluded for new diagnosis of myocardial infarction or stroke in the previous 2 months, diagnosis of dementia if living alone, or nonambulatory status. Of 613 patients invited to participate, 312 agreed. MEASUREMENTS: One week after hospitalization, patients were assessed in the home for demographic information, medications, cognition, and self-report of prehospital and current mobility and function in activities of daily living (ADLs) and independent activities of daily living (IADLs). One month later, patients were asked about current function and nursing home utilization. The outcomes were lack of improvement in ADL function and nursing home utilization 1 month after hospitalization. RESULTS: One hundred forty-one (45%) patients lived alone. After hospital discharge, 40% of those living alone and 62% of those living with others had at least 1 ADL dependency (P =.0001). Patients who were ADL-dependent and lived alone were 3.3 (95% confidence interval [95% CI], 1.4 to 7. 6) times less likely to improve in ADLs and 3.5 (95% CI, 1.0 to 11. 9) times more likely to be admitted to a nursing home in the month after hospitalization. CONCLUSION: Patients who live alone and receive home nursing after hospitalization are less likely to improve in function and more likely to be admitted to a nursing home, compared with those who live with others. More intensive resources may be required to continue community living and maximize independence.

Adverse drug events in elderly patients receiving home health services following hospital discharge.

OBJECTIVE: To assess incidence, healthcare consequences, and identify risk factors for adverse drug events (ADEs) in elderly patients receiving home health services during the month following hospital discharge. METHOD: This was a prospective cohort study of three home health agencies in Madison, Wisconsin, and its surrounding area. The sample consisted of 256 participants aged > or =65 years who were hospitalized for medical illness, received home nursing after discharge, and completed the one-month interview. The main outcome measure was self-reported ADEs (possible, probable, or definite) during the month following hospital discharge. RESULTS: Incidence of ADEs was 20%. Fifty-two participants (20.3%) reported 64 ADEs: 23 possible, 37 probable, and four definite. The most common ADEs involved the gastrointestinal tract (31.3%) and the central nervous system (31.3%). Of 53 ADEs reported to providers, 59% of the drugs were discontinued or altered. One ADE resulted in hospitalization. In logistic regression, female gender (OR = 2.26; 95% CI 1.06 to 4.77) and the interaction between number of new medications and cognition were significantly associated with ADEs. The risk of an event increased with the number of new medications at discharge; however, risk was elevated primarily for participants with lower cognition. CONCLUSIONS: ADEs were common during the month following hospital discharge, were more frequent in women, and often resulted in medication changes. Individuals at particular risk were those with lower cognition who were discharged with several new medications.

Use of an ambulation assistive device predicts functional decline associated with hospitalization.

BACKGROUND: Loss of functional independence occurs frequently with hospitalization. In community-dwelling elders, lower extremity disability is an important predictor of functional loss. Ambulation assistive devices (canes, walkers), as markers of lower extremity disability, may predict functional decline associated with hospitalization, but this has not been evaluated previously. We sought to determine the association of mobility impairment, as indicated by cane or walker use prehospitalization, with adverse outcomes at hospital discharge and 3 months post discharge. METHODS: Subjects were community-dwelling adults (N = 1212) aged 70 and older, hospitalized for acute medical illness. The study was a secondary analysis of the Hospital Outcomes Project for the Elderly, a prospective randomized trial at three university and two private acute-care hospitals, which randomized patients to usual care or an intervention group designed to maintain functional abilities. RESULTS: After controlling for demographic and illness-related characteristics and prehospital function, mobility impairment was significantly associated with functional decline. Use of a walker was associated with 2.8 times increased risk for decline in ADL function by hospital discharge (p = .0002). Three months after discharge, patients who used assistive devices prior to hospitalization were more likely to have declined in both ADLs (p = .02) and IADLs (p = .003). CONCLUSIONS: Hospitalized patients with mobility impairment, as indicated by use of a cane or a walker, are at high risk for functional decline. Such patients may benefit from more intensive in-hospital and post-hospital rehabilitative therapy to maintain function.

Falls in the elderly: office-based evaluation, prevention, and treatment.

Falls are serious and relatively common, and can result in significant morbidity and mortality for older adults. The office evaluation should focus on detecting underlying risk factors, adjusting high-risk medications, modifying unsafe behaviors, assessing home safety, and referring for physical therapy. Recent randomized trials have demonstrated successful interventions to decrease falls.

Gender differences in hallway ambulation by older adults hospitalized for medical illness.

