[Polypharmacy and medication review in the context of prehabilitation]. / Polypharmazie und Medikamentencheck im Kontext der Prähabilitation.

Against the background of typical geriatric multimorbidity and with the particular vulnerability of geriatric patients, polypharmacy deserves special attention. In accordance with the guidelines, medication should not only be reviewed regularly, but also on an ad hoc basis and with each hospital stay-and also in the context of prehabilitation. Thus, not only substances that interfere with the currently planned intervention, anesthesia, or risk of bleeding should be considered, but any medication that increases common risks for geriatric patients. These include drugs that cause or increase a tendency to fall, induce delirium, or alter the comedication through potential drug-drug interactions. Measures to minimize the risk include the following: exact documentation of medications, structured and complete transfer of information, patient and family training about any side effects that may occur, a recall system for possible laboratory checks, and compliance with the instructions for taking the medication.

The role of temperament in evaluating the relationship between symptoms and signs in dry eye disease.

OBJECTIVES: In this study, we aimed to evaluate the relationship between symptoms and objective findings and dry eye (DE) patients' personalities and levels of depression and anxiety. METHODS: The study group consisted of 67 DE patients who presented to the ophthalmology clinic with symptoms of dry eye disease (DED) and were first diagnosed. Patients underwent a complete ophthalmologic examination, including tear-film break-up time (TBUT), Schirmer 1 and Ocular Surface Disease Index (OSDI). All subjects also completed the Temperament and Character Inventory (TCI), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). RESULTS: No relationship was found for the Schirmer 1 Test and TBUT with psychological parameters or OSDI scores. When compared with the normal values for the Turkish population, sub-dimensions of temperament in DED; novelty seeking (NS) was significantly lower (P<0.001); harm avoidance (HA) (P=0.014), and persistence (P<0.001) were significantly higher. Significant positive correlation with HA and significant negative correlation with NS were found for the OSDI results. Furthermore, our mediation model revealed that anxiety mediated the effect of NS and HA on OSDI. CONCLUSION: The significant association of temperament sub-dimensions with OSDI scores in the DED group may play a role in explaining the inconsistency between symptoms and signs. Professionals who care for DED should consider temperament sub-dimensions when they detect discordance between symptoms and signs.

[Fusion biopsies for primary diagnosis of prostate cancer : Implementation, benefits, and clinical aspects]. / Die Fusionsbiopsie in der Primärdiagnostik des Prostatakarzinoms : Durchführung, Nutzen und klinische Aspekte.

Prostate carcinoma is one of the most common tumors worldwide. Histological confirmation by biopsy is an obligatory part of the diagnostic approach. The main problem of the 10-12-fold transrectal ultrasound-guided (TRUS) biopsy, which has so far been regarded as the gold standard, is the underdiagnosis of clinically significant cancer. MRI-based procedures, so-called fusion biopsies, have shown superior results when compared to conventional biopsies. There are three different approaches (cognitive and software-based MRI/TRUS fusion and in-bore biopsy) with comparable detection rates but differences in the technical aspects and time involvement. In order to reduce fusion errors, targeted biopsies should consist of multiple cores. There is currently no clear preference for the access pathway (transrectal or transperineal), but clinical parameters such as infection risk or location of the tumor can influence the decision. While the German S3 guideline considers MRI prior to primary biopsy to be optional, the 2019 European Association of Urology guidelines already recommend MRI prior to biopsy for all patients. The combination of MRI-targeted and systematic biopsy offers the highest detection rates with the disadvantage that more low-risk tumors are diagnosed. Both the patient and the urologist benefit from an improved informative value of the biopsy when deciding on active surveillance as well as when planning invasive therapies.

Twelve-month prostate volume reduction after MRI-guided transurethral ultrasound ablation of the prostate.

