Hyungjin Myra Kim

Complications in postmastectomy breast reconstruction: two-year results of the Michigan Breast Reconstruction Outcome Study.

&NA; In this study, the effects of procedure type, timing, and other clinical variables on complication rates in mastectomy reconstruction were prospectively evaluated. Using a prospective cohort design, women undergoing firsttime, immediate or delayed breast reconstruction were recruited from 12 centers and 23 plastic surgeons. Complication data for expander/implant, pedicle transverse rectus abdominis musculocutaneous (TRAM) flap, and free TRAM flap procedures were evaluated 2 years after surgery in 326 patients. For each patient, the total number of complications was recorded and the complication data were dichotomized in two ways: (1) total complications and (2) major complications (those requiring reoperation, rehospitalization, or nonperioperative intravenous antibiotic treatment). The effects of procedure type, timing, radiotherapy, chemotherapy, age, smoking, and body mass index on complication rates were analyzed using logistic regression. Immediate reconstructions had significantly higher total as well as major complication rates, compared with delayed procedures (p = 0.011 and 0.005, respectively). Furthermore, higher body mass indexes were associated with significantly higher total and major complication rates (p = 0.005 and p < 0.001, respectively). No significant effects on complication rates were noted for procedure type or for the other independent variables, although there was evidence of trends for higher total and major complication rates in implant patients who received radiotherapy and a trend for higher major complication rates in TRAM flap patients who received chemotherapy. It was concluded that (1) immediate reconstructions were associated with significantly higher complication rates than delayed procedures, and (2) procedure type had no significant effect on complication rates. (Plast. Reconstr. Surg. 109: 2265, 2002.)

Prospective analysis of psychosocial outcomes in breast reconstruction: one-year postoperative results from the Michigan Breast Reconstruction Outcome Study.

In the past decade, changing attitudes toward breast reconstruction among both patients and providers have led a growing number of women to seek breast reconstruction after mastectomy. Although investigators have documented the psychological, social, emotional, and functional benefits of breast reconstruction, little research has evaluated the effects of procedure choice on these outcomes. The current study prospectively evaluated and compared psychosocial outcomes for three common options for mastectomy reconstruction: tissue expander/implant, pedicle TRAM, and free TRAM techniques. In a prospective cohort design, patients undergoing postmastectomy reconstruction for the first time with expander/implant, pedicle TRAM, or free TRAM procedures were recruited from 12 centers and 23 plastic surgeons in the United States and Canada. Before reconstruction and at 1 year after reconstruction, patients were evaluated by a battery of questionnaires consisting of both generic and condition-specific surveys. Outcomes assessed included emotional well-being, vitality, general mental health, social functioning, functional well-being, social well-being, and body image. Baseline (preoperative) scores and the change in scores (the difference between postoperative and preoperative scores) were compared across procedure types using t tests and analysis of covariance. Preoperative and 1-year postoperative surveys were obtained from 273 patients. Procedure type was reported in 250 patients, of whom 56 received implant reconstructions, 128 pedicle TRAM flaps, and 66 free TRAM flaps. A total of 161 immediate and 89 delayed reconstructions were performed. Among women receiving immediate reconstruction, significant improvements were observed in all psychosocial variables except body image. However, no significant effects of procedure type on these changes over time existed. Similarly, delayed reconstruction patients had significant increases in emotional well-being, vitality, general mental health, functional well-being, and body image. Although the choice of reconstructive technique did not significantly impact most of these outcomes, significant differences existed among procedure types for three psychosocial subscales. Patients undergoing delayed expander/implant reconstructions reported greater improvements in vitality and social well-being relative to women receiving delayed TRAM procedures. By contrast, delayed TRAM patients noted significantly greater gains in body image compared with women choosing delayed expander-implant reconstruction. The authors conclude that both immediate and delayed breast reconstructions provide substantial psychosocial benefits for mastectomy patients. Although the choice of reconstructive procedure does not seem to significantly affect improvements in psychosocial status with immediate reconstruction, our data suggest that procedure type does have a significant effect on gains in vitality and body image for women undergoing delayed reconstruction.

