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PubMed1997

The economic theory of fertility over three decades.

After a promising start some three decades ago, the application of micro-economic analysis to fertility studies has proved disappointing. It has not led to an increased understanding of fertility decisions nor to the policy insights which had been expected. This paper considers the reasons for this disappointment. It reviews briefly the development of the now dominant version of the economic approach to fertility analysis, the so-called "Chicago Model". It concludes that several basic conceptual and theoretical weaknesses of this approach have led it up a blind alley. The paper concludes with suggestions for new assumptions and approaches which may make the theory more relevant for policy programmes.

Economics↗

PubMed2000

Treatment approaches for relapsing and refractory multiple myeloma.

Relapsing patients with multiple myeloma show a response rate higher than 50% with the resumption of the initial chemotherapy. However, since the duration of second responses are short, HDT/autotransplantation is recommended in patients with sensitive relapse. In patients with primary refractory myeloma the best treatment approach seems to be early HDT/autotransplantation. It is crucial to recognize a subset of patients who do not respond to the initial chemotherapy but who have non-progressive disease in order to avoid the administration of salvage regimens until clinical disease progression occurs. The treatment of patients with refractory relapse is disappointing. The most promising agent in this situation is thalidomide. Patients with late relapse after autologous transplantation can benefit from a second autologous transplant. The results of the allogeneic transplantation after autotransplantation are disappointing. In heavily pretreated resistant patients a conservative approach with alternate day prednisone (30 to 50 mg) along with pulse cyclophosphamide (800 to 1,200 mg every 2 to 3 weeks) is recommended.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Imaging probes targeting matrix metalloproteinases.

During the past few years, several imaging probes targeting matrix metalloproteinases (MMPs) have been developed. Most of these probes have been validated in animal models. Overall, results derived from most of these studies have been disappointing. Whether or not this relates to shortcomings of the imaging probes used or to the set-up of the reported studies is currently unclear. Firstly, MMPs targeted in these studies, MMP-1, -2 and -9, are cell secreted and their expression is known to vary extensively within one tumor type, depending on the stage of development of the tumor and on the presence of naturally occurring TIMPs. Given the lack of data on the levels of MMP expression by incoculated tumor tissue at the time of imaging in most studies reported, it cannot be excluded that the negative results reported are, in fact, false-negative imaging results. Secondly, given that most of the agents used for imaging are intrinsically broad-spectrum agents, their higher affinity for specific subsets of MMPs does not necessarily imply that a positive imaging result also corresponds to overexpression of specific subsets of MMPs, as suggested in some papers published. Accordingly, well-characterized tumor models need to be developed for the purpose of validating currently available, as well as future, MMP-imaging probes. So far, only 111In-DTPA-N-TIMP-2 has been injected in patients, respectively suffering from Kaposi Sarcoma. Imaging results obtained with this agent proved disappointing. Imaging results obtained with other MMP-targeting probes in patients are awaited.

Animals↗

PubMed1988

Diet and blood cholesterol in population surveys--lessons from analysis of the data from a major survey in Israel.

A careful survey of the diet and serum cholesterol of civil servants in Israel covered 8829 men, aged 40-60 y born in six different areas. The authors were disappointed in their failure to find relationships between the diets and serum cholesterol of the individual men. Their report gives mean values for calories, diet fatty acids, and serum cholesterol for the men grouped by areas of birth. Regression analysis shows highly significant relations of serum cholesterol means to means of diet fatty acids for areas of birth. The relations found conform closely to expectations from dietary experiments in metabolic wards. Failure to consider intraindividual relations in the variables explains the disappointment of the authors of the report on the Israelis. Similar lack of attention to intraindividual variability is frequent in surveys and epidemiological studies and leads to error, controversy, and waste of time and money.

Adult↗

PubMed1992

Combined-modality therapies for non-small cell lung cancer.

