Meta-Analysis of the Role of Intermittent Pneumatic Compression of the Lower Limbs to Prevent Venous Thromboembolism in Critically Ill Patients.

Critically ill patients (patients treated in a medical or surgical intensive care unit) are at high risk of venous thromboembolism (VTE) development (deep vein thrombosis [DVT] and/or pulmonary embolism). Multiple thromboprophylaxis strategies have been used for the prevention of VTE in this population with various outcomes. Therefore, we aimed to evaluate the efficacy of intermittent pneumatic compression (IPC) prophylaxis in the lower limb compared with no treatment, anticoagulant use, or their combinations in reducing risk. A comprehensive electronic database search was conducted for all randomized clinical trials (RCTs) comparing the clinical outcomes of IPC versus anticoagulants or no treatment or their combinations for the prevention of VTE for critically ill patients. The primary outcome was VTE. The secondary outcome was DVT. We performed a Bayesian network meta-analysis to calculate odds ratios (ORs) and 95% credible intervals (CrIs). We included 5 RCTs with 3133 total patients, represented by a mean age of 49.61 ± 18 years, while 60.28% were male. There was a significant reduction of the primary outcome (incidence of VTE events) when no treatment was compared with IPC (OR = 0.36; 95% CrI = 0.18-0.71), anticoagulation alone (OR = 0.30; 95% CrI = 0.12-0.68), or anticoagulation with IPC (OR = 0.34; 95% CrI = 0.13-0.81). In addition, there was a significant reduction in DVT when no treatment was compared with IPC (OR = 0.45; 95% CrI = 0.21-0.9), anticoagulation alone (OR = 0.16; 95% CrI = 0.03-0.66), or anticoagulation with IPC (OR = 0.18; 95% CrI = 0.03-0.84). However, there were no significant differences between other comparisons (IPC vs anticoagulation alone, anticoagulation alone vs anticoagulation with IPC, or anticoagulation with IPC vs IPC alone) regarding VTE or DVT incidence. Among critically ill patients, IPC alone, anticoagulation alone, and IPC with anticoagulation were associated with a significant reduction of VTE and DVT incidence compared with no treatment. However, there was no significant difference between these modalities when compared together. Therefore, further larger studies comparing those different thromboprophylaxis modalities and their combinations are needed to provide more robust results for future clinical recommendations.

Proton Pump Inhibitors Versus Histamine-2-Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients: A Meta-analysis and Trial Sequential Analysis.

GOALS AND BACKGROUND: Stress ulcer prophylaxis has been shown to lower gastrointestinal bleeding (GIB) rates. Various agents have been studied, and the optimal strategy continues to be contested. This study evaluates the efficacy between proton pump inhibitors (PPIs) and histamine-2-receptor antagonists. Small sample sizes and methodology flaws limited prior studies. STUDY: A systematic search of MEDLINE, EMBASE, CENTRAL, Web of Science, and ClinicalTrials.gov for randomized controlled trials reporting the use of PPI and histamine-2-receptor antagonist reporting rates of GIB and standardized intensive care outcomes. Risk ratios (RR) and standardized mean difference (SMD) with 95% confidence intervals (CIs). A trial sequential analysis was performed to guard against errors. RESULTS: A total of 14 randomized controlled trials of 28,526 patients with a mean age of 57.83±17.35 years and 30.82% females. In our pooled analysis, PPI outperformed its comparator (RR: 0.68; 95% CI: 0.57-0.82) in clinically significant GIB. PPI re-demonstrated significant reduction in overt GIB (RR: 0.61; 95% CI: 0.39-0.97). No differences between groups was noted toward all-cause mortality (RR: 1.05; 95% CI: 1.00-1.10) or incidence of pneumonia (RR: 1.11; 95% CI: 0.82-1.51). Duration of stay (SMD: 0.07; 95% CI: -0.04-0.17) and ventilator days (SMD: 0.01; 95% CI: -0.01-0.04) were indifferent between the groups. CONCLUSIONS: Among critically ill patients, PPI was associated with reduced clinically significant or overt GIB. No differences in pneumonia were seen with the use of either agent. Trial sequential analysis for clinically significant GIB ruled out the risk for false-positive results, and thereby it is unlikely that future trials will affect our conclusions.

