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Systematic review of randomised trials of interventions to assist patients to follow prescriptions for medications.

BACKGROUND: Low adherence of patients to prescribed, self-administered medical interventions is ubiquitous. Low adherence limits the benefits of current medical care. Efforts to assist patients to follow treatments might improve the efficiency of care and substantially enhance benefits. Our objective was to summarise the results of randomised controlled trials (RCTs) of interventions to help patients follow prescriptions for medications. METHODS: A previous systematic review was updated through computerised searches in Medline, International Pharmaceutical Abstracts, Psychinfo, and HSTAR online databases; bibliographies in articles on patient adherence; articles in the reviewers' personal collections; and contact with authors. Articles were judged of interest if they reported original data concerning an unconfounded RCT of an intervention to improve adherence with prescribed medications, with one or more measure of medication adherence, one or more measure of treatment outcome, at least 80% follow-up of each group studied, and, for long-term treatments, at least 6 months of follow-up for studies with positive initial findings. Information on study design features, interventions and controls, and findings were extracted by one reviewer (RK) and checked by the other two reviewers. FINDINGS: 1,553 relevant citations and abstracts were screened, 252 full text articles were reviewed in detail, and 13 RCTs met all criteria. The studies were too disparate in clinical problems, adherence interventions, measures and reporting of adherence, and the clinical outcomes studied to warrant meta-analysis. Seven of 15 interventions were associated with improvements in adherence and six interventions led to improvements in treatment outcomes. For short-term treatments, one study showed an effect on adherence and outcome of counselling and written information. The interventions that were effective for long-term care were complex, including various combinations of more convenient care, information, counselling, reminders, self-monitoring, reinforcement, family therapy, and other forms of additional supervision or attention. Even the most effective interventions did not lead to substantial improvements in adherence. INTERPRETATION: Although adherence and treatment outcomes can be improved by certain-usually complex-interventions, full benefits of medications cannot be realised at currently achievable levels of adherence. It is time that additional efforts be directed towards developing and testing innovative approaches to assist patients to follow treatment prescriptions.

Drug Therapy

[Relapse symptom complex in rectal cancer after radical surgical interventions].

The analysis of 78 questionnaires of patients with recurrence of rectal cancer was performed which revealed this complication of surgery to occur in 60% of cases within a year after operation. Recurrences of the rectum cancer show a characteristic complex of symptoms with a certain structure of painful sensations as a central criterion.

Anal Canal

Fractal analysis of role of smooth muscle Ca2+ fluxes in genesis of chaotic arterial pressure oscillations.

We have investigated the role of vascular smooth muscle Ca2+ fluxes in the genesis of chaotic pressure oscillations induced by histamine in isolated resistance arteries from the rabbit ear. The responses exhibited distinct "fast" and "slow" components, with periods of 5-20 s and 1-5 min, respectively, which could be dissociated pharmacologically. The fast subsystem involved ion movements at the cell membrane and was inhibited by both low (< 2 mM) and high (> 5 mM) extracellular Ca2+ concentration ([Ca2+]o) by verapamil (which inhibits voltage-dependent Ca2+ influx) and by charybdotoxin (ChTX) and apamin (which block Ca(2+)-activated K+ channels). In contrast, the slow subsystem was intracellular and was selectively attenuated by ryanodine, which inhibits Ca(2+)-induced Ca2+ release from sarcoplasmic reticulum. The effects of these interventions on the complexity of the responses were quantified by calculating their fractal dimension, a parameter that estimates the minimum number of independent variables contributing to an irregular time series. Its mean value was generally > 2 under control conditions but decreased to < 2 in a concentration-dependent fashion in the presence of verapamil, ChTX, apamin, or ryanodine and when [Ca2+]o was outside the range of 2-3 mM. Each intervention thus removed one dimension of complexity from the mechanisms generating the rhythmic activity. We conclude that the interaction of a fast membrane oscillator, which involves Ca2+ influx, Ca(2+)-activated K+ efflux, and therefore presumably changes in membrane potential, and a slow intracellular oscillator involving Ca2+ sequestration and release from stores is responsible for vascular chaos in our model. The coupling between these subsystems is likely to be mediated by cytosolic [Ca2+].