Regionally advanced stage III non-small cell lung cancer (NSCLC) accounts for nearly 40% of all presentations of NSCLC. In the past, such patients received radiotherapy alone, but the median and long-term survival durations were disappointingly poor. Past attempts at combining chemotherapy and radiation were also disappointing, and were troubled by low doses of radiation or orthovoltage equipment or both. Recently, cisplatin-containing regimens have shown some efficacy in stage IV disease. The response rate for these combinations in stage III disease is nearly double that in stage IV disease. The greater response in stage III has led to a series of trials of sequenced chemotherapy and radiotherapy for treatment of regionally advanced (unresectable stage IIIA and IIIB) NSCLC. Several randomized trials have now shown a statistically significant advantage for the combined modality over radiation alone regarding time to treatment failure, median survival duration, and percent of long-term survivors. Other trials have focused on the concurrent use of chemotherapy and radiotherapy. Several pilot studies have suggested that concurrent cisplatin plus chest irradiation can produce apparently beneficial results with respect to local control and are the subject of ongoing clinical trials. At the University of Maryland Cancer Center, we have combined weekly carboplatin 100 mg/m2 with concurrent chest irradiation. The preliminary results are very encouraging. The toxicity of this treatment program is very manageable, and preliminary data suggest excellent local control and survival. Other pilot studies have suggested that combination chemotherapy with concurrent radiotherapy is also technically feasible.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Chemotherapy with cyclophosphamide, doxorubicin, etoposide, vincristine and prednisone (CHOEP) is not effective in patients with enteropathy-type intestinal T-cell lymphoma.

BACKGROUND: Enteropathy-type intestinal T-cell lymphoma (ETCL) is a highly aggressive disease with poor response to conventional CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy. According to promising data with the addition of etoposide (E) to the CHOP regimen (CHOEP) in aggressive lymphomas including T-cell lymphomas, we have treated patients with ETCL with CHOEP chemotherapy. PATIENTS AND METHODS: Ten consecutive patients (six female, four male) suffering from ETCL were given CHOEP at our institution. Four patients had advanced disease (stage III/IV), while five patients were rated to be in stage II and one in stage I. Treatment consisted of doxorubicin 50 mg/m2, cyclophosphamide 750 mg/m2 and vincristine 1.4 mg/m2 by intravenous infusion on day 1, etoposide 100 mg/m2 intravenously days 1-3 and oral prednisone days 1-5. Cycles were repeated every 3 weeks for a maximum of six courses. Assessment of response was done by means of conventional computed tomography scanning, endoscopy and also [18F]fluorodeoxyglucose positron emission tomography (FDG PET) in seven patients. RESULTS: A total of 41 cycles (median six, range one to six) were administered to our patients. Leukocytopenia/neutropenia WHO grade IV necessitating granulocyte colony-stimulating factor support occurred in all patients evaluable for toxicity, and febrile neutropenia was seen in two patients. Two patients had to undergo emergency surgery due to intestinal perforation after one and three courses of treatment, respectively. Therapeutic results, however, were disappointing: two patients had complete remission (CR), three had partial remissions and five patients progressed during treatment. Remissions, however, where only short-lasting, as only two patients are alive at a median follow-up of 7 months (range 2-16). One patient is in ongoing CR 10 months after initiation of chemotherapy and the other is currently undergoing second-line treatment for progressive disease as judged by follow-up investigations after three cycles of CHOEP. CONCLUSIONS: Our data demonstrate that CHOEP chemotherapy results in a high rate of hematotoxicity in patients with ETCL. In spite of this, therapeutic results were disappointing and do not appear to be superior to conventional CHOP chemotherapy. We conclude that CHOEP cannot be recommended for routine use in patients with ETCL.

Administration, Oral↗

PubMed1995

Do parents excuse the misbehavior of children with physical or emotional symptoms? An investigation of the pediatric sick role.

Assessed attributions and responses to descriptions of the misbehavior of children with symptoms of physical and emotional illnesses. Subjects (160 mothers; 160 fathers) read a vignette about a child in one of four illness conditions (medically explained pain with organic etiology; medically unexplained pain, depression, well) who was described as misbehaving at home and school. Within each illness condition, the child protagonist varied by age (8 vs. 16) and gender. A between-subjects design was used in which subjects made judgments regarding causes and responsibility for the child's misbehavior, affective reactions to the child, and the consequences that should be administered to the child. Results indicated that, in comparison to subjects' perceptions of the misbehavior of children in the other conditions, subjects viewed the misbehavior of children with medically explained pain as less intentional, more excusable, and due to causes that were less internal to the child. Subjects held children with medically explained pain less responsible for their misbehavior and indicated that they would respond to them with less anger, disappointment, blame, and punishment than to children in the other conditions. Subjects did not hold children with symptoms of depression and children with unexplained pain complaints less responsible for their misbehavior, but indicated that they would respond to them with less anger, disappointment, and punishment than to well children.

