Integrated safety summary of phase II and III studies comparing oral nemonoxacin and levofloxacin in community-acquired pneumonia

BackgroundNemonoxacin, a novel nonfluorinated quinolone, has broad-spectrum antibacterial activity, including activity against antibiotic-resistant strains, and was developed for treating community-acquired pneumonia (CAP). This report provides an integrated safety summary of oral nemonoxacin from two phase II and one phase III clinical studies.MethodsPatients with mild CAP were randomized for treatment with nemonoxacin 500 mg (NEMO-500MG), nemonoxacin 750 mg (NEMO-750MG), or levofloxacin 500 mg (LEVO), orally, once daily, for 7–10 days. Hematological, gastrointestinal, and hepatic disorders; electrocardiography abnormalities; and reported quinolone-associated clinical concerns were included in this analysis.ResultsA total of 520, 155, and 320 subjects were assigned to receive NEMO-500MG, NEMO-750MG, and LEVO, respectively. The incidence of adverse events (AEs) was the highest (54.8%) in the NEMO-750MG group (NEMO-500MG, 36.9%; NEMO-750MG, 54.8%; LEVO, 39.7%) and that of drug-related AEs was comparable between the three groups (NEMO-500MG, 22.9%; NEMO-750MG, 31.0%; LEVO, 22.5%). The majority (>80%) of the patients showed mild drug-related AEs and the distribution based on severity was similar between the groups. The most commonly reported drug-related AEs included neutropenia (NEMO-500MG, 2.5%; NEMO-750MG, 8.4%; LEVO, 4.4%), nausea (NEMO-500MG, 2.5%; NEMO-750MG, 7.1%; LEVO, 2.5%), leukopenia (NEMO-500MG, 2.3%; NEMO-750MG, 4.5%; LEVO, 3.1%), and increased alanine aminotransferase level (NEMO-500MG, 4.4%; NEMO-750MG, 0%; LEVO, 2.5%).ConclusionNemonoxacin was well tolerated and no clinically significant safety concerns were identified, suggesting that it possesses a desirable safety and tolerability profile similar to that of levofloxacin, and may be a suitable alternative to fluoroquinolones for treating patients with CAP.     

Ceftriaxone versus ceftriaxone plus a macrolide for community-acquired pneumonia in hospitalized patients with HIV/AIDS: a randomized controlled trial

ObjectivesTo evaluate if treatment with ceftriaxone and a macrolide, improved patient outcome when compared with monotherapy with ceftriaxone, in hospitalized patients with human immunodeficiency virus/acquired immunodeficient syndrome (HIV/AIDS) with community-acquired pneumonia (CAP).MethodsAdult patients with HIV hospitalized due to suspected CAP were randomized to receive one of two regimens, ceftriaxone plus macrolide or ceftriaxone plus placebo, at a 1:1 proportion (Brazilian Clinical Trials Registry: RBR-8wtq2b). The primary outcome was in-hospital mortality and the secondary outcomes were mortality within 14 days, need for vasoactive drugs, need for mechanical ventilation, time to clinical stability and length of hospitalization.ResultsA total of 227 patients were randomized, two were excluded after randomization; 225 patients were analysed (112 receiving ceftriaxone plus placebo and 113 receiving ceftriaxone plus macrolide). The frequency of the primary outcome, in-hospital mortality, was not statistically different between the regimens: 12/112 (11%) patients who received ceftriaxone plus placebo and 17/113 (15%) who received ceftriaxone plus macrolide died during hospitalization (hazard ratio 1.22, 95% CI 0.57–2.59). We did not find differences between the regimens for any of the secondary outcomes, including mortality within 14 days, which occurred in 5/112 (4%) patients with ceftriaxone plus placebo and in 12/113 (11%) patients with ceftriaxone plus macrolide (relative risk 2.38, 95% CI 0.87–6.53).ConclusionsAmong hospitalized patients with HIV/AIDS with CAP, treatment with ceftriaxone and a macrolide did not improve patient outcomes, when compared with ceftriaxone monotherapy.     