QUALITY OF LIFE AFTER PAROTID-SPARING IMRT FOR HEAD-AND- NECK CANCER: A PROSPECTIVE LONGITUDINAL STUDY

PURPOSE Parotid-sparing intensity-modulated radiotherapy (IMRT) for head-and-neck cancer reduces xerostomia compared with standard RT. To assess potential improvements in broader aspects of quality of life (QOL), we initiated a study of patient-reported QOL and its predictors after IMRT. MATERIALS AND METHODS This was a prospective longitudinal study of head-and-neck cancer patients receiving multisegmental static IMRT. Patients were given a validated xerostomia questionnaire (XQ), and a validated head-and-neck cancer-related QOL questionnaire consisting of four multi-item domains: Eating, Communication, Pain, and Emotion. The Eating domain contains one question (total of six) asking directly about xerostomia. In both questionnaires, higher scores denote worse symptoms or QOL. The questionnaires and measurements of salivary output from the major glands were completed before RT started (pre-RT) and at 3, 6, and 12 months after RT. The association between the QOL scores and patient-, tumor-, and therapy-related factors was assessed using the random effects model. RESULTS Thirty-six patients participating in the study completed the questionnaires through 12 months. The XQ scores worsened significantly at 3 months compared with the pre-RT scores, but later they improved gradually through 12 months (p = 0.003), in parallel with an increase in the salivary output from the spared salivary glands. The QOL summary scores were stable between the baseline (pre-RT) and 3 months after RT scores. Patients receiving postoperative RT (whose pre-RT questionnaires were taken a few weeks after surgery) tended to have improved scores after RT, reflecting the subsidence of acute postoperative sequelae, compared with a tendency toward worsened scores in patients receiving definitive RT. After 3 months, statistically significant improvement was noted in the summary QOL scores for all patients, through 12 months after RT (p = 0.01). The salivary flow rates, tumor doses, mean oral cavity dose, age, gender, sites or stages of tumor, surgery, and use of chemotherapy were not associated with the QOL scores at any point. The mean dose to the parotid glands correlated with the QOL scores at 3 months (p = 0.05) but not at other post-RT periods. The XQ and QOL summary scores did not correlate before RT but were significantly correlated at each post-RT point (p < 0.01), with a linear correlation coefficient (r) of 0.59, 0.72, and 0.67 at 3, 6, and 12 months, respectively. At these points, the XQ scores also correlated significantly with the scores of each of the individual QOL domains (p < or = 0.01), including the domains Pain and Emotion, which did not contain any xerostomia-related question. CONCLUSION After parotid-sparing IMRT, a statistically significant correlation was noted between patient-reported xerostomia and each of the domains of QOL: Eating, Communication, Pain, and Emotion. Both xerostomia and QOL scores improved significantly over time during the first year after therapy. These results suggest that the efforts to improve xerostomia using IMRT may yield improvements in broad aspects of QOL.

Levofloxacin-Based Triple Therapy versus Bismuth-Based Quadruple Therapy for Persistent Helicobacter pylori Infection: A Meta-Analysis

BACKGROUND:Levofloxacin-based triple therapy has been suggested as an alternative salvage therapy to bismuth-based quadruple therapy for persistent Helicobacter pylori (H. pylori) infection.METHODS:A search of PUBMED, EMBASE, EBM Review databases and abstracts from recent Digestive Disease Week, United European Gastroenterology Week, and European Helicobacter Study Group conferences was performed. Randomized controlled trials (RCTs) comparing levofloxacin-based triple salvage therapy (levofloxacin + amoxicillin + PPI) to bismuth-based quadruple salvage therapy (bismuth + tetracycline + metronidazole + PPI) were selected for meta-analysis. Additionally, all prospective trials evaluating this levofloxacin-based triple therapy as salvage therapy were pooled to analyze optimal levofloxacin treatment duration and dosing. All selected trials confirmed prior treatment failure and post-salvage treatment eradication.RESULTS:Four RCTs compared a 10-day regimen of levofloxacin-based triple therapy to 7-day bismuth-based quadruple therapy (n = 391 patients). Levofloxacin-based triple therapy was superior to quadruple therapy (RR = 1.41 [95% CI: 1.25–1.59]). Levofloxacin-based triple therapy was better tolerated than quadruple therapy with a lower incidence of side effects (RR = 0.51 [95% CI: 0.34–0.75]) and side effects prompting discontinuation of therapy (RR = 0.30 [95% CI: 0.10–0.89]). Eleven trials (n = 547 patients) evaluating levofloxacin-based triple therapy demonstrated higher eradication rates with 10-day versus 7-day regimen (87%[95% CI: 82%-92%]vs 68%[95% CI: 62%-74%]) yet eight trials (n = 477 patients) demonstrated no difference with 500 mg daily versus 250 mg b.i.d. dosing of levofloxacin (81%[95% CI: 78%-89%]vs 84%[95% CI: 66%-97%]).CONCLUSIONS:A 10-day course levofloxacin triple therapy is more effective and better tolerated than 7-day bismuth-based quadruple therapy in the treatment of persistent H. pylori infection.

