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[A systematic approach for removable partial denture design].

Patients' attitudes, medical, surgical and financial considerations lead to the use of a removable partial denture (RPD) as the chosen prosthetic restoration even in the "dental implant era". The aim of this article is to describe a systematic approach to RPD design, so the RPD will be a long-term solution that will not harm the remaining oral tissues. There is an unlimited RPD design options. Choosing the right one involves considering biochemical factors, aesthetics and patients' comfort. A systematic approach starts with a correct diagnosis of the remaining hard and soft tissues, followed by a careful planning of support, stability and retention in that order. Additional elements should be added only at a later stage. A systematic track starting with a preliminary design, surveying of the model and analyzing the preliminary design on that surveyed model. If needed, that track should be reversed until an acceptable design is found. Support should ideally be achieved by using metal rests on healthy tooth structure. Tooth supported RPD are the most convenient ones and have a very good long-term prognosis. Old restorations or caries might impose changes from the ideal supporting rests. When posterior teeth are missing or when the edentulous area is vast, tooth-tissue supported RPD are used. In these cases one should gain initial support from the teeth and an additional support from the soft tissues. A denture base that is similar to a full denture base that would have been prepared for a fully edentulous patient should achieve this. If the prognosis of the potential supporting teeth is poor, a tissue-tooth supported RPD is considered. In these cases, the denture base is the primary supporting element, and stress relieving clasp-assemblies such as the RPI/RPA should be considered. Stability is achieved primarily by metal contacts between teeth and the metal framework of the RPD. In fact, any embracing part of the clasp assembly and a correct denture base can contribute to the stability. The distal parts of the retentive clasps produce the active retention. Since these parts generate lateral forces on the abutment teeth, a reciprocating element should be used. True reciprocation can only be achieved if the reciprocating element touches the tooth before the retentive clasp. After designing support, stability and retention, other parts should be considered. When a distal extension RPD is considered, an indirect retainer should be incorporated into the framework in order to prevent upward rotational movement of the denture. The major connector converts forces from one side to the other. In the upper jaw, that part acts also as a supporting element in Kennedy class I and class II cases. In other cases, a minimal type of a major connector should be chosen. As for minor connectors, these should only be added if other parts--such as guiding planes--couldn't be used for the purpose of connecting functional elements to the major connector. In any case, a 5 mm distance between two adjacent minor connectors should be allowed in order to prevent food from being trapped in that space. A systematic approach starts with diagnosis of the remaining tissues and with finding the correct prosthetic solution with the patient. If a RPD is the chosen solution, start designing with analysis of support, followed by stability and only then, decide upon the necessary retentive elements. All other parts should be considered later. Such a systematic approach will ensure a long-term solution and a happy patient.

Dental Abutments↗

Scope for improvement in the quality of reporting of systematic reviews. From the Cochrane Musculoskeletal Group.

OBJECTIVE: To assess the quality of reporting in Cochrane musculoskeletal systematic reviews (excluding back and injury reviews). METHODS: This study assessed all the Cochrane Musculoskeletal Group's systematic reviews from Issue 4, 2002, of the Cochrane Library Database of Systematic Reviews. Two reviewers independently extracted data and assessed quality. Two assessment tools were used, including an 18 item checklist and flow chart developed by the Quality of Reporting of Meta-analysis (QUOROM) consensus group, and a 10 item scale, the Oxman-Guyatt Overview Quality Assessment Questionnaire (OQAQ). One question on the latter scale (item 10) scores overall quality on a 7 point scale, with high scores indicating superior quality. Data were analyzed using univariate approaches. RESULTS: The 57 systematic reviews assessed were found to have good overall quality, with scores on individual items revealing only minor flaws. Documenting the flow of included and excluded studies and summarizing the results are 2 areas needing improvement in reporting. According to the Oxman-Guyatt scale the overall scientific quality of the Cochrane musculoskeletal reviews was good [mean 5.02 (95% CI 3.71-6.32)]. CONCLUSION: Our study found that the reporting quality of Cochrane musculoskeletal systematic reviews was generally good, although there was room for improvement. For example, it might be feasible to develop specific guidelines for reporting protocols. Certainly more work is needed in reporting search results, documentation of the flow of studies, identification of the type of studies, and summarization of the key findings.