Comparative study of levofloxacin and amoxycillin/clavulanic acid in adults with mild-to-moderate community-acquired pneumonia

Objective: To compare the efficacy and safety of two different doses of levofloxacin with amoxycillin/clavulanic acid in the treatment of community-acquired pneumonia.
Methods: A double-blind, randomized (1:1:1), double-dummy, three-arm parallel design, multicenter study was conducted in adult patients with mild-to-moderate community-acquired pneumonia. In total, 518 patients were randomized to receive levofloxacin 500 mg once daily, levofloxacin 500 mg twice daily or amoxycillin/clavulanic acid 625 mg three times daily for 7–10 days.
Results: The clinical cure rates post-therapy (2–5 days after the end of treatment) in the intent-to-treat population were 84.2% (144/171) in the levofloxacin once-daily group, 80.2% (142/177) in the levofloxacin twice-daily group and 85.7% (144/168) in the amoxycillin/clavulanic acid group. In the per-protocol population, the clinical cure rates post-therapy were 95.2% (138/145), 93.8% (137/146) and 95.3% (141/148), respectively. The total pathogen eradication rates were 97.8%, 100% and 97.5%, respectively. Both drugs were equally well tolerated and no major adverse events were observed.
Conclusions: Levofloxacin was effective, safe and well tolerated in the treatment of mild-to-moderate community-acquired pneumonia. A complementary analysis indicated that there was no difference in therapeutic outcome between levofloxacin 500 mg once daily and twice daily. Levofloxacin 500 mg once daily, for 7–10 days, is an effective and safe treatment for mild-to-moderate community-acquired pneumonia in adults.     

A randomised, double-blind, double-dummy comparative study of gatifloxacin with clarithromycin in the treatment of community-acquired pneumonia

Eligible patients were randomised in this multicentre, randomised, double-blind, double-dummy parallel-group study in a ratio of 1:1 to either gatifloxacin 400 mg once-daily for 5-14 days plus matching placebo, or clarithromycin 500 mg twice-daily for 5-14 days. The primary outcome measure was clinical response (clinical cure plus improvement) at the end of treatment. Secondary endpoints were clinical response at end of study, clinical cure at end of treatment and end of study, bacteriological response at end of treatment and end of study, and treatment duration. The overall clinical response was similar in the two treatment groups, with 92.2% of gatifloxacin-treated patients cured or improved at the end of treatment, compared with 93.1% of those receiving clarithromycin. Corresponding bacteriological response rates (eradication plus presumed eradication) were 96.7% and 87.5%, respectively. The study drugs were well-tolerated, with nausea (gatifloxacin) and bitter taste (clarithromycin) being the only treatment-related adverse events with a frequency of > 5%. No patients experienced phototoxicity, hepatic or renal dysfunction, tendonitis or crystalluria. Oral gatifloxacin 400 mg once-daily appeared to be a safe and effective alternative to clarithromycin in the treatment of community-acquired pneumonia.     

Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis: a multicentre randomized,double-blind,placebo-controlled,non-inferiority trial

