Evidence-based Guidelines For Therapy Research Articles

Methanol toxicity in a pediatric patient treated with fomepizole and hemodialysis.

Methanol toxicity is an important cause of toxic alcohol exposure resulting in morbidity and mortality in both adult and pediatric populations. Methanol is metabolized into formaldehyde and formic acid: toxic metabolites that can cause altered mental status, visual disturbances, multisystem organ failure, and death. Recognition of methanol intoxication and rapid treatment are critical for the prevention of long-term sequelae. We present the case of a 16-year-old male with a past medical history of depression who intentionally ingested windshield wiper fluid containing methanol. Based on the patient's osmolal gap, he was estimated to have a serum methanol level of 374mg/dL; a send-out laboratory measurement later revealed a serum methanol level of 436mg/dL. Therapy included two hemodialysis treatments as well as fomepizole and supportive care. The patient recovered remarkably with no long-term sequelae. This case demonstrates the effectiveness of swift recognition and treatment of methanol ingestion. Optimization of methods of measuring serum methanol and evidence-based guidelines for therapy are needed to improve the care of patients with methanol intoxication.

Colorectal neuroendocrine carcinoma with squamous cell differentiation: a rare and unusual tumour

Background: Neuroendocrine carcinoma (NEC) of the colorectum is rare, accounting for 0.4% of all colorectal neoplasms.1 Squamous cell carcinoma (SCC) of the gastrointestinal tract is also a rare entity and accounts for 0.1–0.25% per 1000 cases of colorectal carcinoma.2 World Health Organization (WHO) classification defines mixed adeno-neuro-endocrine carcinoma as a neoplasm with both exocrine and neuroendocrine components, with each component exceeding 30%. Aim: We present a rare case of a patient with colorectal neuroendocrine carcinoma with squamous differentiation. Method: An 86-year-old gentleman presented with right sided abdominal pain. A colonic mass was noted on CT scan with multiple liver lesions. Subsequent right hemicolectomy revealed an obstructive hepatic flexure tumour. Results and conclusions: Histopathological examination of the mass revealed a high grade neuroendocrine carcinoma (NEC) with diffuse sheets and cords of epithelial cells with crowded nuclei, scant cytoplasm and frequent mitotic figures (23 per 10 high-power field). Amongst the NEC component, small areas (less than 30% of the tumour volume) comprising larger epithelial cells with abundant eosinophilic cytoplasm and areas suggestive of keratinisation were noted. The NEC component was positive for synaptophysin and CD56 immunohistochemistry with a Ki67 proliferation index of 80–90% and negative for P40 and CK5/6 immunohistochemistry. In contrast, the areas with large eosinophilic cells were positive for P40 and CK5/6 immunohistochemistry, whilst negative for synaptophysin and CD56 immunohistochemistry. The tumour exhibited aggressive behaviour with lymphovascular, perineural and venous invasion and lymph node metastases. Neuroendocrine carcinomas and squamous cell carcinomas of the colorectum are rare and extremely aggressive neoplasms3 on their own merits. This phenomenon of mixed neuroendocrine carcinoma with squamous cell differentiation is an unusual and rare pathology which lacks evidence-based guidelines for therapy. It is worth documenting as the optimal therapeutic strategy remains the main challenge.

EP1.08-02 Surgical Indication for Postoperative Regional Lymph Node Oligo-Recurrence in Non-Small Cell Lung Cancer

