Optimal Treatment Regimen For Patients Research Articles

The Evolution of Systemic Therapy in Metastatic Renal Cell Carcinoma

The treatment landscape for renal cell carcinoma (RCC) is a dynamic process that has seen considerable change in recent years. We have seen a rebirth of original breakthroughs with immune checkpoint inhibitors showing promise in patients with treatment-refractory disease. The optimal sequencing of treatments and incorporation of novel therapeutics are actively being investigated and have yet to be determined. The clinical challenges of this evolving treatment paradigm can be attributed to cost considerations, toxicity, and defining endpoints in the management of advanced RCC. As novel therapeutics emerge, finding the optimal treatment regimen for patients will have an increasing focus on patient-centered outcomes and improvement in quality of life in addition to improving survival.

Clinical Outcomes of Primary Palatal Surgery in Children with Nonsyndromic Cleft Palate with and without Lip.

This study presents clinical outcomes of primary cleft palate surgery, including rate of oronasal fistula development, rate of velopharyngeal insufficiency (VPI) requiring secondary surgery, and speech outcomes. We examined the effect of cleft type on the clinical outcomes. Retrospective analysis was performed using clinical records of all patients who received a primary palatoplasty at the Cleft Palate Clinic at Seoul Asan Medical Center, South Korea, between 2007 and 2012. The study included 292 patients with nonsyndromic overt cleft palate (±cleft lip). The results revealed that the rate of oronasal fistula was 7.9% and the incidence of VPI based on the rate of secondary palatal surgery was 19.2%. The results showed that 50.3% of all the patients had received speech therapy and 28.8% and 51.4% demonstrated significant hypernasality and articulatory deficits, respectively. The results of the rate of VPI and speech outcomes were significantly different in terms of cleft type. Except for the rate of oronasal fistula, patients with cleft palate generally exhibited better clinical outcomes compared to those with bilateral or unilateral cleft lip and palate. This study suggests that several factors, including cleft type, should be identified and comprehensively considered to establish an optimal treatment regimen for patients with cleft palate.

Management of Cerebral Brain Metastasis

Brain metastasis is associated with a poor overall prognosis, but combination therapies have emerged that may prevent recurrence or serve as palliative therapies. There is a wide range of treatment options for those with 1–3 intracranial metastases and stable disease, including combinations of surgery, whole brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). Those with few, small metastases may be served well by SRS and adjuvant WBRT, whereas those with larger metastases that are amenable to resection may be treated with surgical excision and adjuvant WBRT. Whole brain radiation alone is reserved for individuals with greater than three brain metastases or unstable disease. A number of studies have been conducted to clarify the optimal treatment regimen for patients with varying intracranial disease. This review aims to synthesize the most current findings pertaining to the neurosurgical treatment of brain metastases.

Pharmacotherapy for allergic rhinitis.

Pharmacotherapy for allergic rhinitis is a mainstay of treatment for patients with mild to severe nasal allergy symptoms. A wide array of medical treatment options is available for both episodic relief and prevention of symptoms. Treatment regimens can be tailored to individual patients based on nasal symptoms, severity, and associated atopic disorders. The purposes of this review are to identify available pharmacotherapies for allergic rhinitis, to discuss the benefits and limitations of each treatment option, and to help guide practitioners in providing optimal medical treatment for patients with allergic rhinitis. A comprehensive review of pharmacotherapies for allergic rhinitis was performed using a PubMed search. Secondary sources within indexed studies were also compiled to review current medication options for patients with allergic rhinitis. The benefits and limitations of each class of allergy medication were reviewed to provide information on selecting the optimal treatment regimen for patients with allergic rhinitis. Pharmacotherapies for allergic rhinitis that are currently used in clinical practice include antihistamines, corticosteroids, leukotriene modifiers, mast cell stabilizers, expectorants, and decongestants. Symptoms of nasal congestion, itching, sneezing, and rhinorrhea can be targeted with specific therapies that modulate the acute-phase or late-phase allergic reactions. Associated atopic disorders, including conjunctivitis and asthma, can help guide medication selection. Pharmacotherapies for allergic rhinitis offer numerous options that are safe, effective, and readily available to target specific nasal symptoms. Symptom-based selection of allergy medications can result in optimal treatment for patients with allergic rhinitis.