PURPOSE: To quantitatively assess 12-month prostate volume (PV) reduction based on T2-weighted MRI and immediate post-treatment contrast-enhanced MRI non-perfused volume (NPV), and to compare measurements with predictions of acute and delayed ablation volumes based on MR-thermometry (MR-t), in a central radiology review of the Phase I clinical trial of MRI-guided transurethral ultrasound ablation (TULSA) in patients with localized prostate cancer. MATERIALS AND METHODS: Treatment day MRI and 12-month follow-up MRI and biopsy were available for central radiology review in 29 of 30 patients from the published institutional review board-approved, prospective, multi-centre, single-arm Phase I clinical trial of TULSA. Viable PV at 12 months was measured as the remaining PV on T2-weighted MRI, less 12-month NPV, scaled by the fraction of fibrosis in 12-month biopsy cores. Reduction of viable PV was compared to predictions based on the fraction of the prostate covered by the MR-t derived acute thermal ablation volume (ATAV, 55°C isotherm), delayed thermal ablation volume (DTAV, 240 cumulative equivalent minutes at 43°C thermal dose isocontour) and treatment-day NPV. We also report linear and volumetric comparisons between metrics. RESULTS: After TULSA, the median 12-month reduction in viable PV was 88%. DTAV predicted a reduction of 90%. Treatment day NPV predicted only 53% volume reduction, and underestimated ATAV and DTAV by 36% and 51%. CONCLUSION: Quantitative volumetry of the TULSA phase I MR and biopsy data identifies DTAV (240 CEM43 thermal dose boundary) as a useful predictor of viable prostate tissue reduction at 12 months. Immediate post-treatment NPV underestimates tissue ablation. KEY POINTS: • MRI-guided transurethral ultrasound ablation (TULSA) achieved an 88% reduction of viable prostate tissue volume at 12 months, in excellent agreement with expectation from thermal dose calculations. • Non-perfused volume on immediate post-treatment contrast-enhanced MRI represents only 64% of the acute thermal ablation volume (ATAV), and reports only 60% (53% instead of 88% achieved) of the reduction in viable prostate tissue volume at 12 months. • MR-thermometry-based predictions of 12-month prostate volume reduction based on 240 cumulative equivalent minute thermal dose volume are in excellent agreement with reduction in viable prostate tissue volume measured on pre- and 12-month post-treatment T2w-MRI.

[Focal therapy of prostate cancer]. / Fokale Therapie des Prostatakarzinoms.

The target of focal therapy (FT) in prostate cancer (PC) is partial treatment of the prostate aiming at preserving surrounding anatomical structures. The intention is to minimize typical side effects of radical treatment options combined with local tumor control. Numerous established and new technologies are used. Results of published studies showed a good safety profile, few side effects and good preservation of functional results. Oncologic long-term data are lacking so far. Photodynamic therapy (PDT) is the only technology that has been studied in a published prospective randomized trial. The FT is challenged by the multifocality of PC; therefore, the quality of prostate biopsy, histopathological assessment as well as imaging are of paramount importance. Multiparametric magnetic resonance imaging (MRI) has gained increasing importance. The FT is experimental and should only be offered within clinical trials.

The role of salvage extended lymph node dissection in patients with rising PSA and PET/CT scan detected nodal recurrence of prostate cancer.

BACKGROUND: Non-prostatic bed recurrence of prostate cancer (PCa) is usually treated with androgen deprivation therapy (ADT). We analyzed the impact of salvage extended lymph node dissection (sLND) on cancer control in patients with rising PSA and lymph node (LN) metastases. METHODS: Between 2009 and 2016 we performed sLND in 87 patients with biochemical recurrence (BCR) and positive LNs on 18FEC and 68Ga-PSMA positron emission tomography/X-ray computer tomography (PET/CT) after primary treatment (PT) of PCa. Intra- and postoperative complications according to Clavien-Dindo were assessed and the rates of biochemical response (BR), BCR-free and clinical recurrence (CR)-free survival, as well as time to initiation of systemic treatment were evaluated. RESULTS: Mean age of patients and mean PSA at sLND was 66.7 years (46-80 years) and 2.63 ng ml-1 (1.27-3.75 ng ml-1), respectively. With 87.4% radical prostatectomy (RP) was the most common PT. In all, 57.9% of patients additionally underwent adjuvant/salvage radiation therapy (RT) and 18.4% received ADT before sLND. Complete BR (cBR) was diagnosed in 27.5% of patients and incomplete BR in 40.6%. In total, 62.2% of patients remained without ADT at follow-up. With a median follow-up of 21 months (1-75 months), the cancer-specific mortality rate was 3.7%. The 3-year BCR-free, systemic therapy-free and CR-free survival rates for patients with cBR were 69.3%, 77.0% and 75%, respectively. CONCLUSIONS: sLND can be performed without significant complications and achieves an immediate BR, thus allowing a significant postponement of systemic therapy in selected patients with BCR and nodal recurrence of PCa. Therefore, sLND following 68Ga-PSMA PET/CT should be considered as part of a multimodal diagnostic and treatment concept for selective patients.

