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Fusidic acid in staphylococcal bone and joint infection.

Over 25 years experience with fusidic acid in the treatment of bone and joint infections is reviewed. Fusidic acid, usually given concurrently with another antibiotic, has proved effective in a wide variety of staphylococcal infections, including acute osteomyelitis and septic arthritis. It is a valuable adjunct to surgery in patients with chronic osteomyelitis. Oral therapy is generally well tolerated, apart from gastrointestinal side effects in a small proportion of cases. Use of fusidic acid in other orthopaedic situations is considered in the light of recent information.

Bone Diseases↗

Concurrence of metaphyseal fibrous defect and osteosarcoma. Report of a case and review of the literature.

The case of a 15-year-old girl with juxtaposition of a femoral metaphyseal fibrous defect (fibrous cortical defect) and an osteosarcoma is reported. Despite the relatively common occurrence of metaphyseal fibrous defects, their reported association with other bone tumors is exceedingly rare. Only two previous acceptable examples of this association were found. Reports of malignant transformation of metaphyseal fibrous defect were reviewed and rejected because they lacked convincing radiologic or histopathologic evidence of a pre-existent benign fibrous lesion. The finding of a malignant bone tumor in association with a metaphyseal fibrous defect appears to be a chance occurrence.

Adolescent↗

Cryptococcal ventricular-peritoneal shunt infection: clinical and epidemiological evaluation of two closely associated cases.

OBJECTIVE: To determine the cause of meningitis associated with Cryptococcus neoformans in two patients with recent ventricular-peritoneal (VP) shunt placement. DESIGN: A retrospective review of materials, records, and concurrent cases of VP shunt procedures. Isolates of C neoformans from each patient were submitted for analysis by colony morphology, biochemical testing, and karyotyping by pulsed-field electrophoresis. SETTING: Two 400-bed community hospitals. PATIENTS: Two immunocompetent patients presented with symptoms of progressive hydrocephalus in August 1991. Each received a VP shunt on the same day by the same surgeon using materials from a common vendor and hospital. RESULTS: Both patients presented within six to eight weeks with symptoms of fever, headache, rash, and cultures of cerebrospinal fluid (CSF) that yielded C neoformans. Each patient recovered after therapy with amphotericin B and flucytosine followed by several months of fluconazole, although one required replacement of the VP shunt for cure. Review of each patient's history and CSF characteristics at the time of shunt placement suggested reactivation of a preexisting infection. Isolates of C neoformans from each patient were submitted for analysis by colony morphology, biochemical testing, and karyotyping by pulsed-field electrophoresis. Each isolate was found to be unique by chromosomal karyotyping. CONCLUSIONS: Our data and previous reports suggest that cryptococcal VP shunt infections appear to be a complication of shunts placed in previously infected persons rather than nosocomial transmission of cryptococcus during placement.

Adult↗

Primary hyperparathyroidism and acute pancreatitis during pregnancy. Report of a case and a review of the English and Japanese literature.

The simultaneous occurrence of primary hyperparathyroidism (PHPT) and pancreatitis during pregnancy is very rare. We present a case of concurrent PHPT and pancreatitis in pregnancy and review 13 cases reported in the English and Japanese literature. Two maternal and three fetal deaths occurred. Mortality seemed to be related to delayed resection of the parathyroid tumor. Morphologically, severe pancreatitis was only seen in three cases, whereas even edematous or focal pancreatitis caused the same symptoms as clinically severe pancreatitis. Acute pancreatitis should be kept in mind in the differential diagnosis of unexplained nausea and abdominal pain during pregnancy, and hyper-or normocalcemia in the severe form of pancreatitis should be a clue to concurrent PHPT.

Acute Disease↗

The Addition of Concurrent Immune Checkpoint Inhibitors for Chemoradiotherapy With Consolidative Immune Checkpoint Inhibitors in Unresectable Cancers: A Systematic Review and Meta-Analysis.

