First-choice Treatments Research Articles

Challenges to a Cure for HBV Infection.

AbstractCurrent first-choice treatments for chronic hepatitis B are able to efficiently induce viral suppression in the majority of patients, but life-long therapy is needed to maintain infection under control due to their inability to eliminate the virus from infected hepatocytes. The residual viral replication and antigen production in most patients under treatment substantially contributes to the residual risk of hepatocarcinogenesis. New therapeutic approaches are needed to overcome hepatitis B virus persistence in the infected cells, or at least to control its transcriptional and replicative activity. In this review, the authors discuss the key points of the viral life cycle and host immune responses that need to be addressed to achieve a “functional cure,” or even a “complete cure,” allowing a finite duration of treatment and preventing virus reactivation and liver disease progression in a significantly higher number of patients than what is currently attained.

Impact of epidermal growth factor receptor gene expression level on clinical outcomes in epidermal growth factor receptor mutant lung adenocarcinoma patients taking first-line epidermal growth factor receptor-tyrosine kinase inhibitors.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are first-choice treatments for advanced non-small-cell lung cancer patients harboring EGFR mutations. Although EGFR mutations are strongly predictive of patients' outcomes and their response to treatment with EGFR-TKIs, early failure of first-line therapy with EGFR-TKIs in patients with EGFR mutations is not rare. Besides several clinical factors influencing EGFR-TKI efficacies studied earlier such as the Eastern Cooperative Oncology Group performance status or uncommon mutation, we would like to see whether semi-quantify EGFR mutation gene expression calculated by 2-ΔΔct was a prognostic factor in EGFR-mutant non-small cell lung cancer patients receiving first-line EGFR-TKIs. This retrospective study reviews 926 lung cancer patients diagnosed from January 2011 to October 2013 at the Kaohsiung Chang Gung Memorial Hospital in Taiwan. Of 224 EGFR-mutant adenocarcinoma patients, 148 patients who had 2-ΔΔct data were included. The best cutoff values of 2-ΔΔct for in-frame deletions in exon 19 (19 deletion) and a position 858 substituted from leucine (L) to an arginine (R) in exon 21 (L858R) were determined using receiver operating characteristic curves. Patients were divided into high and low 2-ΔΔct expression based on the above cutoff level. The best cutoff point of 2-ΔΔct value of 19 deletion and L858R was 31.1 and 104.7, respectively. In all, 92 (62.1%) patients showed high 2-ΔΔct expression and 56 patients (37.9%) low 2-ΔΔct expression. The mean age was 65.6 years. Progression-free survival of 19 deletion mutant patients with low versus high expression level was 17.07 versus 12.04 months (P = 0.004), respectively. Progression-free survival of L858 mutant patients was 13.75 and 7.96 months (P = 0.008), respectively. EGFR-mutant lung adenocarcinoma patients with lower EGFR gene expression had longer progression-free survival duration without interfering overall survival.

61. Natural history and outcome of 200 outpatients with classical trigeminal neuralgia treated with carbamazepine or oxcarbazepine in a tertiary centre for neuropathic pain

Carbamazepine (CBZ) and oxcarbazepine (OXC) are the first-choice medical treatments in patients with trigeminal neuralgia (TN). The aim of this retrospective study was to analyze the natural history of classical TN in a large cohort of patients, focusing on drug responsiveness, side effects, and changes in pain characteristics during the course of disease. We selected the last 100 consecutive patients with typical TN treated with CBZ and the last 100 with OXC. All had MRI scans and a complete neurophysiological study of trigeminal reflexes. The initial number of responders was 98% with CBZ and 94% with OXC. In a mean period of 8.6 months, 26% of responders to CBZ incurred in undesired effects leading to interruption of treatment or a dosage reduction to an unsatisfactory level. In a mean period of 13 months, the same occurred to 18% of responders to OXC. We found that the worsening of pain with time and the development of late resistance occurred in a small minority of patients. CBZ and OXC were efficacious in a large majority of patients, but the side effects caused withdrawal from treatment in an important percentage of patients, suggesting the opportunity to develop a drug better tolerated.

