Efficacy Of Prolonged Treatment Research Articles

542 Prolonged VTE Prophylaxis Post Abdominal Cancer Surgery: Is It Necessary?

Abstract Aim NICE guidance currently recommends extending venous thromboembolism (VTE) prophylaxis to 28 days for patients who have undergone major cancer surgery in the abdomen. Literature highlights controversy around the efficacy of prolonged treatment preventing deep vein thrombosis (DVT) and pulmonary embolism (PE) and potential areas for improvement. Method Retrospective study of urology and colorectal cancer patients undergoing surgery between October 2020 and September 2022. Electronic patient notes were used to determine adherence to guideline and prevalence of PE and/or DVT in post-operative patients. Comparison was made between both cohorts. Results Patient cohort n = 802, colorectal n = 345 and urology n = 457. Average age 66.6±10.4. M:F ratio = 543:258. Colorectal cohort 20.9%(n = 71) received extended prophylaxis, 79.1%(n = 269) did not, of which 19.7%(n = 53) prophylaxis was contraindicated. 5 excluded as died or an inpatient. Urology cohort 53.4%(n = 244) received extended prophylaxis, 46.6%(n = 213) did not, of which 28.2%(n = 60) prophylaxis was contraindicated. Overall, 39.5%(n = 315) received extended prophylaxis vs 60.5%(n = 482) did not. n = 4 developed PE/DVT. Of which, n = 1 on extended prophylaxis and n = 3 not, Chi-squared 0.35, P value = 0.55. Conclusions Very few patients developed symptomatic PE and/or DVT despite a significant proportion of patients not receiving extended prophylaxis. No significant difference in symptomatic PE or DVT in patients with extended prophylaxis vs patients without. Prolonged administration of low molecular weight heparin as anticoagulation has repercussions such as cost and patients’ ability to self-administer which may subsequently require community support or a longer hospital stay. Therefore, a more targeted approach to extended VTE should be explored.

PINK1-Mediated Mitophagy Promotes Oxidative Phosphorylation and Redox Homeostasis to Induce Drug-Tolerant Persister Cancer Cells.

DTP cancer cells that cause relapse after anticancer therapy critically depend on PINK1-mediated mitophagy and metabolic reprogramming, providing a therapeutic opportunity to eradicate persister cells to prolong treatment efficacy.

Safety and efficacy of propranolol for treatment of familial cerebral cavernous malformations (Treat_CCM): a randomised, open-label, blinded-endpoint, phase 2 pilot trial

Observations in people with cerebral cavernous malformations, and in preclinical models of this disorder, suggest that the β-blocker propranolol might reduce the risk of intracerebral haemorrhage. We aimed to evaluate the safety and efficacy of prolonged treatment with propranolol to reduce the incidence of symptomatic intracerebral haemorrhage or focal neurological deficit in people with familial cerebral cavernous malformations. We conducted a randomised, open-label, blinded-endpoint, phase 2 pilot trial (Treat_CCM) at six national reference centres for rare diseases in Italy. People aged 18 years or older with symptomatic familial cerebral cavernous malformation were eligible for enrolment. Participants were randomly assigned (2:1) to receive either oral propranolol (20-320 mg daily) plus standard care (intervention group), or standard care alone (control group), for 24 months. Participants, caregivers, and investigators were aware of treatment group assignment. Participants had clinical assessments and 3 T brain MRI at baseline and at 12 and 24 months. The primary outcome was new occurrence of symptomatic intracerebral haemorrhage or focal neurological deficit attributable to cerebral cavernous malformation over 24 months. Outcome assessors were masked to treatment group assignment. The primary analysis was done in the intention-to-treat population. Because of the pilot study design, we chose a one-sided 80% CI, which could either exclude a clinically meaningful effect or show a signal of efficacy. This trial is registered with EudraCT, 2017-003595-30, and ClinicalTrials.gov, NCT03589014, and is closed to recruitment. Between April 11, 2018, and Dec 5, 2019, 95 people were assessed for eligibility and 83 were enrolled, of whom 57 were assigned to the propranolol plus standard care group and 26 to the standard care alone group. The mean age of participants was 46 years (SD 15); 48 (58%) were female and 35 (42%) were male. The incidence of symptomatic intracerebral haemorrhage or focal neurological deficit was 1·7 (95% CI 1·4-2·0) cases per 100 person-years (two [4%] of 57 participants) in the propranolol plus standard care group and 3·9 (3·1-4·7) per 100 person-years (two [8%] of 26) in the standard care alone group (univariable hazard ratio [HR] 0·43, 80% CI 0·18-0·98). The univariable HR showed a signal of efficacy, according to predefined criteria. The incidence of hospitalisation did not differ between groups (8·2 cases [95% CI 7·5-8·9] per 100 person-years in the propranolol plus standard care group vs 8·2 [95% CI 7·1-9·3] per 100 person-years in the standard care alone group). One participant in the standard care alone group died of sepsis. Three participants in the propranolol plus standard care group discontinued propranolol due to side-effects (two reported hypotension and one reported weakness). Propranolol was safe and well tolerated in this population. Propranolol might be beneficial for reducing the incidence of clinical events in people with symptomatic familial cerebral cavernous malformations, although this trial was not designed to be adequately powered to investigate efficacy. A definitive phase 3 trial of propranolol in people with symptomatic familial cerebral cavernous malformations is justified. Italian Medicines Agency, Associazione Italiana per la Ricerca sul Cancro, Swedish Science Council, Knut and Alice Wallenberg Foundation, CARIPLO Foundation, Italian Ministry of Health.

Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer.

In the absence of curative therapies, treatment of metastatic castrate-resistant prostate cancer (mCRPC) using currently available drugs can be improved by integrating evolutionary principles that govern proliferation of resistant subpopulations into current treatment protocols. Here we develop what is coined as an ‘evolutionary stable therapy’, within the context of the mathematical model that has been used to inform the first adaptive therapy clinical trial of mCRPC. The objective of this therapy is to maintain a stable polymorphic tumor heterogeneity of sensitive and resistant cells to therapy in order to prolong treatment efficacy and progression free survival. Optimal control analysis shows that an increasing dose titration protocol, a very common clinical dosing process, can achieve tumor stabilization for a wide range of potential initial tumor compositions and volumes. Furthermore, larger tumor volumes may counter intuitively be more likely to be stabilized if sensitive cells dominate the tumor composition at time of initial treatment, suggesting a delay of initial treatment could prove beneficial. While it remains uncertain if metastatic disease in humans has the properties that allow it to be truly stabilized, the benefits of a dose titration protocol warrant additional pre-clinical and clinical investigations.

The effect of low level laser therapy for pain in major muscles controlling two joints.

Chronic pain is a significant health care problem which is often encountered in medical institute out-patient clinics . In previous studies we have reported on the benefits of low level laser therapy (LLLT) for chronic musculoskeletal pain patients. The present study is a report on the effects of LLLT in patients with pain in major muscles which govern the motion of two joints (2-joint muscles). Over the past 5 years, 19 subjects visited our out-patient clinic with complaints of pain in 2-joint muscles (biceps brachii muscle or gastrocnemius muscle). They were treated with LLLT using a 1000 mW semi-conductor laser device delivering 20.1 J/cm2 per point at 830 nm in continuous wave. Four shots were given per session (1 treatment) twice a week for 2 months (total of 16 treatments). A treatment approach modified from the methods of Shiroto and Ohshiro, was used, and the efficacy of LLLT for pain attenuation in the affected muscle was determined. After the end of the treatment regimen, excellent and good improvement was observed in 16 patients out of 19. Discussions with the patients revealed that it was important for them to learn how to modify their everyday life to avoid posture and activities of daily life that could cause them pain in the 2-joint muscles, in order to enjoy continuous benefits from the treatment. The present study demonstrated that LLLT was an effective form of treatment for pain in the biceps brachii and gastrocnemius muscles. To maximize and prolong treatment efficacy, advice should be given to patients to avoid adopting any posture and activities of daily living which would cause pain in these specific muscles.

Efficacy of Prolonged Treatment With Pegylated Interferon (Peg-IFN) and Ribavirin in Thalassemic Patients With Hepatitis C Who Relapsed After Previous Peg-IFN-Based Therapy.