Following the success of chemoradiotherapy (CRT) combined with consolidative immune checkpoint inhibitors (ICIs) in locally advanced tumors, over 30 ongoing randomized controlled trials (RCTs) are investigating the potential benefits of adding concurrent ICIs. To investigate the differences in efficacy and safety between adding and not adding concurrent ICIs to CRT followed by consolidative ICIs, a literature search was conducted in PubMed, Embase, and the Cochrane Library, incorporating RCTs comparing CRT combined with consolidative ICIs versus CRT alone, or CRT with both concurrent and consolidative ICIs versus CRT alone. The primary outcomes were overall survival (OS) and progression-free survival (PFS). To reduce potential bias, an additional mirror-design analysis was performed through network meta-analysis. A total of 13 RCTs comprising 6868 patients and 14 cohort studies comprising 4724 patients were included. While patients treated with CRT and consolidative ICIs demonstrated significantly superior OS and PFS to patients treated with CRT alone in RCTs (HR of OS, 0.743, 95% CI, 0.654-0.843; HR of PFS, 0.674, 95% CI, 0.577-0.786), CRT and concurrent-plus-consolidative ICIs did not improve OS and PFS compared with CRT alone (HR of OS, 0.942, 95% CI, 0.782-1.134; HR of PFS, 0.880, 95% CI, 0.752-1.030). Significant differences were detected in OS (p = 0.038) and PFS (p = 0.017) between CRT combined with consolidative ICIs treatment versus CRT combined with concurrent and consolidative ICIs treatment from RCTs. In conclusion, adding concurrent ICIs may dampen the survival benefits of CRT combined with consolidative ICIs. This evidence informs future RCT design strategies.

Humans↗

Person-related predictors of employment outcomes after participation in psychiatric vocational rehabilitation programmes--a systematic review.

BACKGROUND: There is increasing recognition of the importance of psychiatric vocational rehabilitation (PVR) programmes in helping individuals with severe mental illnesses to find and secure jobs. However, little is known concerning the factors related to PVR outcomes. OBJECTIVE: This review identifies those person-related factors which most strongly influence employment outcomes after participation in PVR programmes. METHOD: Medline, Psychinfo, Pubmed and CINAHL were searched for studies using multivariate analysis of longitudinal data, which analysed employment outcomes after at least 6 months of programme participation, and which analysed at least three predictor domains. RESULTS: Eight studies presented in 16 publications met all the criteria. Better employment outcomes were most strongly related to better work performance measured during PVR participation and to higher work-related self-efficacy. Better social functioning during PVR participation was also significantly related to positive employment outcomes, but this relationship was generally weaker than those of the two aforementioned factors. In most studies, employment outcomes after PVR were not related to past functioning, including work history and diagnosis. Findings on the severity of psychiatric symptoms measured during PVR were mixed. In terms of contribution to outcome, severity of symptoms usually ranked below work performance, when measured concurrently. CONCLUSION: Contrary to previous reviews, this study suggests that the influence of past functioning, including work history, diagnosis and psychiatric history, is outweighed by work performance in PVR. Further prospective and controlled studies are needed to reach more definite conclusions about the individual contributions of person-related factors.

Disability Evaluation↗

Surgical treatment of thyroid cancers with concurrent Graves disease.

BACKGROUND: Thyroid cancers with concurrent Graves disease are relatively rare. Accordingly, the natural history and optimal surgical treatment of thyroid cancers with Graves disease are controversial. METHODS: Sixty-one thyroid cancers with concurrent Graves disease were retrospectively reviewed. Histopathologic diagnoses included 58 papillary thyroid carcinomas (95.1%), 1 follicular carcinoma (1.6%), 1 medullary carcinoma (1.6%), and 1 Hürthle cell carcinoma (1.6%). RESULTS: The sample included 54 females and seven males. Subjects' ages ranged from 20 to 73 years (mean +/- SD, 35.9 +/- 10.6 years; median, 37 years). Average tumor size was 10.7 +/- 15.9 mm (range, 1-70 mm). Forty-nine tumors (80.3%) were 10 mm or smaller. Surgical procedures included subtotal thyroidectomy (40 patients), total thyroidectomy (16 patients), total thyroidectomy plus neck dissection (2 patients), near-total thyroidectomy (1 patient), and lobectomy with contralateral subtotal lobectomy (1 patient). Thirty-seven patients (60.7%) underwent postoperative 131I ablation for thyroid remnant. Neck lymph node metastases occurred in three patients and lung metastases in two patients. Patients who developed metastases were younger and had significantly larger tumors and higher pretreatment serum T3 level than those who did not develop metastases. No deaths occurred during the 6.2 +/- 4.1 year follow-up period (range, 1 year and 2 months to 18 years and 11 months). CONCLUSIONS: Most thyroid cancers with concurrent Graves disease were 10 mm or smaller. Subtotal thyroidectomy is adequate for patients with Graves disease with concurrent carcinoma 10 mm or smaller.