Thromboprophylaxis for orthopedic surgery; An updated meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is a serious complication of orthopedic surgery. Low molecular weight heparin (LMWH) has been the standard of care for thromboprophylaxis in this population. However, direct oral anticoagulants (DOACs) are increasingly being used as alternatives. OBJECTIVE: To assess the efficacy and safety of DOACs versus LMWH for thromboprophylaxis in orthopedic surgery. METHODS: We searched MEDLINE, Embase, and the Cochrane Collaboration Central Register of Controlled Trials from inception until April 2020, for randomized controlled trials (RCTs) comparing DOACs with LMWH for thromboprophylaxis in orthopedic surgery. RESULTS: Twenty-five RCTs met inclusion criteria, including 40,438 patients, with a mean age of 68 years and 50% were males. Compared to LMWH, DOACs were associated with a significant reduction of major VTE; defined as the composite events of proximal deep vein thrombosis (DVT), pulmonary embolism (PE), and VTE-related mortality (RR 0.33; 95% CI: 0.20-0.53; P<0.01), and total DVT (RR: 0.59; 95% CI: 0.48-0.73; P<0.01), but not PE (RR 0.81; 95% CI: 0.49-1.34; P=0.42). There was no statistically significant difference between both groups on the incidence of major bleeding (RR 0.99; 95% CI: 0.77-1.27; P=0.92), clinically relevant non-major bleeding (RR 1.04; 95% CI: 0.92-1.17; P=0.52), all-cause mortality (RR 1.06; 95% CI: 0.64-1.76; P=0.83), VTE-related mortality (RR 0.84; 95% CI: 0.40-1.74; P=0.64) and bleeding-related mortality (RR 1.24; 95% CI: 0.30-5.18; P=0.77). CONCLUSION: For patients undergoing orthopedic surgery, thromboprophylaxis with DOACs is associated with a significant reduction of major VTE and DVT, compared to LMWH. Safety outcomes were not significantly different between both treatment groups.

Cyclical Hemoptysis and Pelvic Pain in a Young Female: A Sign of Thoracic Endometriosis Syndrome.

Distant autoimplantation of endometrial implants presents with signs and symptoms specific to the affected site. The constellation of cyclical hemoptysis, pleuritic chest pain, dyspnea, or cough in the right gynaecologic setting should raise concern for thoracic endometriosis syndrome (TES). Although extra-pelvic implications of endometriosis are well known, TES is exceedingly rare. We present an unusual case of aggressive TES that re-emerged after a period of latency despite suppressive therapy, making the case for future studies to establish surveillance schedules and advanced therapies. As these implants become sizable, they require a combination of medical and surgical therapies often with psychological support. This case illustrates the importance of prompt diagnosis and a multidisciplinary approach to TES.

Kounis Syndrome: Allergic Vasospastic Cardiac Event.

Kounis syndrome (KS) is an acute coronary event secondary to an allergic reaction. It is provoked by environmental agents, food, and medications. KS is caused by the release of allergic mediators. We are reporting a case of a 39-year-old man who had a syncopal episode after he took cephalexin and ibuprofen for toothache. He developed chest pain and erythematous rash later. His electrocardiography did not show any ST-segment elevation changes and cardiac troponins were elevated. He was started on the acute coronary syndrome treatment protocol. Coronary angiography revealed no significant obstructive or culprit lesions. The patient was discharged home in stable condition. He is advised to adhere to lifestyle modification and outpatient follow-up with cardiology and allergy/immunology. KS is infrequently reported in the medical literature. Physicians should pay attention to any allergic reaction preceding the acute cardiac event and consider KS in the differential diagnosis.