Currently, evidence-based guidelines for therapy to treat regional lymph node (LN) oligo-recurrence in post-resection non-small cell lung cancer (NSCLC) are limited. We investigated the clinical outcome of surgery for LN oligo-recurrence in post-resection NSCLC. From 2008 to 2017, 14 patients received R0 resection for regional LN oligo-recurrence after initial NSCLC R0 surgery. Eligible patients met these criteria: A, no recurrences without regional LN by PET-CT and brain-MRI; B, LN recurrence within 3 regions. We investigated the characteristics of surgically curable NSCLC patients with postoperative regional LN oligo-recurrence, including recurrence-free survival (RFS) and overall survival (OS). Ten patients were male and 4 were women. The median age was 69 years (62-86). Pathological findings in initial surgery was as follow; adenocarcinoma in 9, squamous cell carcinoma in 5, pathological stage I in 6, II in 4, and IIIA. The regional number of LN recurrence was as follow; 1 region in 11, 2 regions in 1, and 3 regions in 2. The median number of pathological metastatic LN were 2 (1-8). The median size of LN oligo-recurrence was 19 mm (14-38). All the oligo-recurrence LN had uptake in PET-CT. All the recurrent LN site was out of the dissection range at initial surgery. The median period from the initial surgery to oligo-recurrence was 18.1 months (7.0-66.5). The median operation time was 134 minutes (52-452), and median bleeding volume was 15 ml (2-2593). SVC reconstruction was performed in 1. Postoperative complication was detected in 3 cases; arrhythmia in 2 and graft occlusion in 1. There were no cases of perioperative death. EGFR mutation was detected in 4 cases. After LN dissection, 9 patients were followed up without treatment, and the other 5 patients underwent chemotherapy. Six patients (42.8%) out of 14 were recurrence-free after LD dissection. Compared recurrence-free patients with recurrence patients after LN dissection, pathological only one LN of oligo-recurrence (p <0.01) and EGFR wild type (p = 0.04) were significant in the recurrence-free group. LN oligo-recurrence in only one region also tended to be more frequent in the recurrence-free group (p = 0.09). Pathological N or stage in initial surgery, size of LN oligo-recurrence, recurrence-free interval after initial surgery were no significant difference between recurrence-free and recurrent group. The median RFS and OS after LN resection in all 14 patients was 24.2 and 66.3 months. The 2-year and 5-year RFS rates after LN resection were 52.7% and 35.2%. Eight patients were recurrence after LN dissection; 4 were locoregional and the others were distant. Of the 8 relapsed patients, only 2 patients survive with EGFR-TKI. Surgery for postoperative regional LN oligo-recurrence in NSCLC should be indicated for the patients with only one LN of oligo-recurrence in only one region or EGFR wild type.

Precision Surgical Therapy for Adenocarcinoma of the Esophagus and Esophagogastric Junction

IntroductionTo facilitate the initial clinical decision regarding whether to use esophagectomy alone or neoadjuvant therapy in surgical care for individual patients with adenocarcinoma of the esophagus and esophagogastric junction—information not available from randomized trials—a machine-learning analysis was performed using worldwide real-world data on patients undergoing different therapies for this rare adenocarcinoma. MethodsUsing random forest technology in a sequential analysis, we (1) identified eligibility for each of four therapies among 13,365 patients: esophagectomy alone (n = 6649), neoadjuvant therapy (n = 4706), esophagectomy and adjuvant therapy (n = 998), and neoadjuvant and adjuvant therapy (n = 1022); (2) performed survival analyses incorporating interactions of patient and cancer characteristics with therapy; (3) determined optimal therapy as that predicted to maximize lifetime within 10 years (restricted mean survival time; RMST) for each patient; and (4) compared lifetime gained from optimal versus actual therapies. ResultsActual therapy was optimal in 61% of those receiving esophagectomy alone; neoadjuvant therapy was optimal for 36% receiving neoadjuvant therapy. Many patients were predicted to benefit from postoperative adjuvant therapy. Total RMST for actual therapy received was 58,825 years. Had patients received optimal therapy, total RMST was predicted to be 62,982 years, a 7% gain. ConclusionsAverage treatment effect for adenocarcinoma of the esophagus yields only crude evidence-based therapy guidelines. However, patient response to therapy is widely variable, and survival after data-driven predicted optimal therapy often differs from actual therapy received. Therapy must address an individual patient’s cancer and clinical characteristics to provide precision surgical therapy for adenocarcinoma of the esophagus and esophagogastric junction.

Practice patterns for herpes simplex keratitis: A survey of ophthalmologists in Gulf Coast countries

PurposeHerpes simplex is a common cause of visual disability, and there are published evidence-based guidelines for therapy. This survey aims to determine the preferred practice patterns of ophthalmologists in Gulf Coast Countries regarding herpetic eye disease, as well as identify areas of controversy or barriers to acceptance of evidence-based protocols. MethodsAnonymous web-based survey of ophthalmologists in Saudi Arabia, Bahrain, the United Arab Emirates, and Oman. ResultsThere were 48 responses to the survey. For a first episode of epithelial dendritic keratitis, 28.2% reported “observation” rather than specific therapy. The majority of respondents utilize oral or topical antiviral for epithelial keratitis, with oral antiviral being the most popular (43.6%). The majority also included a corticosteroid with antiviral for stromal keratitis (83.9%) or iritis (70.3%). Over 90% prescribe a prophylactic antiviral after keratoplasty for herpetic eye disease, although the length of therapy ranged widely from <6months to indefinite. The perceived risk of recurrent disease was ranked as the most important factor when considering antiviral prophylaxis, followed by risk of adverse effects. Topical cyclosporine was utilized “never or almost never” by 76.9% of respondents. ConclusionsMost respondents report following evidence-based guidelines. There was less consensus in areas where there are remaining knowledge gaps, such as the length of antiviral prophylaxis after keratoplasty and the potential role for topical cyclosporine.