Further reduction of disqualification rates by additional MRI-targeted biopsy with transperineal saturation biopsy compared with standard 12-core systematic biopsies for the selection of prostate cancer patients for active surveillance.

BACKGROUND: Active surveillance (AS) is commonly based on standard 10-12-core prostate biopsies, which misclassify ~50% of cases compared with radical prostatectomy. We assessed the value of multiparametric magnetic resonance imaging (mpMRI)-targeted transperineal fusion-biopsies in men under AS. METHODS: In all, 149 low-risk prostate cancer (PC) patients were included in AS between 2010 and 2015. Forty-five patients were initially diagnosed by combined 24-core systematic transperineal saturation biopsy (SB) and MRI/transurethral ultrasound (TRUS)-fusion targeted lesion biopsy (TB). A total of 104 patients first underwent 12-core TRUS-biopsy. All patients were followed-up by combined SB and TB for restratification after 1 and 2 years. All mpMRI examinations were analyzed using PIRADS. AS was performed according to PRIAS-criteria and a NIH-nomogram for AS-disqualification was investigated. AS-disqualification rates for men initially diagnosed by standard or fusion biopsy were compared using Kaplan-Meier estimates and log-rank tests. Differences in detection rates of the SB and TB components were evaluated with a paired-sample analysis. Regression analyses were performed to predict AS-disqualification. RESULTS: A total of, 48.1% of patients diagnosed by 12-core TRUS-biopsy were disqualified from AS based on the MRI/TRUS-fusion biopsy results. In the initial fusion-biopsy cohort, upgrading occurred significantly less frequently during 2-year follow-up (20%, P<0.001). TBs alone were significantly superior compared with SBs alone to detect Gleason-score-upgrading. NPV for Gleason-upgrading was 93.5% for PIRADS⩽2. PSA level, PSA density, NIH-nomogram, initial PIRADS score (P<0.001 each) and PIRADS-progression on consecutive MRI (P=0.007) were significant predictors of AS-disqualification. CONCLUSIONS: Standard TRUS-biopsies lead to significant underestimation of PC under AS. MRI/TRUS-fusion biopsies, and especially the TB component allow more reliable risk classification, leading to a significantly decreased chance of subsequent AS-disqualification. Cancer detection with mpMRI alone is not yet sensitive enough to omit SB on follow-up after initial 12-core TRUS-biopsy. After MRI/TRUS-fusion biopsy confirmed AS, it may be appropriate to biopsy only those men with suspected progression on MRI.

[Focal therapy for small renal masses : Observation, ablation or surgery]. / Fokale Therapie von kleinen Nierentumoren : Beobachtung, Ablation oder Operation.

BACKGROUND: The rising incidence of renal cell carcinoma, its more frequent early detection (stage T1a) and the increasing prevalence of chronic renal failure with higher morbidity and shorter life expectancy underscore the need for multimodal focal nephron-sparing therapy. DISCUSSION: During the past decade, the gold standard shifted from radical to partial nephrectomy. Depending on the surgeon's experience, the patient's constitution and the tumor's location, the intervention can be performed laparoscopically with the corresponding advantages of lower invasiveness. A treatment alternative can be advantageous for selected patients with high morbidity and/or an increased risk of complications associated with anesthesia or surgery. Corresponding risk stratification necessitates previous confirmation of the small renal mass (cT1a) by histological examination of biopsy samples. Active surveillance represents a controlled delay in the initiation of treatment. RESULTS: Percutaneous radiofrequency ablation (RFA) and laparoscopic cryoablation are currently the most common treatment alternatives, although there are limitations particularly for renal tumors located centrally near the hilum. More recent ablation procedures such as high intensity focused ultrasound (HIFU), irreversible electroporation, microwave ablation, percutaneous stereotactic ablative radiotherapy and high-dose brachytherapy have high potential in some cases but are currently regarded as experimental for the treatment of renal cell carcinoma.