Bed rest during hospitalization predisposes patients to declines in balance, strength, and bone mass, and may contribute to falls and fractures after discharge. Periodic ambulation may help prevent these adverse consequences. However it is unknown to what extent men and women ambulate during hospitalization. We observed hallway ambulation by adults age 55 and over hospitalized on 3 medical units of the University of Wisconsin Hospital. Hallways were observed during 24 three-hour periods covering the interval from 8 AM to 8 PM. Prior to each 3-hour observation, nursing staff were asked about characteristics of older patients who were able to ambulate in the hallways. Results showed that women spent significantly less time ambulating compared to men (1.6 versus 4.2 minutes per 3-hour period, p = .047), and were less likely to walk independent of hospital staff (10.4% versus 23.5%, p = .049). If these findings of gender differences in mobility are validated in other studies, they imply that in-hospital rehabilitation programs may need to particularly target women.

Immobility and falls.

Immobility is a common problem for hospitalized older adults. Excessive bed rest results in multiple adverse physiologic consequences and may contribute to functional decline and increased risk for falls in the hospital setting. About 2% of hospitalized older adults fall during hospitalization. Risk factors for in-hospital falls includes cognitive impairment, mobility impairment, specific diagnoses, multiple comorbidities, and psychotropic medications. Appropriate actions to prevent immobility and falls include increasing exercise and activity levels, improving the hospital environment, and decreasing the use of psychotropic medications. Bed alarms and increased supervision for high-risk patients also may help prevent falls.

Iatrogenic ureteric injuries: approaches to etiology and management.

Injury to the ureter is a risk of any pelvic or abdominal surgery, including laparoscopy and ureteroscopy. The morbidity associated with such injury may be serious, resulting in increased hospital stay, compromise of the original surgical outcome, secondary invasive interventions, reoperation, potential loss of renal function and deterioration of the patient's quality of life. Management of ureteric injuries, in conjunction with frank and open dialogue with the patient, can lead to an optimal outcome. For ureteral ligation, removal of the suture and assessment of ureteral viability are recommended, with surgical correction if necessary. For partial transection primary closure is suggested over stent placement. For uncomplicated upper- and middle-third ureteral injury ureteroureterostomy is the procedure of choice. For injuries above the pelvic brim several procedures are available: ureteroureterostomy, ureteroileal interposition and nephrectomy. For injuries below the pelvic brim ureteroneocystostomy is recommended with a psoas hitch or Boari bladder flap. To decrease the incidence of iatrogenic ureteral injury, a sound knowledge of abdominal and pelvic anatomy is the best prevention. If the proposed operation is likely to be close to the ureter, the ureter should be identified at the pelvic brim. If the dissection is likely to be difficult, preoperative intravenous pyelography and placement of a ureteral catheter may help in identifying and protecting the ureter.

A randomized controlled trial to assess the incidence of new onset hypertension in patients after shock wave lithotripsy for asymptomatic renal calculi.

PURPOSE: To answer the question of whether extracorporeal shock wave lithotripsy (ESWL*) induces hypertension, a prospective, randomized controlled trial of normotensive patients with asymptomatic renal calculi was designed. MATERIALS AND METHODS: Patients were randomized to receive immediate ESWL versus observation, reserving ESWL for the onset of symptoms. The rates of new onset hypertension were evaluated for both groups. RESULTS: There was no observed difference in the incidence of hypertension between the treatment and observation groups. CONCLUSIONS: The risk of hypertension in patients undergoing ESWL therapy is similar to that of a control cohort of initially observed asymptomatic patients.

New walking dependence associated with hospitalization for acute medical illness: incidence and significance.

BACKGROUND: The ability to walk independently may become jeopardized during hospitalization. It is unknown which patients are at risk for decline in walking, or to what extent patients will recover. The purpose of this study was to determine the incidence of, risk factors for, and outcomes associated with new walking dependence after hospitalization. METHODS: Baseline characteristics and functional outcomes at hospital discharge and 3 months after discharge were measured for 1,181 community-dwelling adults aged 70 and over who were hospitalized for medical illness and who walked independently prior to hospitalization. RESULTS: At discharge, 16.8% of patients were newly dependent in walking. Risk factors included age > 85 (odds ratio [OR] 2.7 vs age <75, 95% confidence interval [CI] 1.5-4.9), functional impairment before hospitalization (OR 1.4 for each impairment, CI 1.1-1.7), Caucasian race (OR 1.9, CI 1.1-3.3), and use of a walker (OR 1.8, CI 1.04-3.2) or wheelchair (OR 3.2, CI 1.3-7.6) before admission. A cancer diagnosis (OR 2.3, CI 1.2-4.6) and more than four comorbid conditions (OR 1.9, CI 1.2-3.0) were also predictive. New walking dependence was associated with discharge to a nursing home (p = .0001) and higher postdischarge mortality (p < .001). Twenty-seven percent of patients who developed new walking dependence and survived 3 months continued to be dependent in walking. CONCLUSIONS: New walking dependence occurs frequently with hospitalization, may be predicted by specific risk factors, and portends a poor prognosis. Strategies are needed to help at-risk patients maintain walking independence during and after hospitalization.

