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Debate exists regarding whether the use of topical agents and Botox injections are as efficacious as sphincterotomy for the treatment of chronic anal fissure. A retrospective review was performed to assess changes in management and outcomes of chronic anal fissure care in a community based colorectal practice between the individual years 1994 and 2003. Forty-seven patients in 1994 underwent lateral partial internal sphincterotomy and had a 100% healing rate. Thirty-nine patients were treated in 2003, with 32 undergoing Botox injection and 7 undergoing sphincterotomy initially. Of the Botox patients, 35% had recurrence, and 7 subsequently required sphincterotomy. Ultimate healing rates in 2003 were 97%. Time to heal was markedly prolonged in 2003 compared with 1994. Complication rates were similar, and there was no lifestyle-altering incontinence. Our review documents a significant change in the community approach to chronic fissure management. The addition of multiple treatment modalities prolongs time to healing from initial evaluation, but they allowed 72% of patients to avoid the need for permanent sphincter division while maintaining ultimate rates of healing.

Major comorbidities are recognized risk factors in colorectal surgery. We examine here the feasibility and safety of laparoscopic colorectal surgery (LC) in the complicated, high-risk patient. From July 2003 to October 2004, 107 consecutive patients undergoing LC were prospectively studied. Complicated patients were defined as age >80 years, body mass index (BMI) >30, and/or American Society of Anesthesiology level III or IV. A group of case-matched controls undergoing open surgery (OC) during a similar time period were retrospectively reviewed. The 2 groups were compared and assessed for major and minor morbidity and mortality. Overall morbidity was higher in the OC group 52% versus 26%. Minor complications compared at 31% OC versus 9% LC and major at 21% and 17%, respectively. With LC, advancement to discharge was more rapid and discharge home more likely than to a care facility. With proper patient selection and laparoscopic experience, LC can be performed in the complicated patient without undue morbidity and mortality.

To evaluate the efficacy and safety of a dexamethasone intracanalicular insert (DEX) for treatment of allergic conjunctivitis (AC). In this multicenter, randomized, double-masked, placebo-controlled phase 3 study, adults (≥18 years) with AC were randomized 1:1 to DEX or placebo insert (PBO) placed bilaterally. Subjects underwent repetitive conjunctival allergen challenges (CAC) across 30 days and were assessed for changes in AC signs and symptoms. The primary endpoint was ocular itching score at 3, 5, and 7 minutes post-CAC at Day 8 (7 days post-insertion). This trial is registered on ClinicalTrials.gov (NCT04050865). Ninety-six subjects were randomized (n=48 DEX, n=48 PBO). Compared to PBO, there were statistically significant treatment differences favoring DEX for the primary endpoint of mean ocular itching score at Day 8 (-0.86, -0.98, -0.96 at 3, 5, and 7 minutes post-CAC respectively; <0.0001 for all). Treatment differences favored DEX for all 24 time points across 6 visits and were statistically significant ( <0.05) except for the first post-insertion (Day 7, 3 minutes). For the 18 time points at which conjunctival redness was assessed, DEX had lower scores than PBO ( <0.05 for all). The most common ocular adverse events (AEs) in DEX subjects were eye discharge and irritation. No serious AEs, elevated intraocular pressure, dacryocanaliculitis, or use of rescue medications were reported. Results of this study support the potential use of dexamethasone insert as a physician-administered, preservative-free treatment for AC, with significant improvements in ocular itching and conjunctival redness compared with placebo. The dexamethasone insert was generally safe with a favorable safety profile.

Objective: We sought to estimate the undercount in the existing national surveillance system of occupational injuries and illnesses. Methods: Adhering to the strict confidentiality rules of the U.S. Bureau of Labor Statistics, we matched the companies and individuals who reported work-rented injuries and illnesses to the Bureau in 1999, 2000, and 2001 in Michigan with companies and individuals reported in four other Michigan data bases, workers' compensation, OSHA Annual Survey, OSHA Integrated Management Information System, and the Occupational Disease Report. We performed capture-recapture analysis to estimate the number of cases missed by the combined systems. Results: We calculated that the current national surveillance system did not include 61% and with capture-recapture analysis up to 68% of the work-related injuries and illnesses that occurred annually in Michigan. This was true for injuries alone, 60% and 67%, and illnesses alone 66% and 69%, respectively. Conclusions: The current national system for work-rented injuries and illnesses markedly underestimates the magnitude of these conditions. A more comprehensive system, such as the one developed for traumatic workplace fatalities, that is not solely dependent on employer based data sources is needed to better guide decision-making and evaluation of public health programs to reduce work-related conditions.

Abstract Rationale Patients with severe chronic obstructive pulmonary disease (COPD) may have varying levels of disability despite similar levels of lung function. This variation may reflect different COPD subtypes, which may have different genetic predispositions. Objectives To identify genetic associations for COPD-related phenotypes, including measures of exercise capacity, pulmonary function, and respiratory symptoms. Methods In 304 subjects from the National Emphysema Treatment Trial, we genotyped 80 markers in 22 positional and/or biologically plausible candidate genes. Regression models were used to test for association, using a test–replication approach to guard against false-positive results. For significant associations, effect estimates were recalculated using the entire cohort. Positive associations with dyspnea were confirmed in families from the Boston Early-Onset COPD Study. Results The test–replication approach identified four genes—microsomal epoxide hydrolase (EPHX1), latent transforming growth factor-β binding protein-4 (LTBP4), surfactant protein B (SFTPB), and transforming growth factor-β1 (TGFB1)—that were associated with COPD-related phenotypes. In all subjects, single-nucleotide polymorphisms (SNPs) in EPHX1 (p ⩽ 0.03) and in LTBP4 (p ⩽ 0.03) were associated with maximal output on cardiopulmonary exercise testing. Markers in LTBP4 (p ⩽ 0.05) and SFTPB (p = 0.005) were associated with 6-min walk test distance. SNPs in EPHX1 were associated with carbon monoxide diffusing capacity (p ⩽ 0.04). Three SNPs in TGFB1 were associated with dyspnea (p ⩽ 0.002), one of which replicated in the family study (p = 0.02). Conclusions Polymorphisms in several genes seem to be associated with COPD-related traits other than FEV1. These associations may identify genes in pathways important for COPD pathogenesis.

Vanilloid receptor-1 (VR1, also known as TRPV1) is a thermosensitive, nonselective cation channel that is expressed by capsaicin-sensitive sensory afferents and is activated by noxious heat, acidic pH and the alkaloid irritant capsaicin 1 . Although VR1 gene disruption results in a loss of capsaicin responses, it has minimal effects on thermal nociception 2 , 3 . This and other experiments—such as those showing the existence of capsaicin-insensitive heat sensors in sensory neurons 4 —suggest the existence of thermosensitive receptors distinct from VR1. Here we identify a member of the vanilloid receptor/ TRP gene family, vanilloid receptor-like protein 3 (VRL3, also known as TRPV3), which is heat-sensitive but capsaicin-insensitive. VRL3 is coded for by a 2,370-base-pair open reading frame, transcribed from a gene adjacent to VR1 , and is structurally homologous to VR1. VRL3 responds to noxious heat with a threshold of about 39 °C and is co-expressed in dorsal root ganglion neurons with VR1. Furthermore, when heterologously expressed, VRL3 is able to associate with VR1 and may modulate its responses. Hence, not only is VRL3 a thermosensitive ion channel but it may represent an additional vanilloid receptor subunit involved in the formation of heteromeric vanilloid receptor channels.