Intensity-Modulated Chemoradiotherapy Aiming to Reduce Dysphagia in Patients With Oropharyngeal Cancer: Clinical and Functional Results

PURPOSE To assess clinical and functional results of chemoradiotherapy for oropharyngeal cancer (OPC), utilizing intensity-modulated radiotherapy (IMRT) to spare the important swallowing structures to reduce post-therapy dysphagia. PATIENTS AND METHODS This was a prospective study of weekly chemotherapy (carboplatin dosed at one times the area under the curve [AUC, AUC 1] and paclitaxel 30 mg/m(2)) concurrent with IMRT aiming to spare noninvolved parts of the swallowing structures: pharyngeal constrictors, glottic and supraglottic larynx, and esophagus as well as the oral cavity and major salivary glands. Swallowing was assessed by patient-reported Swallowing and Eating Domain scores, observer-rated scores, and videofluoroscopy (VF) before therapy and periodically after therapy through 2 years. RESULTS Overall, 73 patients with stages III to IV OPC participated. At a median follow-up of 36 months, 3-year disease-free and locoregional recurrence-free survivals were 88% and 96%, respectively. All measures of dysphagia worsened soon after therapy; observer-rated and patient-reported scores recovered over time, but VF scores did not. At 1 year after therapy, observer-rated dysphagia was absent or minimal (scores 0 to 1) in all patients except four: one who was feeding-tube dependent and three who required soft diet. From pretherapy to 12 months post-therapy, the Swallowing and Eating Domain scores worsened on average (+/- standard deviation) by 10 +/- 21 and 13 +/- 19, respectively (on scales of 0 to 100), and VF scores (on scale of 1 to 7) worsened from 2.9 +/- 1.5 (mild dysphagia) to 4.1 +/- 0.9 (mild/moderate dysphagia). CONCLUSION Chemoradiotherapy with IMRT aiming to reduce dysphagia can be performed safely for OPC and has high locoregional tumor control rates. On average, long-term patient-reported, observer-rated, and objective measures of swallowing were only slightly worse than pretherapy measures, representing potential improvement compared with previous studies.

Antipsychotics, Other Psychotropics, and the Risk of Death in Patients With Dementia: Number Needed to Harm

IMPORTANCE Antipsychotic medications are associated with increased mortality in older adults with dementia, yet their absolute effect on risk relative to no treatment or an alternative psychotropic is unclear. OBJECTIVE To determine the absolute mortality risk increase and number needed to harm (NNH) (ie, number of patients who receive treatment that would be associated with 1 death) of antipsychotic, valproic acid and its derivatives, and antidepressant use in patients with dementia relative to either no treatment or antidepressant treatment. DESIGN, SETTING, AND PARTICIPANTS A retrospective case-control study was conducted in the Veterans Health Administration from October 1, 1998, through September 30, 2009. Participants included 90,786 patients 65 years or older with a diagnosis of dementia. Final analyses were conducted in August 2014. EXPOSURES A new prescription for an antipsychotic (haloperidol, olanzapine, quetiapine, and risperidone), valproic acid and its derivatives, or an antidepressant (46,008 medication users). MAIN OUTCOMES AND MEASURES Absolute change in mortality risk and NNH over 180 days of follow-up in medication users compared with nonmedication users matched on several risk factors. Among patients in whom a treatment with medication was initiated, mortality risk associated with each agent was also compared using the antidepressant group as the reference, adjusting for age, sex, years with dementia, presence of delirium, and other clinical and demographic characteristics. Secondary analyses compared dose-adjusted absolute change in mortality risk for olanzapine, quetiapine, and risperidone. RESULTS Compared with respective matched nonusers, individuals receiving haloperidol had an increased mortality risk of 3.8% (95% CI, 1.0%-6.6%; P < .01) with an NNH of 26 (95% CI, 15-99); followed by risperidone, 3.7% (95% CI, 2.2%-5.3%; P < .01) with an NNH of 27 (95% CI, 19-46); olanzapine, 2.5% (95% CI, 0.3%-4.7%; P = .02) with an NNH of 40 (95% CI, 21-312); and quetiapine, 2.0% (95% CI, 0.7%-3.3%; P < .01) with an NNH of 50 (95% CI, 30-150). Compared with antidepressant users, mortality risk ranged from 12.3% (95% CI, 8.6%-16.0%; P < .01) with an NNH of 8 (95% CI, 6-12) for haloperidol users to 3.2% (95% CI, 1.6%-4.9%; P < .01) with an NNH of 31 (95% CI, 21-62) for quetiapine users. As a group, the atypical antipsychotics (olanzapine, quetiapine, and risperidone) showed a dose-response increase in mortality risk, with 3.5% greater mortality (95% CI, 0.5%-6.5%; P = .02) in the high-dose subgroup relative to the low-dose group. When compared directly with quetiapine, dose-adjusted mortality risk was increased with both risperidone (1.7%; 95% CI, 0.6%-2.8%; P = .003) and olanzapine (1.5%; 95% CI, 0.02%-3.0%; P = .047). CONCLUSIONS AND RELEVANCE The absolute effect of antipsychotics on mortality in elderly patients with dementia may be higher than previously reported and increases with dose.

