A qualitative assessment of discharge against medical advice among patients hospitalized for injection-related bacterial infections in West Virginia.

BACKGROUND: The incidence of infective endocarditis (IE) and other systemic bacterial infections is increasing, and people who inject drugs (PWID) have higher rates of discharge against medical advice (AMA) for these infections than patients whose infections are not injection-related. In this study, we characterize factors that contribute to AMA hospital discharge among PWID. METHODS: We conducted qualitative interviews with twenty PWID hospitalized with serious injection-related bacterial infections in West Virginia. Participants completed a brief survey and in-depth qualitative interview. Interviews were recorded and transcribed verbatim and analyzed using a codebook developed based on deductive and inductive thematic analysis. We also conducted medical records abstraction and used descriptive statistics to summarize medical and survey data. RESULTS: Average age was 34 years, 55% were female, 95% identified as white, and 75% had a primary diagnosis of IE. Drugs injected prior to hospitalization were methamphetamine (60%), prescription opioids (38%), and/or heroin/fentanyl (25%). Participants cited multiple contributors to AMA discharge including negative interactions with hospital staff that they perceived as stigmatizing, including being searched or monitored for illicit drug use; inadequate management of pain and withdrawal; boredom and confinement during lengthy hospitalizations; and isolation from family and other social supports. CONCLUSION: We identified multiple factors contributing to AMA discharge that are amenable to intervention. Given the significant morbidity, mortality, and financial costs associated with hospitalizing PWID for serious injection-related bacterial infections, hospitals should be highly motivated to develop and test interventions designed to improve outcomes among these patients.

Abnormally reduced primary motor cortex output is related to impaired hand function in chronic stroke.

Stroke often involves primary motor cortex (M1) and its corticospinal projections (CST). As hand function is critically dependent on these structures, its recovery is often incomplete. The neuronal substrate supporting affected hand function is not well understood but likely involves reorganized M1 and CST of the lesioned hemisphere (M1IL and CSTIL). We hypothesized that affected hand function in chronic stroke is related to structural and functional reorganization of M1IL and CSTIL. We tested 18 patients with chronic ischemic stroke involving M1 or CST. Their hand function was compared with 18 age-matched healthy subjects. M1IL thickness and CSTIL fractional anisotropy (FA) were determined with MRI and compared with measures of the other hemisphere. Transcranial magnetic stimulation (TMS) was applied to M1IL to determine its input-output function [stimulus response curve (SRC)]. The plateau of the SRC (MEPmax), inflection point, and slope parameters of the curve were extracted. Results were compared with measures in 12 age-matched healthy controls. MEPmax of M1IL was significantly smaller ( P = 0.02) in the patients, indicating reduced CSTIL motor output, and was correlated with impaired hand function ( P = 0.02). M1IL thickness ( P < 0.01) and CSTIL-FA ( P < 0.01) were reduced but did not correlate with hand function. The results indicate that employed M1IL or CSTIL structural measures do not explain the extent of impairment in hand function once M1 and CST are sufficiently functional for TMS to evoke a motor potential. Instead, impairment of hand function is best explained by the abnormally low output from M1IL. NEW & NOTEWORTHY Hand function often remains impaired after stroke. While the critical role of the primary motor cortex (M1) and its corticospinal output (CST) for hand function has been described in the nonhuman primate stroke model, their structure and function have not been systematically evaluated for patients after stroke. We report that in chronic stroke patients with injury to M1 and/or CST an abnormally reduced M1 output is related to impaired hand function.

Conditions for enhancing the encoding of an elementary motor memory by rTMS.

OBJECTIVE: Motor learning results in changes of movement representation in primary motor cortex (M1) a process involving long-term potentiation (LTP). Pairing motor training with repetitive transcranial magnetic stimulation (rTMS) of M1 enhances the formation of a motor memory. Here we determined the effect of pairing M1 stimulation and the execution of training movements at different times and frequencies on the formation of a motor memory. METHODS: Formation of a motor memory was defined as increases in motor evoked potentials (MEP) of the training agonist (extensor carpi ulnaris muscle, ECU) and increases in peak acceleration of the trained movements that last more than 60min. Training consisted of auditory-paced ballistic wrist extension movements (30min, 0.5Hz) paired with 0.1, 0.25 or 0.5Hz subthreshold rTMS. The rTMS pulse was applied at either the onset, 100ms prior to or 300ms after the onset of training movement related increases in electromyographic (EMG) activity of ECU. This was compared to a Sham condition. RESULTS: Only 0.1Hz rTMS applied at the onset of the training related increase in ECU-EMG activity resulted in increases in MEP amplitudes and peak acceleration when compared to the Sham. CONCLUSIONS: The formation of motor memory is enhanced above the naïve level by co-administration of low frequency rTMS at the time of execution of training movements. SIGNIFICANCE: These results indicate the importance of time and frequency of rTMS in these settings and should be considered in the design of rehabilitation treatment strategies using rTMS.

