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This paper focuses on the later history of the York Retreat after the initial period for which it is best known. It discusses the marked changes which occurred in the social composition of its patients and the way in which these changes modified the asylum's management and therapy. It argues that the conventional image of the Retreat, based as it is on the institution's earliest years, needs considerable revision.
Two equivalent special care nursing home units for elders with dementing illness were randomly designated as experimental and control units for an intervention called the "stimulation-retreat" model. This model introduced a set of staffing and program changes whose purpose was to diagnose, prescribe, and apply a package of care according to individual needs for additional stimulation or relief from stimulation ("retreat"). A total of 49 experimental and 48 control unit residents completed 12 months of care and were evaluated at baseline, 6 months, and 12 months. It was hypothesized that the intervention would not affect the basic disability (cognitive and activities of daily living functions), would improve negative behaviors and observed affects, and would have maximum impact in increasing positive behaviors and affects. Over time, most functions worsened, including negative attributes and affects. Lesser decline in positive affect and increases in external engagement, however, led to the conclusion that the intervention showed a marginally significant and selective effect on positive behaviors and affect.
The serum levels of soluble beta2-mu-associated and beta2-mu-free HLA class I heavy chains were determined in 28 interferon-alpha nonresponder chronic hepatitis C patients retreated with interferon-alpha plus ribavirin and in 70 healthy subjects. The baseline levels of beta2-mu-associated and beta2-mu-free HLA class I heavy chains were significantly higher in patients than in healthy controls (P = 0.001). The levels of beta2-mu-associated HLA class I heavy chains significantly increased in responder patients with respect to nonresponders at the third month of treatment (P = 0.03). At the sixth month of treatment and after 6 months of follow up the levels of beta2-mu-associated HLA class I heavy chains decreased in responder patients and increased in nonresponders. The levels of beta2-mu-free HLA class I heavy chains showed only minor changes during and after treatment. We suggest that the determination of hepatitis C virus RNA levels combined with soluble beta2-mu-associated HLA class I heavy chains, as a marker of immune activation, could identify interferon-alpha non responder chronic hepatitis C patients most likely to respond to a retreatment with interferon-alpha plus ribavirin.
Two recent studies have shown that retreatment of patients with relapsed indolent NHL with rituximab (RI) can be as effective as primary treatment, provided the lymphoma was initially responsive to primary RI therapy. From the available data, it remains unknown as to whether this approach is also effective for extranodal relapse. Here, we describe a 47-year-old male with stage 4B follicular lymphoma (FL), initially also involving skin, who achieved complete remission (CR) after a combination of fludarabine, cyclophosphamide and RI that lasted only 5 months. He soon relapsed with systemic disease and a number of extranodal sites including liver, lungs and bone marrow. After retreatment with RI alone (four cycles, 375 mg/m(2)), the patient achieved a second CR. Another four infusions of RI were given 6 months later as maintenance therapy. The duration of CR is already 18 months longer than the first CR. This case illustrates the fact that even in relapsed advanced FL, with multiple sites of extranodal disease, RI given as a single agent may be extremely effective in achieving an additional meaningful complete response.
Interferon-alpha (IFN-alpha) induces sustained remission of chronic hepatitis C in approximately 25% of patients. In patients who are non-responders to the first course of therapy, retreatment with IFN-alpha is of limited efficacy. Ribavirin has also been used to treat chronic hepatitis C, but it induces only a transient response. In this study, we evaluated the efficacy of ribavirin and IFN-alpha combination therapy for IFN-alpha resistant chronic hepatitis C. Twenty-four IFN-alpha non-responders and 24 relapsers were randomized to receive either ribavirin (1000 mg per day) together with IFN-alpha (3-6 million units (MU) thrice weekly) or the same dose of IFN-alpha alone, for 6 months. Both at the end of treatment and 6 months later, normal transaminase levels were more common in the patients receiving combination therapy than in the group receiving IFN-alpha alone: 17 (70.8%) vs seven (29.2%) patients (P = 0.009) and six (25%) vs one (4.2%) patient (P = 0.034), respectively. At the end of treatment and 6 months later, serum HCV RNA was no longer detectable in eight (33.3%) and five (20.8%) patients in the combination therapy group and in six (25%) and one (4.2%) patient in the IFN-alpha therapy group, respectively. Three patients (12.5%) were withdrawn prematurely from combination therapy because of side-effects; ribavirin therapy was ceased or dosage reduced in six other patients (25%), again because of side-effects. In conclusion, this combination treatment was more effective than retreatment with IFN-alpha, alone, in inducing sustained biochemical remission of chronic hepatitis C that was resistant to a previous course of IFN-alpha. The combination treatment, however, was frequently associated with significant side-effects.