A systematic review and meta-analysis of gastric cancer treatment in patients with positive peritoneal cytology.

Gastric cancer patients with positive peritoneal cytology as the only marker of metastatic disease have poor prognoses. There is no universal consensus on the most appropriate treatment regimen for this particular patient group. We reviewed and analyzed published data to determine the optimal treatment regimen for patients with peritoneal cytology-positive gastric adenocarcinomas. Six electronic databases were explored [PubMed, Cochrane (Systematic Reviews and Controlled Trials), PROSPERO, DARE, and EMBASE]. The primary outcome was overall survival with secondary outcomes including patterns of recurrence and treatment-related morbidity. Six studies were included for data extraction. There was no significant heterogeneity between studies. The use of S1 monotherapy was associated with a significant survival benefit (HR 0.48; 95% CI 0.32-0.70; p = 0.0002). Intraoperative intraperitoneal chemotherapy (IIPC) with adjuvant chemotherapy showed a trend toward improvement in overall survival (HR 0.70; 9 % CI 0.47-1.04; p = 0.08). A recent randomized controlled trial examining extensive intraperitoneal lavage (EIPL) with IIPC showed a significant improvement in overall survival (5-year overall survival, 43.8% for EIPL-IPC group compared with 4.6% for IPC group). However, these promising results need to be validated in larger prospective randomized trials.

Novel coagulation factor concentrates: Issues relating to their clinical implementation and pharmacokinetic assessment for optimal prophylaxis in haemophilia patients

Prophylaxis is considered the optimal treatment regimen for patients with severe haemophilia, and may be especially important in the prevention of joint disease. Novel coagulation factor concentrates with prolonged half-lives promise to improve patient treatment by enabling prophylaxis with less frequent dosing. With the call to individualize therapy in haemophilia, there is growing awareness of the need to use pharmacokinetic (PK) assessments to tailor prophylaxis. However, for new factor concentrates, it is not yet known which PK values will be most informative for optimizing prophylaxis. This topic was explored at the Eighth Zurich Haemophilia Forum. On the basis of our clinical experience and a discussion of the literature, we report key issues relating to the PK assessment of new coagulation factors and include suggestions on the implementation of PK data to optimize therapy. As both inter- and intra-individual variability in factor half-life have been reported, we suggest that frequent PK assessments should be conducted. However, to diminish the burden of more frequent sampling, sparser sampling strategies and the use of population modelling should be considered. Guidelines on how to assay new factor concentrates, and which PK parameters should be measured, are needed. Concerns were raised regarding the possibility of breakthrough bleeding, and current thinking on how to prevent breakthrough bleeding may no longer be appropriate. Finally, as treatment adherence may be more important to ensure that a therapeutic level of a new coagulation factor concentrate is maintained, behavioural techniques could be implemented to help to improve treatment adherence.

Heartache and heartbreak—the link between depression and cardiovascular disease

The close, bidirectional relationship between depression and cardiovascular disease is well established. Major depression is associated with an increased risk of coronary artery disease and acute cardiovascular sequelae, such as myocardial infarction, congestive heart failure, and isolated systolic hypertension. Morbidity and mortality in patients with cardiovascular disease and depression are significantly higher than in patients with cardiovascular disease who are not depressed. Various pathophysiological mechanisms might underlie the risk of cardiovascular disease in patients with depression: increased inflammation; increased susceptibility to blood clotting (owing to alterations in multiple steps of the clotting cascade, including platelet activation and aggregation); oxidative stress; subclinical hypothyroidism; hyperactivity of the sympatho-adrenomedullary system and the hypothalamic-pituitary-adrenal axis; reductions in numbers of circulating endothelial progenitor cells and associated arterial repair processes; decreased heart rate variability; and the presence of genetic factors. Early identification of patients with depression who are at risk of cardiovascular disease, as well as prevention and appropriate treatment of cardiovascular disease in these patients, is an important and attainable goal. However, adequately powered studies are required to determine the optimal treatment regimen for patients with both depression and cardiovascular disorders.