Reduced frontal white matter volume in long-term childhood leukemia survivors: a voxel-based morphometry study.

BACKGROUND AND PURPOSE: To our knowledge, no published studies have examined whole-brain regional differences to identify more discrete volumetric changes in the brains of childhood leukemia survivors. We used voxel-based morphometry (VBM) to examine regional gray and white matter differences in a group of long-term survivors of acute lymphoblastic leukemia (ALL) compared with a group of healthy controls. Differences in regional white matter volume were expected, given previous reports of white matter changes during treatment for ALL and reduced brain white matter volumes in long-term survivors. Follow-up analyses examined the relationship of regional brain volumes to cognitive function. MATERIALS AND METHODS: We compared 9 long-term survivors of ALL with 14 healthy controls. Survivors of ALL were treated with systemic and intrathecal chemotherapy only. T1-weighted axial 3D spoiled gradient high-resolution images collected on a 1.5T MR imaging scanner were used for the VBM analysis. Neuropsychological evaluations were conducted within 2 months of the MR imaging to assess cognitive function. RESULTS: VBM analysis revealed 2 specific regions of reduced white matter in the right frontal lobes of survivors of ALL compared with healthy controls. Survivors of ALL had lower performances on tests of attention, visual-constructional skills, mental flexibility, and math achievement compared with healthy individuals. Decreased performance on neuropsychological measures was associated with decreased regional white matter volumes. No differences were found between the groups with respect to gray matter regions. CONCLUSION: These findings are consistent with previous literature describing the long-term cognitive, academic, and imaging findings of survivors of ALL and suggest that right frontal white matter is particularly vulnerable to disruption following intensive chemotherapy for ALL. Future studies should focus on further clarifying the white matter changes observed.

Progressing prostate carcinoma.

In the Karnell Cancer Center Grand Rounds, we present a patient who underwent radical prostatectomy with bilateral pelvic lymphadenectomy, but had positive margins and subsequently developed local recurrence and then systemic disease. Pathologic and radiologic aspects of his disease are discussed. Therapeutic options at different stages of the disease are examined from the point of view of the urologist, radiation oncologist, and medical oncologist. The surgical portion of the discussion focuses on the selection of initial therapy. Both the selection of surgical candidates and choice of pre- or post-operative therapy in patients can be aided by prognostic tools looking at several variables, including prostate-specific antigen (PSA) level, Gleason score of the tumor, seminal vesicle invasion, extracapsular invasion, and lymph node involvement. Low-risk patients can be treated with monotherapy, such as radical prostatectomy, external beam radiation therapy, prostate brachytherapy, or cryosurgical ablation of the prostate. Higher risk patients may require adjuvant and possibly neoadjuvant therapy in addition. The radiation portion of the discussion focuses on the use of radiation therapy as salvage for relapsing disease. Of particular importance is the point that treating high-risk patients whose PSA levels have started to rise but are less than 1 ng/ml results in a long-term PSA control rate as high as 75%, but that limiting the use of salvage radiation therapy to patients with high PSA levels or biopsy confirmation of local recurrence in the face of a negative bone scan results in biochemical long-term control of less than 40%. In the medical oncology part of the discussion, the major focus is on the use of chemotherapy to treat patients whose disease has become resistant to hormonal therapy. Mitoxantrone plus a corticosteroid has been found to offer significant palliation for such patients. Combination therapy with estramustine plus taxanes, other microtubule inhibitors, or other agents such as topoisomerase II inhibitors, has been found to cause shrinkage of measurable soft tissue disease and diminution of serum PSA levels. The development of effective hormonal and chemotherapeutic drugs for treatment of metastatic disease has led to new interest in adjuvant and neoadjuvant therapy of high-risk patients.

Neural activation during frequency-memory performance.

Lesion studies have demonstrated that frequency memory, or memory for the frequency of occurrence, is associated with prefrontal and not temporal lobe lesions. This study examined neural activation during performance on a frequency-memory-judgment task and a recognition-memory task, both using words. Relative to a control task, the authors observed peaks of activation during frequency-memory performance in the left ventrolateral prefrontal cortex (BA 45) and other areas typically associated with working memory (dorsolateral prefrontal cortex, posterior parietal cortex). Recognition performance was associated with activation in the same left ventrolateral prefrontal location as was observed with frequency memory. When comparing activation during frequency memory with activation during recognition memory, the authors found a suppression of activation in the hippocampus bilaterally during frequency memory. This study supports a neuroanatomical distinction between frequency and recognition memory.

Verbal working memory and solvent exposure: a positron emission tomography study.