Pharmacist’s involvement in hypertensive patient’s treatment

Globally, cardiovascular diseases are the first cause of mortality. In Romania, hypertension incidence is rising. The present paper reviews antihypertensive drugs available in Romania according with actual, evidence-based therapy guidelines. The paper aims at familiarizing pharmacist with these guidelines, in order to appropriately counsel medication use.

Treatment of acute non-anion gap metabolic acidosis.

Acute non-anion gap metabolic acidosis, also termed hyperchloremic acidosis, is frequently detected in seriously ill patients. The most common mechanisms leading to this acid–base disorder include loss of large quantities of base secondary to diarrhea and administration of large quantities of chloride-containing solutions in the treatment of hypovolemia and various shock states. The resultant acidic milieu can cause cellular dysfunction and contribute to poor clinical outcomes. The associated change in the chloride concentration in the distal tubule lumen might also play a role in reducing the glomerular filtration rate. Administration of base is often recommended for the treatment of acute non-anion gap acidosis. Importantly, the blood pH and/or serum bicarbonate concentration to guide the initiation of treatment has not been established for this type of metabolic acidosis; and most clinicians use guidelines derived from studies of high anion gap metabolic acidosis. Therapeutic complications resulting from base administration such as volume overload, exacerbation of hypertension and reduction in ionized calcium are likely to be as common as with high anion gap metabolic acidosis. On the other hand, exacerbation of intracellular acidosis due to the excessive generation of carbon dioxide might be less frequent than in high anion gap metabolic acidosis because of better tissue perfusion and the ability to eliminate carbon dioxide. Further basic and clinical research is needed to facilitate development of evidence-based guidelines for therapy of this important and increasingly common acid–base disorder.

Molecular profiling of small-bowel adenocarcinomas.

3647 Background: Small-bowel adenocarcinoma (SBA) is a rare malignancy with limited knowledge of the molecular mechanisms, or clinical evidence-based guidelines for therapy. We conducted a comprehe...

Evidence-Based Therapy May Improve Outcome in Glomerulonephritis—A Prospective Field Survey

Introduction and aims: Although glomerulonephritis is rare in the general population it is the second most important cause for end-stage renal failure. The therapy of glomerulonephritis is guided by a limited number of individual clinical trials and treatment recommendations are based on meta-analysis and Cochrane Systematic Reviews. The impact of such therapy standards on the prognosis of glomerulonephritis is not known. Methods: Between October 2002 and December 2008 patients with abnormal urine findings and/or decreasing renal function of unknown cause were referred for renal biopsy. In a collaboration of out-patient nephrologists with a major teaching hospital, all patients received treatment recommendations according to evidence-based therapy guidelines based on Cochrane Systematic Reviews. Patient charts were systematically reviewed and patients were re-examined for follow-up until November 2009. Cox Regression analysis was performed to identify independent prognostic factors. Results: Two hundred patients with primary or secondary glomerulonephritis were identified. Complete follow-up data were available from 196 patients with 324 therapeutic interventions. The mean follow-up was 2.8 ± 2.0 years. Among all patients, 37% remained unchanged ill, 13% died, 17% had progressing renal disease, while 19% had a complete and 14% a partial remission. Proteinuria declined in primary glomerulonephritis (5.0 ± 5.4 g/d to 2.1 ± 3.4 g/d, p Conclusions: In a multivariate model of standardised glomerulonephritis therapy the presence of tubulointerstitial fibrosis was associated with death or progresssive renal disease, while prednisolone-based therapy regimens and intensified nephrological follow-up resulted in a significant delay of endstage-renal failure. This result should direct future health care policies because glomerulonephritis accounts for nearly 20% of the dialysis population.

