Systematic review of the evidence underlying the association between mineral metabolism disturbances and risk of fracture and need for parathyroidectomy in CKD.

BACKGROUND: Chronic kidney disease (CKD) is associated with such complications as fractures and the need for parathyroidectomy. Mineral metabolism control in patients with CKD has been poor. Studies have assessed fractures and parathyroidectomy risk with mineral disturbances, but with considerable diversity in methods. Thus, a systematic review was conducted to assess method or clinical heterogeneity by comparing the design, analytical techniques, and results of studies. STUDY DESIGN: Systematic review of the MEDLINE, EMBASE, and Cochrane databases between 1980 and December 2007. SETTING & POPULATION: Patients with CKD or dialysis patients. SELECTION CRITERIA FOR STUDIES: Observational and clinical trials investigating the risk of fractures or parathyroidectomy with mineral disturbances. PREDICTOR: Mineral metabolism variables (phosphorus, calcium, and parathyroid hormone [PTH] levels). OUTCOMES: Fractures, need for parathyroidectomy. RESULTS: 9 studies were identified that assessed fractures (n = 6) or need for parathyroidectomy (n = 3). Data for fractures or parathyroidectomy risk in predialysis patients are absent. Diversity across studies was observed in populations, methods of exposure assessment, adjusted covariates, and reference mineral levels used in risk estimation. A significant fracture risk was observed with increasing PTH levels. However, additional data are required to understand fracture risk with changes in phosphorus or calcium levels. Data supported greater parathyroidectomy risk with increasing PTH, phosphorus, or calcium levels. LIMITATIONS: Clinical and method heterogeneity across studies precluding the quantitative synthesis of data. CONCLUSIONS: Serious limitations were observed in the number, quality, and method rigor of studies. Despite heterogeneity across studies, data suggest a significant parathyroidectomy risk with mineral disturbances and a fracture risk with increasing PTH levels in dialysis patients. Additional high-quality data for risk of fractures or parathyroidectomy with changes in phosphorus, calcium, or PTH levels is required to highlight the importance of managing such common, but subclinical, conditions as mineral metabolism disturbances.

Systematic review of the evidence underlying the association between mineral metabolism disturbances and risk of all-cause mortality, cardiovascular mortality and cardiovascular events in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a powerful risk factor for all-cause mortality and its most common aetiology, cardiovascular (CV) mortality. Mineral metabolism disturbances occur very early during the course of CKD but their control has been poor. A number of studies have assessed the relationship between all-cause mortality, CV mortality and events with mineral disturbances in CKD patients, but with considerable discrepancy and heterogeneity in results. Thus, a systematic review was conducted to assess methodological and clinical heterogeneity by comparing designs, analytical approaches and results of studies. METHODS: Medline, EMBASE and Cochrane databases were systematically searched for articles published between January 1980 and December 2007. RESULTS: Thirty-five studies were included in the review. All-cause mortality was the most commonly assessed outcome (n = 29). Data on CV mortality risk (n = 11) and CV events (congestive heart failure, stroke, myocardial infarction) (n = 4) are limited. The studies varied in populations scrutinized, exposure assessments, covariates adjusted and reference mineral levels used in risk estimation. A significant risk of mortality (all-cause, CV) and of CV events was observed with mineral disturbances. The data supported a greater mortality risk with phosphorus, followed by calcium and parathyroid hormone (PTH). The threshold associated with a significant all-cause mortality risk varied from 3.5-3.9 mg/dL (reference: 2.5-2.9) to 6.6-7.8 mg/dL (reference: 4.4-5.5) for high phosphorus, <3 mg/dL (reference: 5-7) to <5 mg/dL (reference: 5-6) for low phosphorus, 9.7-10.2 mg/dL (reference: < or =8.7) to >10.5 mg/dL (reference: 9-9.5) for high calcium, < or =8.8 mg/dL (reference: >8.8) to <9 mg/dL (reference: 9-9.5) for low calcium and >300 pg/mL (reference: 200-300) to >480 pg/mL (reference: < or =37) for PTH. Thresholds at which the CV mortality risk significantly increased were >5.5 (reference: 3.5-5.5) and >6.5 mg/dL (reference: <6.5) for phosphorus and >476.1 pg/mL (reference: <476.1) for PTH. CONCLUSIONS: Serious limitations were observed in the quality and methodology across studies. In spite of enormous heterogeneity across studies, a significant mortality risk was observed with mineral disturbances in dialysis patients. Data on risk in pre-dialysis patients were less conclusive due to even more limited (numerically) evidence.