Natural history and outcome of 200 outpatients with classical trigeminal neuralgia treated with carbamazepine or oxcarbazepine in a tertiary centre for neuropathic pain.

BackgroundThe guidelines on trigeminal neuralgia management that have been agreed and jointly published by the American Academy of Neurology and the European Federation of Neurological Societies recommend carbamazepine (CBZ) and oxcarbazepine (OXC) as the first-choice medical treatments in patients with trigeminal neuralgia (TN). The aim of this retrospective study was to analyze the natural history of classical trigeminal neuralgia in a large cohort of patients, focusing on drug responsiveness, side effects related to CBZ and OXC, and changes in pain characteristics during the course of disease.FindingsWe selected the last 100 consecutive patients with typical TN who began treatment with CBZ and the last 100 with OXC. All had MRI scans and a complete neurophysiological study of trigeminal reflexes. Among them, 22 were excluded on the basis of neuroradiological or neurophysiological investigations, to avoid the inclusion of patients with possible secondary TN. The initial number of responders was 98% with CBZ with a median dose of 600 mg (range 200–1200), and of 94% with OXC, with a median dose of 1200 mg (range 600–1800). In a mean period of 8.6 months, 27% of responders to CBZ incurred in undesired effects to a level that caused interruption of treatment or a dosage reduction to an unsatisfactory level. In a mean period of 13 months, the same occurred to 18% of responders to OXC. Among patients who had a good initial response, only 3 patients with CBZ and 2 with OXC developed late resistance. During the course of disease, paroxysms worsened in intensity in 3% of patients, and paroxysms duration increased in 2%. We did not observe the onset of a clinically manifest sensory deficit at any time in any patient.ConclusionsUnlike common notion, in our large patient sample the worsening of pain with time and the development of late resistance only occurred in a very small minority of patients. CBZ and OXC were confirmed to be efficacious in a large majority of patients, but the side effects caused withdrawal from treatment in an important percentage of patients. These results suggest the opportunity to develop a better tolerated drug.

Trends in antiarrhythmic drug use after marketing authorization of dronedarone: comparison between Emilia Romagna (Italy) and Sweden

Our aim was to evaluate whether dronedarone authorization impacts antiarrhythmic drug prescribing in Sweden and Emilia Romagna (Italy). Prescriptions of classes I and III antiarrhythmics, expressed as defined daily doses per thousand inhabitants per day (DDD/TID) were monthly using information collected from pharmacy-reimbursed databases. Interrupted time series analysis was applied to compare prescription data over the 2009-2011 period. In Emilia Romagna, the overall consumption of antiarrhythmics was six times as high as in Sweden (7.6 vs. 1.2 DDD/TID). In the first year on the market, dronedarone represented 1.0 % in Italy and 10.7 % in Sweden of the overall antiarrhythmic prescriptions. In Sweden, dronedarone authorization generated an increase in the prescription trend of antiarrhythmics (trend change +0.02; p < 0.001) without variation in amiodarone use In Emilia Romagna, dronedarone marketing did not influence the prescription pattern of either overall antiarrhythmics or amiodarone. Emilia Romagna and Sweden substantially differ in terms of overall antiarrhythmic use. Although clinical guidelines place dronedarone among first-choice treatments for atrial fibrillation, amiodarone prescribing was not affected in either country by the entry of dronedarone, probably due to a cautious approach by clinicians in line with regulatory recommendations and safety warnings.

Evaluation of intraoperative microwave coagulo‐necrotic therapy (MCN) for hepatocellular carcinoma: a single center experience of 719 consecutive cases

