BACKGROUND: Optimum management to prevent recurrent kidney stones is uncertain.
OBJECTIVE: To evaluate the benefits and harms of interventions to prevent recurrent kidney stones.
METHODS: MEDLINE, Cochrane, and other databases through September 2012 and reference lists of systematic reviews and randomized, controlled trials (RCTs).
METHODS: 28 English-language RCTs that studied treatments to prevent recurrent kidney stones and reported stone outcomes.
METHODS: One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and graded strength of evidence.
RESULTS: In patients with 1 past calcium stone, low-strength evidence showed that increased fluid intake halved recurrent composite stone risk compared with no treatment (relative risk [RR], 0.45 [95% CI, 0.24 to 0.84]). Low-strength evidence showed that reducing soft-drink consumption decreased recurrent symptomatic stone risk (RR, 0.83 [CI, 0.71 to 0.98]). In patients with multiple past calcium stones, most of whom were receiving increased fluid intake, moderate-strength evidence showed that thiazides (RR, 0.52 [CI, 0.39 to 0.69]), citrates (RR, 0.25 [CI, 0.14 to 0.44]), and allopurinol (RR, 0.59 [CI, 0.42 to 0.84]) each further reduced composite stone recurrence risk compared with placebo or control, although the benefit from allopurinol seemed limited to patients with baseline hyperuricemia or hyperuricosuria. Other baseline biochemistry measures did not allow prediction of treatment efficacy. Low-strength evidence showed that neither citrate nor allopurinol combined with thiazide was superior to thiazide alone. There were few withdrawals among patients with increased fluid intake, many among those with other dietary interventions and more among those who received thiazide and citrate than among control patients. Reporting of adverse events was poor.
CONCLUSIONS: Most trial participants had idiopathic calcium stones. Nearly all studies reported a composite (including asymptomatic) stone recurrence outcome.
CONCLUSIONS: In patients with 1 past calcium stone, increased fluid intake reduced recurrence risk. In patients with multiple past calcium stones, addition of thiazide, citrate, or allopurinol further reduced risk.
BACKGROUND: Agency for Healthcare Research and Quality.

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RNA viruses replicate as complex distributions of non-identical but closely related variant genomes termed viral quasispecies. When the error rate during genome replication exceeds a threshold value, the genetic information cannot be maintained and the system enters error catastrophe. This violation of the error threshold results in virus extinction and it is currently being investigated as a new antiviral strategy, based on antiviral activity of some mutagenic agents. Previous studies with the important animal pathogen foot-and-mouth disease virus (FMDV) have shown that FMDV entry into error catastrophe is associated with an increase of complexity (mutation frequency and Shannon entropy) of the mutant spectrum of the quasispecies and that mutated, pre-extinction RNA interferes with the infectivity of standard RNA. Here, we report that despite the increase of complexity, the genomic consensus nucleotide sequence of pre-extinction FMDV RNA remains invariant, and that the fitness of pre-extinction FMDV is at least six-fold lower than the fitness of the parental viral clone, prior to mutagenic treatments. Thus, a low fitness genome ensemble can suppress replication of high fitness virus. Furthermore, the results show that profound genetic modifications associated with fitness decrease of a virus population can take place without any manifestation in the consensus genomic sequence. Thus, increase in mutant spectrum complexity and invariance of the consensus sequence characterizes FMDV extinction through error catastrophe.

To develop and pre-validate an enhanced protocol for OECD Test Guideline 407, we performed a 28-day repeated-dose toxicity study using the administration of propylthiouracil (PTU) and tamoxifen (TAM) in Sprague-Dawley (SD) rats. Six male and female SD rats were treated orally with PTU in corn oil at the dose of 0, 0.1, 1, or 10 mg/kg per day and TAM at dose of 0, 5, 30 or 200 microg/kg per day for 4 weeks. In the study using PTU, the body weights were reduced from the third week of the study in 10 mg/kg per day group. In clinical biochemistry, the levels of 3,5,3\'-triiodothyronine (T3) and thyroxine (T4, 3,5,3\',5\'-tetraiodothyrosine) were also significantly decreased in 10 mg/kg per day group. Also, thyroid glands in 10 mg/kg per day group were bigger than those in the control group. In the histopathological examination, diffuse hyperplasia and hypertrophy of thyroid follicular cells were observed in all treatment groups, leading to the reduction of lumen size and papillary enfolding of lining epithelium. In the study using TAM, the body weights were reduced from the first week of the study in 200 microg/kg per day group. Relative testes and epididymes weights were increased and relative right ovary and uterus weights were reduced in 200 microg/kg per day group. Also, in the histopathological finding severe endometrial squamous metaplasia and endometrial gland atrophy and severe follicular cystic change were observed in TAM 200 microg/kg per day-treated group. On the basis of the results, the thyroid hormone levels, gross findings, and histopathological findings may be useful parameters for the detection of the endocrine-related effect of PTU and also reproductive organ weight and histopathological findings may be good parameters to detect the effect of TAM. Therefore, it is concluded that enhanced OECD TG407 might be useful for screening and detecting endocrine disrupters.

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These guidelines for management of Bowen\'s disease have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.