Christine S. M. Lau

Probiotics are effective at preventing Clostridium difficile-associated diarrhea: a systematic review and meta-analysis

Introduction Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea. CDI has increased in incidence and severity over the past decade, and is a growing worldwide health problem associated with substantial health care costs and significant morbidity and mortality. This meta-analysis examines the impact of probiotics on the incidence of Clostridium difficile-associated diarrhea (CDAD) among children and adults, in both hospital and outpatient settings. Methods A comprehensive literature search of all published randomized control trials (RCTs) assessing the use of probiotics in the prevention of CDAD in patients receiving antibiotic therapy was conducted, and the incidence of CDAD was analyzed. Results Twenty-six RCTs involving 7,957 patients were analyzed. Probiotic use significantly reduced the risk of developing CDAD by 60.5% (relative risk [RR] =0.395; 95% confidence interval [CI], 0.294–0.531; P<0.001). Probiotics proved beneficial in both adults and children (59.5% and 65.9% reduction), especially among hospitalized patients. Lactobacillus, Saccharomyces, and a mixture of probiotics were all beneficial in reducing the risk of developing CDAD (63.7%, 58.5%, and 58.2% reduction). Conclusion Probiotic supplementation is associated with a significant reduction in the risk of developing CDAD in patients receiving antibiotics. Additional studies are required to determine the optimal dose and strain of probiotic.

Probiotic administration can prevent necrotizing enterocolitis in preterm infants: A meta-analysis

PURPOSE Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants, affecting ~6-7% of very-low-birth-weight (VLBW) infants. Early intervention and aggressive treatment has improved clinical outcomes, but considerable morbidity continues to accrue to NEC survivors. This meta-analysis examines the impact of probiotics on the incidence of NEC and complications among VLBW infants. METHODS A comprehensive literature search for all published randomized control trials (RCTs) assessing the use of probiotics to prevent NEC in VLBW infants was conducted using PubMed, Cochrane Central Registry of Controlled Trials, and Google Scholar (1966-2014). The incidences of NEC, sepsis, overall mortality, and time to reach full enteral feeds were analyzed. RESULTS 20 RCTs involving 5982 preterm VLBW infants were analyzed. Risk of NEC was reduced by 49.1% (RR=0.509; 95% CI, 0.385-0.672; p<0.001), and overall mortality by 26.9% among infants receiving probiotics (RR=0.731; 95% CI, 0.577-0.926; p=0.009). An 8.1% reduction in sepsis was also observed in infants receiving probiotics (RR=0.919; 95% CI, 0.823-1.027; p=0.137). Time to reach full enteral feeds was reduced by 1.2 days among infants receiving probiotics (MD: -1.217; 95% CI, -2.151 to -0.283; p=0.011). CONCLUSION The use of probiotic supplementation in preterm VLBW infants is associated with a significant reduction in the risk of NEC and overall mortality. Additional studies are required to determine the optimal genus, species, and dose of probiotic.

Use of preoperative gabapentin significantly reduces postoperative opioid consumption: a meta-analysis

Objectives Effective postoperative pain management is crucial in the care of surgical patients. Opioids, which are commonly used in managing postoperative pain, have a potential for tolerance and addiction, along with sedating side effects. Gabapentin’s use as a multimodal analgesic regimen to treat neuropathic pain has been documented as having favorable side effects. This meta-analysis examined the use of preoperative gabapentin and its impact on postoperative opioid consumption. Materials and methods A comprehensive literature search was conducted to identify randomized control trials that evaluated preoperative gabapentin on postoperative opioid consumption. The outcomes of interest were cumulative opioid consumption following the surgery and the incidence of vomiting, somnolence, and nausea. Results A total of 1,793 patients involved in 17 randomized control trials formed the final analysis for this study. Postoperative opioid consumption was reduced when using gabapentin within the initial 24 hours following surgery (standard mean difference −1.35, 95% confidence interval [CI]: −1.96 to −0.73; P<0.001). There was a significant reduction in morphine, fentanyl, and tramadol consumption (P<0.05). While a significant increase in postoperative somnolence incidence was observed (relative risk 1.30, 95% CI: 1.10–1.54, P<0.05), there were no significant effects on postoperative vomiting and nausea. Conclusion The administration of preoperative gabapentin reduced the consumption of opioids during the initial 24 hours following surgery. The reduction in postoperative opioids with preoperative gabapentin increased postoperative somnolence, but no significant differences were observed in nausea and vomiting incidences. The results from this study demonstrate that gabapentin is more beneficial in mastectomy and spinal, abdominal, and thyroid surgeries. Gabapentin is an effective analgesic adjunct, and clinicians should consider its use in multimodal treatment plans among patients undergoing elective surgery.