Adult↗

Hypothyroidism in children with the Down syndrome: report of three cases.

The cases of three patients with concurrent Down syndrome and hypothyroidism are reported. Review of these and 12 similar cases from the literature suggests an association between the Down syndrome and thyroid autoimmune disease. Studies of autoimmune thyroid antibodies in families of patients with the Down syndrome are also reviewed. Several questions as yet unanswered regarding the possible relationship of these studies to cases of concurrent Down syndrome and hypothyroidism are mentioned.

Adolescent↗

A rheumatological dilemma: is it possible to modify the course of rheumatoid arthritis? Can we answer the question?

The question 'Does the use of second-line therapy confer long-term benefit on outcome measures in rheumatoid arthritis?' remains unanswered. The major obstacle which prevents collection of the necessary data is the lack of a suitable control group. In this report experience with three 'second-line placebo groups' is described, and previous studies in the literature which incorporated a placebo group are reviewed. In the absence of concurrent corticosteroid therapy very few patients remain on placebo second-line medication after one year. Those that do, appear to have milder disease and are not representative of the group as a whole. Data on outcome measures need to be collected over two to five years, but the answer to the question which is posed does not depend upon larger and larger placebo groups which constitute increasing bias. To define the extent of benefit offered by the more powerful therapeutic agents a novel approach in regard to drug assessment will be required.

Anti-Inflammatory Agents↗

Selective serotonin reuptake inhibitors and CNS drug interactions. A critical review of the evidence.

The potential for drug-drug interactions in psychiatric patients is very high as combination psychopharmacotherapy used to treat comorbid psychiatric disorders, to treat the adverse effects of a medication, to augment a medication effect or to treat concomitant medical illnesses. Interactions can be pharmacodynamic or pharmacokinetic in nature. This paper focuses on the metabolic kinetic interactions between selective serotonin reuptake inhibitors (SSRIs) and other central nervous system (CNS) drugs. The evidence for and clinical significance of these interactions are reviewed, with special emphasis on antipsychotics, tricyclic antidepressants and benzodiazepines. Many psychotropic medications have an affinity for the cytochrome P450 (CYP) enzymes which promote elimination by transforming lipid soluble substances into more polar compounds. SSRIs serve both as substrates and inhibitors of these enzymes. In vitro studies provide a screening method for evaluating drug affinities for substrates, inhibitors or inducers of CYP enzymes. Although in vitro data are important as a starting point for predicting these metabolic kinetic drug interactions, case reports and controlled experimental studies in humans are required to fully evaluate their clinical significance. Several factors must be considered when evaluating the clinical significance of a potential interaction including: (a) the nature of each drugs' activity at an enzyme site (substrate, inhibitor or inducer); (b) the potency estimations for the inhibitor/inducer; (c) the concentration of the inhibitor/inducer at the enzyme site; (d) the saturability of the enzyme; (e) the extent of metabolism of the substrate through this enzyme (versus alternative metabolic routes); (f) the presence of active metabolites of the substrate; (g) the therapeutic window of the substrate; (h) the inherent enzyme activity of the individual, phenotyping/genotyping information; (i) the level of risk of the individual experiencing adverse effects (e.g. the elderly) and (j) from an epidemiological perspective, the probability of concurrent use. This paper systematically reviews both the in vitro and in vivo evidence for drug interactions between SSRIs and other CNS drugs. As potent inhibitors of CYP2D6, both paroxetine and fluoxetine have the potential to increase the plasma concentrations of antipsychotic medications metabolised through this enzyme, including perphenazine, haloperidol, thioridazine and risperidone in patients who are CYP2D6 extensive metabolisers. Controlled studies have demonstrated this for perphenazine with paroxetine and haloperidol with fluoxetine. Fluvoxamine, as a potent inhibitor of CYP1A2, can inhibit the metabolism of clozapine, resulting in higher plasma concentrations. Drug interactions between the SSRIs and tricyclic antidepressants (TCAs) can occur. Fluoxetine and paroxetine, as potent inhibitors of CYP2D6, can increase the plasma concentrations of secondary and tertiary tricyclic antidepressants. Sertraline and citalopram are less likely to have this effect. Fluvoxamine can increase the plasma concentrations of tertiary TCAs. Fluvoxamine inhibits, via CYP3A. CYP2C19 and CYP1A2, the metabolism of several benzodiazepines, including alprazolam, bromazepam and diazepam. Fluoxetine increases the plasma concentrations of alprazolam and diazepam by inhibiting CYP3A and CYP2C19, respectively. The clinical importance of the interaction with diazepam is attenuated by the presence of its active metabolite. Sertraline inhibits these enzymes only mildely to moderately at usual therapeutic doses. Therefore the potential for interactions is less; however, the in vivo evidence is minimal. Paroxetine and citalopram are unlikely to cause interactions with benzodiazepines. The evidence is conflicting for an interaction between carbamazepine and the SSRIs fluoxetine and fluvoxamine. These combinations should be used cautiously, and be accompanied by monitoring for adverse events and carb