Historia de abuso sexual y su relación con depresión, autoestima y consumo de sustancias psicoactivas en estudiantes de media vocacional del municipio de Caldas Antioquia, Colombia: 2007 / Sexual abuse history and its relation with depression, self-esteem and consumption of Caldas, Antioquia, Colombia: 2007

Objetivo: Determinar la prevalencia de abuso sexual en estudiantes de los grados décimo y undécimo del municipio de Caldas y su relación con depresión, autoestima y consumo desustancias psicoactivas. Metodología: Estudio descriptivo de corte transversal. Se aplicó una encuesta a 565 estudiantes de los grados décimo y undécimo del municipio de Caldas. Se solicitó información acerca de lacomposición familiar, procedencia, edad del menor al momento del abuso sexual, tipo y frecuencia de este, así como edad, género y relación del abusador con la víctima; también se indagaron datos que permitieron analizar depresión, autoestima y consumo de sustancia psicoactivas. Resultados: El promedio de edad al momento de la encuesta fue de 16 años (DE 2,54). El 12 % de losjóvenes indicó que fue víctima de abuso sexual infantil. El 76,5 % de las víctimas eran mujeres. La edad promedio al momento del abuso fue de 10,3 años (DE 3,52). La edad del agresor osciló entre 12 y 80 años, con promedio de 32,18 años (DE 13,36). En 92,6 % de los casos el abusador era hombre. Del total de los casos de abuso, en 48,5 % el agresor era de la familia del menor. Las cariciasíntimas fueron el tipo de abuso más frecuente, específicamente cuando la víctima fue obligada a recibirlas(79,4 %), seguido de exhibicionismo cuando la víctima fue obligada a ver (45,6 %) y luego penetración vaginal oanal (35,8 %). El 52 % de los casos detectados de depresión fueron victimas de abuso sexual. El 21,1 % delos jóvenes con una mala autoestima fueron abusados en la infancia. El 23 % de los consumidores de marihuana,el 60 % de basuco, el 22 % de cocaína, el 24,3 % de inhalables, el 31,6 % de éxtasis y el 21,4 % de hongos fueron víctimas de abuso...

Objective: To determine the prevalence of sexual abuse in students of grades 10th and 11th in the municipality of Caldas and its relation with depression, low self-esteem and consumption of psychoactive substances. Methodology: Cross section descriptive study. A Surrey was applied to 565 students of grades 10th and 11th of the municipality of Caldas. Information was requested about the family composition, where from, age of the youngsters at the moment of sexual abuse, type and frequency of it, as well as age, gender and relation of the abuser with the victim; data was also collected that allowed to analyze depression, low self-esteem and consumption of psychoactive drugs. Results: The average age at the moment of the Surrey was 16 years (DE 2,54). 12% of the youngsters saidthat they were victims of child sexual abuse. 76,5 % of the victims were girls. The average age at the moment of abuse was 10,3 years (DE 3,52). The age of the aggressor varies between 12 and 80 years old, with an average of 32,18 (DE 13,36). In 92,6% of the cases the abuser was a man. Of the total cases of abuses 48,5% of theaggressors were relatives of the youngsters. The intimate caresses were the most frequent type of abuse, specifically when the victim was forced to receive them (79,4%).Second comes the exhibitionism when the victim was forced to see (45,6%) and then vaginal or anal penetration(35,8%). 52% of the depression cases detected were victims of sexual abuse. 21,1% of the youngsters withlow self-esteem were abused in their childhood. 23% of the marihuana smokers, 60% of crack consumer, 22%of cocaine consumer, 23,3 % of inhalants, 31,6% of Ecstasies and 21,4% of mushrooms were victims of abuse...