Atypical teratoid rhabdoid tumors: a population-based clinical outcomes study involving 174 patients from the Surveillance, Epidemiology, and End Results database (1973–2010)

Introduction Atypical teratoid rhabdoid tumors (ATRTs) are rare, highly malignant embryonal tumors of the central nervous system (CNS) accounting for 20% of CNS tumors in children under the age of 3. This study examines a large cohort of ATRT patients to determine demographic, clinical, and pathologic factors which impact prognosis and survival. Methods Demographic and clinical data were abstracted on 174 ATRT patients (171 pediatric patients age <20 and 3 adult patients age ≥20) from the Surveillance, Epidemiology, and End Results database (1973–2010). Standard statistical methodology was used. Results A total of 174 ATRT cases (mean age of 2.84 years) were identified. ATRT had a higher incidence in males (56.3%), Caucasians (59.1%), and children <3 years of age (80.5%), P<0.001. The most common primary sites were the cerebellum (17.8%), ventricles (16.1%), and frontal lobe (12.6%). Mean overall survival was 3.2±0.4 years, while overall and cancer-specific mortality were 63.2% and 56.3%, respectively, P=0.005. Most ATRT cases were treated with surgery alone (58.0%), followed by a combination of surgery and radiation (34.3%), no treatment (6.5%), and radiation alone (1.2%). The use of combination therapy has increased significantly (16.1%) since 2005 (P<0.001), while primary surgical resection and radiation therapy rates remain relatively unchanged. The longest survival was observed among ATRT patients receiving combination therapy (5.9±0.7 years), followed by radiation alone (2.8±1.2 years), and surgery alone (1.9±0.4 years), P<0.001. Multivariable analysis identified only distant metastases (OR =4.6) as independently associated with increased mortality, whereas combination therapy (OR =0.4) was associated with reduced mortality, P<0.005. Conclusion ATRT is a rare and highly aggressive embryonal malignancy of the CNS that presents more often as locoregional tumors >4 cm in male Caucasian children of age <3 years, involving the cerebellum, ventricles, or frontal lobe. Combination therapy significantly improves survival, and its use has been increasing since 2005.

Ultrasound-guided central venous catheter placement increases success rates in pediatric patients: a meta-analysis

Background:Real-time ultrasound (US) guidance for central venous catheter (CVC) insertion has been shown to increase cannulation success rates and reduce complications in adults. Literature regarding US-guided CVC placement in children remains limited and conflicting. This meta-analysis examines the efficacy and safety of US-guided CVC placement among pediatric patients.Methods:A comprehensive literature search of all published randomized control trials (RCTs) comparing the use of real-time US-guided CVC insertion with anatomic landmark (LM)-guided CVC insertion in pediatric patients <18 y of age was conducted. Outcomes analyzed were cannulation success rate, number of attempts required, incidence of accidental arterial puncture, and time to cannulation.Results:Eight RCTs involving 760 patients were analyzed. US-guided CVC insertion significantly increased success rates by 31.8% and decreased the mean number of attempts required. A trend toward a decrease in the risk of accidental arterial puncture with the use of US-guided CVC insertion was also observed. US-guided CVC insertion was not associated with a significant difference in time required for CVC placement.Conclusion:US-guided CVC placement is associated with significantly higher success rates and decreased mean number of attempts required for cannulation. US-guided CVC insertion improves success rates, and should be utilized in pediatric patients.

Probiotics improve the efficacy of standard triple therapy in the eradication of Helicobacter pylori : a meta-analysis