Evidence-Based Medicine↗

[Comparison of the efficacy of different methods for the prevention of anti-D allo-immunization during pregnancy: targeted strategy limited to risk situations or associated with systematic prevention in the 3rd trimester].

BACKGROUND: In France, anti-Rh prophylaxis is currently based on systematic postnatal prevention which has validated efficacy (relative risk=0.04 versus placebo), associated with targeted antenatal prevention in the event of situations raising a risk of fetomaternal hemorrhage. In most industrialized countries, a systematic prevention policy is applied with immunoglobulin injections for the above cited situations and during the third trimester to cover the risk of spontaneous occult fetomaternal hemorrhage occurring at the end of pregnancy. OBJECTIVE: Compare the efficacy of two strategies for antenatal prevention. MATERIAL AND METHODS: Review of the literature of published comparative studies. Eleven studies were retained (two randomized trials, seven comparative studies, one before-after study, one population-based study) including more than 30,000 treated patients. RESULTS: Globally, immunization rate was to the order of 1.5% (1.2-1.9%) for targeted prevention limited to situations at risk and to the order of 0.2% (0-0.9%), all parities included, for systematic antenatal prevention. Comparative analyses have reported significant odds ratios of 0.20 and 0.37 in all subgroups. CONCLUSION: Despite the heterogeneous nature of the published studies, available data are in favor of systematic prevention: either with a 300g dose at 28GW or 100g at 28GW and 34GW complementary to the postnatal prevention. Few data are available on the real perinatal benefit of systematic prevention.

Female↗

Effect of systematic psychological preparation using visual illustration prior to gastrointestinal endoscopy on the anxiety of both pediatric patients and parents.

BACKGROUND: Anxiety, a psychological response to stress, can affect a child undergoing medical procedures, and their family members. The purpose of the present study was to evaluate the benefit of detailed systematic information using a set of real photograph-based technical illustrations provided to both parents and patients before performing endoscopy on the level of anxiety. MATERIAL AND METHOD: All children eligible for gastrointestinal endoscopy were consecutively enrolled from December 2003 to May 2004. Before and after providing systematic psychological preparation, the parents and patients older than five years of age were asked to score their anxiety on the procedures using visual analogue scale (VAS). RESULTS: There were fifty-four patients enrolled during the study period Of these, twenty-five children were older than five years of age. The most common indication of gastrointestinal endoscopy was lower gastrointestinal bleeding. The esophagogastroduodenoscopy, colonoscopy, and both upper and lower endoscopies were performed in 50%, 37%, and 13% of the cases, respectively. The mean and standard deviation of VAS on anxiety of the parents (n = 54) before and after providing systematic information were 3.89 +/- 3.45 and 1.90 +/- 2.46, respectively (p < 0.001). These values on anxiety of the children older than 5 years of age before and after providing systematic information were 4.38 +/- 3.72 and 3.36 +/- 3.69, respectively (p = 0.143). There was no statistically significant impact of types ofp rocedure, level of education, family s income, age of children, and birth order on the level of anxiety. CONCLUSION: The preparatory intervention using systematic visual illustration of the technical procedures in children undergoing gastrointestinal endoscopy could significantly reduce the parents' anxiety.

Adult↗

[Family satisfaction with systematic nursing instructions in a pediatric emergency department].