Anti-Anxiety Agents↗

Drug-induced hypertrichosis: case report and review of the literature.

Hypertrichosis is a well-recognized adverse effect of therapy with either cyclosporine or minoxidil. We present a case of extreme hypertrichosis in an eight-year-old male liver transplant recipient who received concurrent cyclosporine and minoxidil therapy. A review of drug-induced hypertrichosis is presented.

Child↗

The efficacy of bacillus Calmette-Guérin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature.

OBJECTIVE: To quantify the efficacy of vaccination of infants with bacillus Calmette-Guérin (BCG) against tuberculosis. DATA SOURCES: MEDLINE with index terms BCG vaccine, tuberculosis, and human; lists of all known studies provided by experts at the Centers for Disease Control and Prevention, the World Health Organization, and other organizations. STUDY SELECTION: A total of 1264 articles and abstracts were reviewed for details on BCG vaccination, the availability of concurrent vaccinated and unvaccinated groups, and a tuberculosis outcome. Seventy articles were reviewed in depth for method of vaccine allocation used to create comparable groups, age at vaccination of study participants, comparability of surveillance and follow-up of recipient and concurrent control groups in trials, an appropriately defined control group in case-control studies, and outcome measures (tuberculosis cases and/or deaths). Five prospective trials and eleven case-control studies of vaccination during infancy were included in the present analyses. DATA EXTRACTION: We recorded study design, age range of study population, number of patients enrolled, efficacy of vaccine, location of the study, and a series of items to assess the potential for bias in study design, follow-up, and diagnosis. We extracted or computed vaccine efficacy by years since vaccination wherever possible. At least two readers independently extracted data and evaluated data validity. DATA SYNTHESIS: The relative risk (RR) or odds ratio (OR) for tuberculosis in vaccinated versus unvaccinated infants was the measure of vaccine efficacy analyzed. A random-effects method estimated a weighted average RR or OR from data extracted from the trials and case-control studies. The protective effect was then computed by 1-RR or 1-OR. Overall, the protective effect of vaccination against cases of tuberculosis was 0.74 (95% confidence interval [95% CI], 0.62 to 0.83) when estimated from four randomized controlled trials, and 0.52 (95% CI, 0.38 to 0.64) when estimated from nine case-control studies. Five trials reporting deaths from tuberculosis showed a BCG protective effect of 0.65 (95% CI, 0.12 to 0.86), five studies reporting on meningitis showed a protective effect of 0.64 (95% CI, 0.30 to 0.82), and three studies of disseminated tuberculosis showed a protective effect of 0.78 (95% CI, 0.58 to 0.88). Three case-control studies included separate results for laboratory-confirmed cases of tuberculosis. These studies documented a protective effect of 0.83 (95% CI, 0.58 to 0.93). In a random-effects regression model of the nine case-control studies, study validity score explained 15% of the heterogeneity among study-estimated protective effects, suggesting that better studies reported greater efficacy. Three trials and six case-control studies provided some age-specific information that allowed us to examine the duration of BCG efficacy. Most of this evidence suggested that BCG efficacy may persist through 10 years after infant vaccination. CONCLUSION: BCG vaccination of newborns and infants significantly reduces the risk of tuberculosis--by over 50%, on average. Protection has been observed across many populations, study designs, and forms of tuberculosis. Rates of protection against cases that are confirmed by laboratory tests, reflecting reduced error in disease classification and consequently more accurate estimates of BCG efficacy, are highest at 83%.