Adolescent↗

PubMed2005

Engineering a pharmacologically superior form of leptin for the treatment of obesity.

Leptin plays a central role in the homeostasis of body weight through its regulatory effects on appetite and energy expenditure, yet in trials as a therapeutic agent for the treatment of obesity in humans it has been disappointing. The poor clinical efficacy of leptin results from its short circulating half-life, low potency and poor solubility, necessitating large and frequent doses to obtain even modest clinical benefit. Engineered Fc-leptin immunofusins, consisting of the Fc fragment of an immunoglobulin gamma chain followed by leptin, exhibit improved pharmacological properties with very consistent and potent biological activities. Furthermore, in extending the circulating half-life of the protein in vivo from a few minutes for leptin to many hours for Fc-leptin, these proteins have the potential to reduce drastically the dosage and frequency of administration required to obtain clinical benefit. The results of this study show that the engineered leptin immunofusins described here have significantly enhanced pharmacological properties in comparison with the recombinant leptin that was used in clinical trials. As such, they could represent an important step towards a therapeutically superior form of leptin if the disappointing performance of leptin in early clinical trials was due to its poor pharmacological properties rather than any conceptual weakness in the strategy of using leptin for the treatment of obesity and its related disorders.

Animals↗

PubMed1997

An outcome analysis of 100 women after explantation of silicone gel breast implants.

A prospective outcome analysis was conducted on 100 consecutive women who requested explantation of their silicone gel breast implants from January 6, 1992 (the moratorium), through 1995. Eighteen patients were referred by rheumatologists with a diagnosis of autoimmune or rheumatic disease. Six had autoimmune disease (systemic lupus, 2 patients; rheumatoid arthritis, 2 patients; multiple sclerosis, 1 patient; and Raynaud's disease, 1 patient). Twelve had rheumatic disease (fibromyalgia, 10 patients; inflammatory arthritis, 2 patients). All of these 18 patients had developed symptoms of their disease after they had received implants. All 100 patients were extensively evaluated pre- and postoperatively by interviews, clinical assessment, and by assay of the following laboratory tests: rheumatoid factor, ESR, ANA, and anti-Ro/SSA, -La/SSP, -Sm, -RNP, -double-stranded deoxyribonucleic acid, -Scl-70, -centromere, and -cardiolipin. Patients were also evaluated by a questionnaire that was sent at a mean time of 2.7 years postexplantation (range, 1-5 years), which had a 75% response rate. Reasons for implants were augmentation, 75%; lifting, 11%; reconstruction, 12%; and congenital aplasia, 2%. The mean age at first implant was 28.9 years (range, 13-55 years) and at explantation was 41.5 years (range, 25-65 years). The mean duration of implantation was 12.0 years (range, 1-27 years). Thirty-six percent of the patients had undergone at least one closed capsulotomy and 54% at least one open capsulotomy. The mean reasons for explantation were suspected silicone-related health problems, 76%; suspected rupture, 59%; breast firmness, 36%; breast pain, 36%; and musculoskeletal pain, 23%. Before explantation 75% of the questionnaire respondees had lost some sensitivity in their nipples following their breast augmentation. In 36% of those 75 patients, that loss was almost complete. Loss of sensitivity was related to capsular contracture and to pain (p < 0.05). Following explantation there was significant improvement in nipple sensitivity in 38% of breasts in the 75 respondees. A total of 186 implants were removed. Fifty-seven percent had failed by rupturing or leaking. Only 3.2% demonstrated extravasation extracapsularly. Twenty-five percent of the capsules were calcified, demonstrating visible plaques of calcification on their inner surface. Forty-two percent were colonized by bacteria. The prevalence of class III-IV capsular contracture was 61% and it was related to implant location, duration in situ, and capsular calcification (p < 0.05), but not to capsular colonization or implant integrity (p > 0.05). Only 43 of the 100 patients elected to have saline implants inserted. Of the others, 56% felt that the shell of the saline implant could be associated with medical problems. The others felt that breast size was of minor importance to them at this time. There were few complications from the explantation procedure. Two "masses" were discovered-one was an occult carcinoma, the other a galactocele. There was one wound infection, which responded to antibiotics. Three patients developed decreased sensitivity and 3 developed increased breast pain. From the patient questionnaires, in those women who did not have saline implants inserted, 15% felt that their breast appearance was improved after explantation, 36% were "pleased," 33% were disappointed, and 13% felt "mutilated". In women who did have saline implants inserted, 18% felt that their breast appearance was now improved, 60% were "pleased," and 14% were disappointed, mainly because of wrinkling. At a mean time of 2.7 years (range, 1-5 years) after explantation, 45% of the 75 questionnaire respondees felt that their implants had caused permanent health problems and 56% felt that they had not been given adequate informed consent by their original surgeon (particularly regarding implant rupture and a possible relationship to medical disease). (ABSTRACT TRUNCATED)