Risk of mortality among individual antipsychotics in patients with dementia.

OBJECTIVE The use of antipsychotics to treat the behavioral symptoms of dementia is associated with greater mortality. The authors examined the mortality risk of individual agents to augment the limited information on individual antipsychotic risk. METHOD The authors conducted a retrospective cohort study using national data from the U.S. Department of Veterans Affairs (fiscal years 1999-2008) for dementia patients age 65 and older who began outpatient treatment with an antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) or valproic acid and its derivatives (as a nonantipsychotic comparison). The total sample included 33,604 patients, and individual drug groups were compared for 180-day mortality rates. The authors analyzed the data using multivariate models and propensity adjustments. RESULTS In covariate-adjusted intent-to-treat analyses, haloperidol was associated with the highest mortality rates (relative risk=1.54, 95% confidence interval [CI]=1.38-1.73) followed by risperidone (reference), olanzapine (relative risk=0.99, 95% CI=0.89-1.10), valproic acid and its derivatives (relative risk=0.91, 95% CI=0.78-1.06), and quetiapine (relative risk=0.73, 95% CI=0.67-0.80). Propensity-stratified and propensity-weighted models as well as analyses controlling for site of care and medication dosage revealed similar patterns. The mortality risk with haloperidol was highest in the first 30 days but decreased significantly and sharply thereafter. Among the other agents, mortality risk differences were most significant in the first 120 days and declined in the subsequent 60 days during follow-up. CONCLUSIONS There may be differences in mortality risks among individual antipsychotic agents used for treating patients with dementia. The use of valproic acid and its derivatives as alternative agents to address the neuropsychiatric symptoms of dementia may carry associated risks as well.

Salivary Gland Sparing and Improved Target Irradiation by Conformal and Intensity Modulated Irradiation of Head and Neck Cancer

The goals of this study were to facilitate sparing of the major salivary glands while adequately treating tumor targets in patients requiring comprehensive bilateral neck irradiation (RT), and to assess the potential for improved xerostomia. Since 1994 techniques of target irradiation and locoregional tumor control with conformal and intensity modulated radiation therapy (IMRT) have been developed. In patients treated with these modalities, the salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands’ dose volume histograms (DVHs). In addition, subjective xerostomia questionnaires have been developed and validated. The pattern of locoregional recurrence has been examined from computed tomography (CT) scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans, and regenerating the dose distributions at the recurrence sites. Treatment plans for target coverage and dose homogeneity using static, multisegmental IMRT were found to be significantly better than standard RT plans. In addition, significant parotid gland sparing was achieved in the conformal plans. The relationships among dose, irradiated volume, and the residual saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean radiation dose of 26 Gy was found to be the threshold for preserved stimulated saliva flow. Xerostomia questionnaire scores suggested that xerostomia was significantly reduced in patients irradiated with bilateral neck, parotid-sparing RT, compared to patients with similar tumors treated with standard RT. Examination of locoregional tumor recurrence patterns revealed that the large majority of recurrences occurred inside targets, in areas that had been judged to be at high risk and that had received RT doses according to the perceived risk. Tangible gains in salivary gland sparing and target coverage are being achieved, and an improvement in some measures of quality of life is suggested by our findings. Additional reduction of xerostomia may be achieved by further sparing of the salivary glands and the non-involved oral cavity. A mean parotid gland dose of ≤ 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to areas judged to be at highest risk may improve tumor control.