Animals

Genetic screening for colorectal cancer and intervention.

There is a complex interaction between environmental/dietary factors and genetics underlying the pathogenesis of colon carcinogenesis. Little data exist concerning the impact of diet on the phenotypic expression of genetically linked colon cancer. As a result, it has been difficult to develop rationally designed dietary intervention studies in first-degree relatives of patients with established familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) and other familial colon cancer syndromes. Only 2 double-blinded, placebo-controlled trials have been published concerning the use of preventive strategies in patients with genetically inherited colorectal cancer syndromes, both in patients with FAP. One study evaluated the effects of vitamin C plus vitamin E with or without a high-dose wheat bran fiber supplement on the recurrence of rectal adenomas. Over a 48-month intervention period, only the wheat bran fiber intervention significantly reduced polyp growth. A second study reported that intervention with the NSAID sulindac for 9 months in young patients with FAP resulted in a significant reduction in both polyp number and size in the rectosigmoid colon. All of the large-scale (i.e., >500 randomized participants) phase III nutrient or chemopreventive agent intervention studies thus far have targeted participants with a history of non-familial, sporadic colorectal adenomas. Current clinical adenoma trials do not measure whether the regimen being tested can prevent genotoxic events occurring in early stages of abnormal cell development that contribute to the eventual formation of adenomas nor whether the agent(s) can inhibit events occurring during the progression of adenomas to carcinomas. Therefore, future clinical trial designs may have to consider (i) lengthening the clinical trial period before adenomas develop, (ii) testing at early patient ages and/or (iii) measuring the growth of adenomas as they progress to carcinomas.

Clinical Trials as Topic

Vector population responses to control interventions.

In 1981, Kenyan authorities attempted eradication of tsetse (Glossina pallidipes) from the Lambwe valley, by sequential aerial spraying of endosulfan. Fly populations were reduced by over 99.9% in the main habitats, but recovered to their original levels within one year. In 1986, an Argentine research team attempted local elimination of domestic Triatominae (Triatoma infestans) in an area of Santiago del Estero. House infestation rates were reduced to an apparent zero, but recovered to pre-control levels in two years. In Sri Lanka, a combination of mosquito control with active case detection and treatment reduced malaria incidence to just 17 cases in 1964. Interruption of the programme then saw case incidence return to over 500,000 by 1969. These three examples-from African trypanosomiasis, South American Chagas disease and malaria-all illustrate the same process. Vector populations, infestation rates, and rates of disease transmission, can be reduced. The real problem is not in achieving the initial reduction, but in subsequently either driving the disease to extinction or maintaining it below acceptable levels. And this problem takes us beyond the simple analysis of interventions, into the complex realms of population behaviour set in its political, social and economic context. It seems that we have been too rarely concerned to plan and implement the long term surveillance and selective interventions that are required to translate initial gains into real success. In biological terms, we tend to ignore the complexity and robustness of vector populations and disease transmission cycles, especially their varied capacity to recover from interference. Moreover, in socio-political terms, a reduced problem-even one representing potential for future catastrophe-tends to claim less priority than present problems, even though premature redeployment of resources may abnegate gains already achieved. The problem is strongly compounded by methods of economic analysis where the benefits of avoiding future problems are strongly discounted in favour of short-term temporary gains. This paper seeks to open discussion on these long-term planning issues.

Animals

Poverty and early childhood parenting: toward a framework for intervention.

The relationship between poverty and child rearing has been a persistent source of social concern in the United States. Drawing on available literature, this paper seeks to establish a conceptual approach to the interaction of these two complex variables. Appropriate interventions and strategies for their implementation are considered.

Child

Effect of cholesterol lowering on intravascular pools of TFPI and its anticoagulant potential in type II hyperlipoproteinemia.