Adolescent↗

PubMed1999

New therapies and changing patterns of treatment for malaria.

The launch of the Roll Back Malaria initiative by the World Health Organization in the period under review confirms malaria's place as one of the great public health priorities worldwide. The period 1998-1999 has seen some advances and some disappointments in the treatment of malaria, against a backdrop of spreading drug resistance. Most encouraging is the clear demonstration that intermittent prospective treatment of asymptomatic pregnant women in endemic areas reduces morbidity. The greatest disappointment has been the result of trials with the artemether-benflumetol fixed-dose combination therapy. Questions have been raised about several widely accepted practices, including measurement of quinine levels, exchange transfusion, and the prophylactic use of anticonvulsants in children with cerebral malaria.

Journal Article↗

PubMed1999

Cancer chemoprevention.

Chemoprevention is defined as nutritional or pharmaceutical interventions designed to prevent or delay cellular transformation. Over the last year, the great excitement and interest in the mechanism, epidemiology, and preclinical and clinical chemopreventive effects in the lower intestine of nonsteroidal anti-inflammatory drugs continues and is reflected in the large number of publications on this topic. Investigators from Japan and the United States published preclinical studies of a number of new compounds derived from citrus products and Asian foods and spices with potential clinical promise. Disappointment in the lack of efficacy of epidemiologically predicted micronutrient chemopreventives continues with the publication of an additional clinical trial. This disappointment is tempered by a potentially important observation suggesting that pharmacologic approaches of measuring an individual's food intake and assessing individual variation in disposition, bioavailability, and metabolism of micronutrients might allow for more accurate and individualized nutritional chemopreventive approaches in the future.

Journal Article↗

PubMed2001

Surgery, radiotherapy, and chemotherapy for esophageal carcinoma.

Over the last year, several interesting studies have been published on the treatment of esophageal carcinoma. Surprisingly, none of them was a randomized phase III trial. The debate on the necessary extent of a potentially curative surgical resection is ongoing. After initially disappointing results, the innovative technique of minimally invasive surgery draws new attention, but clear advantages for the endoscopic approach are yet to emerge. An updated meta-analysis on the value of preoperative radiotherapy showed negative results. There is a clear tendency toward combined-modality treatment, especially in patients with more advanced disease. Some new chemotherapeutic agents showed promising preliminary results (especially paclitaxel), whereas others were clearly disappointing (eg, gemcitabine, topotecan). Concurrent chemoradiation as primary treatment for proximal (cervical) tumors was remarkably effective.

Journal Article↗

PubMed2005

Factors influencing preceptors' responses to medical errors: a factorial survey.