A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics.

OBJECTIVE: This literature review was performed to elucidate the relationship between bisphosphonate use and development of osteonecrosis of the jaw (ONJ) in patients receiving oral bisphosphonates for the treatment of osteoporosis. METHODS: MEDLINE, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and EMBASE were searched for English-language articles published from 1966 to September 2006 whose titles included the term osteonecrosis of the jaw in conjunction with bisphosphonates, alendronate, risedronate, ibandronate, etidronate, clodronate, zoledronic acid, or pamidronate. Articles were included in the review if the population consisted of adults with ONJ; patients received bisphosphonates for the treatment of osteoporosis only; the reported data included baseline characteristics of the study population (age; sex; comorbidities; concomitant medications; history of dental surgery, trauma, or infection), characteristics of bisphosphonate treatment (specific bisphosphonate, dose, duration of treatment, mode of administration), clinical features of ONJ (signs, symptoms, site), the treatment protocol used to manage ONJ, or the prevalence of ONJ in patients with osteoporosis treated with bisphosphonates; and the publication involved a case report, case series, or observational study. RESULTS: After application of the search strategy and the inclusion/exclusion criteria, 11 publications reporting 26 cases of ONJ in patients receiving bisphosphonates for the treatment of osteoporosis were included in the review. The most commonly affected site was the mandible (16 patients), followed by the maxilla (6 patients). Among the 23 patients whose age was reported, 18 (78%) were aged >or=60 years. Among the 23 patients whose sex was reported, only 3 (13%) were men. Of 15 patients with a history of invasive dental treatment, 12 (80%) had undergone dental surgery or experienced dental trauma at the site of ONJ. Among the 10 patients for whom the duration of bisphosphonate treatment was reported, no clear relationship between the duration of bisphosphonate treatment and the development of ONJ was observed. CONCLUSIONS: Considering that millions of patients have been prescribed bisphosphonates for the treatment of osteoporosis, the relative prevalence of ONJ in these patients was low. Age >or=60 years, female sex, and previous invasive dental treatment were the most common characteristics of those who developed ONJ. However, it is not possible to draw further conclusions about the potential association between oral bisphosphonate use and ONJ in the identified studies because of incomplete reporting and the presence of confounding factors.

Comparison of pegfilgrastim with filgrastim on febrile neutropenia, grade IV neutropenia and bone pain: a meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: While head-to-head clinical trials demonstrate pegfilgrastim to be as efficacious as filgrastim in reducing chemotherapy-induced neutropenia, these studies lacked the statistical power to demonstrate better outcomes with one therapy compared to the other. Our objective was to obtain a pooled estimate of the effect of pegfilgrastim compared with filgrastim on incidence of febrile neutropenia (FN), and related outcomes among patients with solid tumors and malignant lymphomas receiving myelosuppressive chemotherapy. RESEARCH DESIGN AND METHODS: We searched PubMed and EMBASE for articles published from January 1, 1990 to August 31, 2006 reporting on randomized controlled trials (RCTs) that compared the efficacy and safety of pegfilgrastim versus filgrastim. We only accepted studies in which filgrastim (5 microg/kg/day) and pegfilgrastim (100 microg/kg or a fixed dose of 6 mg) were administered at approved doses indicated on the package insert. Pooled relative risk (RR) was estimated using the conservative random effects, empirical Bayesian method of Hedges and Olkin. MAIN OUTCOME MEASURES: Rates of grade IV neutropenia and of FN, time to absolute neutrophil count (ANC) recovery, and bone pain. RESULTS: We identified five RCTs, with a total of 617 patients, evaluating the efficacy of a single dose of pegfilgrastim per cycle versus daily filgrastim injections. Although only one study had a statistically significant difference in FN reductions favoring pegfilgrastim over filgrastim (relative risk reduction of 50%; p = 0.027), the pooled RR showed a statistically significant favorable result for pegfilgrastim (RR = 0.64; 95% CI, 0.43-0.97). Grade IV neutropenia rates (for cycle 1: RR = 0.99; 95% CI, 0.91-1.08; cycle 2: RR = 0.88; 95% CI, 0.70-1.11; cycle 3: RR = 0.80; 95% CI, 0.47-1.36; cycle 4: RR = 0.90; 95% CI, 0.71-1.13), time to ANC (SMD = 0.11, 95% CI, -0.34-0.56), and incidence of bone pain (RR = 0.95; 95% CI, 0.76-1.19) were similar between the two G-CSFs. The included trials varied in the type of cancer, chemotherapy regimen and type of trial. CONCLUSION: A single dose of pegfilgrastim performed better than a median of 10-14 days of filgrastim in reducing FN rates for patients undergoing myelosuppressive chemotherapy.