BCG Vaccine↗

The role of parental presence in the context of children's medical procedures: a systematic review.

BACKGROUND: There are conflicting views and practices regarding whether or not parents should be present at the time of their child's medical procedure. A systematic review was conducted to assess the effects of parental presence in the paediatric treatment room on child, parent and health professional outcomes and to synthesize this body of literature. METHODS: Based on a comprehensive literature search, studies investigating parental presence in the paediatric treatment room were included in the review if they had a concurrent control group (i.e. a parent-absent group). RESULTS: A total of 28 studies met inclusion criteria, which included 1256 children with a parent present and 1025 children without a parent present. There were mixed findings regarding the effect of parental presence on measures of child distress and affect, however, studies of lower levels of evidence were more likely to report significant results. Parents who were present during their child's medical intervention were either better off or no different from parents who were absent with regard to their levels of distress and satisfaction. There was no evidence of increased technical complications nor elevated staff anxiety for health professionals attending to children with a parent present as compared to attending to children without their parents. DISCUSSION: Although parental presence may not have a clear, direct influence on child distress and behavioural outcomes, there are potential advantages for parents. It seems appropriate that clinicians provide parents with the opportunity to be present during their child's painful procedure.

Adolescent↗

Combined radiation therapy and chemotherapy for carcinoma of the cervix.

Cervical cancer is the third most common cancer affecting women worldwide. Surgery, radiation therapy, and chemotherapy have been used in various settings in an effort to improve survival rates of patients with cervical cancer. Recent cooperative clinical trials have demonstrated a benefit from the concurrent use of chemotherapy and radiation therapy to treat cervical cancer. These studies have provided the most significant improvement in the treatment of locally advanced disease in more than 30 years. This review summarizes studies of sequential and concurrent combinations of chemotherapy and radiation therapy for the treatment of cervical cancer, as well as the recent controversies related to this treatment.

Animals↗

Cytologic correlates of benign versus dysplastic abnormal keratinization.

The purpose of this study was to determine the cytologic and histologic features that differentiate benign from squamous intraepithelial lesion (SIL)-associated cervical abnormal keratinization, defined as hyperkeratosis, parakeratosis, or individual cell dyskeratosis. Fifty-four cervical Papanicoloau (Pap) smears that contained abnormally keratinized cells were reviewed without knowledge of the concurrent biopsy. Twenty-three Pap smears were diagnosed as SIL and the corresponding biopsy showed SIL in 21 (91%) of these cases. Of the 23 Pap smears diagnosed as negative for SIL, the corresponding biopsy in 20 cases (87%) showed benign (SIL negative) abnormal keratinization. Eight Pap smears showed squamous atypia, of these 5 showed SIL on biopsy, and the other 3 revealed benign keratinization. The Pap smear correlates of the 25 biopsies that were negative for SIL included marked hyperkeratosis (18/25-72 vs. 5/29-17% for biopsies with SIL) and regular nuclear membranes (16/18-89% cases with nucleated dyskeratotic cells vs. 5/29-17% for biopsies with SIL). The cytologic correlates of the 29 biopsies that showed SIL included irregular chromatin clumping (27/29-93% vs. 3/18-17% for biopsies without SIL), and a disorganized growth pattern (24/29-83 vs. 5/25-20% for biopsies without SIL). It is concluded that the cytologic distinction between benign and SIL-related Pap smears with abnormal keratinization can be reliably made by the degree of hyperkeratosis, nuclear chromaticity pattern and contour, and the growth pattern of the dyskeratotic cells.