BACKGROUND: Preceptors must respond to trainees' medical errors, but little is known about what factors influence their responses. METHOD: A total of 115 primary care preceptors from 16 medical schools responded to two medical error vignettes involving a trainee. Nine trainee-related factors were randomly varied. Preceptors indicated whether they would discuss what led to the error, provide reassurance, share responsibility, express disappointment, and adjust their written evaluation of the trainee. RESULTS: Almost all preceptors would discuss what led to the error; relatively few would express disappointment. The trainee's prior history of errors, knowledge level relative to peers, receptivity to feedback, training level, emotional reaction, offering to apologize, and offering an excuse were predictive of preceptors' responses; gender and time-in-office were not. CONCLUSION: This study identified seven trainee-related factors as predictive of preceptors' responses to medical errors. More research is needed to identify other influential factors, and to improve teaching from medical errors.

Communication↗

PubMed1998

Hypertension optimal treatment (HOT) study: a brilliant concept, but a qualified success.

BACKGROUND TO THE STUDY: The Hypertension Optimal Treatment (HOT) study was designed to answer two questions: whether low-dose aspirin (75 mg/day) is effective in the primary prevention of myocardial infarction, without an increase in cerebral haemorrhage in hypertensive patients whose blood pressure is well controlled, and whether there are additional benefits with a progressive reduction of diastolic blood pressure from 90 mmHg to below 80 mmHg. SUCCESSES: In a landmark outcome, low-dose aspirin was indeed shown to be effective in the primary prevention of myocardial infarction. Moreover, the study has shed light on many important issues for blood pressure lowering in the treatment of hypertension, providing an excellent demonstration that with aggressive combination therapy, the elevated blood pressure in hypertensive subjects can be lowered and maintained in the normotensive range in over 90% of cases. DISAPPOINTMENT: The biggest disappointment was that the intention to treat analysis failed to demonstrate a significant difference between the three randomized target blood pressure groups for the majority of cardiovascular events.

Antihypertensive Agents↗

PubMed1999

Psychological complications in 281 plastic surgery practices.

Surgery is a high-stakes stressor with possible consequences that include death, pain, disfigurement, economic losses, and alterations in social roles. Often, the most disturbing complications to surgeons and patients are psychological rather than physical. Ineffective management of psychological complications of surgery can have profound consequences, resulting in delayed recuperative times, delayed return to work, poor patient compliance, dissatisfaction with the surgical outcome, hostility toward surgeons, and anxiety. The purpose of this study was to investigate in a large randomized group of plastic surgery practices the relative incidence of negative psychological outcomes and to compare these with the incidence of adverse physical outcomes to gain a greater appreciation of the relative magnitude of each type of perioperative complication. The study design was a descriptive, correlational survey that assessed psychological complications reported by plastic surgeons. The Plastic Surgery Questionnaire was sent to 702 randomly selected board-certified plastic surgeons. The sample consisted of 281 board-certified plastic surgeons (40 percent response rate). The study instrument was found to be highly reliable, with inter-item Cronbach's alpha r = 0.85. The demographics were representative of the specialty as a whole. It was found in general that psychological complications were much more prevalent than physical problems such as hematoma or infection. Anxiety reactions were commonly encountered by 95.4 percent of surgeons; disappointment (96.8 percent), depression (95.0 percent), nonspecific physical complaints (92.2 percent), and sleep disorders (88.5 percent) were the next most commonly reported complications. Most surgeons (75.8 percent) reported that screening for depression was important, but only 18.8 percent identified screening for post-traumatic stress disorder as important, even though 86 percent had diagnosed post-traumatic stress disorder in their postoperative patients. Psychological complications occur at rates equal to or greater than those of physical complications in the plastic surgery practice. Patients who experience physical complications are much more likely to simultaneously experience psychological complications. Patients with preexisting psychological conditions are more at risk for postoperative psychological complications. Disappointment, anxiety, and depression were the most frequently seen psychological complications. Nursing personnel are perceived by plastic surgeons to have the primary role in screening patients for pertinent psychological history. Directed research should be undertaken to determine which treatment regimens are most effective in reducing preoperative psychological complications. Controlled clinical trials of pharmaceuticals and alternative therapies must be designed and carried out in a prospective manner to establish the optimum treatment for alleviation of adverse emotional consequences of surgery. The next frontier for the specialty is to actively and consciously investigate and improve our patients' emotional and psychological results from surgery.