Background:Most thalassemic patients with chronic hepatitis C virus (HCV) infection do not respond to therapy with pegylated interferon (Peg-IFN) plus ribavirin (RBV) due to hepatic siderosis and RBV dose reduction caused by RBV-induced anemia.Objectives:In the present study, we recruited HCV genotype 1-infected thalassemic patients who had relapsed after a 48-week treatment with Peg-IFN plus RBV in order to evaluate the efficacy of a 72-week regimen of Peg-IFN plus RBV.Patients and Methods:In this retrospective study, 23 thalassemic patients with HCV genotype 1 infection who had prior relapse after treatment with Peg-IFN and RBV for 48 weeks were consecutively enrolled in this study for evaluation of the efficacy of a 72-week treatment regimen.Results:For the 21 included cases, mean age was 29.7 years; 81% were men and 28.6% had cirrhosis. At the end of the treatment, nine (42.9%) patients had an undetectable level of HCV RNA in their sera. However, six months after treatment completion four of these patients relapsed and a sustained virological response (SVR) was found in five (23.8%) patients. Undetectable HCV RNA level at week 4 (P = 0.03) and undetectable HCV RNA level at week 12 (P < 0.01) were found to be predictors of SVR. There was an average 47.9% increase in blood transfusion during therapy and treatment was discontinued for 12 (57.1%) patients prematurely.Conclusions:The present study suggests that thalassemic patients with chronic hepatitis C genotype 1 infection who did not achieve SVR after a course of therapy with Peg-IFN and RBV may benefit from being retreated with a 72-week regimen.

Therapy of Endocrine disease: Long-term effects of recombinant human GH replacement in adults with GH deficiency: a systematic review

BackgroundThe beneficial effects of recombinant human GH (rhGH) therapy in GH deficient (GHD) adults are well-established in the short term. However, data documenting the effects during prolonged follow-up are relatively scarce.ObjectiveTo evaluate the reported effects of rhGH replacement (≥5 years) in GHD adults on biochemical and anthropometric parameters, quality of life (QoL), bone metabolism, muscle strength, serious adverse events and mortality.MethodsWe conducted a systematic literature search. Quality assessment of retrieved papers was performed using a quality assessment based on the modified STROBE statement.ResultsWe included 23 prospective studies with a rhGH treatment duration ranging from 5 to 15 years. Overall, beneficial effects were reported on QoL, body composition, lipid profile, carotid intima media thickness and bone mineral density. In contrast, the prevalence of the metabolic syndrome, glucose levels, BMI and muscle strength were not, or negatively, influenced. Most of the studies were uncontrolled, lacked the presence of a control group (of non-treated GHD patients), and reported no data on lipid-lowering and anti-diabetic medication. Overall mortality was not increased.ConclusionrhGH treatment in adult GHD patients is well-tolerated and positively affects QoL in the long term. However, the metabolic and cardiovascular effects during long-term treatment are variable. The low numbers of long-term studies and studied patients and lack of control data hamper definite statements on the efficacy of prolonged treatment. Therefore continuous monitoring of the effects of rhGH replacement to enable an adequate risk-benefit analysis that may justify prolonged, potentially life-long, treatment is advisable.

Thalidomide for improving cutaneous and pulmonary sarcoidosis in patients resistant or with contraindications to corticosteroids

BackgroundLimited data report thalidomide improves cutaneous sarcoidosis; no benefit has been reported for pulmonary localization. ObjectivesTo evaluate feasibility and efficacy of prolonged treatment with thalidomide for cutaneous sarcoidosis associated to pulmonary involvement in patients with resistance or contraindications to steroids. MethodsNineteen patients were treated with thalidomide for 24months starting with 200mg/d for first 2weeks, followed by 100mg/d for 11weeks and a maintenance dose of 100mg on alternate days for 35weeks, and a gradual scaling down until therapy interruption. Criteria of efficacy were: skin score, serum ACE levels (s-ACE), chest X-ray (CXR), lung function tests (LFTs), and diffusing lung capacity for CO (DLCO). The skin score was computed as arithmetic sum of seven score parameters (min: 0, max: 28). ResultsSkin score significantly decreased (P<0.001). Lower skin scores occurred after 3 and 6months (P<0.05). s-ACE levels decreased over time at the third month (P<0.001). CXR assessed by radiological stage significantly improved during the first 6months (P<0.001). DLCO showed a continuous trend of improvement. Minor side effects that have forced the suspension of the drug were drowsiness/sedation (74%), constipation (68%), and weight gain (53%). Deep vein thrombosis of the lower limbs occurred in one patient (who did not drop out the study). Eight patients (42%) abandoned thalidomide for axonal sensitive peripheral neuropathy (PN) between the ninth and the 24th month of treatment. ConclusionsThalidomide, long-term at mid-low doses, can be considered as an effective therapeutic alternative in chronic sarcoidosis with resistance or contraindications to steroids.