Improved detection of anterior fibromuscular stroma and transition zone prostate cancer using biparametric and multiparametric MRI with MRI-targeted biopsy and MRI-US fusion guidance.

BACKGROUND: The objective of this study was to analyze the potential of prostate magnetic resonance imaging (MRI) and MRI/transrectal ultrasound-fusion biopsies to detect and to characterize significant prostate cancer (sPC) in the anterior fibromuscular stroma (AFMS) and in the transition zone (TZ) of the prostate and to assess the accuracy of multiparametric MRI (mpMRI) and biparametric MRI (bpMRI) (T2w and diffusion-weighted imaging (DWI)). METHODS: Seven hundred and fifty-five consecutive patients underwent prebiopsy 3 T mpMRI and transperineal biopsy between October 2012 and September 2014. MRI images were analyzed using PIRADS (Prostate Imaging-Reporting and Data System). All patients had systematic biopsies (SBs, median n=24) as reference test and targeted biopsies (TBs) with rigid software registration in case of MRI-suspicious lesions. Detection rates of SBs and TBs were assessed for all PC and sPC patients defined by Gleason score (GS)⩾3+4 and GS⩾4+3. For PC, which were not concordantly detected by TBs and SBs, prostatectomy specimens were assessed. We further compared bpMRI with mpMRI. RESULTS: One hundred and ninety-one patients harbored 194 lesions in AFMS and TZ on mpMRI. Patient-based analysis detected no difference in the detection of all PC for SBs vs TBs in the overall cohort, but in the repeat-biopsy population TBs performed significantly better compared with SBs (P=0.004 for GS⩾3+4 and P=0.022 for GS⩾4+3, respectively). Nine GS⩾4+3 sPCs were overlooked by SBs, whereas TBs missed two sPC in men undergoing primary biopsy. The combination of SBs and TBs provided optimal local staging. Non-inferiority analysis showed no relevant difference of bpMRI to mpMRI in sPC detection. CONCLUSIONS: MRI-targeted biopsies detected significantly more anteriorly located sPC compared with SBs in the repeat-biopsy setting. The more cost-efficient bpMRI was statistically not inferior to mpMRI in sPC detection in TZ/AFMS.

Evaluation of the ESUR PI-RADS scoring system for multiparametric MRI of the prostate with targeted MR/TRUS fusion-guided biopsy at 3.0 Tesla.

OBJECTIVES: To evaluate the Prostate Imaging Reporting and Data System (PI-RADS) proposed by the European Society of Urogenital Radiology (ESUR) for detection of prostate cancer (PCa) by multiparametric magnetic resonance imaging (mpMRI) in a consecutive cohort of patients with magnetic resonance/transrectal ultrasound (MR/TRUS) fusion-guided biopsy. METHODS: Suspicious lesions on mpMRI at 3.0 T were scored according to the PI-RADS system before MR/TRUS fusion-guided biopsy and correlated to histopathology results. Statistical correlation was obtained by a Mann-Whitney U test. Receiver operating characteristics (ROC) and optimal thresholds were calculated. RESULTS: In 64 patients, 128/445 positive biopsy cores were obtained out of 95 suspicious regions of interest (ROIs). PCa was present in 27/64 (42%) of the patients. ROC results for the aggregated PI-RADS scores exhibited higher areas under the curve compared to those of the Likert score. Sensitivity/Specificity for the following thresholds were calculated: 85 %/73 % and 67 %/92 % for PI-RADS scores of 9 and 10, respectively; 85 %/60 % and 56 %/97 % for Likert scores of 3 and 4, respectively [corrected. CONCLUSIONS: The standardised ESUR PI-RADS system is beneficial to indicate the likelihood of PCa of suspicious lesions on mpMRI. It is also valuable to identify locations to be targeted with biopsy. The aggregated PI-RADS score achieved better results compared to the single five-point Likert score. KEY POINTS: • The ESUR PI-RADS scoring system was evaluated using multiparametric 3.0-T MRI. • To investigate suspicious findings, transperineal MR/TRUS fusion-guided biopsy was used. • PI-RADS can guide biopsy locations and improve detection of clinically significant cancer. • Biopsy procedures can be optimised, reducing unnecessary negative biopsies for patients. • The PI-RADS scoring system may contribute to more effective prostate MRI.