This study aimed to evaluate satisfaction with systematic nursing instructions among family members of pediatric emergency patients and to determine the degree to which family members complied with instructions provided. All subjects recruited were from a single medical center. A structured questionnaire was used to collect data. Written systematic nursing instructions were given to patient family members, supplemented by verbal interpretation. Family members were then contacted by telephone at 24 and 72 hours, respectively, after emergency department (ED) discharge. Questionnaires were completed and mailed back to the hospital within 72 hours. The 362 valid responses returned out of 700 questionnaires dispensed represented a response rate of 51.7%. Data were analyzed using descriptive statistics, t-test, one-way ANOVA and Scheffe's test. Main study findings included: (1) Family member satisfaction with systematic nursing instructions was 83.8%; (2) Families with higher educational levels had higher expectations in terms of health education and were less satisfied with instructions provided; and (3) 61.4% of participants reported symptom relief after following systematic nursing instructions and, as a result, did not need to return for further clinical help. Results demonstrate that systematic nursing instructions are effective in improving family satisfaction and compliance with nursing instructions. In addition, these instructions help reduce the rate of unplanned return visits to the pediatric ED.

Adult↗

[Clinical evaluation of systematic lymph node dissection for the intrathoracic esophageal carcinoma].

We evaluated the effectiveness and complication of systematic lymph node dissection for the intrathoracic esophageal carcinoma, which includes cervical, intrathoracic and abdominal lymph node dissection. Two hundred and thirteen individuals with intrathoracic esophageal carcinoma underwent esophageal resection in the Department of Surgery II, Kyushu University from 1979 to 1988. Of these 213, systematic lymph node dissection in addition to esophageal resection was performed on 19 patients. Lymph node recurrence has been reduced with this procedure and survival rate was more favorable in the cases with systematic lymph node dissection than those without it at present. On the other hand, although the occurrence of postoperative recurrent nerve palsy in the cases with systematic lymph node dissection and in those without it were 47.4 and 11.9%, rates of postoperative pulmonary complications were 5.2 and 16.0%, respectively. Operative death was none in those with systematic lymph node dissection. Therefore, this procedure has been performed in safety with intensive perioperative cares and it would contribute more favorable prognosis.

Aged↗

[Genetic heterogeneity of schizophrenia. Results of a systematic twin study].

One reason for the inconsistent findings in schizophrenia research is the lack of diagnostic conformity. In the face of modern operational "atheoretical" diagnostic systems, this dilemma is still present. In order to examine specificity and validity of diagnoses, we carried out a systematic twin study with index twins suffering from schizophrenic spectrum psychoses. We compared the diagnostic systems of DSM-III-R, which is based on consensus of international experts, with Leonhards' nosology developed on sophisticated clinical observation and description of psychopathological phenomena occurring during the long-term course of psychiatric diseases. We examined twin concordance, family history, and the frequency and severity of complications of pregnancy and child-birth. The results suggest that the schizophrenic spectrum has to be divided into clinically and etiologically heterogeneous subgroups. This was much more striking when Leonhard's diagnostic criteria were used than with DSM-III-R diagnostic criteria. There seem to be three valid and etiologically different groups: cycloid psychoses, unsystematic schizophrenias and systematic schizophrenias as proposed by Leonhard. In cycloid psychoses genetic loading seems to be low (proband concordance MZ 38%, DZ 29%), but pregnancy and birth complications may have an important role in the etiology. On the other hand, unsystematic schizophrenias are obviously predominantly inherited (proband concordance MZ 88%, DZ 17%) and "environmental" factors are not very prominent. It is striking that MZ twins with a diagnosis of systematic schizophrenia have not yet been found, whereas 32% of DZ index twins (6 out of 19) were diagnosed as having systematic schizophrenia. Further, all DZ twins with the diagnosis of systematic schizophrenia were discordant and the affected twins had threetimes as many and as severe pregnancy and birth complications in the history than their healthy co-twins.

Adult↗

[Primary hyperparathyroidism. Optimization of surgical results with systematic preoperative 99mTc-Sestamibi scintigraphy].