Acute Esophageal Necrosis (Gurvits Syndrome) Presenting as Globus and Altered Phonation.

BACKGROUND Acute esophageal necrosis (AEN), also known as black esophagus or Gurvits syndrome, is an infrequently seen clinical condition distinguishable by a visually striking endoscopic appearance of necrotic esophageal mucosa that involves the distal esophagus with proximal extensions ending at the gastroesophageal junction. Since its early recognition pathologically in the 1960s and endoscopically in the 1990s, AEN, despite its rarity, is being increasingly recognized as a demonstratable cause of upper gastrointestinal bleeding. Cases of pan-esophageal necrosis are sparsely reported, leaving management guidance to isolated case reports. CASE REPORT An 80-year-old female smoker with advanced chronic obstructive pulmonary disease presented with signs and symptoms of acute pharyngitis and globus sensation that had been evolving over the preceding weeks. An esophagogastroduodenoscopy revealed circumferential necrotic mucosa encircling the entire lumen of the esophagus. The patient was made nil-per-os and started on high-dose anti-reflux therapy with adequate hemodynamic resuscitation. CONCLUSIONS AEN is multifactorial but primarily a combination of decreased tissue perfusion and a massive influx of gastric contents in settings of impaired local defense barriers. Despite its dramatic presentation, the majority of cases resolve with conservative medical management, foregoing surgical interventions.

A Cause-Effect Relationship of Infliximab and Pulmonary Embolism: A Case Report.

Biological monoclonal antibodies such as infliximab have significantly remodeled inflammatory bowel disease's treatment course. Despite multiple side effects reported with infliximab, this medication has shown to be robust and practical. There is a paucity of cases reporting venous thromboembolism (VTE) occurrence during the treatment with infliximab. Although such an association's exact mechanism is still not precise, we should be aware of the drug thromboembolic aptitude. Close attention should be given to patients who started infliximab infusion for any symptoms of pulmonary embolism or deep vein thrombosis.

Use of glucocorticoids in patients with acute respiratory distress syndrome: a meta-analysis and trial sequential analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common and disabling disease with high rates of mortality and morbidity. The role of steroids in treating ARDS remains controversial. We aim to examine the evidence behind using glucocorticoids in the management of ARDS from the available studies. METHODS: We performed a literature review of major electronic databases for randomized controlled trials (RCTs) comparing glucocorticoids versus placebo in treating patients with ARDS. Our primary outcome was hospital mortality. Other outcomes included ICU mortality, number of ventilator-free days at day 28, incidence of nosocomial infections, and hyperglycemia. We performed a meta-analysis using a random effects model to calculate risk ratios (RR) and mean difference (MD) with their corresponding 95% confidence intervals (CI). A subsequent trial sequential analysis was performed to examine the strength of evidence and to guard against statistical type I and type II errors for our results. RESULTS: Eight RCTs were included in the final analysis totaling of 1091 patients, with a mean age of 57 ± 16, and 56.2% were male. In our pooled analysis, use of glucocorticoids was associated with a significant reduction in hospital mortality (RR 0.79; 95% CI 0.64-0.98; P = 0.03) and ICU mortality (RR 0.64; 95% CI 0.42-0.97; P = 0.04). Furthermore, glucocorticoid use was associated with an increased number of ventilator-free days at day 28 (MD 4.06 days; 95% CI 2.66-5.45; P < 0.01). Regarding adverse events, glucocorticoids use was not associated with an increased risk for nosocomial infections (RR 0.82; 95% CI 0.68-1.00; P = 0.05); however, it was associated with an increased risk of hyperglycemia (RR 1.11; 95% CI 1.01-1.24; P = 0.04). In our trial sequential analysis, the required diversity-adjusted information size (sample size = 2692 patients) was not reached, and the evidence was insufficient from the available RCTs. CONCLUSION: Among patients with ARDS, use of glucocorticoids is associated with a significant reduction in mortality and duration of mechanical ventilation, without increased risk of hospital-acquired infections. However, based on a trial sequential analysis, these findings may be secondary to a false-positive (type I) error. Further studies are needed for a firm conclusion with guarding against possible statistical errors.