The activity and tolerability of a retreatment cycle with leucocyte interferon-alpha (IFN-alpha) (6 million units (MU) three times weekly for 12 months) was evaluated in a group of 22 hepatitis C patients who had been intolerant to a previous course of lymphoblastoid IFN-alpha. Seven patients (31%) discontinued the new therapy owing to either a lack of response (six patients) or to severe leucopenia (one patient). Fifteen patients (68%) completed the 12-month treatment: all had a biochemical response and 10 (45%) also had disappearance of serum HCV RNA (complete response). Mild adverse reactions (fever, headaches and diarrhoea) were seen in these patients during retreatment. After 12 months of follow-up, 11 patients (50%) still maintained the biochemical response (long-term response); seven of these patients (32%) were also negative for serum HCV RNA. Biochemical and complete responses, at the end of both treatment and follow-up, were similar to those seen with lymphoblastoid IFN-alpha. The full dose of leucocyte IFN-alpha, when used in patients previously intolerant to the same dosage of lymphoblastoid IFN-alpha, was better tolerated: only one of the 15 patients who completed the 12-month treatment had a severe adverse event leading to withdrawal vs 22 of 68 patients treated with lymphoblastoid IFN-alpha. Furthermore, there were no manifestations of serological or clinical autoimmunity caused by leucocyte IFN-alpha, even in patients with autoantibodies associated with previous IFN therapy.
In crustaceans, as in most animal species, the amine serotonin has been suggested to serve important roles in aggression. Here we show that injection of serotonin into the hemolymph of subordinate, freely moving animals results in a renewed willingness of these animals to engage the dominants in further agonistic encounters. By multivariate statistical analysis, we demonstrate that this reversal results principally from a reduction in the likelihood of retreat and an increase in the duration of fighting. Serotonin infusion does not alter other aspects of fighting behavior, including which animal initiates an encounter, how quickly fighting escalates, or which animal eventually retreats. Preliminary studies suggest that serotonin uptake plays an important role in this behavioral reversal.
Ivermectin, a new antifilarial drug and currently the drug of choice for the treatment of onchocerciasis, has been shown to be effective in bancroftian filariasis. We report here, for the first time, the efficacy and safety of the drug in the treatment of filariasis caused by periodic Brugia malayi. Sixty male, asymptomatic microfilaraemics of Alleppey district, Kerala, South India, received single oral doses of ivermectin in a double blind study. Four dosages were used: 20, 50, 100 and 200 micrograms kg-1 body weight. Clearance of microfilariae, which was not complete, began as early as 12 hours post-treatment and was maximal at the end of one month. Microfilaria levels began to rise thereafter and reached 20-50% of pretreatment levels at six months. The two higher doses (100 and 200 micrograms kg-1) were more effective in suppressing microfilaraemia at six months (P < 0.05). After six months, 32 patients were retreated using the same dose of ivermectin that they had received initially. The pattern of clearance was essentially similar to that seen during the first treatment phase and microfilaria levels were 10-35% of pretreatment levels at the end of the next six months. Twenty-eight individuals who were not retreated at six months continued to have increasing levels of microfilariae, reaching 60% of pretreatment levels at the end of the next six months. Side effects (such as fever, headache, myalgia), which were mild to moderate, were seen in most patients and were unrelated to the dose (P > 0.05) or pretreatment levels of microfilariae.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: The challenge of teaching end-of-life care involves finding ways to incorporate both the science and the art of medicine. OBJECTIVES: To develop a curriculum so that internal medicine residents could more effectively (1) elicit patient's values, goals, and preferences for health care at the end of life, (2) communicate "bad news," (3) discuss patient preferences for nutrition and hydration, ventilator withdrawal, and cardiopulmonary resuscitation, (4) prescribe opioids using different routes of administration and, (5) recommend appropriate treatment of symptoms common at the end of life. DESIGN: The daylong retreat utilized case presentations and problems for presenting scientific content and the film Wit to convey information related to communication, whole-patient assessment, and the palliative care approach. Materials from the Education for Physicians on End-of-Life Care (EPEC) project and the film Wit provided the main educational resources. SETTING: All second-year internal medicine, and family medicine residents, and geriatric fellows from a community hospital in South Carolina attended. RESULTS: The residents positively evaluated the seminar content and format. Pretests and posttests revealed that residents significantly improved their knowledge regarding pain management (p<0.001), symptom management (p<0.001) and whole-patient assessment (p<0.014). Scores on the pretest and posttest related to communication skills did not significantly change (p=0.092). Yet, qualitative postretreat evaluations showed that residents perceived that the retreat would affect their communication with patients and other less easily quantifiable factors. CONCLUSION: Quantitative methods that work well for documenting scientific principles and learning may not apply as well in assessing the art of medicine.