Biopsy↗

The psychological construct of word fluency.

Measures of word fluency have been convincingly linked in the literature to damage in the left prefrontal lobe region. Yet, a reduction in word fluency has also been reported with diffuse, multifocal and nonfrontal lobe damage. Despite the undisputed neuropsychological application of multiple word fluency measures, the psychological construct underlying this measure is not well understood. In a sample of 360 normal adults stratified by age, gender, and level of education, we found that auditory attention and word knowledge were among the most important determinants. With respect to memory, short-term memory was not significantly correlated, but long-term memory was. Despite these three determinants, a large share of the variance of the multiple regression was still not accounted for, which underscores the partial independence of word fluency per se. Thus, we propose a distinction between (1) poor word fluency secondary to deficient verbal attention, word knowledge, and/or verbal long-term memory and (2) impaired word fluency without these three areas concurrently affected. Based on a review of the literature, it seems likely that in the latter condition, the profile is more associated with prefrontal lobe impairment, versus in the former condition, diffuse multifocal or nonfrontal lobe factors can play a role.

Adolescent↗

Preoperative embolization of carotid body tumors: when is it appropriate?

To determine when to use preoperative embolization, we retrospectively reviewed a consecutive series of concurrently treated patients who underwent carotid body tumor resection between 1984 and 1994. Eleven nonembolized tumors (N-EMB group) and 11 embolized tumors (EMB group) were resected. The two groups were similar with respect to demographics and presentation, with the exception that more patients in the EMB group complained of painful neck masses. There was no significant difference in the pretreatment size of the neck mass between the two groups (N-EMB = 4.3 +/- 1.5 cm; N-EMB = 5.1 +/- 2.1 cm). Zero to 6 days after embolization, surgical resection was performed. There was no difference in the distribution of tumors, which were grouped according to Shamblin's classification, between the N-EMB and EMB patients. Two patients in each group required resection of the internal carotid artery, whereas a total of seven cranial nerves were resected. There were no differences in blood loss, number of blood transfusions, operative time, or perioperative morbidity between the N-EMB and EMB groups. Ten patients had new cranial nerve deficits and four of these patients required treatment for tenth nerve paralysis. Overall the total hospital stay was similar in the two groups, but the EMB group had a significantly longer preoperative stay compared to the N-EMB group (1.5 +/- 0.8 vs. 0.8 +/- 0.4 days; p = 0.02). These data show that preoperative embolization does not significantly improve outcome in patients undergoing resection of carotid body tumors measuring 4 to 5 cm. Therefore, in this era of costcontainment, preoperative embolization should not be used in the treatment of midsized carotid body tumors.

Adult↗

Is infrapopliteal bypass compromised by distal origin of the proximal anastomosis?

Distal origination of the proximal anastomosis (DOPA) of an infrapopliteal bypass beyond the adductor hiatus minimizes the length of graft required and optimizes use of scarce autogenous conduit. Sixty-two DOPA infrapopliteal revascularizations using autogenous vein performed for limb salvage over a 7-year period were reviewed and compared with 203 concurrent infrapopliteal bypasses originating more proximally (POPA). Life-table analysis revealed no difference at 54 months between DOPA and POPA bypass with regard to primary patency (57% vs. 50%, respectively) or secondary patency (67% vs. 65%, respectively). Differences in limb salvage at 54 months between DOPA and POPA bypasses did not reach statistical significance (53% vs. 66%, p = 0.12), although DOPA fared worse. Inferior limb salvage results in all infrapopliteal bypasses were correlated with the presence of tissue necrosis (52% vs. 70%, p < 0.001), which was more prevalent in patients undergoing DOPA bypass (71% vs. 49%, p < 0.01). The long-term patency of infrapopliteal bypass appears only marginally affected by DOPA. However, the prognosis for limb salvage in this setting is compromised as a result of the virulent behavior of the atherosclerotic disease that spares the superficial femoral artery while predominantly involving the popliteal and tibial vessels.

Aged↗