Neuropsychological studies have documented frontal dysfunction in patients with a history of exposure to organic solvents. The deficits typically observed in these patients appear to be related to working memory (WM). This study used [15O] water positron emission tomography (PET) to examine the pattern of neural activation during verbal working memory in patients with a history of exposure to solvents. Six individuals with solvent exposure were compared with 6 age- and education-matched controls. On the 2 WM tasks examined with PET, with equivalent task performance, participants with solvent exposure demonstrated frontal peaks that were atypical for the tasks, whereas the posterior peaks were typical for the tasks. The results support frontal dysfunction and compensatory use within anterior regions of the WM system in patients with solvent exposure.

Clinical features of chronic subdural hematoma: neuropsychiatric and neuropsychologic changes in patients with chronic subdural hematoma.

This article provides a background review of the cognitive and behavioral symptoms associated with chronic subdural hematoma (CSH). The areas addressed include the initial cognitive and behavioral symptom presentation, lateralization and localizing signs, differences between older and younger patients, and differential diagnosis. Although it is clear that behavioral and cognitive abnormalities are seen in CSH, further work is needed to objectively clarify the range of symptoms and signs.

Amnesia due to fornix infarction.

Background and Purpose-The fornix connects various structures involved in memory. We report a patient with anterograde amnesia after an acute ischemic infarct in the anterior fornix. Case Description-A 71-year-old female with acute-onset amnesia had neuroimaging studies showing ischemic infarction of both columns and the body of the fornix and the genu of the corpus callosum. Neuropsychological evaluation revealed anterograde amnesia without evidence of callosal disconnection. The patient showed marked improvement in her memory function on the follow-up visit. Conclusions-Amnesia in this case is likely due to infarction of the anterior fornix structures.

Neural activation during performance of number-letter sequencing.

Recent advances in neuroimaging have enabled researchers to establish relatively specific areas of the brain that are involved in working memory. In this positron emission tomography study we examined the pattern of neural activation associated with performance on number-letter sequencing, a purported measure of working memory included in the new Wechsler scales for memory and intelligence. After controlling for basic audition, verbalization, and attention, areas of activation were observed in the orbital frontal lobe, dorsolateral prefrontal cortex, and posterior parietal cortex. This is highly consistent with reports from the literature on activation patterns associated with working memory. More activation peaks were observed in the right hemisphere, suggesting the participants utilized visualization of the verbal information. Consistent with task conceptualization, this study provides support for number-letter sequencing as a task involving working memory.

Neurobehavioral effects of acute exposure to inorganic mercury vapor.

Mercury has well-established toxic effects on the central nervous system. This article describes comprehensive neuropsychological and emotional functioning of a group of 13 workers exposed to inorganic mercury vapor compared to that of a normal control group. The exposed group was exposed over a 2- to 4-week period and had elevated blood mercury levels. The evaluations were conducted between 10 and 15 months after exposure was terminated. Observed cognitive deficits included impairment in the following domains: motor coordination, speeded processing with and without a motor component, cognitive flexibility, verbal fluency, verbal memory, and visual problem solving and conceptualization. Emotional problems included increased focus on physical functioning, depression, anxiety, and social withdrawal. Cognitive deficits were, for the most part, not significantly associated with the degree of depression present.

Noninvasive prenatal diagnosis. Use of density gradient centrifugation, magnetically activated cell sorting and in situ hybridization.

OBJECTIVE: To develop a noninvasive method suitable for clinical prenatal diagnosis. STUDY DESIGN: Fetal nucleated erythrocytes were separated from peripheral blood of 17 healthy pregnant women using small magnetically activated cell sorting columns (MiniMACS) following density gradient centrifugation and dual antibody labeling methods. The protocol was designed to compare the efficacy of antitransferrin receptor (CD71)/antiglycophorin A (GPA) antibodies with antithrom-bospondin receptor (CD36)/anti-GPA antibodies in identifying nucleated erythrocytes in maternal blood. Cytospin preparations of the isolated cells were subjected to in situ hybridization with specific DNA probes for the Y chromosome and chromosome 21 to confirm the fetal origin. RESULTS: After MiniMACS the enrichment factors for the CD71/GPA- and CD36/GPA-positive cells from maternal blood were similar, and the percentages of fetal cells recovered did not differ. Seven of seven male pregnancies were correctly identified. One case of trisomy 21 was detected. CONCLUSION: The in situ hybridization analysis of fetal nucleated erythrocytes isolated from maternal blood using single density gradient centrifugation, anti-CD71/anti-GPA immunostaining and MiniMACS could be an accurate, sensitive and noninvasive method for prenatal diagnosis.

On the nature of Wisconsin Card Sorting Test performance in schizophrenia.