Effect of oxygenation modalities among patients with postoperative respiratory failure: a pairwise and network meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative respiratory failure is associated with increased perioperative complications. Our aim is to compare outcomes between non-invasive ventilation (NIV), high-flow nasal cannula (HFNC), and standard oxygen in patients at high-risk for or with established postoperative respiratory failure. METHODS: Electronic databases including PubMed, Embase, and the Cochrane Library were reviewed from inception to September 2019. We included only randomized controlled trials (RCTs) that compared NIV, HFNC, and standard oxygen in patients at high risk for or with established postoperative respiratory failure. We performed a Bayesian network meta-analysis to calculate the odds ratio (OR) and Bayesian 95% credible intervals (CrIs). RESULTS: Nine RCTs representing 1865 patients were included (the mean age was 61.6 ± 10.2 and 64.4% were males). In comparison with standard oxygen, NIV was associated with a significant reduction in intubation rate (OR 0.23; 95% Cr.I. 0.10-0.46), mortality (OR 0.45; 95% Cr.I. 0.27-0.71), and intensive care unit (ICU)-acquired infections (OR 0.43, 95% Cr.I. 0.25-0.70). Compared to standard oxygen, HFNC was associated with a significant reduction in intubation rate (OR 0.28, 95% Cr.I. 0.08-0.76) and ICU-acquired infections (OR 0.41; 95% Cr.I. 0.20-0.80), but not mortality (OR 0.58; 95% Cr.I. 0.26-1.22). There were no significant differences between HFNC and NIV regarding different outcomes. In a subgroup analysis, we observed a mortality benefit with NIV over standard oxygen in patients undergoing cardiothoracic surgeries but not in abdominal surgeries. Furthermore, in comparison with standard oxygen, NIV and HFNC were associated with lower intubation rates following cardiothoracic surgeries while only NIV reduced the intubation rates following abdominal surgeries. CONCLUSIONS: Among patients with post-operative respiratory failure, HFNC and NIV were associated with significantly reduced rates of intubation and ICU-acquired infections compared with standard oxygen. Moreover, NIV was associated with reduced mortality in comparison with standard oxygen.

Effect of Vitamin D Supplementation on the Incidence of Diabetes Mellitus.

CONTEXT: The effect of vitamin D supplementation on the risk of type 2 diabetes mellitus (T2DM) remains controversial because most randomized controlled trials (RCTs) have been small or have reported low doses of vitamin D. OBJECTIVE: To conduct a meta-analysis of RCTs testing vitamin D supplementation in the prevention of T2DM. DATA SOURCES: Database search of PubMed/MEDLINE, EMBASE, and the Cochrane Library was performed by 2 reviewers from inception through September 15, 2019. STUDY SELECTION: We included RCTs that reported the effect of vitamin D supplementation for at least 1 year on T2DM prevention. DATA EXTRACTION: Two independent reviewers extracted the data. The risk ratios (RRs) and 95% confidence intervals (CIs) were reported. Primary outcome of the meta-analysis was the incidence of T2DM. DATA SYNTHESIS: Nine RCTs were included (43 559 participants). The mean age (standard deviation) was 63.5 (6.7) years. The RR for vitamin D compared with placebo was 0.96 (95% CI, 0.90-1.03); P = 0.30. In trials testing moderate to high doses of supplementation (≥1000 IU/day), all conducted among participants with prediabetes, the RR for vitamin D compared with placebo was 0.88 (95% CI, 0.79-0.99). In contrast, the trials testing lower doses, which were conducted in general population samples, showed no risk reduction (RR, 1.02; 95% CI, 0.94-1.10; P, interaction by dose = 0.04). CONCLUSION: In patients with prediabetes, vitamin D supplementation at moderate to high doses (≥1000 IU/day), significantly reduced the incidence risk of T2DM, compared with placebo.