BackgroundHepatic resection (HRx) or radiofrequency ablation may be carried out as the first-line treatment of hepatocellular carcinoma (HCC). However, we have used intraoperative microwave ablation, named microwave coagulo-necrotic therapy (MCN) as part of our strategy for the treatment of HCCs for more than 15 years. Here we describe the treatment outcomes achieved at our institution as a high-volume center for microwave ablation.MethodsBetween July 1994 and December 2010, 719 consecutive patients received MCN as their initial therapy for HCC (mean tumor size 26.9 mm, mean number of lesions 2.51) at our institute. The therapeutic survival effect, local tumor progression, and overall recurrence were prospectively evaluated and statistically analyzed.ResultsThe 1-, 3-, 5-, 7-, and 10-year overall survival rates of all 719 patients were 97.7, 79.8, 62.1, 45.3, and 34.1 %, respectively. Thirty percent of the patients had Child–Pugh class B cirrhosis and the 5-year survival rate of these patients was 46.6 %. The 5-year survival of patients with ≥4 lesions (n = 168) was 49.6 % and that of patients meeting the Milan criteria (n = 470) was 70.9 %. The 1-, 3-, 5-, 7-, and 10-year overall survival rates for 390 patients treated with MCN who had ≤3 lesions with diameter ≤3 cm were 97.9, 85.1, 70.0, 57.1, and 43.0 %. No significant differences were found between the overall survival rates after MCN and the overall survival rates in 34 patients treated with HRx during the same period at our institute and under the same (P = 0.3592), nor were there any differences in disease-free survival (P = 0.3496) and local recurrence rates between the MCN and HRx groups (P = 0.5926).ConclusionMCN is effective for the locoregional control of HCC, with results comparable to those of HRx. MCN should be considered as one of the first-choice treatments for HCC, even for patients with poor liver function or multiple lesions.

Case Reports on Cancer Therapies: The Urgent Need to Improve the Reporting Quality

Current guidelines for certain cancer therapies mainly provide recommendations for therapy options treating the primary tumors. However, first-choice treatments for advanced or metastasizing tumors are described only rarely if at all. In such cases, one or more individual treatment options are chosen by the physician depending on the medical need of the patient and considering the acceptance of this treatment by the patient. Often, well-known drugs are selected with a different dosing than is indicated in the drug information leaflet. In other cases, drugs not yet approved for this particular type of cancer are used off label or certain therapies are used in combination or consecutively in a manner not reported before. With the increasing research on personalized medicine, particularly in treating cancer, case reports on innovative drug therapies or newly developed surgical interventions may provide extremely valuable information in instances where randomized controlled trials may not be feasible (eg, because of a low patient number or ethical considerations).

Meta‐analysis: nonsteroidal anti‐inflammatory drugs in biliary colic

Biliary colic is a common manifestation of cholelithiasis, developing in about one-third of patients. Even if nonsteroid anti-inflammatory drugs (NSAIDs) have widely been used to relieve biliary pain, there is a lack of systematic review of treatments on this issue. To assess the potential benefits in terms of both pain control and reduction of complications, and the potential harms of NSAIDs in patients with biliary colic. Data from randomised clinical trials (RCTs) comparing NSAIDs with no treatment, placebo or other drugs in patients with biliary colic, were collected from Medline and Embase. The outcome measures were expressed as odds ratio and relative risk and then pooled using fixed or random-effect models. Eleven RCTs involving 1076 subjects (268 men, 808 women; 18-86 years), including 442 controls were analysed. In comparison with placebo, NSAIDs led to a significantly higher proportion of patients with complete pain relief (RR 3.77, 95%CI 1.65-8.61; I(2) : 73%) and a significantly lower rate of complications (RR 0.53, 95% CI 0.31-0.89; I(2) : 35%). In comparison with other drugs, NSAIDs were more efficacious in controlling pain than spasmolytics (RR 1.47, 95% CI 1.03-2.10; I(2) : 55%); there was no difference between NSAIDs and opioids (RR 1.05, 95% CI 0.82-1.33; I(2) : 74%). In patients with biliary colic NSAIDs are the first-choice treatments as they control pain with the same efficacy of opioids and significantly reduce the proportion of patients with severe complications. However, the lack of high-quality RCTs and the presence of consistent heterogeneity among studies may partially flaw these results.