OBJECTIVE: The importance of preoperative 99mTc Sestamibi (MIBI) scintigraphy in case of reoperation for persistent hyperparathyroidism is well recognized, but it use as a systematic exploration technique remains a question of debate. We conducted this study to determine whether preoperative MIBI scans performed in all cases before surgery have any real impact. METHOD: Two successive series of 65 operated patients were included in the study. In the first group, the MIBI scan was not performed prior to surgery while in the second group the MIBI scan was part of the systematic work-up. RESULTS: The sensitivity and positive predictive value of MIBI were 92% and 96% respectively. Sensitivity for unique adenomas was 95% and 80% for multiple forms. In the first group without systematic scans, there were two unproductive procedures. In the second group, all procedures were productive and no reoperations were required. Two mediastinal adenomas were removed at the first cervicotomy in this group. The rate of complications was similar for both groups. Mean operation time was 2 hours in the first group and 1 hour 30 minutes for the second. CONCLUSION: Our series shows that there are three main advantages of using MIBI scintigraphy systematically prior to surgery for hyperparathyroidism: the procedure is easier in patients with cervical adenomas, particularly in case of ectopic localizations; the mean duration of the operation is shortened by 30 minutes; mediastinal ectopic localizations can be removed by sternotomy at the first operation. These advantages appear to be great enough to propose systematic use of MIBI scan prior to surgery. When MIBI scan shows a single gland, the risk of missing a multiple localization is less than 2% in our experience. It appears possible to operate under local anesthesia via a single-sided approach in elderly patients or high-risk patients.

Adenoma↗

A narrative systematic review of definitions and diagnostic criteria for disordered eating and eating disorders in type 1 diabetes.

AIMS/HYPOTHESIS: Type 1 diabetes and disordered eating (T1DE) affects 8-37.1% of adults and is associated with high rates of morbidity and mortality. The absence of a standardised case definition of T1DE and its severity hinders effective screening, diagnosis and treatment. This systematic review aimed to (1) synthesise existing case definitions and diagnostic criteria for T1DE in adults and (2) identify key characteristics to inform consensus for future diagnostic criteria. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. Eligible studies involved adults (&#x2265;18 years) with type 1 diabetes assessing disordered eating; paediatric studies, mixed samples without disaggregated data, non-empirical designs and non-English publications were excluded. PubMed, MEDLINE, EMBASE, CINAHL and PsycINFO were searched up to November 2025 for peer-reviewed studies involving adults with T1DE. Qualitative and quantitative data on definitions, diagnostic criteria and assessment tools were extracted. Study quality was appraised using a modified Graphical Appraisal Tool for Epidemiological studies (GATE) checklist. Due to heterogeneity of data, a narrative synthesis of findings was performed to describe current definitions of T1DE. RESULTS: Sixty-one studies met the inclusion criteria, with a pooled sample of 111,208 participants (76% women) from over 22 countries. T1DE was defined using a heterogeneous array of terms, diagnostic frameworks and assessment tools (29 distinct methods). The Diabetes Eating Problem Survey-Revised (DEPS-R) was the most used questionnaire, but many studies relied on criteria adapted from general eating disorder classifications or generic questionnaires. Approximately three-quarters of the studies assessed insulin omission behaviours, but the operationalisation of the cognitions for insulin omission varied widely. Beyond physiological markers such as HbA1c and BMI, studies explored various diabetes-related and psychological constructs, although often considering diabetes and disordered eating separately rather than as an integrated condition. CONCLUSIONS/INTERPRETATION: This systematic review highlights the lack of a unified, evidence-based definition of T1DE, resulting in inconsistent screening, diagnostic and reporting practices. Establishing clear, consistent, evidence-based diagnostic criteria and screening questionnaires for T1DE is critical to improving early detection and developing targeted interventions. These findings provide a foundation for refining T1DE definitions as a stepping stone to an international consensus definition. STUDY REGISTRATION: PROSPERO registration no. CRD420250223622 FUNDING: King's College London and King's College Hospital through the KMRT KCH Joint Research Committee studentship. This work was also conducted as part of the National Institute for Health Research (NIHR; CS-2017-17-023)-funded STEADY project (Safe management of people with Type 1 diabetes and EAting Disorders studY). NZ's salary was part-funded by the NIHR via the NIHR Clinician Scientist award to MS; JT and KI are part-funded by the NIHR Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. MS was funded through her NIHR Clinician Scientist Fellowship (CS-2017-17-023).