ObjectivesTo investigate whether antibiotic treatment of 6 days' duration is non-inferior to treatment for 12 days in patients hospitalized for cellulitis.MethodsThis multicentre, randomized, double-blind, placebo-controlled, non-inferiority trial enrolled adult patients hospitalized for severe cellulitis who were treated with intravenous flucloxacillin. At day 6 participants with symptom improvement who were afebrile were randomized between an additional 6 days of oral flucloxacillin or placebo in a 1:1 ratio, stratified for diabetes and hospital. The primary outcome was cure by day 14, without relapse by day 28. Secondary outcomes included a modified cure assessment and relapse rate by day 90.ResultsBetween August 2014 and June 2017, 151 of 248 included participants were randomized. The intention-to-treat population consisted of 76 and 73 participants allocated to 12 and 6 days of antibiotic therapy, respectively (mean age 62 years, 67% males, 24% diabetics); 38/76 (50.0%) and 36/73 (49.3%) were cured in the 12- and 6-day groups respectively (ARR 0.7 percentage points, 95%CI: –15.0 to 16.3). Cure rates were 56/76 (73.7%) and 49/73 (67.1%) with the modified cure assessment (ARR 6.6, 95%CI: –8.0 to 20.8). After initial cure without relapse, day 90 relapse rates were higher in the 6-day group (6% versus 24%, p < 0.05).ConclusionsGiven the wide confidence intervals, we can neither confirm nor refute our hypothesis that 6 days of therapy is non-inferior to 12 days of therapy. However, a 6-day course resulted in significantly more frequent relapses by day 90. These findings require confirmation in future studies.     

Valomaciclovir versus valacyclovir for the treatment of acute herpes zoster in immunocompetent adults: a randomized, double-blind, active-controlled trial

Herpes zoster is a common infectious disease that can result in significant acute and chronic morbidity. The safety and efficacy of once-daily oral valomaciclovir (EPB-348) was evaluated for non-inferiority to 3-times daily valacyclovir, an approved therapy. In this study, 373 immunocompetent adults with onset of a herpes zoster rash within the preceding 72 hr were randomly assigned to receive one of four treatments for 7 days: (1) EPB-348 1,000 mg once-daily; (2) EPB-348 2,000 mg once-daily; (3) EPB-348 3,000 mg once-daily; or (4) valacyclovir 1,000 mg 3-times daily. A 20% margin was the reference for non-inferiority assessment. For the primary efficacy measure of time to complete crusting of the zoster rash by Day 28, non-inferiority criteria were met for once-daily EPB-348 2,000 mg and once-daily EPB-348 3,000 mg compared to 3-times daily valacyclovir. Additionally, EPB-348 3,000 mg significantly shortened the time to complete rash crusting by Day 28 compared to valacyclovir. For secondary efficacy measures, non-inferiority was achieved for the EPB-348 1,000 and 2,000 mg groups compared to the valacyclovir group for time to rash resolution by Day 28. No EPB-348 group was non-inferior to valacyclovir for time to cessation of new lesion formation or time to cessation of pain by Day 120, though no significant differences occurred between treatment groups. Nausea, headache, and vomiting were the most common adverse events. Based on these results, additional studies are warranted to define further EPB-348's potential as an effective and safe therapy for acute herpes zoster.     

Efficacy of a Carrageenan gel Against Transmission of Cervical HPV (CATCH): interim analysis of a randomized,double-blind,placebo-controlled,phase 2B trial

Objectives

To evaluate the efficacy of a carrageenan-based lubricant gel in reducing the risk of genital human papillomavirus (HPV) infections in women.

Safety and immunogenicity of the epicutaneous reactivation of pertussis toxin immunity in healthy adults: a phase I,randomized, double-blind,placebo-controlled trial