[MRI navigated stereotactic prostate biopsy: fusion of MRI and real-time transrectal ultrasound images for perineal prostate biopsies]. / MRT-navigierte stereotaktische Prostatabiopsie : Echtzeitfusion von MRT und transrektalem Ultraschall zu perinealen Prostatastanzbiopsien.

BACKGROUND: A key challenge for prostate cancer (PC) therapy is to exactly diagnose tumor lesions. In this context we describe a new stereotactic prostate biopsy system, which integrates pre-interventional MRI with peri-interventional ultrasound for targeted perineal prostate biopsies. Furthermore, the novel system allows exact documentation of biopsies in three dimensions. PATIENTS AND METHODS: Stereotactic biopsy was performed in 50 consecutive men with suspicion of PC [median age 67 years (42-77), mean PSA 8.9±6.8 ng/ml, and mean prostate volume 51±23.7 ml]. Twenty-five of these patients (50%) had already had a negative transrectal ultrasound (TRUS)-guided biopsy. All men underwent multiparametric, contrast-enhanced 3T MRI without endorectal coil. Suspicious lesions were marked before the obtained data were transferred to a novel stereotactic biopsy system. Using a custom-made biplane TRUS probe mounted on a stepper, 3-D ultrasound data were generated and fused with the MRI. As a result, suspicious MRI lesions were superimposed onto the TRUS data. Next, 3-D biopsy planning was performed including systematic biopsies from the peripheral zone of the prostate. According to local standards patients were treated with perioperative quinolone antibiotics and applied a rectal enema the evening before the procedure. Perineal biopsies were taken under live US imaging, and the location of each biopsy was documented in an individual 3-D model. Feasibility, safety, target registration error, and cancer detection were evaluated. RESULTS: The median number of biopsies taken per patient was 24 (12-36). In 27 men of the initial cohort of 50 consecutive patients presented here, biopsy samples showed PC (54%). In patients undergoing their first biopsy, cancerous lesions were diagnosed in 13 of 19 patients (68%). The result was positive in 36% of men undergoing a re-biopsy without previous cancer diagnosis (9/25). A positive correlation between MRI findings and histopathology was found in 72%. In MRI lesions marked as highly suspicious, the tumor detection rate was 100% (13/13). Looking at single cores from highly suspicious lesions, 40 of 75 (53%) biopsies were positive. The target registration error of the first 1,159 biopsy cores was 1.7 mm. Regarding adverse effects, one patient experienced urinary retention and one patient a perineal hematoma. Urinary tract infections did not occur. CONCLUSION: Perineal stereotactic prostate biopsies guided by the combination of MRI and ultrasound allow effective examination of suspicious MRI lesions. Each biopsy core taken is documented accurately for its location in 3-D enabling MRI validation and tailored treatment planning. The morbidity of the procedure was minimal.

Leishmania donovani complex (Kinetoplastida, Trypanosomatidae): comparison of deoxyribonucleic acid based techniques for typing of isolates from Ethiopia.