Humans↗

Enteral nutritional support in prevention and treatment of pressure ulcers: a systematic review and meta-analysis.

BACKGROUND: There have been few systematic reviews and no meta-analyses of the clinical benefits of nutritional support in patients with, or at risk of developing, pressure ulcers. Therefore, this systematic review and meta-analysis was undertaken to address the impact of enteral nutritional support on pressure ulcer incidence and healing and a range of other clinically relevant outcome measures in this group. METHODS: Fifteen studies (including eight randomised controlled trials (RCTs)) of oral nutritional supplements (ONS) or enteral tube feeding (ETF), identified using electronic databases (including Pub Med and Cochrane) and bibliography searches, were included in the systematic review. Outcomes including pressure ulcer incidence, pressure ulcer healing, quality of life, complications, mortality, anthropometry and dietary intake were recorded, with the aim of comparing nutritional support versus routine care (e.g. usual diet and pressure ulcer care) and nutritional formulas of different composition. Of these 15 studies, 5 RCTs comparing ONS (4 RCTs) and ETF (1 RCT) with routine care could be included in a meta-analysis of pressure ulcer incidence. RESULTS: Meta-analysis showed that ONS (250-500 kcal, 2-26 weeks) were associated with a significantly lower incidence of pressure ulcer development in at-risk patients compared to routine care (odds ratio 0.75, 95% CI 0.62-0.89, 4 RCTs, n=1224, elderly, post-surgical, chronically hospitalised patients). Similar results were obtained when a combined meta-analysis of ONS (4 RCT) and ETF (1 RCT) trials was performed (OR 0.74, 95% CI 0.62-0.88, 5 RCTs, n=1325). Individual studies showed a trend towards improved healing of existing pressure ulcers with disease-specific (including high protein) versus standard formulas, although robust RCTs are required to confirm this. Although some studies indicate that total nutritional intake is improved, data on other outcome measures (quality of life) are lacking. CONCLUSIONS: This systematic review shows enteral nutritional support, particularly high protein ONS, can significantly reduce the risk of developing pressure ulcers (by 25%). Although studies suggest ONS and ETF may improve healing of PU, further research to confirm this trend is required.

Aged↗

Complementary therapies for peripheral arterial disease: systematic review.

While peripheral arterial disease (PAD) affects a considerable proportion of patients in the primary care setting, there is a high level of use of complementary treatment options. The aim was to assess the effectiveness of any type of complementary therapy for peripheral arterial disease. A systematic review was performed. Literature searches were conducted on Medline, Embase, Amed, and the Cochrane Library until December 2004. Hand-searches of medical journals and bibliographies were conducted. There were no restrictions regarding the language of publication. The screening of studies, selection, data extraction, the assessment of methodologic quality and validation were performed independently by the two reviewers. Data from randomized controlled trials, and systematic reviews and meta-analyses, which based their findings on the results of randomized controlled trials were included. Seven systematic reviews and meta-analyses and three additional randomized controlled trials met the inclusion criteria and were reviewed. The evidence relates to acupuncture, biofeedback, chelation therapy, CO(2)-applications and the dietary supplements Allium sativum (garlic), Ginkgo biloba (ginkgo), omega-3 fatty acids, padma 28 and Vitamin E. Most studies included only patients with peripheral arterial disease in Fontaine stage II (intermittent claudication). The reviewed RCTs, systematic reviews and meta-analyses which based their findings on the results of RCTs suggest that G. biloba is effective compared with placebo for patients with intermittent claudication. Evidence also suggests that padma 28 is effective for intermittent claudication, although more data are required to confirm these findings. For all other complementary treatment options there is no evidence beyond reasonable doubt to suggest effectiveness for patients with peripheral arterial disease.