Anticoagulants for the treatment of venous thromboembolism in patients with cancer: A comprehensive systematic review, pairwise and network meta-analysis.

Cancer-associated venous thromboembolism (VTE) is associated with high VTE recurrence and bleeding. We included all randomized clinical trials that evaluated the efficacy and safety of various anticoagulants in cancer-associated VTE. Trial-level data were extracted from 13 trials. Aggregate odds ratios (ORs) were calculated using direct and network meta-analysis. The primary outcome was VTE (pulmonary embolism and/or deep vein thrombosis) recurrence. Secondary outcomes were major bleeding and all-cause mortality. We identified 13 trials with 4869 patient-years of follow-up (6595 total patients; mean age 62.4 ± 12.2; 50.4 % female; 17.7 % hematological malignancies). The most common cancer type was colorectal and 48 % had metastatic cancer at baseline. Compared to vitamin-K-antagonists (VKAs), non-vitamin-K-antagonist-oral-anticoagulants (NOACs) were associated with significantly reduced VTE recurrence (OR, 0.58; 95 % CI, 0.40-0.83) and reduced major bleeding risks (OR, 0.56; 95 % CI, 0.35-0.91). However, no differences were observed in the subgroup analysis of patients with active cancer. Although NOACs were associated with reduced VTE recurrence compared with low-molecular-weight-heparin (LMWHs) (OR, 0.46; 95 % CI, 0.25- 0.85), there was a significant increased major bleeding in high-quality trials. LMWHs were associated with significantly reduced VTE recurrence compared with VKAs (OR, 0.52; 95 % CI, 0.39-0.71) and similar bleeding risks. Conclusions: Among patients with cancer-associated VTE, NOACs were associated with significantly reduced VTE recurrence and bleeding compared with VKAs, however, with similar outcomes in the active cancer population. NOACs were associated with reduced VTE recurrence but higher bleeding risks compared with LMWHs. LMWHs were associated with significantly reduced VTE recurrence and similar bleeding compared with VKAs.

The role of anticoagulation in venous thromboembolism primary prophylaxis in patients with malignancy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with cancer. As such, we conducted a meta-analysis of randomized controlled trials (RCTs) that evaluated anticoagulants as primary prophylaxis against VTE in cancer patients. METHODS: Pubmed/MEDLINE, Embase, and the Cochrane Library were screened for all RCTs that used anticoagulation therapy in cancer patients for primary prevention of VTE. The primary outcomes were VTE events. Secondary outcomes included all-cause mortality, VTE-related mortality and major bleeding. A random effects model was used to report the risk ratios (RR) with 95% confidence intervals (CIs), and odds ratios (ORs) with Bayesian 95% credible intervals for both direct and network meta-analyses, respectively. RESULTS: Twenty-four RCTs were included totaling 13,338 patients (7197 received anticoagulation and 6141 received placebo). The mean age ranged between 54.6 and 68.1 years, with 50.5% male. Compared with placebo, low-molecular-weight heparin (LMWH) or direct Xa inhibitors were associated with lower VTE events (RR 0.58; 95%CI 0.48-0.69, P < 0.001) and (RR 0.39; 95%CI 0.24-0.63, p < 0.001), respectively. LMWH was associated with decreased VTE and all-cause mortality when compared with placebo (P < 0.05). Regarding safety outcomes, LMWH and direct Xa inhibitors were not associated with increased risks of major bleeding (P > 0.05) when compared with placebo. Results regarding VTE events and major bleeding were consistent in both lung and pancreatic cancers. CONCLUSIONS: Both LMWH and direct Xa inhibitors were associated with a lower VTE events compared with placebo. However, this potentially protective effect must be balanced against the possible increased risk of bleeding for some patients.