The adherence of GPs to guidelines for the diagnosis and treatment of lower urinary tract infections in women is poor

To assess the adherence of GPs to evidence-based guidelines for the diagnosis and management of lower urinary tract infection (UTI) in women. A cross-sectional study was performed from March to July 2009 in primary care offices. Physicians consecutively registered the first six UTI attended during an 8-week period. Age, days with symptoms, episode of infection, associated morbidity, signs and symptoms, diagnostic procedures performed, antibiotic prescription, allergies and referral or not were registered. The type of antibiotic course (short or long) and first-choice treatments were also taken into account. Of 176 physicians invited to participate, 110 (62.5%) included 658 women with lower UTI. Urine dipstick was performed in 550 cases (83.6%) and urine culture was requested in 235 women (35.7%), with criteria for culture in 49.6% and without criteria in 32.8%. Antibiotic treatment was administered in 634 cases (96.4%). Short courses were given to 385 women (60.7%) and 75 of those with complicated UTI were treated with long courses (66.4%). First-choice antibiotics were administered as empiric treatment in only 92 women with uncomplicated UTI (17.7%). These results highlight the poor adherence of GPs to the current recommendations of clinical practice guidelines with a high number of inappropriate urine cultures requested and a low utilization of first-choice antibiotics.

Strategies for the treatment of hepatocellular carcinoma: HR and MCN

Purpose: To evaluate the prognostic impact of microwave coagulo-necrotic therapy (MCN) versus hepatic resection (HR) on patient survival after treatment for hepatocellular carcinoma (HCC). Materials & methods: Between July 1994 and December 2006, 1567 patients underwent hepatic surgery at our institute. Of these, 613 who received their initial therapy for HCC were analyzed. MCN was performed in 456 patients, hepatic resection (HR) in 111, and HR + MCN in 42. The remaining 4 patients were treated with laparotomic ethanol injection. We analyzed the therapeutic survival, local tumor progression and overall recurrence rates.Results: The cumulative survival rates for patients treated with MCN (mean tumor size, 28.2 mm; mean number of lesions, 2.62) were 97.5, 77.6, 58.7, and 37.3%, at 1, 3, 5 and 10 years, respectively. The 5-year survival rate was 58.7% after MCN and 56.4% after HR (p = 0.9480). The cumulative survival rates for 238 patients treated with MCN who had 3 or fewer lesions of ≤3 cm in diameter were 98.1, 85.2, 70.3 and 43.5% at 1, 3, 5 and 10 years,. There were no significant differences in cumulative survival (p = 0.7358), disease-free survival or local recurrence rates between patients treated with MCN versus those treated with HR. Of the 613 patients receiving their initial treatment, 319 had recurrences after an average of 639.6 days after operation; 61 of these had 4 or more recurrent lesions, while 204 patients could be treated with MCN (mean tumor size, 23.7 mm; mean number of lesions, 3.08). Conclusion: Our findings suggest that MCN is an effective treatment for loco-regional control of HCC and is comparable to HR. MCN is particularly suitable for the treatment of patients presenting with multiple tumors or tumor recurrence. We recommend that HR and MCN should both be considered as first-choice treatments for HCC.

Antenatal Depression: Navigating the Treatment Dilemmas

“Ms. A” was a 35-year-old married Caucasian health care professional with a history of recurrent major depressive disorder that responded well to treatment with a selective serotonin reuptake inhibitor (SSRI). She discontinued her antidepressant prior to conception for a planned pregnancy because she did not want to expose her baby to medication. She soon relapsed, and by the first trimester of her pregnancy, she was in a major depressive episode. Her symptoms included anhedonia, tearfulness, irritability, insomnia, and diminished appetite. She presented for participation in an open-label pilot trial of omega-3 fatty acids for antenatal major depressive disorder (1). At intake, after hearing the risks and benefits of available treatment options, Ms. A declined antidepressant medication and a referral for psychotherapy and consented to participate in the study of omega-3 fatty acids, which she started at 16 weeks’ gestation. She was assessed every 2 weeks throughout pregnancy. At 8 weeks she had not responded to omega-3 fatty acids and was again presented with other treatment options, including medication and psychotherapy. She again declined these treatments and continued to do so throughout the remainder of her pregnancy. She was concerned about the safety of medications in pregnancy and believed that taking medication would make her a bad mother. She also declined referral for psychotherapy, stating that she was “too busy.”