Tissue factor pathway inhibitor (TFPI) inhibits the extrinsic coagulation system. A major pool of TFPI is associated with the vascular endothelium and can be mobilized into the circulation by heparin. In circulating blood, TFPI is mainly associated with LDL (80%), whereas 10% to 20% is carrier free. In this study, heparin administration caused a 2.2-fold and a 7.5-fold increase in TFPI activity and TFPI antigen, respectively, in 25 patients with phenotypes IIa and IIb hyperbetalipoproteinemia. Because the antigen determination of TFPI almost exclusively measures carrier-free TFPI, more than 90% of the heparin-induced increase in TFPI activity was caused by mobilization of carrier-free TFPI from the vascular endothelium. Therapeutic lowering of total cholesterol (a decrease of 31.1 +/- 11.6%, P < .001) by 40 mg/d lovastatin in 17 patients with hyperbetalipoproteinemia was accompanied by a parallel decrease in TFPI activity (of 27.7 +/- 24.2%, P < .001) because of a reduction in LDL-TFPI complexes. However, drug intervention did not affect carrier-free TFPI or the magnitude of the vascular pool of TFPI that could be mobilized into the circulation by heparin. Moreover, this reduction of LDL-TFPI complexes did not reduce the anticoagulant potency of TFPI in plasma or of the vascular endothelial pool. The results of this study may imply that the anticoagulant potency of TFPI is associated with its carrier-free form in plasma or on the endothelium and that downregulation of LDL affects neither the size nor the anticoagulant potency of the endothelial pool of TFPI.

Adult

A data-based approach to assessing clinical interventions in the setting of chronic disease.

Accurately assessing the effect of a clinical intervention is a complex task based on observing patients and their outcomes. Two strategies, the randomized trial and the observational data bank, represent different approaches toward detecting an outcome gradient across treatments. The observational data base is rooted on prospective data collected on an unselected group of patients with continuous surveillance of outcome events. As such, this approach captures a broad spectrum of patients within which prognostically important factors can be identified. In addition, the ongoing nature of the observational approach provides a means for capturing the dynamics of the disease process as well as the dynamics of the surrounding technology. These factors are particularly useful in the study of chronic illness where time frames of years to decades are encountered. In assessing treatment effects, both the randomized trial and the observational data base are subject to inferential errors due to multiple comparisons. In this paper, we describe some of the complexity associated with the study of chronic illness and demonstrate the multiple comparison problem. We have found multivariate models helpful in attenuating multiple comparison problems, but it still seems that independent confirmatory studies are required to establish confidence in a questionable intervention.

Analysis of Variance

Diarrhoeal disease: current concepts and future challenges. Water, sanitation and diarrhoea: the limits of understanding.

This paper reviews the application of epidemiological understanding of diarrhoeal disease to interventions in water and sanitation. Over the past 20 years, great efforts have been made to elucidate the relationships between water supply, sanitation and diarrhoeal disease. At the outset, it was hoped that improved understanding of these relations could provide a rational framework for the planning of public health engineering interventions. This paper also reviews historical and recent perceptions of water, sanitation, and diarrhoeal disease, and summarizes progress to date. On the one hand, some fundamental ideas about the relative importance of water quality and quantity in the transmission of diarrhoeal disease have changed, and there is increased recognition of the complex interrelationships between interventions, hygiene behaviour and health. On the other hand, our understanding of the impact of interventions is painfully incomplete, and is unlikely to improve dramatically in the near future. While further research can usefully illustrate a variety of interactions in specific contexts, globally applicable planning guidelines and design criteria appear a dangerous will-o'-the-wisp. While we know more than ever before about water, sanitation and diarrhoea, much remains unknown, and is perhaps unknowable.

Child

Pathophysiology and management of VIPoma: a case study.