Post-SSRI Sexual Dysfunction: A Literature Review.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are a widely used class of drug. Post-SSRI sexual dysfunction (PSSD) is a condition in which patients continue to have sexual side effects after discontinuation of SSRI use. The prevalence of persistent sexual side effects after discontinuing SSRIs is unknown. The recognition and study of PSSD will increase our knowledge base of this underreported and distressing condition. AIM: To provide coverage of the current literature on PSSD, update information on the pathophysiology of PSSD, and discuss potential management options. METHODS: Comprehensive review of literature pertaining to PSSD. MAIN OUTCOME MEASURES: The symptoms, classification, pathophysiology, diagnostic considerations, and management of PSSD were reviewed. RESULTS: Common PSSD symptoms include genital anesthesia, pleasure-less or weak orgasm, decreased sex drive, erectile dysfunction, and premature ejaculation. Different theories have been proposed to explain the pathophysiology of PSSD: epigenetic gene expression theory, cytochrome actions, dopamine-serotonin interactions, proopiomelanocortin and melanocortin effects, serotonin neurotoxicity, downregulation of 5-hydroxytryptamine receptor 1A, and hormonal changes in the central and peripheral nervous systems. The diagnosis of PSSD is achieved by excluding all other etiologies of sexual dysfunction. Treating PSSD is challenging, and many strategies have been suggested and tried, including serotonergic antagonists and dopaminergic agonists. There is still no definitive treatment for PSSD. Low-power laser irradiation and phototherapy have shown some promising results. CONCLUSION: PSSD is a debilitating condition that adversely affects quality of life. Further studies are warranted to investigate the prevalence, pathophysiology, and treatment of PSSD. Bala A, Nguyen HMT, Hellstrom WJG. Post-SSRI Sexual Dysfunction: A Literature Review. Sex Med Rev 2018;6:29-34.

Post-Orgasmic Illness Syndrome: A Review.

INTRODUCTION: Post-orgasmic illness syndrome (POIS) is a rare but debilitating cluster of postejaculatory symptoms affecting men. It is a chronic disorder manifesting as a constellation of flulike and allergic symptoms within seconds, minutes, or hours after ejaculation. POIS can be followed by mental sequelae such as diminished concentration and irritability. POIS negatively affects the life of patients by limiting sexual encounters, dampening romantic prospects, creating internal struggles to avoid eroticism, and affecting patients' schedules. First described in 2002, the prevalence and incidence of POIS are still unknown owing to a paucity of studies but is likely under-reported. There are approximately 50 cases of POIS in the literature. Despite the debilitating effects of POIS, the pathophysiology of POIS is still not well elucidated. AIM: To provide an update on the current literature on POIS, provide updated information on the pathophysiology of POIS, and discuss potential management options. METHODS: Comprehensive review of literature pertaining to POIS. MAIN OUTCOME MEASURES: The symptoms, classification, pathophysiology, diagnostic considerations, and management of POIS were reviewed. RESULTS: There are 5 preliminary diagnostic criteria for diagnosing this condition. POIS is categorized as primary or secondary. The autoimmune-allergy hypothesis is the most accepted hypothesis explaining the pathogenesis of POIS. A competing hypothesis involves a disorder involving endogenous µ-opioid receptors. Another hypothesis invokes impairment of the cytokine and neuroendocrine responses. There are no known treatment modalities for POIS; patients have been symptomatically treated with antihistamines, selective serotonin reuptake inhibitors, and benzodiazepines. A trial of hyposensitization therapy with autologous semen was successful. A trial of non-steroidal anti-inflammatory medication helped 1 patient described in a single case report, but failed to successfully treat other patients. CONCLUSIONS: POIS is a rare condition that is underdiagnosed and under-reported. Further studies are warranted to investigate the prevalence, pathophysiology, and treatment of this debilitating condition. Nguyen HMT, Bala A, Gabrielson AT, Hellstrom WJG. Post-Orgasmic Illness Syndrome: A Review. Sex Med Rev 2018;6:11-15.