Arteries↗

Early mortality in children with homozygous familial hypercholesterolemia: Case reports of deaths at ages 5 and 7&#xa0;and a systematic review of global evidence.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a leading cause of premature atherosclerotic cardiovascular disease (ASCVD) and early mortality if left untreated or inadequately treated. OBJECTIVE: This study presents&#xa0;2&#xa0;pediatric cases of early death&#xa0;from Pakistan due to familial hypercholesterolemia (FH) and provides a systematic review of similar cases reported globally. METHODS: Genetic analysis was conducted using next-generation sequencing to confirm pathogenic variants. For the systematic review, published reports of individuals with FH who died before the age of 18 years were identified. Data were extracted on demographic features, personal and family history, genetic variants, treatment given, and cause of death. RESULTS: Both patients, born to consanguineous families, presented with markedly elevated low-density lipoprotein cholesterol&#xa0;(LDL-C) levels (792&#xa0;mg/dL [20.48&#xa0;mmol/L] and 896&#xa0;mg/dL [23&#xa0;mmol/L], respectively), multiple xanthomas, and early-onset myocardial infarction, and died at the ages of 5 and 7 years, respectively. Their genetic analysis revealed a pathogenic frameshift variant in the LDLR gene: NM_000527.5: c.2416dupG (p.Val806GlyfsTer11). The systematic review included 12 studies reporting pediatric FH-related mortality. Common clinical features included tendon xanthomas, elevated LDL-C levels, family history, and early-onset ASCVD. Genetic testing was performed in a few cases, which revealed pathogenic variations in the&#xa0;LDLR gene. Most of the patients received inadequate lipid-lowering therapy. The most common causes of death were severe coronary artery disease, myocardial infarction, and sudden cardiac arrest. CONCLUSION: Our 2&#xa0;cases and the accompanying systematic review identified additional cases of premature mortality. Collectively, these findings highlight diagnostic delays and inadequate treatment as common factors among patients who died prematurely.

Child↗

Malnutrition and adverse outcomes after spine surgery: a systematic review and meta-analysis.

BACKGROUND CONTEXT: Malnutrition is linked to adverse surgical outcomes, but its impact in spine surgery remains unclear due to inconsistent findings and heterogeneous definitions, including use of serum albumin, prealbumin, lymphocyte count, the Geriatric Nutritional Risk Index, and the Prognostic Nutritional Index. We conducted a systematic review and meta-analysis to evaluate the relationship between malnutrition and postoperative outcomes in spine surgery. PURPOSE: To systematically evaluate the association between preoperative malnutrition and postoperative outcomes in patients undergoing spine surgery. STUDY DESIGN: Systematic review and meta-analysis. PATIENT SAMPLE: Patients undergoing elective or urgent spine surgery across included observational studies comparing malnourished vs well-nourished cohorts. OUTCOME MEASURES: Primary outcomes included postoperative mortality and overall surgical complications. Secondary outcomes included infectious complications (sepsis, urinary tract infection, wound complications), delirium, reoperation, 30-day and 90-day readmission, and prolonged length of hospital stay. METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was performed on April 7, 2025, following PRISMA guidelines. Studies directly comparing postoperative outcomes in malnourished vs well-nourished spine surgery patients were included. A random-effects model generated pooled odds ratios for complications. Outcomes assessed included mortality, surgical complications, infectious outcomes, readmission, reoperation, delirium, prolonged length of stay, and wound complications. RESULTS: Of 2,851 screened articles, 37 met the inclusion criteria, encompassing 16,987 malnourished patients. Malnutrition was associated with significantly increased odds of mortality (OR: 4.05, 95% CI [2.97-5.54]), delirium (OR: 3.95, 95% CI [2.49-6.27]), sepsis (OR: 2.77, 95% CI [2.31-3.33]), surgical complications (OR: 1.79, 95% CI [1.57-2.04]), urinary tract infection (OR: 1.81, 95% CI [1.59-2.06), wound complications (OR: 2.10, 95% CI [1.80-2.45]), reoperation (OR: 1.70, 95% CI [1.46-1.97]), prolonged length of hospital stay (OR: 3.46, 95% CI [2.57-4.65]), 30-day readmission (OR: 1.59, 95% CI [1.36-1.86]), and 90-day readmission (OR: 2.13, 95% CI [1.67-2.71]). CONCLUSIONS: Malnutrition was consistently associated with adverse outcomes after spine surgery. Routine nutritional assessment and targeted preoperative optimization should be considered a standard component of perioperative spine care to help reduce postoperative complications and improve recovery.