PURPOSE/OBJECTIVES: To review the pathophysiology and clinical treatment of VIPomas, neuroendocrine tumors that secrete vasoactive intestinal polypeptide, and VIPoma syndrome. DATA SOURCES: Published clinical treatments and case studies in the medical literature and case study data from a patient's medical record. DATA SYNTHESIS: VIPomas are rare neuroendocrine tumors that cause a syndrome of life-threatening symptoms. Clinical management is complex, yet little information is available in the medical and nursing literature to guide the clinician. CONCLUSIONS: Information about the pathophysiology and management of the disease may facilitate care of these patients. IMPLICATIONS FOR NURSING PRACTICE: A case study presentation provides an example of the care required by one patient with VIPoma. The nurse has an important role in assessing, educating, and caring for the patient with VIPoma. Interventions include managing complex fluid and electrolyte imbalances, chemotherapy administration and management of side effects, activity and rest alterations, safety issues, altered social roles, and educational needs regarding medications, central lines, and follow-up care.

Adult

Generation of in vitro natural cytotoxicity of horse lymphocytes against sarcoid-derived tumor cells not expressing major histocompatibility complex antigens.

OBJECTIVE: To analyze in vitro lymphocyte-mediated immune responses of horses with sarcoids against allogeneic sarcoid cells containing endogenous retrovirus but not expressing major histocompatibility complex antigens. DESIGN: Lymphocyte-mediated immune reactions were assessed by means of proliferative responses in mixed lymphocyte tumor cell culture (MLTC) assay and lymphocyte-mediated cytotoxicity against various equine target cells. ANIMALS: 12 horses with sarcoid tumors and 15 control horses. PROCEDURE: Blood lymphocytes were cocultured in MLTC with allogeneic sarcoid cells (Mc-1, BayMc-1), equine testis cells, or normal equine dermal fibroblasts. Lymphocytes were assayed for proliferative responses by [3H]thymidine uptake and for cytotoxicity against the same targets by 51Cr release assay. The lymphocyte populations were analyzed for some common surface markers. RESULTS: Lymphocytes from horses with sarcoids exerted an anamnestic proliferative response in MLTC against Mc-1 cells, but this procedure never generated cytotoxic lymphocytes. However, lymphocytes from all horses cultured in medium with 10% allogeneic serum only had selective. natural cytotoxicity against Mc-1 that was generated without DNA synthesis. Approximately 80% of the lymphocytes disappeared during culture; however the remaining population of small, viable lymphocytes indicated a decrease of CD4+ T lymphocytes, but numbers of T cells with receptors for Helix pomatia A hemagglutinin were unaffected. Few lymphocytes had Fc-receptors for IgG, were complement-reactive positive cells or were B cells expressing surface immunoglobulin. CONCLUSIONS: Results may indicate a natural defense system, which preferentially recognizes and lyses tumor cells that are deficient in surface expression of major histocompatibility complex antigens, without intervention of conventional T-cell receptors or antibodies.

Animals

Selfobjects in psychosis--the twinship compensation.

Psychoanalysts and psychotherapists who work with psychotic patients often encounter unusual clinical phenomena. In this article, a certain kind of phenomena is described, wherein the patient refers to a body part of the therapist as being owned by the patient. This "body part borrowing" or "merger" can be explained by the classical and object relations schools in terms of part and transitional object concepts. These diagnostic formulations will then guide therapeutic intervention. Newer concepts, from the psychoanalytic school of self psychology, particularly that of the twinship selfobject experience, provide for a more effective intervention in these complex clinical situations. Certain psychotic responses, in these cases, delusional misperceptions, can be viewed as the patient's attempt to stave off empathic rupture and fragmentation. "Body-part borrowing" in the treatment setting thus serves as a twinship selfobject compensation; it attenuates the unbearable affects generated by empathic failure. In this article, we offered clinical vignettes to illustrate these processes in two patients with psychosis and one with neurosis. We then offered various suggestions for clinical intervention based on a selfobject understanding of these phenomena.

Adult

Community psychiatric nurse caseloads and the 'worried well': misspent time vital work?