A phase II trial of erlotinib in patients with EGFR wild-type advanced non-small-cell lung cancer

There is as yet no optimal treatment regimen for patients with epidermal growth factor receptor (EGFR) gene wild-type non-small-cell lung cancer (NSCLC) that has progressed despite cytotoxic chemotherapy. This trial was performed to evaluate the efficacy and toxicity of erlotinib, a tyrosine kinase inhibitor of EGFR, in Japanese patients with EGFR wild-type tumors. Patients with stage III/IV or postoperative recurrence of NSCLC whose tumors have wild-type EGFR were eligible. Erlotinib (150 mg/day) was administered until disease progression or unacceptable toxicity occurred. The primary end point was disease control rate (DCR). Thirty-one patients (23 men and 8 women; median age, 71 years; range, 31-89) were enrolled between January 2008 and June 2011. Twenty-one had adenocarcinoma, nine had squamous cell carcinoma, and one had large cell carcinoma. Ten, nine, eight, and four patients showed performance status 0, 1, 2, and 3, respectively. Erlotinib was administered following the median 3.1 regimens of cytotoxic chemotherapies. One patient achieved complete response, four showed partial response, and eight had stable disease. Thus, response rate was 17.2%, and DCR was 44.8%. Skin rash was the most common side effect (80.6%). Two patients developed interstitial lung disease. Nevertheless, all of these events were reversible, and there were no treatment-related deaths. The median progression-free survival and survival times were 2.1 and 7.7 months, respectively. Erlotinib might be an alternative option for patients resistant to cytotoxic chemotherapy even in those with EGFR wild-type NSCLC.

Assessment of disease activity and treatment outcomes in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease which primarily causes a symmetric polyarthritis. Clinical manifestations of the disease include joint pain, stiffness, and swelling. Unless treated, this debilitating disease can progress into long-term disability. Medications for RA include synthetic disease-modifying antirheumatic drugs (DMARDs) and biologic agents. The rapid expansion of new RA drugs into the market has led to a need for health care practitioners to understand the effectiveness of each medication and the indications of use including when to initiate and stop therapies. Clinical assessment tools, including biomarkers used to indicate RA and the progression of the disease, have been proven effective for making a diagnosis and determining effective treatment regimens. Disease activity scales are also useful for guiding diagnoses and monitoring patients to assess treatment effectiveness. To review the various clinical assessment tools that have been designed to confirm an early diagnosis of RA, measure disease progression, and assist in determining the most optimal treatment regimens for patients with RA. The diagnosis of RA combines the patient history of joint pain and stiffness and the physical examination documentation of symmetric polyarticular joint swelling (synovitis). Laboratory tests including radiographs and blood tests for biomarkers can provide useful information to confirm the diagnosis of RA. Various autoantibodies have been reported in the blood of RA patients, but only the rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) have been incorporated as diagnostic measures in routine clinical practice. Monitoring and assessment instruments for RA include the Disease Activity Score 28 (DAS28), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Although these clinical assessment tools have limitations, health care providers can use them as measures of disease progression and to assist in planning treatment strategies to modify disease activity and improve the quality of life for the patient.

Outcomes for patients with anaplastic astrocytomas treated with radiation and temozolomide (TMZ) and maintenance TMZ.