Humans↗

A guide to developing a systematic review.

Systematic reviews are used to gather information from a variety of sources and distill information based on best evidence synthesis, while also excluding poor quality studies via explicit validity checks. This article provides a roadmap to conducting a systematic review with the Cochrane Collaboration and uses an example of a completed systematic review. The literature is drawn upon to provide rationale for the processes undertaken. The aim of the sample systematic review was to identify and review all randomized controlled trials evaluating disposable surgical face masks worn by surgical team members during clean surgery to prevent postoperative surgical wound infection.

Female↗

Systematic review of amodiaquine treatment in uncomplicated malaria.

BACKGROUND: Opinion and policy over the use of amodiaquine for treating malaria vary. Amodiaquine is more palatable than chloroquine and may be more effective but serious adverse events have been reported in travellers taking it as prophylaxis. It is not recommended as first-line treatment. In the light of the global debate over the use of this drug, we conducted a systematic review of the effectiveness and tolerability of amodiaquine in the treatment of uncomplicated falciparum malaria. METHODS: This is a systematic review of published and unpublished randomised or pseudorandomised trials of amodiaquine. Observational reports were also systematically identified and reviewed to access evidence of serious adverse events. FINDINGS: 40 trials met the inclusion criteria. Symptomatic patients were enrolled in 24 studies in comparisons of amodiaquine (n = 1071) with chloroquine (n = 1097). Amodiaquine was significantly more effective than chloroquine, with odds ratios and 99% confidence intervals (OR [99% CI]) of 4.29 (3.30-5.58) on day 7 and 6.00 (3.97-9.06) on day 14. Time to parasite clearance was significantly shorter with amodiaquine and fever clearance times were marginally faster. Eight studies compared amodiaquine with chloroquine in asymptomatic parasitaemia, with effects on parasitological outcomes similar to those for symptomatic malaria. At twelve sites, 692 amodiaquine and 679 sulfadoxine/pyrimethamine (S/P) recipients were enrolled. The two drugs did not differ significantly on day 7 (OR 0.74 [0.48-1.15]) but the odds ratios favoured S/P on day 14 (OR 0.51 [0.28-0.93]) and on day 28 (OR 0.30 [0.16-0.55]). The time to parasitological clearance was similar in the two groups; fever clearance times were significantly shorter with amodiaquine. Tolerability was assessed for both comparative and non-comparative trials. The rates of adverse events in controlled trials were 10.7%, 8.8%, and 14.3% with amodiaquine, chloroquine, and S/P, respectively. No life-threatening adverse events and no significant shifts in laboratory indices were reported. INTERPRETATION: This systematic review of published and unpublished trials supports the use of amodiaquine in the treatment of uncomplicated malaria. However, there is partial cross-resistance between chloroquine and amodiaquine, and monitoring of the effectiveness of this drug and surveillance for evidence of toxicity must continue.

Amodiaquine↗

A systematic review of the scientific evidence for the efficacy of a palliative care approach in advanced dementia.