Treatment of patients with metastatic renal cell cancer: a RAND Appropriateness Panel.

BACKGROUND: New developments in the treatment of patients with metastatic renal cell cancer (MRCC) have suggested a need to reevaluate the role of systemic therapies. The authors convened a panel of medical and urologic oncologists to rate the appropriateness of the main options. METHODS: The authors used the RAND/University of California-Los Angeles Appropriateness Method to evaluate systemic therapy options and cytoreductive nephrectomy. After a comprehensive literature review, an expert panel rated the appropriateness of systemic options (108 permutations) and cytoreductive nephrectomy (24 permutations) for patients with MRCC. RESULTS: The appropriateness evaluation indicated that 27.3% of permutations were rated "appropriate," 46.9% were rated "inappropriate," and 25.8% were rated "uncertain." There was a high rate of agreement (95%). Sunitinib and sorafenib were rated appropriate for patients with low-to-moderate risk regardless of prior treatment. Temsirolimus was rated appropriate for first-line therapy for higher risk patients. Interferon-alpha and low-dose interleukin-2 were rated inappropriate or uncertain. In patients who received prior immunotherapy, cytokines were rated inappropriate. In all permutations for evaluating systemic therapy, enrollment into an investigational trial was considered appropriate, treatment with bevacizumab was uncertain, and thalidomide was inappropriate regardless of risk status or prior therapy. For good surgical risk patients with planned immunotherapy, nephrectomy was rated appropriate in patients who had limited metastatic burden regardless of tumor-related symptoms and in symptomatic patients regardless of metastatic burden. Only the most favorable combination of surgical risk, metastatic burden, and symptoms generated an "appropriate" rating for patients with planned targeted therapy. CONCLUSIONS: The current results begin the process of defining an appropriate role for cytokines, newer targeted therapies, and surgery in the treatment of MRCC.

Benefits of GM-CSF Versus Placebo or G-CSF in Reducing Chemotherapy-Induced Complications: A Systematic Review of the Literature.

Unlike granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) is not approved for reducing the incidence or duration of chemotherapy-induced febrile neutropenia. However, some studies have been conducted in this setting. A systematic review assessing the efficacy of GM-CSF versus placebo or G-CSF in reducing chemotherapy-induced febrile neutropenia and related complications was performed. Medline was reviewed for articles published between January 1987 and March 2003 that contained specific search terms. Explicit inclusion/exclusion criteria were developed for titles, abstracts, and articles. Two researchers reviewed (kappa>/= 0.7) and divided studies according to their evaluation of GM-CSF versus placebo or versus G-CSF. Nine studies were accepted: 6 randomized controlled trials compared GM-CSF versus placebo and 3 studies compared GM-CSF versus GCSF. Three placebo-controlled trials showed that GM-CSF was ineffective in reducing the risk of chemotherapy-induced febrile neutropenia. The remaining 3 trials reported incidence of fever and not febrile neutropenia: 2 reported a significantly increased incidence of fever in the GM-CSF group, and 1 reported that more patients receiving placebo experienced fever compared with patients in the GMCSF group (P > 0.05). The 3 studies comparing GM-CSF versus G-CSF reported fever as a primary outcome also. All 3 reported higher incidence of fever in the GM-CSF group (P < 0.05). Head-to-head trials of G-CSF and GM-CSF in reducing chemotherapy-induced complications are lacking. Identified GM-CSF studies did not show significant reduction in febrile neutropenia and fever.