Early poststroke seizures

Seizures are one of the most common complications of stroke.1,2 Overall, 5%–15% of stroke patients will experience a seizure within 2 years of stroke. The reported risk factors for and incidence of seizures after stroke vary widely, likely secondary to differences in study design, study populations, and use of antiepileptic drugs (AEDs). In previous studies, the main risk factors for poststroke seizures include stroke subtype, location, and severity. Poststroke seizure rates are highest in those with intraparenchymal hemorrhage and large supratentorial ischemic strokes, and lowest after transient ischemic attacks, lacunar infarcts, and brainstem strokes.1,2 Although frequently encountered in clinical practice, there are few evidence-based guidelines for therapy of poststroke seizures. Poststroke seizures are classified as “early” or “late” according to their temporal proximity to the stroke.3 Early seizures, also termed acute symptomatic seizures, occur within the first week following stroke. These early seizures are likely provoked by the metabolic and physiologic derangements associated with acute infarction or hemorrhage. Late seizures begin after a latent period of variable duration, usually weeks to years. Late seizures are thought to result from epileptogenesis, changes in neurons and networks that result in permanent hyperexcitability. Prior studies do not elucidate whether early seizures are merely epiphenomena of acute brain injury, and whether they may have a negative effect on long-term neurologic outcome or increase the risk for development of subsequent late seizures and epilepsy. Two studies in this issue of Neurology ® provide important new information about incidence and risk factors for early poststroke seizures, and the consequences of early seizures on outcome.4, …

Treatment of seizures in childhood

The field of pediatric epilepsy is a rewarding yet challenging area of medicine. A fairly significant proportion of children remain refractory to current antiepileptic drugs, and may require alternative treatment options. Challenges also arise because many of the antiepileptic drugs available for use since 1993 are US FDA approved only for use over the age of 2–4 years, hence presenting a medicolegal conundrum to the treating physician. However, their more favorable side-effect profile and tolerability have led to their widespread use even in those less than 2 years of age. This review briefly outlines their indications, pharmacokinetic profile and dosages, and covers evidence-based guidelines for therapy in common epilepsy syndromes of childhood.

Plattenepithelkarzinom des Nierenbeckens

Squamous cell carcinoma (SCC) of the upper urinary tract is a rare condition. The late stage of the tumour at diagnosis and the absence of evidence-based guidelines for therapy give rise to a poor prognosis in most cases. The patient with SCC described here showed an above-average survival of 18 months after adjuvant radiochemotherapy. Treatment was initiated according to the guidelines for squamous cell carcinoma in non-urological localisations.

Plattenepithelkarzinom des Nierenbeckens

Squamous cell carcinoma (SCC) of the upper urinary tract is a rare condition. The late stage of the tumour at diagnosis and the absence of evidence-based guidelines for therapy give rise to a poor prognosis in most cases. The patient with SCC described here showed an above-average survival of 18 months after adjuvant radiochemotherapy. Treatment was initiated according to the guidelines for squamous cell carcinoma in non-urological localisations.

Use of base in the treatment of acute severe organic acidosis by nephrologists and critical care physicians: results of an online survey

Acute severe metabolic acidosis associated with lactic acidosis or ketoacidosis can have severe detrimental effects on organ function, and might contribute to mortality. A general consensus exists that elimination of the cause of the acidosis is essential for treatment, but there is controversy concerning the use of base for the treatment of these disorders. Some physicians advocate administration of base when the acidosis is severe to prevent a decrease in cardiac output, whereas others oppose administration of base even when the acidosis is severe given the potential compromise of cardiac function. Nephrologists and critical care specialists are often the physicians developing recommendations for the treatment of severe acid-base disorders. A short online survey of 20 questions was developed to assess the approach to the treatment of acute metabolic acidosis of program directors of fellowship programs and experts from the specialties of critical care and nephrology. Although there was variability among individual physicians from both specialties, a larger percentage of nephrologists than critical care physicians queried recommended administration of base for the treatment of lactic acidosis (86% vs 67%) and ketoacidosis (60% vs 28%). Also, critical care physicians in general used a lower level of blood pH when deciding when to initiate treatment. Of the physicians who gave base, most utilized sodium bicarbonate as the form of base given. The results of this survey indicate that the decisions whether to use base for the treatment of acute severe metabolic acidosis, and under which circumstances, vary among physicians, and indicate the need for further studies to develop evidence-based guidelines for therapy.

Review article - Internal carotid artery dissection

The purpose of this review is to increase the awareness of internal carotid artery dissection (ICAD), a potentially serious and probably underdiagnosed condition. ICAD is a not uncommon cause of stroke in young patients. ICAD may occur spontaneously or as a result of trauma. However, the "spontaneous" dissection is often preceded by a trivial trauma. The typical patient presents with ipsilateral headache or neck pain, ipsilateral Horner's syndrome and delayed ischemic symptoms from the ipsilateral hemisphere or retina. Conventional angiography, the gold standard for diagnosis, tends to be replaced by non-invasive diagnostic methods. There are no evidence-based guidelines for therapy although anticoagulation is most commonly used. The references are selected from the Medline database for the years 1966-1997.