In Ethiopia, visceral leishmaniasis (VL) is an increasing public health concern. Recently, a new outbreak of VL claimed the lives of hundreds of Ethiopians. Mapping its distribution and the identification of the causative Leishmania species is important for proper use of resources and for control planning. The choice of appropriate typing technique is the key for determining the infecting species. Here we compared three deoxyribonucleic acid (DNA) based markers. We used, for the first time, cpbE and cpbF (cpbE/F) PCR-RFLP and demonstrated that it clearly differentiates Leishmania donovani from Leishmania infantum. The cpbE/F PCR-RFLP gave identical banding pattern for all L. donovani strains irrespective of their geographic origin. With the K26 (primers) PCR-RFLP, the L. donovani strains gave a banding pattern different from L. infantum and showed variation with geographic origin. The Ethiopian isolates typed as L. donovani by the PCR-RFLP of the cpbE/F (gene) and K26 (primers) showed two types of patterns with the T2/B4 (primers) PCR-RFLP; one group with L. infantum-like and the other L. donovani-like pattern. Phylogenetic analysis using cpbE/F sequences showed variation with geographic origin of strains and the African strains of L. donovani are more distantly related to L. infantum. Moreover, the Ethiopian isolates were seen to be closely related to the Sudanese, Kenyan and Indian strains. Thus, we recommend the use of more than one marker to study the population genetics of L. donovani complex.

Leishmania (Kinetoplastida): species typing with isoenzyme and PCR-RFLP from cutaneous leishmaniasis patients in Ethiopia.

Cutaneous leishmaniasis (CL) is an increasing public health problem in Ethiopia. There is a concern that it is spreading with increased incidence. In this study, we used isoenzyme electrophoresis and internal transcribed spacer one (ITS1) PCR-RFLP techniques to identify Leishmania species from CL patients in Ethiopia. We obtained isolates from 55 localized cutaneous leishmaniasis (LCL), 3 diffused cutaneous leishmaniasis (DCL) and 36 biopsy samples from 34 LCL and 2 DCL cases from All Africa Leprosy and Tuberculosis Rehabilitation and Training Center (ALERT) and clinically diagnosed CL cases from Ochollo village. Both isoenzyme and ITS1 PCR-RFLP techniques showed that Leishmania aethiopica (L. aethiopica) was the aetiologic agent in all cases. Our study also showed that ITS1 PCR-RFLP could identify Leishmania species from biopsy samples and suggests the method could be used for epidemiological surveillance of leishmaniasis in Ethiopia and for species-specific diagnosis.

Nonresolving or slowly resolving pneumonia.

Given the variability in rate of radiographic resolution, it remains controversial to decide when to initiate an invasive diagnostic work-up for nonresolving or slowly resolving pulmonary infiltrates. In immunocompetent patients who present with classical features of CAP (i.e., fever, chills, productive cough, new pulmonary infiltrate), clinical response to therapy is the most important determinant for further diagnostic studies. Within the first few days, persistence or even progression of infiltrates on chest radiographs is not unusual. Defervescence, diminished symptoms, and resolution of leukocytosis strongly support a response to antibiotic therapy, even when chest radiographic abnormalities persist. In this context, observation alone is reasonable, and invasive procedures can be deferred. Serial radiographs and clinical examinations dictate subsequent evaluation. In contrast, when clinical improvement has not occurred and chest radiographs are unchanged or worse, a more aggressive approach is warranted. In this setting, we advise fiberoptic bronchoscopy with BAL and appropriate cultures for bacteria, legionella, fungi, and mycobacteria. When endobronchial anatomy is normal and there is no purulence to suggest infection, TBBs should be done to exclude noninfectious causes (discussed earlier) or infections attributable to mycobacteria or fungi. An aggressive approach is also warranted in patients who are clinically stable or improving when the rate of radiographic resolution is delayed. As discussed earlier, what constitutes excessive delay is controversial, and depends upon the acuity of illness, specific pathogen, extent of involvement (i.e., lobar versus multilobar), comorbidities, and diverse host factors. Stable infiltrates even 2 to 4 weeks after institution of antibiotic therapy does not mandate intervention provided patients are improving clinically. Invasive techniques can also be deferred when unequivocal, albeit incomplete, radiographic resolution can be demonstrated. Lack of at least partial radiographic resolution by 6 weeks, even in asymptomatic patients, however, deserves consideration of alternative causes (e.g., endobronchial obstructing lesions, or noninfectious causes). Fiberoptic bronchoscopy with BAL and TBBs has minimal morbidity and is the preferred initial invasive procedure for detecting endobronchial lesions or substantiating noninfectious causes. The yield of bronchoscopy depends on demographics, radiographic features, and pre-test likelihood. In the absence of specific risk factors, the incidence of obstructing lesions (e.g., bronchogenic carcinomas, bronchial adenomas, obstructive foreign body) is low. Bronchogenic carcinoma is rare in nonsmoking, young (< 50 years) patients but is a legitimate consideration in older patients with a history of tobacco abuse. Non-neoplastic causes (e.g., pulmonary vasculitis, hypersensitivity pneumonia, etc.) should be considered when specific features are present (e.g., hematuria, appropriate epidemiologic exposures). Ancillary serologic tests or biopsies of extrapulmonary sites are invaluable in some cases. In rare instances, surgical (open or VATS) biopsy is necessary to diagnose refractory or non-resolving "pneumonias."