Risk of Upper Gastrointestinal Injury and Events in Patients Treated With Cyclooxygenase (COX)-1/COX-2 Nonsteroidal Antiinflammatory Drugs (NSAIDs), COX-2 Selective NSAIDs, and Gastroprotective Cotherapy: An Appraisal of the Literature.

Numerous studies using varying methodologies and outcome measures have examined the gastrointestinal risks of aspirin and nonaspirin nonsteroidal antiinflammatory drug (NSAID) use. Despite the large volume of literature, clarity regarding the key risk factors and their quantitative importance is lacking. We performed a comprehensive review of the literature to summarize the incidence of gastrointestinal injury in populations with varying risk characteristics using agents that inhibit both isoforms of cyclooxygenase and those that selectively inhibit only cyclooxygenase-2 (COX-2).Although risk estimates vary, the risk of serious gastrointestinal complications in NSAID users is approximately 2.5 to 4.5 times that of nonusers. The risk of NSAID-related gastrointestinal bleeding is augmented by concomitant low-dose aspirin and could approach double the risk of NSAID use alone. The preponderance of evidence shows that the risk of NSAID-related gastrointestinal bleeding is reduced approximately 50% with a coxib as compared with traditional NSAID. The relative risk of hospitalization resulting from upper gastrointestinal bleeding for patients treated with a nonselective NSAID was 4.4 (95% confidence interval [CI], 2.3-8.5) and 1.9 (95% CI, 1.0-3.5) when compared with celecoxib and rofecoxib, respectively. Aspirin increases the risk of NSAID-related gastrointestinal bleeding in patients taking COX-2 selective inhibitors, with odds ratios ranging from 5.8 to 7.7; however, it is unknown whether this risk is greater than the risk from aspirin alone. The risks from both traditional NSAIDs and COX-2 inhibitors are increased in the elderly, patients on anticoagulation, and patients with prior gastrointestinal events.Gastroprotective agents have been found to significantly reduce the risk for gastrointestinal injury in patients receiving NSAID therapy, especially those receiving concurrent low-dose cardioprotective doses of aspirin. Proton pump inhibitors (PPIs) and misoprostol both reduce the incidence of gastric and duodenal ulcers, as well as recurrence of ulcer complications in patients receiving NSAIDs. The relative risk for gastric ulcers ranged from 0.17 to 0.38, whereas for duodenal ulcers, the range was 0.11 to 0.28. Although misoprostol is slightly more effective in preventing gastric ulcers in these patients, PPIs are better tolerated. Although NSAIDs appear safe in "low-risk" populations, our review suggests that the use of gastroprotective cotherapy should be considered in patients at higher risk of NSAID-related upper gastrointestinal bleeding.

Association between protease inhibitor use and increased cardiovascular risk in patients infected with human immunodeficiency virus: a systematic review.

Some studies have shown that currently available protease inhibitors (PIs) are associated with an increased risk of cardiovascular disease. We have systematically reviewed the published literature and conference abstracts for studies evaluating cardiovascular risk factors and events in patients receiving highly active antiretroviral therapy, with and without PIs. The majority of studies showed that the use of PIs was associated with increased levels of total cholesterol (36 [75%] of 48 studies), triglycerides (35 [73%] of 48 studies), and low-density lipoprotein (12 [100%] of 12 studies). PI use was often associated with morphological signs of cardiovascular disease, such as increased carotid intima thickness or atherosclerotic lesions (7 [88%] of 8 studies). Finally, 2 (67%) of 3 long-term observational studies that met our inclusion criteria demonstrated an association between use of PIs and subsequent myocardial infarction. The benefits of the currently available PIs should be balanced against the long-term risk of cardiovascular disease.