Performance on the Wisconsin Card Sorting Test (WCST) is widely reported to be impaired in patients with schizophrenia. It has been hypothesized that the performance deficit on the WCST in schizophrenia is related to a dysfunction of the frontal lobe, specifically the dorsolateral prefrontal cortex. This hypothesis was tested by comparing a group of patients with schizophrenia to patients with low grade right or left frontal lobe tumors and a group of patients with non-frontal high grade tumors. The results demonstrated a remarkable similarity in performance on the WCST between patients with schizophrenia and patients with right frontal lobe tumors. Patients with left frontal lobe tumors, non-frontal tumors, and normal control subjects did not show the same pattern of performance. This study provides support for frontal lobe dysfunction in the symptomatology of schizophrenia.

Neuropsychological functioning in a patient with paraneoplastic limbic encephalitis.

A 54-year-old woman with clinically diagnosed paraneoplastic limbic encephalitis secondary to adenocarcinoma of the lung is described. Neuropsychological evaluation revealed intact visual perception, visual construction, language, speeded processing, and verbal abstract reasoning in the presence of a severe anterograde amnesia for both verbal and visual information. A profound consolidation problem is discussed in view of other diseases of the mesial temporal lobes resulting in impaired consolidation of new material.

A case of bilateral thalamic lesions with anterograde amnesia and impaired implicit memory.

Thalamic nuclei appear to play an important role in memory functioning. Severe anterograde amnesia has been reported with lesions of the dorsomedial and anterior nuclei and their connections. We report the case of a woman with discrete thalamic lesions involving the anterior and dorsomedial nuclei who had a persistent anterograde amnesia. Contrary to a previous case report describing impairment only with explicit memory, this patient had impairment with both implicit and explicit memory. This case is discussed in terms of the relevant literature associating the diencephalon, amnesia, and implicit memory.

The factor structure of the Wechsler Memory Scale-Revised and several brief neuropsychological screening instruments in recently detoxified substance abusers.

The Wechsler Memory Scale-Revised (WMS-R) has attracted a fair amount of research activity since its publication. Much of this activity has centered on the factor structure of the WMS-R. The present study examines the factor structure of the WMS-R, both when the indices are used as variables and when the scale scores themselves are used as variables. Three hundred fifty-two recently detoxified substance abusers were used as subjects. Both sets of analyses included other neuropsychological variables in order to facilitate clear explications of memorial and cognitive functions tapped by the WMS-R. The results indicate support both for use of the indices and for use of the subscale scores. Differences between these results and the results of earlier factor analyses are discussed in terms of sample characteristics.

The establishment of clinical cutoffs in measuring caregiver burden in dementia.

Although several scales have been developed to assess burden, their clinical utility has been limited by the absence of relevant cutoff points. Clinical data from 140 primary caregivers seeking a dementia evaluation for a family member were analyzed to establish the psychometric properties of a caregiver burden screen. Results indicate that the cutoff values were both sensitive and specific to negative caregiving outcomes. These findings suggest that use of a burden screen may assist clinicians when assessing the adequacy of caregiving arrangements in dementia.

Platelet disorders in pregnancy: implications for mother and fetus.

Platelet disorders in pregnancy are not uncommon. Most often, obstetricians are faced with a patient with undiagnosed thrombocytopenia and have the responsibility of deciding if the condition is ITP, gestational thrombocytopenia, or a process related to pre-eclampsia. Correct diagnosis is important because ITP can be associated with fetal thrombocytopenia, making route of delivery important. In alloimmune thrombocytopenia, the mother develops antibodies to a specific platelet antigen present on the fetal platelet but absent on her own. Severe AIT can cause intracranial hemorrhage and have disastrous consequences for the fetus and neonate. In preliminary studies antenatal intravenous gamma globulin therapy has shown promise in preventing the development of intracranial hemorrhage and ameliorating fetal thrombocytopenia. Essential thrombocythemia with a platelet count of greater than 600 x 10(9) platelet/L can occur in pregnancy; therapy consists of antiplatelet aggregating agents such as aspirin, and plateletpheresis. Platelet function disorders can be acquired or inherited. Acquired platelet dysfunction disorders are usually caused by drugs such as aspirin or indomethacin, or by a systemic disease. Hereditary disorders of platelet function can be diagnosed in utero, but cordocentesis may represent an unacceptably high risk. For prenatal diagnosis, other methods, such as chorionic villus sampling or amniocentesis, should be investigated as an alternative to the potentially high risk of cordocentesis.

Heparin therapy for congenital antithrombin III deficiency in pregnancy.

A patient with congenital antithrombin III deficiency and a history of thromboembolic events prior to pregnancy was successfully treated with subcutaneous heparin alone throughout two pregnancies. Although adjuvant antithrombin III infusions may have a role in the treatment of this disorder, especially in the peripartum period, there is no evidence that this approach is superior to heparin therapy alone. We present this case as further evidence that heparin therapy alone appears to be a safe and effective treatment for pregnant patients with this rare but serious disorder.