ObjectivesProtection induced by acellular vaccines can be short, requiring novel immunization strategies. Objectives of this study were to evaluate safety and capacity of a recombinant pertussis toxin (PTgen) -coated Viaskin® epicutaneous patch to recall memory responses in healthy adults.MethodsThis double-blind, placebo-controlled randomized trial (Phase I) assessed the safety and immunogenicity of PTgen administered on days 0 and 14 to healthy adults using Viaskin® patches applied directly or after epidermal laser-based skin preparation. Patch administration was followed by Boostrix®dTpa on day 42. Antibodies were assessed at days 0, 14, 28, 42 and 70.ResultsAmong 102 volunteers enrolled, 80 received Viaskin-PT (Viaskin-PT 25 μg (n = 25), Viaskin-PT 50 μg (n = 25), laser + Viaskin-PT 25 μg (n = 5), laser + Viaskin-PT 50 μg (n = 25)), Viaskin-placebo (n = 10) or laser + Viaskin-placebo (n = 2). Incidence of adverse events was similar across groups (any local event: 21/25 (84.0%), 24/25 (96.0%), 4/5 (80.0%), 24/25 (96.0%), 8/10 (80.0%), 10/12 (83.0%), respectively). Direct application induced no detectable response. On day 42, PT-IgG geometric mean concentrations were significantly higher following laser + Viaskin-PT 25 μg and 50 μg (139.87 (95% CI 87.30–224.10) and 121.76 (95% CI 95.04–156.00), respectively), than laser + Viaskin-placebo (59.49, 95% CI 39.37–89.90). Seroresponse rates were higher following laser + Viaskin-PT 25 μg (4/5 (80.0%), 95% CI 28.4–99.5) and 50 μg (22/25 (88.0%), 95% CI 68.8–97.5) than laser + Viaskin-placebo (0/12 (0.0%), 95% CI 0.0–26.5).ConclusionsViaskin-PT applied after laser-based epidermal skin preparation showed encouraging safety and immunogenicity results: anti-PT booster responses were not inferior to those elicited by Boostrix®dTpa. This study is registered at ClinicalTrials.gov (NCT 03035370) and was funded by DBV Technologies.     

Effect of vitamin D3 supplementation on Staphylococcus aureus nasal carriage: a randomized,double-blind,placebo-controlled trial in healthy adults

Observational studies have reported an inverse association between serum 25-hydroxyvitamin D (25OHD) concentrations and Staphylococcus aureus nasal carriage; however, clinical trials of vitamin D supplementation are lacking. To assess the effect of vitamin D3 supplementation on persistent S. aureus nasal carriage we conducted a randomized, double-blind, placebo-controlled trial among 322 healthy adults. Participants were given an oral dose of either 200 000 IU vitamin D3 for each of 2 months, followed by 100 000 IU monthly or placebo in an identical dosing regimen, for a total of 18 months. Nasal swabs for S. aureus culture and serum for 25OHD measurement were obtained at baseline, 6, 12 and 18 months of study. The mean baseline concentration of 25OHD was 72 nM (SD 22 nM). Vitamin D3 supplementation increased 25OHD levels which were maintained at >120 nM throughout the study. Nasal colonization by S. aureus was found in 31% of participants at baseline. Persistent carriage, defined as those that had positive S. aureus nasal cultures for all post-baseline swabs, occurred in 20% of the participants but vitamin D3 supplementation was not associated with a reduction in persistent carriage (OR = 1.39, 95% CI 0.63–3.06). Risk factor analysis showed that only gender was significantly associated with carriage, where women were less likely to be carriers than men (relative risk 0.83, 95% CI 0.54–0.99). Serum 25OHD concentrations were not associated with the risk of carriage. In conclusion, monthly administration of 100 000 IU of vitamin D3 did not reduce persistent S. aureus nasal carriage.     

Efficacy and safety of emtricitabine/tenofovir alafenamide (FTC/TAF) vs. emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) as a backbone for treatment of HIV-1 infection in virologically suppressed adults: subgroup analysis by third agent of a randomized,double-blind,active-controlled phase 3 trial*

Background: FTC/TAF was shown to be noninferior to FTC/TDF with advantages in markers of renal and bone safety.

Objective: To evaluate the efficacy and safety of switching to FTC/TAF from FTC/TDF by third agent (boosted protease inhibitor [PI] vs. unboosted third agent).

Methods: We conducted a 48-week subgroup analysis based on third agent from a randomized, double blind study in virologically suppressed adults on a FTC/TDF-containing regimen who switched to FTC/TAF vs. continued FTC/TDF while remaining on the same third agent.