BACKGROUND: Patients with dementia often receive poor end-of-life care, with inadequate pain control and without access to the palliative care services that patients with cancer are offered. This has been identified as an area of need in recent UK. Government reports and by the Alzheimer's Society (UK). Our objective was to perform a systematic review of the scientific literature regarding the efficacy of a palliative care model in patients with dementia. METHODS: A systematic review was carried out to identify controlled trials that investigated the efficacy of palliative care in patients with dementia. Data sources included were Medline, EMBASE, PsycINFO, CINAHL, British Nursing Index, AMED, Cochrane Database of Systematic Reviews, Web of Science, Cochrane Central Register of Controlled Trials, International Standard Randomised Controlled Trial register, the NHS Economic Evaluation Database and the System for Information on Grey Literature in Europe. Other data was sourced from hand searches of papers identified on electronic databases and review articles. RESULTS: The search identified 30 review articles, but only four papers were eligible for full appraisal and only two of these met the full criteria for inclusion. These papers gave equivocal evidence of the efficacy for a palliative model of care in dementia. CONCLUSION: Despite the increased interest in palliative care for patients with dementia there is currently little evidence on which to base such an approach. This may in part be due to the ethical difficulties surrounding such research, prognostic uncertainty in clinicians and the lack of clear outcome measures for patients who are unable to express their needs or wishes. Further systematic research is urgently needed to educate an important and developing area of clinical practice.

Aged↗

A rapid and systematic review of the effectiveness of temozolomide for the treatment of recurrent malignant glioma.

A rapid and systematic review of the effectiveness and cost-effectiveness of temozolomide in the treatment of recurrent malignant glioma was commissioned by the NHS HTA Programme on behalf of NICE. The full report has been published elsewhere. This paper summarizes the results for the effectiveness of temozolomide in people with recurrent glioblastoma multiforme and anaplastic astrocytoma. The review was conducted using standard systematic review methodology involving a systematic literature search, quality assessment of included studies with systematic data extraction and data synthesis. One randomized controlled trial and four uncontrolled studies were identified for inclusion. The key results were that temozolomide may increase progression-free survival but has no significant impact on overall length of survival. The main effect from temozolomide may have been in those patients who had not received any prior chemotherapy regimens, however further randomized controlled trials are required to confirm this suggestion. Temozolomide appears to produce few serious adverse effects and may also have a positive impact on health-related quality of life. Overall the evidence-base is weak and few strong conclusions can be drawn regarding the effectiveness of temozolomide. Large, well-designed randomized controlled trails conducted in a wider patient population are needed.

Antineoplastic Agents, Alkylating↗

The mind of a failing heart: a systematic review of the association between congestive heart failure and cognitive functioning.

BACKGROUND: Congestive heart failure (CHF) is a frequent complication of most diseases of the heart. CHF is associated with impairment in several aspects of the quality of life of patients, including mood and cognitive performance. Early reports indicated that patients with CHF display deficits in memory and other intellectual abilities, although the clinical relevance of these findings remains unclear. AIM: We reviewed systematically the medical literature with the aim of clarifying the association between CHF and cognitive functioning. METHODS: Systematic review of Medline database for studies published between 1966 and June 2000 using the following key words: congestive heart failure, cognition, cognitive disorders, memory, memory disorders, short-term memory, attention. RESULTS: Thirteen studies reported cognitive information on patients with CHF, but only five met inclusion criteria for systematic review. Three reports described attention (total number of subjects = 369 patients and 882 controls) and memory scores (total number of subjects = 247 patients and 748 controls), two studies reported measures of general cognitive functioning (total number of subjects = 203 patients and 704 controls) and one reported the rate of cognitive impairment (total number of subjects = 88 patients and 987 controls). Pooled analysis indicated that CHF is associated with a pattern of generalized cognitive impairment that includes memory and attention deficits. CONCLUSIONS: The results of the present review highlight the enormous paucity of systematic information about the association between CHF and cognitive functioning, with only five studies reporting data suitable for analysis. We expect that new case-control and cohort studies will be designed to confirm the presence of cognitive impairment in patients with CHF and trust that this information will improve the management of CHF patients and our understanding of the mechanisms associated with cognitive decline in later life.

Attention↗