Community psychiatric nurses (CPNs) in the United Kingdom are being repeatedly urged to focus their attention upon those with serious and enduring psychotic illnesses, and to withdraw from working with the 'worried well' in the primary health care setting. In view of this pressure, it is important to discover the nature of community psychiatric nurses' non-psychotic caseloads. The aim of this study was to describe these cases, what precipitated their referral, what problems they suffered from, what effects these problems had upon their lives and what kinds of therapeutic interventions they were receiving. A random sample was drawn of non-psychotic CPN patients. The community psychiatric nurses then received a structured interview about the history, care and treatment of these patients. These patients did not, in general, suffer from minor, self-limiting conditions. They typically had had 5 years of contact with psychiatric services, and their psychiatric symptoms blighted their occupational, social and personal lives. Their condition caused significant carer burden, and there was frequently a risk of suicide. The CPNs case-managed a complex combination of interventions for these patients, of which psychotherapeutic methods were only one part. The findings show that community psychiatric nurses have a valid role to play in the care of those with non-psychotic mental disorders, and should continue to receive the opportunity, and appropriate training, to do so.

Case Management

Management of ventricular arrhythmias.

Left ventricular dysfunction and complex VPCs are independent risk factors for subsequent cardiac death in patients with ischemic or nonischemic heart disease. The use of antiarrhythmic drugs during acute myocardial infarction is discussed. Patients with complex VPCs associated with heart disease should be treated with antiarrhythmic drugs. Drug efficacy should be evaluated by a 24-hour ambulatory ECG recording and by a treadmill exercise stress test. Blood drug levels should be measured at appropriate times. Maintenance doses of the various antiarrhythmic drugs are listed. Electrophysiologic testing with induction of ventricular tachycardia by extrastimulation may predict the clinical efficacy of the antiarrhythmic drug or combination of drugs needed for the long-term treatment of ventricular tachyarrhythmias. Electrophysiologic testing must be used for selecting antiarrhythmic drugs in patients who have experienced sustained ventricular tachycardia or ventricular fibrillation but who are free of VPCs during ambulatory ECG monitoring and exercise stress testing. If patients have life-threatening ventricular tachycardia or fibrillation resistant to antiarrhythmic drugs, surgical intervention is indicated. Complex VPCs in asymptomatic patients without heart disease should not be treated with antiarrhythmic drugs.

Anti-Arrhythmia Agents

A clinician-friendly version of the interpersonal circumplex: structural analysis of social behavior (SASB).

Like the original Interpersonal Circumplex (IPC), the Structural Analysis of Social Behavior (SASB) model was developed in the clinic. Different from and more complicated than the IPC, the SASB model nonetheless is parsimonious. It is consistent with Leary's (1957) original goal of bringing objectivity and clarity to the diagnostic process while acknowledging the complexity and variety of human nature. SASB applications extend from diagnosis into the domains of etiology and treatment. Specific advantages that accrue from the SASB model's more complex structure and assessment techniques include the ability to: (a) define both hostile and friendly differentiation, (b) specifically link social learning experiences with self-concept, (c) define several predictive principles on an a priori basis and confirm them in a variety of data sets, (d) assess personality at all 5 of Leary's levels, (e) define normality and pathology in qualitative rather than quantitative terms, (f) compare and contrast self-ratings with observer ratings using the same metric, (g) generate reasonable parallel models for affect and cognitive style that can help account for "comorbidity" between Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) Axes I and II, (h) make contributions to understanding personality as a hypothetical construct (i.e., to make testable predictions about etiology and specific treatment interventions), (i) dissect complex communications into their underlying components, and (j) accurately characterize a given relationship through a relatively brief sample of behavior.

Humans

[Australia antigen in rheumatoid arthritis].