The Efficacy and Safety of Rifaximin for the Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis

OBJECTIVES:Irritable bowel syndrome (IBS) affects 10–15% of the population, and treatment options are limited. Rifaximin is a minimally absorbed antibiotic that has shown efficacy in IBS patients. The objective of our study was to perform a meta-analysis and systematic review of available randomized, placebo controlled trials evaluating the efficacy and tolerability of rifaximin in patients with IBS.METHODS:We performed a systematic literature search of multiple online electronic databases regardless of language. Inclusion criteria entailed randomized, placebo controlled trials and IBS defined by accepted symptom-based criteria. Meta-analysis was conducted to evaluate the summary odds ratios (ORs) and 95% confidence intervals (CIs) of combined studies for the primary and secondary outcomes using a random-effects model based on the DerSimonian and Laird method to reflect both within- and between study variability. We assessed heterogeneity using χ2 test and the inconsistency index statistic (I2). Significant heterogeneity was defined as I2 ≥25%. Meta-regression was performed using generalized linear mixed-effects model and study as random effects to estimate the summary OR adjusting for covariate differences across studies and treatment group. Publication bias was assessed by funnel plot analysis.RESULTS:Systematic review identified 13,700 citations. Eighteen were deemed to be potentially relevant, of which five articles met eligibility. Meta-analysis found rifaximin to be more efficacious than placebo for global IBS symptom improvement (OR=1.57; 95% CI=1.22, 2.01; therapeutic gain=9.8%; number needed to treat (NNT)=10.2), with mild heterogeneity (P=0.25, I2=26%). For the key secondary outcome of bloating, raw data were available for four studies. Rifaximin was significantly more likely to improve bloating than placebo (OR=1.55; 95% CI=1.23–1.96; therapeutic gain=9.9%; NNT=10.1), with no significant heterogeneity (P=0.27, I2=23%). We found that studies with older patients and more females demonstrated higher response rates, which was consistent regardless of treatment group. In addition, studies with higher cumulative dose tended to report a higher response rate. Of the covariates evaluated, we found age to be most predictive of response, with a correlation coefficient of 0.97 between aggregate response rate and mean age in the placebo groups. Although studies with higher cumulative dose tended to show increased response rates, this was also seen consistently in both the treated and placebo groups. Adverse effects were similar among patients receiving rifaximin or placebo in all studies. The most common adverse events (AEs) (≤10%) with rifaximin were headache, upper respiratory infection, nausea, nasopharygitis, diarrhea, and abdominal pain. Serious AEs were rare (<1%) and similar with rifaximin and placebo.CONCLUSIONS:Rifaximin proved more effective than placebo for global symptoms and bloating in IBS patients. The modest therapeutic gain was similar to that yielded by other currently available therapies for IBS. AEs were similar between rifaximin and placebo.

Maternal cigarette smoking during pregnancy and the risk of having a child with cleft lip/palate.

Maternal cigarette smoking during pregnancy as a risk factor for having a child with cleft lip/palate has been suggested by several epidemiologic studies. However, most of these studies contained small sample sizes, and a clear association between these two factors could not be established. The U.S. Natality database from 1996 and a case-control study design were used to investigate the association between maternal smoking during pregnancy and having a child with cleft lip/palate. The records of 3,891,494 live births from the 1996 U.S. Natality database were extracted to obtain cleft lip/palate cases and random controls. The National Center for Health Statistics collects maternal and newborn demographic and medical data from the birth certificates of all 50 states. New York (excluding New York City), California, Indiana, and South Dakota did not collect smoking data, and the data from these states were excluded from the analysis. A total of 2207 live births with cleft lip/palate cases were identified, and 4414 controls (1:2 ratio) were randomly selected (using the SAS program) from live births with no congenital defects. Odds ratios and 95 percent confidence intervals were determined from logistic regression models, adjusting for confounding variables, including maternal demographic and medical risk factors. A significant association was found between any amount of maternal cigarette use during pregnancy and having a child with cleft lip/palate [unadjusted odds ratio 1.55 (1.36, 1.76), p < 0.001]. Univariate analysis showed that maternal education level, age, race, and maternal medical conditions (diabetes and pregnancy-associated hypertension) were potential confounders. After adjusting for these confounders, the odds ratio remained significant [Mantel-Haenszel odds ratio 1.34 (1.16, 1.54), p < 0.001]. To determine the dose response of cigarette smoking during pregnancy, the cigarette consumption per day was divided into four groups: none, 1 to 10, 11 to 20, and 21 or more. A dose-response relationship was found when comparing each smoking category with the no smoking reference group: 1.50 (1.28, 1.76), 1.55 (1.23, 1.95), and 1.78 (1.22, 2.59), respectively. This means that increased cigarette smoking during pregnancy resulted in increased odds of having a child with cleft lip/palate. This is the largest study to date to test the association between maternal cigarette smoking during pregnancy and having a newborn with cleft lip/palate. The significant trend in the dose-response relationship strongly suggests the association of smoking tobacco and this common congenital deformity. These results emphasize the public health risks associated with smoking during pregnancy. To prevent this devastating craniofacial anomaly, educational initiatives should be considered that will alert expectant mothers to the association between smoking during pregnancy and the occurrence of cleft lip/palate.