Iatrogenic congestive heart failure in older adults: clinical course and prognosis.

OBJECTIVE: To determine the prevalence, risk factors, clinical course, and prognosis of iatrogenic congestive heart failure in older patients. DESIGN AND SETTING: Prospective observational study at a university teaching hospital. PARTICIPANTS: A total of 401 patients 70 years of age or older hospitalized with congestive heart failure. The mean age was 80 +/- 6 years; 59% were female, and 65% were white. MEASUREMENTS: Comprehensive data, including an assessment of the etiology and precipitating factors leading to the development of heart failure, were collected at the time of diagnosis. Iatrogenic heart failure was defined as heart failure precipitated by medications or excessive fluid administration, or occurring as a procedural complication. All patients were followed for 1 year, and the primary outcome measure was total mortality. RESULTS: Using strict criteria, 28 patients (7.0%) were considered to have iatrogenic heart failure. Compared with noniatrogenic patients (n = 373), iatrogenic cases had less severe premorbid cardiac disease but more marked noncardiac disability and longer hospital stays (29 +/- 24 vs 13 +/- 12 days, P < .001). Hospital mortality was 32% in iatrogenic heart failure patients compared with 9% in noniatrogenic cases (P < .001). Cumulative mortality at 1 year was 68% in iatrogenic patients versus 39% in noniatrogenic patients (P < .01). Using a Cox proportional hazards model, iatrogenic congestive heart failure was associated with a relative mortality risk during follow-up of 2.5 (95% confidence interval 1.5-4.3) after adjusting for age, sex, prior history of heart failure, New York Heart Association class, diabetes mellitus, systolic blood pressure, hemoglobin, blood urea nitrogen, and serum albumin. CONCLUSIONS: Frail, debilitated older patients are at increased risk for developing iatrogenic heart failure, even in the absence of clinically evident cardiac disease. In this population, iatrogenic heart failure serves as a marker for poor short- and long-term prognosis, but further study is required to determine the optimal approach to management of these patients.

Effect of moricizine on heart rate variability in normal subjects.

We investigated the effects of moricizine HCl, a type Ic anti-arrhythmic agent, on heart rate variability. Decreased heart rate variability is a risk factor for mortality in post-MI and other patient populations, and some antiarrhythmic drugs decrease heart rate variability. Normal volunteers (10 M, 11 F, age 19-39 years) received blinded placebo and moricizine HCl at 200 mg twice daily for 5 days. On day 4, a 24-h ECG was obtained, and time and frequency domain measures of heart rate variability based on normal-to-normal intervals were computed. Moricizine decreased both time and frequency domain measures of heart rate variability. Significant reductions were seen for SDNNIDX (the average S.D. for N-Ns for each 5-min interval in ms) and pNN50 (the proportion of successive N-N differences > 50 ms in percent) in the time domain, and very low (0.0033-0.04 Hz), low (0.04-0.15 Hz) and high (0.15-0.4 Hz) frequency power. Similar patterns of change in heart rate variability were seen when data for daytime and nighttime periods were analyzed separately. rMSSD (the root mean square successive difference of N-N intervals in ms), pNN50 and high frequency power are primarily indices of parasympathetic tone. SDNNIDX, and very low and low frequency power reflect both sympathetic and parasympathetic tone and longer term variability. Thus, moricizine decreases both vagal tone and longer term components of heart rate variability. This decrease produced by moricizine is similar to that reported with other type 1 antiarrhythmics.