High rates of HBsAg loss and seroconversion result from prolonged course of pegasys treatment

HBsAg loss and seroconversion in patients with chronic hepatitis B leads to long-lasting good clinical outcomes. The aim of this paper was to investigate to improve the rate of HBsAg loss and seroconversion in chronic hepatitis B patients by prolonged treatment of PEG-IFNa-2a. 217 cases of HBeAg-positive or negative patients were collected from inpatient and outpatient in Beijing Ditan Hospital from May 2005 to October 2009 and subcutaneous injection of 135 ug or 180 ug PEGASYS were given once a week according to body weights. The drug doses were adjusted according to the neutrophilic granulocyte and platelet counts during treatment course. Quantitative HBV DNA test was conducted using a commercially available real-time fluorescence quantitative PCR kit. The serum HBsAg/anti-HBs and HBeAg/anti-HBe were quantitatively detected by Abbott i 2000 chemiluminescent kit before and during treatment every three months. Patients with HBsAg steadily decreased and reached serum HBsAg level below 200 IU/ml after 48 weeks of treatment would receive prolonged treatment. Patients with more than 12 weeks of treatment entered into analysis. Main efficacy of prolonged treatment was evaluated by the incidences of HBsAg loss and seroconversion. The treatment courses of the 217 patients ranged from 12.0 to 197.6 weeks with an average of 53.1+/-33.4 weeks, 118 cases took more than 48 weeks and another 89 cases less than 48 weeks. 13.4% (29/217) of patients achieved HBsAg loss or HBsAg seroconversion with treatment courses from 17.6 to 197.6 weeks (average 75.4+/-42.8 weeks). Among these 29 patients 24 (82.8%) received more than 48 weeks of treatment, but the treatment courses of HBV DNA reached undetectable level were 20.8+/-8.9 weeks. In this study, 9.5% (14/148) of HBeAg-positive patients achieved HBsAg loss or seroconversion, all of them treated more than 48 weeks, from 48 to 194 weeks, average 81.32+/-39.36 weeks. 21.7% (15/69) of HBeAg-negative patients achieved HBsAg loss or seroconversion, significantly higher than that of HBeAg-positive patients (9.5%) (x2 = 6.129, P = 0.013). The average treatment course for HBeAg-negative patients with HBsAg loss was 70.2+/-48.0 weeks, shorter than that of HBeAg-positive patients with HBsAg loss (81.3+/-39.4 weeks), but no significant difference (t = -0.522, P = 0.602) found between. Higher rate of HBsAg loss and seroconversion could be obtained by individual extended treatment courses in patients with rapid HBV DNA and HBsAg response to PEG-IFNa-2a treatment and the HBeAg-negative patients could got higher rate of HBsAg loss than HBeAg-positive patients.

Long-term treatment of relapsing Wegener's granulomatosis with 15-deoxyspergualin