Australian antigen (Au Ag) was first described by Blumberg in the serum of an Australian aborigen. Its main clinical significance is based on the fact of its association with the presence of hepatitis B (Okochi, Nurakami, 1968; Prince, 1968) (9). Almeida (1969) outlines the intervention of immune complexes on the production of the referred illness. Later works show the importance of the type of immunologic response created by Au Ag (2). Alpert et al. (1) (1970) state the possibility that immune complexes developed by Au Ag and anti Au Ag antibodies may produce in patients with hepatitis B other allied manifestations including arthritis. On the basis of similar immunopathological findings (illnesses including immunocomplexes on their production), Au Ag investigation in rheumatoid arthritis (RA) has been the object of several works, whose results reveal certain discrepancies. We have investigated the presence of Au Ag on 70 patients whose diagnostic was RA "classical (according to the judgement of the American Rheumatism Association). We used immunoelectrophoresis (counter immunoelectrophoresis-CIEP-) and radioimmunoassay (RIA) techniques. We prepared individual records including clinical, epidemic, biochemical and personal data. Au Ag investigation both through different techniques gave negative results in 70 cases, of which only four referred a possible previous hepatitis B clinic history, not showing during the investigation suggestive clinical data of hepatitis or biochemical alterations. Panus et al. (1970) (5), Desche-Labarte et al. (1972), Trempo (1972), Burrel (1973) (6), Serré et al. (1973) (8), obtained negative results in the matter, with similar or lower casuistics than ours. Notwithstanding Roqués et al. (1975) (7), in 300 cases of RA showed the presence of Au Ag in a significant number of cases (5%) as compared to Au Ag incidence in the French population (estimated in about 0.22%) (6). However, Roqués did not find in their Au Ag positive cases any evidence which enables to think that this antigen has played an important role on the origin and development of the rheumatic illness. These important discrepancies may be due to different reasons: a) Use of different techniques for Au Ag detection. b) The transitory character of the presence of Au Ag in the serum. c) Important differences in the antigen geographic distribution. d) Previous hepatitis B. There are som other factors which have attained importance recently, as a consequence of the broad epidemiological studies carried out. So, Au Ag increased incidence has been found--statistically significant--on groups of persons who have been submitted to several surgical interventions and/or have needed repeated hospitalizations or reiterated blood transfusions (6). These three conditions--especially the first two--are accomplished in an illness with chronic and invalidating characteristics as RA...

Arthritis, Rheumatoid

Dietary strategies for cancer prevention.

BACKGROUND: Two-thirds of cancer cases are associated with two lifestyle practices: 35% with the typical American diet, and 30% with tobacco use. In contrast to the field of tobacco control, research and resources dedicated to the field of nutrition have been limited, in part because dietary change has been considered controversial and requires a more complex set of interventions. METHODS: This series of papers reviews the science base underlying diet as a cancer control strategy, including research about diet-cancer relationships, current nutrition policy recommendations, American dietary trends, models of dietary behavior change, and diet in health care delivery. The history of technology transfer of new knowledge into widespread application will be compared and contrasted with other cancer control measures. RESULTS: There is scientific and policy agreement about three priority dietary goals for the year 2000: increase fruit and vegetable consumption to 5 or more servings every day, increase breads, cereals, and legumes to 6 or more servings daily, and decrease fat to no more than 30% of total calories. Current data do not indicate that these goals will be reached. As yet there is no organized effort, with clearly identified steps, to translate research into practice. The parallel with delays in implementing other cancer control measures, including Papanicolaou testing, mammography, and tobacco intervention, is striking. CONCLUSION: Without resources dedicated to dietary modification in the general population, it is not likely that the potential savings of more than 300,000 new cases, 160,000 deaths, and the $25 billion in associated costs will be realized in the foreseeable future.

American Cancer Society

Diagnostic laparoscopy in the intensive care patient. Avoiding the nontherapeutic laparotomy.

Evaluation of a potential acute abdomen in patients who require intensive care for concurrent medical/surgical problems is often difficult due to ambiguities in the physical exam and ancillary diagnostic tests. Between August 1990, and February 1992, 25 ICU patients underwent diagnostic laparoscopy to evaluate a suspected acute intraabdominal process. Thirteen laparoscopies were negative, and 12 were positive. The overall accuracy for laparoscopy was 96% as confirmed by subsequent laparotomy, autopsy, or clinical course. Laparoscopic findings led to a change in management in nine patients (36%), leading to earlier exploration in four patients, and avoidance of laparotomy in five. No significant hemodynamic effects were noted during laparoscopy, and the procedure-related morbidity was low (8.0%). Diagnostic laparoscopy is a safe and accurate guide for managing the ICU patient with a suspected acute surgical abdomen. The use of laparoscopy can help avoid nontherapeutic laparotomy or confirm the need for operative intervention in these complex cases.

Abdomen, Acute