Anxiety↗

PubMed1992

The treatment of chronic extremity pain in failed lumbar surgery. The role of lumbar sympathectomy.

Persistent lower extremity pain after unsuccessful lumbar surgery continues to be a disabling condition. The results of deafferentation procedures for radiculopathy have been disappointing. Hence, the prospect of isolating a potentially reversible component of extremity pain is quite attractive. Given the frequency with which vasomotor complaints occur in this setting, the occurrence of autonomic dysfunction seems quite plausible. Autonomic dysfunction was investigated in 17 patients who had undergone previous lumbar surgery and had chronic limb pain. Patients underwent a preblockade thermogram, sympathetic blockade, and postblockade thermograms. All patients reported substantial relief after blockade, and all underwent retroperitoneal sympathectomy. All patients were followed for at least 2 years. The clinical results were disappointing, with only one patient reporting substantial relief. Although the results of thermography initially seemed to correlate with clinical outcome, further follow-up failed to yield any correlation. Additionally, no specific combination of response to blockade or thermogram was predictive of the clinical success after sympathectomy. Now, lumbar sympathectomy is not recommended in the setting of chronic radiculopathy and persistent extremity pain.

Female↗

PubMed1998

Neurological involvement in systemic lupus erythematosus.

The aetiology of neurological involvement in systemic lupus erythematosus (SLE) still remains largely uncertain, but there are some recent reports of retrovirus activity linked to human and mouse models of SLE. Antiribosomal P antibodies appear specific to SLE and tend to be associated with psychiatric disease, but not exclusively so. The role of antiphospholipid antibodies in the pathogenesis of SLE may not be solely to cause thrombotic events, but also to act directly on neuronal tissue. The importance of another group of antibodies, those against Beta 2 glycoprotein I, a phospholipid binding protein, is now being recognized. Amongst the many neurological manifestations of SLE, cognitive impairment is becoming increasingly recognized and appears not to be simply a response to chronic disease or its treatment. Of the newer imaging techniques applied to SLE, positron emission tomography has proved inconsistent and somewhat disappointing but single photon emission computed tomography in active disease appears more sensitive compared to MRI, although it still remains a nonspecific technique. The treatment of SLE remains disappointing and no controlled trials for neurological disease have been published to date but a number of experimental approaches do offer hope for the future.

Animals↗

PubMed2002

Neurogenic bladder dysfunction in patients with myelomeningocele.

PURPOSE OF REVIEW: The general management strategies in children with myelodysplasia are widely accepted, however diagnostic and therapeutic details still need to be discussed and clarified. RECENT FINDINGS: Ten articles are reviewed. Two articles are dealing with general clinical aspects; one underlines the need for urodynamics as a prerequisite for an adequate treatment strategy, the other recommends to evaluate adolescents and adults with myelodysplasia, because only the ultimate outcome allows a judgement of how effective our efforts are to achieve the goals. Increased excretion of glycosaminoglycan in myelodysplasia children above 5 years of age could become a marker for beginning bladder damage and deserves further interest. The question whether children with normal urodynamics after closing the spinal cord should be followed or not is clearly answered in a further article which also discusses the results of detethering in these patients. Four articles report on pharmacotherapy with new substances or new ways of application (intravesical oxybutynin, extended release oxybutynin formulation, intravesical resiniferatoxin). The results of collagen injections in children with neurogenic sphincter underactivity clearly demonstrate that the long-term results are disappointing. Last, but not least, a retrospective review on acute abdominal symptoms and signs in children with myelodysplasia clearly shows that these patients should be transferred to a centre because of complex reasons and treatment modalities. SUMMARY: Urodynamics - abnormal or normal - are a prerequisite for adequate treatment and follow-up in children with myelodysplasia. More studies should focus on adolescents and adults with myelodysplasia to judge the effectiveness of our diagnostic and therapeutic efforts. New ways of application and new developments in pharmacotherapy to relax the overactive detrusor may possibly further decrease the need for surgery in the future. With regards to sphincter underactivity, results with collagen injections in this group of patients are disappointing and provide no alternative to operative treatment options.

Adolescent↗