To determine the safety and efficacy of prolonged treatment with 15-deoxyspergualin (DSG, gusperimus) in patients with relapsing WG. Patients with relapsing WG treated with DSG were studied. Other immunosuppressants except corticosteroids were withdrawn and DSG, 0.5 mg/kg/day, self-administered subcutaneously for up to 21 days, in 28-day cycles. The cycle was terminated early for white blood cell count <4 x 10(9)/l. The prednisolone dose was adjusted according to the clinical state. End points were disease remission, relapse, Birmingham Vasculitis Activity Score (BVAS), prednisolone dose and safety. Eleven patients, five (45%) of whom were female, received a total of 15 treatment periods with DSG. The median (range) duration of each treatment period was 6.8 (3.3-15.9) months. Ten (90.9%) patients responded in 13/15 courses after a median of 1.7 (0.7-2.7) months and six (54.5%) achieved remission after 7.7 (1.9-13.5) months. Two (18.2%) patients relapsed while continuing to receive DSG. Remission was maintained in other patients while DSG was continued. However, 7/8 relapsed after DSG withdrawal. The median BVAS fell from 10 (3-22) at baseline to 3 (0-16) at the end of each treatment period (P = 0.002). Median prednisolone doses were reduced from 20 (5-30) mg/day at baseline to 10 (5-25) mg/day at the end of each treatment period (P = 0.052). Three severe adverse events occurred in two patients. Extended treatment with DSG was effective in the majority of patients with relapsing WG and permitted prednisolone reduction. There was no unexpected toxicity associated with prolonged DSG administration.

Efficacy of prolonged treatment following combination with ribavirin and interferon for chronic hepatitis type C: A pilot study

The aim of the present study was to assess the efficacy of the prolonged interferon monotherapy following combination treatment. Seventy-six patients were enrolled. Of these, 7 were withdrawn while undergoing treatment with interferon combined with ribavirin, and 12 remained positive for HCV-RNA at the completion of the combination treatment. We studied 57 Japanese patients with chronic hepatitis C due to genotype 1b HCV of a high viral load. These patients tested negative for HCV-RNA at the completion of the combination treatment for 24 weeks. After the combination treatment, 29 patients of the prolonged treatment group successively received interferon-alpha monotherapy for 24 weeks, while 28 patients in the combination treatment alone group received no medication. The rate of a sustained virologic response (SVR) was higher in the prolonged treatment group (41%, 12/29) than in the combination treatment alone group (25%, 7/28), but not significantly. Patients who became HCV-RNA negative by 4 weeks after the start of the combination treatment showed an SVR rate of 86%. The prolonged treatment resulted in SVR in all five patients who newly became HCV-RNA negative at 12 weeks. In conclusion, the prolonged treatment was effective for patients who newly became HCV-RNA negative at 12 weeks.

Preservative-free diclofenac sodium 0.1% for vernal keratoconjunctivitis

The aim of this study is to evaluate the efficacy of prolonged treatment with preservative-free diclofenac sodium 0.1% eye drops in patients with vernal keratoconjunctivitis (VKC). A prospective open study was performed in 22 patients with VKC treated with preservative-free diclofenac sodium 0.1% eye drops. Patients used the eye drops four times daily in both eyes for 120 days. Signs (papillae, hyperaemia and corneal lesions) and symptoms (itching, redness and photophobia) of the ocular surface were graded and statistically evaluated before and after treatment by a non-parametric test (Mann-Whitney U-test). Forty per cent of the patients showed an improvement in their symptoms at the end of the treatment. Total signs and symptoms scores were significantly decreased at the end of treatment compared with the baseline values (from 6.13+/-1.45 to 0.81+/-0.90 and from 5.40+/-1.18 to 2.63+/-0.95, respectively; P<0.001). Significant decreases in conjunctival redness (P<0.001), itching (P<0.001) and photophobia (P<0.001 ) were observed at the end of treatment. Conjunctival hyperaemia was significantly reduced (P<0.001) at the end of treatment, while no significant differences were observed for corneal lesions and for papillary size. No patient showed exacerbation of the disease during the treatment. VKC is a chronic disease that requires prolonged treatment to control the inflammatory process. Our preliminary study demonstrates the efficacy and safety of preservative-free diclofenac sodium 0.1% eye drops in controlling the signs and symptoms of VKC in prolonged treatment.

Alpha-interferon for chronic hepatitis B infection: increased efficacy of prolonged treatment

Alpha-interferon for chronic hepatitis B infection: increased efficacy of prolonged treatment

Paroxysmal Nocturnal Hemoglobinuria: Efficacy of Prolonged Treatment With Granulocyte Colony-Stimulating Factor

Paroxysmal Nocturnal Hemoglobinuria: Efficacy of Prolonged Treatment With Granulocyte Colony-Stimulating Factor