Meanings of alleviated suffering in persons living with life-threatening cancer are explored in this life-world phenomenologic study. In repeated conversations, 16 patients with cancer who were receiving palliative care shared their embodied experiences in personal narratives. When interpreting the narratives, the following meanings of experiencing alleviation of suffering were disclosed: an endurable body being independent and feeling at home, feelings of connectedness, taking a long view of the suffering, being lifted out of the suffering, and an inner peace. Movements that were found in alleviation were dampening the suffering, arousing a zest for life, and focusing on both the present and the patient's dignity. As an interpreted whole, alleviation of suffering was found to be an embodied experience of "being in a lived retreat." This is a symbolic place owned by the person and is experienced in either the company of others or solitude. This lived retreat can provide a feeling of being at home, creating peace, rest, confidence, and breathing space in the person's suffering. It means coping with the altered lived body and feeling dignified. This is a personal experience that is both intersubjectively created and dependent. The importance of openness and responsibility in palliative care is emphasized in the findings and the notion of control of suffering in palliative care is accordingly rejected.
Ribavirin, a nucleoside analogue, inhibits replication of RNA and DNA viruses and may control hepatitis C virus (HCV) infection through modulation of anti-inflammatory and antiviral actions. Ribavirin monotherapy has no effect on serum HCV RNA levels. In combination with interferon, this agent appears to enhance the efficacy of interferon. The aim of this study was to monitor serum HCV RNA levels early during therapy with interferon and ribavirin compared with that previously seen in the same patients during interferon monotherapy. Five patients who previously showed no response to therapy with interferon alfa 3 MU three times weekly for 6 months were retreated with the identical dose of interferon alfa 2b in combination with oral ribavirin 1,000 mg/day. Serum HCV RNA levels were monitored at baseline, week 4, week 8, and week 12 of therapy by a quantitative multicycle polymerase chain reaction assay. In the first 8 to 12 weeks, serum HCV RNA levels showed a greater decrease in all patients when retreated with combination therapy compared with interferon alone. Mean (+/- SEM) serum HCV RNA levels for interferon therapy alone were 3.3 +/- 0.95, 1.2 +/- 0.95, 1.6 +/- 1.2, and 2.3 +/- 1.2 x 10(6) copies/ml at week 0, 4, 8, and 12, respectively. This was compared with 3.3 +/- 0.83, 0.3 +/- 0.2, 0.03 +/- 0.02, and 0.15 +/- 0.14 x 10(6), respectively, for the interferon and ribavirin group (p < 0.07 at week 8). Two of five patients had undetectable serum HCV RNA during combination therapy. Combination therapy with interferon and ribavirin in prior interferon nonresponders reduces serum HCV RNA levels compared with interferon alone. This may suggest some additional antiviral effect of ribavirin when given with interferon.
BACKGROUND: More than 50% of children with chronic hepatitis B infection do not respond to interferon-alpha (IFN-alpha) treatment and are prone to have progressive liver disease. The best treatment modality is unknown in these children. The aim of this study was to evaluate the possible benefit of a second higher dose IFN-alpha therapy for children with chronic hepatitis B diseases who failed previous therapy. METHODS: Twenty-four children with chronic hepatitis B infection who had not responded to previous IFN-alpha treatment were enrolled into the study. All were hepatitis B virus DNA- and hepatitis B e antigen-positive for >6 months after initial treatment. They received 10 megaunits (MU)/m2 of IFN-alpha 2a three times a week for 24 weeks. Liver function tests, hepatitis B virus markers and hepatitis B virus DNA were determined regularly during treatment and follow-up. A complete response was defined as clearance of both hepatitis B virus DNA and hepatitis B e antigen (HBeAg). RESULTS: At the end of therapy 8 (33.3%) patients cleared hepatitis B virus DNA and seroconverted to anti-HBeAg. Patients were followed for an average period of 12.2 +/- 4.7 months after retreatment. During follow-up an additional 4 patients cleared hepatitis B virus DNA and seroconverted to anti-HBe, whereas one seroconverted patient became HBeAg-positive again. Thus 11 patients (45.8%) had complete response at the end of the follow-up period. Alanine aminotransferase normalized in 11 responder patients and in 5 nonresponders. Positive predictive factors were low baseline titers of hepatitis B virus DNA and elevated transaminase values (> 100 IU/l). CONCLUSIONS: IFN-alpha retreatment with a higher dose may be an alternative modality for treatment of children with chronic hepatitis B infections who failed previous IFN-alpha, especially in those with favorable predictive factors.