Introduction Helicobacter pylori colonization is present in half of the world’s population and can lead to numerous gastrointestinal diseases if left untreated, including peptic ulcer disease and gastric cancer. Although concurrent triple therapy remains the recommended treatment regimen for H. pylori eradication, its success rate and efficacy have been declining. Recent studies have shown that the addition of probiotics can significantly increase eradication rates by up to 50%. This meta-analysis examines the impact of probiotic supplementation on the efficacy of standard triple therapy in eradicating H. pylori. Methods A comprehensive literature search was conducted using PubMed, Cochrane Central Registry of Controlled Trials, and Google Scholar (time of inception to 2016) to identify all published randomized control trials (RCTs) assessing the use of probiotics in addition to triple therapy for the treatment of H. pylori. Searches were conducted using the keywords “probiotics”, “triple therapy”, and “Helicobacter pylori”. RCTs comparing the use of probiotics and standard triple therapy with standard triple therapy alone for any duration in patients of any age diagnosed with H. pylori infection were included. H. pylori eradication rates (detected using urea breath test or stool antigen) were analyzed as-per-protocol (APP) and intention-to-treat (ITT). Results A total of 30 RCTs involving 4,302 patients APP and 4,515 patients ITT were analyzed. The addition of probiotics significantly increased eradication rates by 12.2% (relative risk [RR] =1.122; 95% confidence interval [CI], 1.091–1.153; P<0.001) APP and 14.1% (RR =1.141; 95% CI, 1.106–1.175; P<0.001) ITT. Probiotics were beneficial among children and adults, as well as Asians and non-Asians. No significant difference was observed in efficacy between the various types of probiotics. The risk of diarrhea, nausea, vomiting, and epigastric pain was also reduced. Conclusion The addition of probiotics is associated with improved H. pylori eradication rates in both children and adults, as well as Asians and non-Asians. Lactobacillus, Bifidobacterium, Saccharomyces, and mixtures of probiotics appear beneficial in H. pylori eradication. Furthermore, the reduction in antibiotic-associated side effects such as nausea, vomiting, diarrhea, and epigastric pain improves medication tolerance and patient compliance. Given the consequences associated with chronic H. pylori infection, the addition of probiotics to the concurrent triple therapy regimen should be considered in all patients with H. pylori infection. However, further studies are required to identify the optimal probiotic species and dose.

Hepatocellular Carcinoma in the Pediatric Population: A Population Based Clinical Outcomes Study Involving 257 Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (1973–2011)

Introduction. Hepatocellular carcinoma (HCC) is a rare pediatric cancer accounting for 0.5% of all pediatric malignancies. This study examines a large cohort of HCC patients in an effort to define the factors impacting clinical outcomes in pediatric HCC patients compared to adults. Methods. Demographic and clinical data on 63,771 HCC patients (257 pediatric patients ≤ 19 and 63,514 adult patients age ≥ 20) were abstracted from the SEER database (1973–2011). Results. HCC was more common among males (59.5% pediatric and 75.1% adults) and Caucasians (50.4% and 50.5%), p < 0.05. Children more often presented with fibrolamellar variant HCC (24.1% versus 0.3%, p = 0.71) and advanced HCC, including distant disease (33.1% versus 20.8%, p < 0.001), and tumors > 4 cm in size (79.6% versus 62.0%, p = 0.02). Pediatric HCC patients undergoing surgery (13.107 versus 8.324 years, p < 0.001) had longer survival than adult HCC patients. Overall mortality was lower (65.8% versus 82.0%, p < 0.001) in the pediatric HCC group. Conclusion. HCC is a rare pediatric malignancy that presents most often as an advanced tumor, >4 cm in Caucasian males. Children with HCC achieve significantly longer mean overall survival compared to adults with HCC, primarily attributable to the more favorable fibrolamellar histologic variant, and more aggressive surgical intervention, which significantly improves survival.

Trends in incidence, survival, and management of uveal melanoma: a population-based study of 7,516 patients from the Surveillance, Epidemiology, and End Results database (1973–2012)