e12511 Background: The optimal treatment regimen for patients with anaplastic astrocytomas (AAs) is not defined. Patients are treated at diagnosis with Radiation Therapy, Chemotherapy or similar to GBM with chemoradiation. Studies are underway to determine the optimal treatment for AA. We did a retrospective review of our patients with AA treated with the Stupp regimen to assess TTP and OS. Methods: We reviewed our database for patients diagnosed with an anaplastic glioma between 8/1/2003-6/15/2010 who were treated with chemoradiation followed by maintenance chemotherapy. Inclusion criteria were age > 18 yrs, newly diagnosed with no prior treatment and sufficient data/follow up. Those without sufficient data were excluded. Data was analyzed to determine PFS, TTP and OS. Results: There were 28 pts identified (14 M and 14 W) with a median age of 45 yrs (24-76) and KPS of 90 (70-100). All patients were treated with chemoradiation, 2 received arsenic trioxide during RT and 1 received bevacizumab during the maintenance phase of TMZ. Pathology was 23 AA, 3 AOA, and 2 with anaplastic glioneuronal tumor. Resection was as follows: GTR 25%, STR 57% and Biopsy 18%. Median # of cycles was 10.5 (0-24). The median time to progression was 18. 5 m and PFS-6, 12 and 24 was 96.1%, 73.1%, and 51.6%. Median OS was 34.4 m with OS at 12, 24 and 60 m of 92%, 63% and 53.2%. Conclusions: There is no standard treatment for AA’s. Treating with the Stupp regimen is one option but how it compares to other regimens is unclear. Our data appear comparable to that of NOA-04 where pts were initially treated with chemotherapy or RT at diagnosis.

Evidence-based pharmacotherapy for cerebral vasospasm

Introduction: The vast amount of literature on the pharmaceutical treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage remains daunting. Optimal treatment regimens for patients can be obscured by studies not statistically powered to draw evidenced-based conclusions.Methods: In this chapter, we reviewed the English literature using the National Library of Medicine for studies regarding pharmacotherapies for the treatment of cerebral vasospasm. These studies were then categorized according to the US Preventative Services Task Force ranking system for evidence based medicine and reviewed each pharmacotherapy for its efficacy in the treatment of cerebral vasospasm.Results: Nimodipine (Nimotop), HMG Co-A reductase inhibitor (statins) and enoxaparin (Lovenox) were the only drugs with level-1 evidence available for the treatment of vasospasm from aneurysmal subarachnoid hemorrhage as defined by the US Preventative Services Task Force.Conclusion: As the understanding of the pathophysiological mechanisms of vasospasm after aneurysmal subarachnoid hemorrhage evolves in the basic science laboratory, novel medications are being trialed in humans. However, significantly more work must be carried out in this area before we have an effective medical treatment that can prevent or reverse the devastating events of cerebral vasospasm.

How can we identify better those with recurrent hepatitis C who will respond to therapy? What are the optimal treatment regimen and treatment duration?

1. Treatment responses are lower in immune compromised patients such as those with hepatitis C virus (HCV) disease following liver transplantation than in immune competent patients with HCV disease. 2. Predictors of nonresponse, extrapolated from studies of immune competent patients, are overly represented in liver transplantation patients (high levels of HCV RNA and genotype 1 infection). 3. Tolerability of peginterferon plus ribavirin therapy is lower in transplant patients than in immune competent patients with HCV disease, in part because of a baseline renal insufficiency that increases the likelihood of ribavirin-associated anemia. 4. Clear recommendations regarding optimal treatment regimens for patients with posttransplantation HCV disease are problematic since there are few prospective, randomized, controlled trials that evaluated different treatment regimens. 5. If treatment is undertaken, baseline creatinine clearance should be measured and patients should be started on a dose of ribavirin of 400mg bid, or lower if renal function is impaired. 6. Tolerated peginterferon doses may be somewhat lower than for the standard immune competent patients. It is likely that lower doses will not greatly compromise response (1.0 ug/kg/week for peginterferon alfa 2b and 135 ug/week for peginterferon alfa 2a). 7. Optimal treatment duration is unknown. In patients with an on-treatment response, at least 12 months of therapy is recommended. 8. More potent drugs with fewer toxicities are needed for patients with progressive posttransplantation liver disease.