We conducted a study to evaluate the efficacy of pegylated interferon/ribavirin in patients who did not respond to previous posttransplant recurrent HCV treatment with IFN/ribavirin combination. Twenty-seven patients were consecutively included in this study and retreated with pegylated interferon alfa-2b (1.5 microg/kg/week) with ribavirin (800-1000 mg daily) for 48 weeks for genotype 1 and 4 and 24 weeks for other genotypes. We compared them with 21 untreated patients enrolled during the same period. Primary endpoint was the SVR and secondary endpoint was histological evaluation 24 weeks after ending therapy. Twenty-seven patients started therapy but 2 (7%) stopped because of side effects. On an intent-to-treat basis, eight patients (30%) had an SVR. Cyclosporine as immunosuppressive therapy during antiviral therapy (p = 0.03) and EVR (p = 0.02) were significantly associated with viral clearance. In 46 patients in whom paired graft biopsies were available, fibrosis score was improved in 76% of treated patients versus 5% in untreated patients. Among treated patients, improvement of fibrosis was not correlated to SVR. Our data show that 30% of patients who have failed prior posttransplantation treatment achieved an SVR when retreated with pegylated interferon alfa-2b/ribavirin. More interesting is that fibrosis score was improved in 65% of treated patients despite failure of HCV eradication.
The history of deglaciation of the West Antarctic Ice Sheet (WAIS) gives clues about its future. Southward grounding-line migration was dated past three locations in the Ross Sea Embayment. Results indicate that most recession occurred during the middle to late Holocene in the absence of substantial sea level or climate forcing. Current grounding-line retreat may reflect ongoing ice recession that has been under way since the early Holocene. If so, the WAIS could continue to retreat even in the absence of further external forcing.
Despite growing support for the adoption of electronic health records (EHR) to improve U.S. healthcare delivery, EHR adoption in the United States is slow to date due to a fundamental failure of the healthcare information technology marketplace. Reasons for the slow adoption of healthcare information technology include a misalignment of incentives, limited purchasing power among providers, variability in the viability of EHR products and companies, and limited demonstrated value of EHRs in practice. At the 2004 American College of Medical Informatics (ACMI) Retreat, attendees discussed the current state of EHR adoption in this country and identified steps that could be taken to stimulate adoption. In this paper, based upon the ACMI retreat, and building upon the experiences of the authors developing EHR in academic and commercial settings we identify a set of recommendations to stimulate adoption of EHR, including financial incentives, promotion of EHR standards, enabling policy, and educational, marketing, and supporting activities for both the provider community and healthcare consumers.
Nonsurgical endodontic retreatment can be a successful treatment option, especially if the existing root canal therapy is technically deficient. It is the preferred treatment for most endodontic failures unless iatrogenic, restorative, or morphological factors dictate otherwise. A restorative post in the involved canal is usually considered an indication for apical surgery; however, in cases where nonsurgical retreatment is preferable to surgical management, many posts can be removed.
Orthogonal contrasts of Adjective Checklist pretest-posttest change scores obtained from adolescents who attended three-day Buddhist or Roman Catholic retreats (n = 204) and no treatment control participants (n = 102) indicated those who attended had higher change scores and greater change occurred among those attending the Buddhist meditation retreat.
PURPOSE: To report the results of complex wavefront-guided LASIK retreatments. METHODS: Twenty eyes (15 patients) with histories of conventional LASIK surgery and significant visual complaints of glare and halos due to higher order aberrations were treated. Wavefront-guided retreatments were performed with the LADARVision CustomCornea system (Alcon, Ft Worth, Tex). Pre- and postoperative topographies, wavefront measurements, and subjective reports were analyzed. RESULTS: Postoperatively, patients had an expanded optical zone, many with improved centration. Lower and higher order aberrations decreased following wavefront-guided ablation. Mean higher order root-mean-square decreased from 1.01 +/- 0.25 microm preoperatively to 0.84 +/- 0.23 microm postoperatively. Mean coma decreased from 0.59 +/- 0.26 microm to 0.43 +/- 0.21 microm. Mean spherical aberration decreased from 0.66 +/- 0.25 microm to 0.54 +/- 0.27 microm. Subjective reports of glare and halo symptoms improved in all patients. CONCLUSIONS: CustomCornea wavefront-guided treatments are effective in reducing lower and higher order aberrations, expanding optical zones, and improving subjective reports of adverse aberration sequelae such as glare and halos.