Introduction Uveal melanoma (UM) is the most common primary intraocular malignancy, despite comprising <5% of all melanomas. To date, relatively few case series of UM have been published. Moreover, the factors influencing survival remain largely unknown. This study sought to analyze the impact of demographics, histology, clinical presentation, and treatments on the clinical outcomes of UM in a large modern nationwide patient cohort. Methods Demographics and clinical data were abstracted on 277,120 histologically confirmed melanoma patients from the Surveillance, Epidemiology, and End Results database between 1973 and 2012. Results A total of 7,516 cases of UM represented 3.2% of all recorded cases of melanoma. The mean age-adjusted incidence was 5.1 per million (95% CI 4.2–6.1) and was higher in males (5.9, CI =4.4–7.6) compared to females (4.5, CI =3.3–5.8), P<0.001. UM occurred most commonly in the sixth decade of life (61.4±15) and among Caucasians (94.7%). A total of 52.3% of cases were reported in the Western US (35.7% in California). The initial diagnoses in 65.2% of cases were by histopathology, followed by clinical diagnosis (18.8%) and radiographic imaging (16.0%). The percentage of UM cases managed by surgery alone decreased by 69.4% between the 1973–1977 and 2006–2012 time periods, concomitant with a 62% increase in primary radiotherapy, P<0.001. The UM mean overall and cancer-specific 5-year relative survival rates were 79.8%±5.8% and 76%±5.3%, respectively. The mean 5-year cancer-specific survival rate (76%) remained stable during the study period between 1973 and 2012. The mean survival for patients treated with primary radiotherapy was significantly improved compared to those treated with surgery alone (15.4±0.4 vs 13.6±0.3, P<0.001). Multivariate analysis identified male sex (odds ratio [OR] 1.1, CI =1.0–1.3), age >50 years (OR 4.0, CI =3.4–4.6), distant metastases (OR 8.6, CI =4.7–15), and primary surgical treatment (OR 2.6, CI =2.0–3.3) as independently associated with increased mortality, P<0.005. Conversely, patients identified as Hispanic (OR 0.6, CI =0.5–0.8) and patients receiving radiation treatment (OR 0.5, CI =0.4–0.7) were independently associated with reduced mortality, P<0.005. Conclusion UM remains a rare form of melanoma that occurs primarily in Caucasian patients older than 50 years. More than two-thirds of UM patients are curatively treated with primary radiotherapy as opposed to surgery, which has resulted in a significant improvement in both overall survival and cancer-specific survival. Despite this shift in management strategy, the mean 5-year cancer-specific survival rate remained relatively unchanged during the study period. Male sex, older age, distant disease, and primary surgical therapy rather than radiotherapy are associated with an increased risk of mortality.

Malignant Melanoma in African–Americans: A Population-Based Clinical Outcomes Study Involving 1106 African–American Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (1988–2011)

Abstract Malignant melanoma accounts for 75% of all skin cancer deaths and is potentially curable if identified early. Although melanoma is rare in African–Americans (AA), it is associated with a worse prognosis than in Caucasians. This study examines the demographic, pathologic, and clinical factors impacting AA melanoma outcomes. Data for 1106 AA and 212,721 Caucasian cutaneous melanoma patients were abstracted from the Surveillance, Epidemiology, and End Result (SEER) database (1988–2011). Data were grouped on the basis of histological subtypes: “Superficial Spreading” (SS), “Nodular” (NM), “Lentigo Maligna” (LM), “Acral Lentiginous” (AL), and “Not otherwise specified” (NOS). Cutaneous malignant melanoma occurs most commonly in the sixth and seventh decade of life. Caucasian patients presented most commonly with trunk melanomas (34.5%), while lower extremity melanomas were more common in AAs (56.1%), P < 0.001. AAs presented with deeper tumors, more advanced stage of disease, and higher rates of ulceration and lymph node positivity than Caucasians. Cancer-specific mortality was significantly higher, while 5-year cancer-specific survival was significantly lower among AAs for NM and AL subtypes. Multivariate analysis identified male gender, regional and distant stage, NM and AL subtypes as independently associated with increased mortality among both ethnic groups. AAs present most often with AL melanoma on the lower extremities, and with deeper and more advanced stage lesions. AAs have higher cancer-specific mortality for NM and LM than Caucasians. Melanoma education for AA patients and health care providers is needed to increase disease awareness, facilitate early detection, and promote access to effective treatment.

Pediatric Chordomas: A Population-Based Clinical Outcome Study Involving 86 Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (1973-2011)

Background/Aims: Primary chordomas, rare cancers arising from the notochord remnants, are extremely rare in the pediatric population. This study examined a large cohort of primary chordoma patients to determine factors impacting prognosis and survival. Methods: Demographic and clinical data on 1,358 primary chordoma patients (86 pediatric patients ≤19 years of age and 1,272 adult patients ≥20 years of age) were abstracted from the Surveillance, Epidemiology, and End Result (SEER) database (1973-2011). Results: Pediatric primary chordomas present most often as small tumors <4 cm in the cranium of male Caucasians. Despite the majority of primary chordomas presenting with locoregional involvement (90.4%), pediatric patients had more distant disease (14.8 vs. 9.2%, p < 0.05). Survival among pediatric patients having surgery only was significantly longer than for adults (22.5 vs. 14.3 years, p < 0.001). Overall survival was longer (17.2 vs. 12.6 years) and overall mortality was lower in pediatric patients (38.4 vs. 49.8%), but cancer-specific mortality was higher (37.2 vs. 28.6%, p < 0.005). Conclusions: Pediatric primary chordomas present most often as small tumors <4 cm in the cranium of male Caucasians. Despite having a higher rate of metastasis, they have prolonged survival compared to adults. Surgical resection significantly improves survival in pediatric primary chordoma patients, and should be considered as first-line therapy in all eligible children.