Treatment of Isoniazid-Resistant Tuberculosis in Southeastern Texas

Isoniazid-resistant tuberculosis (INHr-TB) can be treated successfully with several treatment regimens. However, the optimal regimen and duration are unclear. To analyze the efficacy of treatment regimens used for INHr-TB in the southeastern Texas region. Retrospective cohort study. Health-care facilities reporting tuberculosis (TB) patients in the Houston and Tyler areas. All patients reported to have INHr-TB from 1991 to 1998. Exclusion criteria included poor compliance, additional first-line drug-resistance (except aminoglycosides), and death before completion of 1 month of treatment. Main treatment outcomes were treatment failure, relapse, and TB-related death. Fifty-three of 83 patients were included in the study; aminoglycoside resistance coexisted in 37.5% of isolates. Seven types of treatment regimens were identified. Eighteen patients (34%) received rifampin, pyrazinamide, and ethambutol thrice weekly for 9 months. Four patients (7.5%) had a total effective treatment duration of < 9 months. Thirty patients (56.6%) and 16 patients (30.2%) received thrice-daily and daily treatment regimens, respectively. Forty-nine patients achieved sputum conversion. Treatment failure and death occurred in one patient (1.9%). Three patients (5.7%) experienced relapses. There was a significant difference in total effective treatment time between patients with and without relapses (8.3 +/- 1.1 months vs 11.1 +/- 2.1 months; p < 0.02). Twice-weekly treatment regimens were associated with relapse (p = 0.05). Several treatment regimens were prescribed for INHr-TB in southeastern Texas. INHr-TB treatment durations were > 7 months, and treatment regimen efficacy was adequate. Twice-weekly treatment was associated with relapse, whereas thrice-weekly and daily treatments performed similarly. A prospective study with different treatment durations is needed to determine the optimal treatment regimen for patients with INHr-TB.

A novel phenotypic drug susceptibility assay for human immunodeficiency virus type 1.

Although combination antiretroviral therapy has resulted in a considerable improvement in the treatment of human immunodeficiency virus (HIV) type 1 (HIV-1) infection, the emergence of resistant virus is a significant obstacle to the effective management of HIV infection and AIDS. We have developed a novel phenotypic drug susceptibility assay that may be useful in guiding therapy and improving long-term suppression of HIV replication. Susceptibility to protease (PR) and reverse transcriptase (RT) inhibitors is measured by using resistance test vectors (RTVs) that contain a luciferase indicator gene and PR and RT sequences derived from HIV-1 in patient plasma. Cells are transfected with RTV DNA, resulting in the production of virus particles that are used to infect target cells. Since RTVs are replication defective, luciferase activity is measured following a single round of replication. The assay has been automated to increase throughput and is completed in 8 to 10 days. Test results may be useful in facilitating the selection of optimal treatment regimens for patients who have failed prior therapy or drug-naive patients infected with drug-resistant virus. In addition, the assay can be used to evaluate candidate drugs and assist in the development of new drugs that are active against resistant strains of HIV-1.

Achilles Tendon Disorders

In conclusion, the sports medicine specialist is able to use a spectrum of diagnostic, surgical, and rehabilitation techniques to identify etiologic factors and to choose optimal treatment regimens for patients with Achilles tendinitis or traumatic rupture. Correction of pathomechanic factors, anatomic restoration, and aggressive postoperative rehabilitation allows an early return to sport without significant loss of strength or mobility.

Beta-lactams in sexually transmitted diseases: rationale for selection and dosing regimens.

A review is given of the selection and rational of optimal treatment regimens for patients with sexually transmitted pathogens, e.g. in cases of gonorrhea, chlamydial infections, chancroid, syphilis, pelvic inflammatory diseases and ophthalmia neonatorum. The scientific basis for the selection of a beta-lactam agent is discussed, including dose, MIC, the critical serum level and maintenance interval, and the duration of therapy. Except in the case of penicillinase-producing Neiserria gonorrhoeae, penicillin remained until recently the most effective agent available against many sexually transmitted diseases. However, ceftriaxone, a new third-generation cephalosporin, has been shown to have a long half-life (8 h) and excellent in vitro efficacy against Neiserria gonorrhoeae (including penicillinase-producing strains) and Haemophilis ducreyi. In view of its exceptional clinical efficacy against both gonorrhea and chancroid, clinical studies of its efficacy against other sexually transmitted diseases appear warranted.