Social anxiety disorders

A main feature of social anxiety disorders is the fear or avoidance of social situations in which one is the center of attention and fears criticism or negative judgement. According to current diagnostic systems, three types of these disorders can be classified: specific social phobia, generalised social phobia, and avoidant personality disorder. Social anxiety disorders are prevalent mental disorders (lifetime prevalence up to 13%). Other mental disorders often appear together with them. Following the criteria for evidence-based medicine, psychotherapeutic and pharmacologic interventions are described. Regarding psychotherapeutic approaches, the best results have been seen with cognitive-behavioural methods. Among psychopharmacologic treatments, selective serotonin reuptake inhibitors and the selective noradrenalin reuptake inhibitor Venlafaxin are the first-choice treatments.

Assessment of antibiotic prescription in acute urinary tract infections in adults

To assess the appropriateness of antibiotic prescription for urinary tract infections in several hospital emergency services and to evaluate the variability of antibiotic prescription among these services. A cross-sectional study was carried out in the emergency services of 10 hospitals from different Spanish regions. The sample was composed of patients diagnosed with acute urinary infection, aged> or =14 years. A Consensus Conference, held by a panel of experts, established first-choice, second-choice and inappropriate antibiotic treatments for each type of urinary tract infection, based on the available scientific evidence. All the observed prescriptions in our study were classified according to this pattern. The main variables were: type of urinary infection, antibiotic prescription, urine culture request, comorbidity and hospital admission. A sample of 3797 acute urinary tract infections was studied. Eighty-one percent were lower urinary tract infections. The most commonly used antibiotics were ciprofloxacin and amoxicillin-clavulanate. The global percentages of first-choice, alternative-choice and inappropriate antibiotic prescriptions were: 42.4% (95% CI: 40.8-43.9), 44.1 (95% CI: 42.5-45.7) and 13.6% (95% CI: 12.5-14.7), respectively. We observed a significant variability in appropriateness of antibiotic prescriptions among the participating centres (p<0.001). Physicians at Spanish emergency rooms prescribe an excessive number of second-choice antibiotics for urinary tract infection treatment. There exists a high variability in antibiotic prescription among hospitals from different regions.

Pharmacological management of postherpetic neuralgia.

Postherpetic neuralgia, which occurs most typically in older persons, is one of the most common and serious complications of herpes zoster (or shingles). It is a chronic neuropathic pain syndrome and remains one of the most difficult pain disorders to treat. Known beneficial agents include antidepressants, antiepileptic drugs, opioid analgesics, local anaesthetics, capsaicin and other, less applied, modalities. Although monotherapy is commonly applied, no single best treatment for postherpetic neuralgia has been identified; nevertheless, gabapentin (antiepileptic) and transdermal lidocaine (anaesthetic) are often used as the first-choice treatments. Recent research has shed light on possible pain mechanisms as well as new avenues of treatment, which are discussed in the article. For patients with pain that is not adequately controlled, individualised treatment plans must be pursued. It is critical to recognise that postherpetic neuralgia, while difficult to manage, can be a treatable neuropathic pain syndrome.

Perspectives on the use of anticonvulsants in the treatment of bipolar disorder.

The authors reviewed the available literature on the efficacy of carbamazepine, valproate, and other newer anticonvulsants for the treatment of bipolar disorder. A comprehensive Medline search was conducted, and all uncontrolled and controlled reports on anticonvulsants used for the treatment of bipolar patients were identified. Carbamazepine and valproate have been shown to be effective in the acute treatment of bipolar disorder, and are the first-choice treatments for lithium-refractory patients. While the efficacy of these drugs in the acute treatment of the illness has been satisfactorily documented, double-blind randomized studies are still necessary to evaluate the long-term effectiveness of both anticonvulsants. Patients on a mixed state and rapid cyclers seem to respond better to valproate and carbamazepine than to lithium. The preliminary data evaluating the efficacy of newer anticonvulsants, such as gabapentin, lamotrigine, and topiramate in bipolar patients is still limited, but some of the available findings are promising, and these new agents may represent appropriate third choices for refractory bipolar individuals. Double-blind, controlled studies with the newer anticonvulsants are still largely unavailable, and it will be necessary to evaluate their acute and prophylactic mood-stabilizing effects. The prospects for future therapeutic advances in this area are also discussed.