Plant extracts in the medical management of benign prostatic hyperplasia: fact or fiction?

The objective of this study was to critically review the published literature on the role of phytotherapeutic agents and phytosterols (also referred to as plant extracts) in the medical management of benign prostatic hyerplasia. Data sources included a bibliographic database that was searched to retrieve articles on benign prostatic hyperplasia with a time constraint of 1985-1993. Indexing terms used included plant extracts, phytosterols, cernilton, paraprost and medical management. Studies selected were randomized trials incorporating plant extracts. English abstracts were reviewed for articles published in other languages and these reviews are noted. English articles were critically reviewed based on study design, patient selection, length of follow up, postulated mechanisms of action and benign prostatic hyperplasia subjective and objective outcome measures. A number of plant extracts are being used in the management of benign prostatic hyperplasia, predominantly in Europe. These plant extracts, which are biochemically heterogenous, have been found to act through a variety of mechanisms: an anti-inflammatory effect, a decrease in globulin, a direct cytotoxic effect, anti-prolactin activity and bladder compliance modification. More importantly, these plant extracts have not been associated with the side effects of chemical castration. Their alleged efficacy may be based upon a mechanism which is currently not understood and a combination of these extracts with accepted medications may have the potential of improving the overall efficacy of medical therapy in the treatment of benign prostatic hyperplasia. Despite the shortcomings of the published trials, there is enough evidence to warrant additional study in the form of randomized control trials using scientific validated outcome measures. Using validated scores with patients of mild to moderate symptomatology would help to further elucidate the relative efficacy of cernilton, curbicin and permixon.

Screening for prostate cancer. A decision analytic view.

OBJECTIVE: To determine the clinical and economic effects of screening for prostate cancer with prostate-specific antigen (PSA), transrectal ultrasound (TRUS), and digital rectal examination (DRE). DESIGN: Decision analytic cost-utility analysis comparing four screening strategies with a strategy of not screening. We assumed that the cancer detection rate and stage distribution were predicted by each combination of tests and that localized cancer was treated with radical prostatectomy. For each strategy, we calculated life expectancy, quality-adjusted life expectancy (QALE), and cost-utility ratios for unselected and high-prevalence populations. DATA: Probabilities and rates for clinical events were gathered from published data. We assessed utilities by the time-trade-off method using urologists, radiation oncologists, and internists as subjects. The Clinical Cost Manager at the New England Medical Center provided cost data. RESULTS: In unselected men between the ages of 50 and 70 years, screening with PSA or TRUS prolonged unadjusted life expectancy but diminished QALE. Screening with DRE alone yielded no reduction in mortality at any age. All programs increased costs. Results were sensitive only to assumptions about the efficacy of treatment. In high-prevalence populations, screening produced a similar pattern: gains in unadjusted life expectancy, losses in QALE, and increased costs. CONCLUSIONS: Our analysis does not support using PSA, TRUS, or DRE to screen asymptomatic men for prostatic cancer. Screening may result in poorer health outcomes and will increase costs dramatically. Assessment of comorbidity, risk attitude, and valuation of sexual function may identify individuals who will benefit from screening, but selecting high-prevalence populations will not improve the benefit of screening.

A biochemical and histological comparison of vascularized and free fat grafts in the rabbit.

An experimental study, in 20 rabbits, of free (i.e., nonvascularized) versus vascularized fat tissue transfer was undertaken. The purpose was to study the biochemical and histological changes in the two types of fat grafts compared with normal fat tissue over a period of 16 weeks. The left inguinal fat pad was transferred freely to the contralateral side; the right inguinal fat pad was transferred to the left side where the pedicle was anastomosed to the left femoral artery and vein. Macroscopically, at all postoperative times, the transferred free fat had a harder consistency, was more adherent to the surroundings, and was less pliable than the vascularized fat, which was similar to normal fat. Histologically, free fat tissue displayed near complete degeneration at 2 and 4 weeks, but recovered to essentially normal appearance by 16 weeks. Apart from some degeneration evident at 2 weeks, vascularized fat tissue retained a normal histological appearance to 16 weeks. Biochemical analysis demonstrated minor increases of collagen deposits in free fat grafts, but negligible changes were observed in the vascularized fat grafts. Free fat grafts were significantly dehydrated relative to the vascularized fat grafts and control fat (p < 0.01). Based on these findings, we suggest that the clinical use of vascularized fat tissue transfer would be preferable in most circumstances to free fat transfer.