Results: We randomized (1:1) 663 participants to either switch to FTC/TAF (N = 333) or continue FTC/TDF (N = 330), each with baseline third agent stratifying by class of third agent in the prior treatment regimen (boosted PI 46%, unboosted third agent 54%). At week 48, significant differences in renal biomarkers and bone mineral density were observed favoring FTC/TAF over FTC/TDF (p < 0.05 for all), with similar improvements in the FTC/TAF arm in those who received boosted PI vs. unboosted third agents. At week 48, virologic success rates were similar between treatment groups for those who received a boosted PI (FTC/TAF 92%, FTC/TDF 93%) and for those who received an unboosted third agent (97% vs. 93%).

Conclusions: In virologically suppressed patients switching to FTC/TAF from FTC/TDF, high rates of virologic suppression were maintained, while renal and bone safety parameters improved, regardless of whether participants were receiving a boosted PI or an unboosted third agent. FTC/TAF offers safety advantages over FTC/TDF and can be an important option as an NRTI backbone given with a variety of third agents.     

Effect of positive microbiological testing on antibiotic de-escalation and outcomes in community-acquired pneumonia: a propensity score analysis

ObjectivesThe usefulness of routine microbiological testing for rationalising antibiotic use in hospitalised patients with community-acquired pneumonia (CAP) continues to be a subject of debate. We aim to determine the effect of positive microbiological testing on antimicrobial de-escalation and clinical outcomes in CAP.MethodsA retrospective analysis of a prospectively collected cohort of non-immunosuppressed adults hospitalised with CAP was performed. The primary study outcome was antimicrobial de-escalation. Secondary outcomes included 30-day case-fatality rate, adverse events, and CAP recurrence. Adjustment for confounders was performed by inverse probability weighting propensity score, logistic regression, and cause-specific Cox model.ResultsOf 3677 patients with CAP, 1924 (52.3%) had any positive microbiological test. Antimicrobial de-escalation was performed in 648/1924 (33.7%) of patients with positive microbiological testing and in 179/1753 (10.2%) of those with non-positive results. When propensity score was entered into the multivariate analysis, positive microbiological testing (adjusted OR (AOR)], 2.59; 1.96–3.41) and clinical stability at day 3 (AOR 1.87; 1.45–2.10) were two of the main factors independently associated with antimicrobial de-escalation. After applying an adjusted cause-specific Cox model, antimicrobial de-escalation was not associated with a higher 30-day case-fatality rate (adjusted hazard ratio (AHR), 0.44 (95% CI, 0.14–1.43)), higher frequency of adverse events (AHR, 0.77 (95% CI, 0.53–1.12)), or CAP recurrence (AHR, 0.65 (95% CI, 0.35–1.14)).DiscussionAntimicrobial de-escalation was more often performed in hospitalised patients with CAP who had positive microbiological tests than in those with non-positive results, and it did not adversely affect relevant clinical outcomes.     

A randomized controlled trial of estrogen treatment in men with mild cognitive impairment

This randomized, placebo-controlled, cross-over study investigated whether estrogen treatment would have a beneficial effect on tests of verbal memory in men with mild cognitive impairment (MCI). Forty-three men newly diagnosed with MCI were administered a battery of neuropsychological tests before randomly receiving 12 weeks of treatment with estrogen or placebo followed by a 12 week cross-over treatment. A significant improvement in the total score, and in two subscale scores of the Buschke Selective Reminding Test occurred following estrogen treatment compared to both pretreatment and post-placebo scores (p < 0.05). However, benefit occurred only in the men who had received estrogen for 12 weeks following 12 weeks of placebo. Although these findings tentatively suggest that treatment with estrogen may improve verbal memory in men with MCI, the fact that the improvement occurred only in the group that received estrogen following 12 weeks of placebo and the absence of improvement on every test of verbal memory administered suggests that these findings need to be replicated using a larger sample size.     

Once- versus twice-daily dosing of eliglustat in adults with Gaucher disease type 1: The Phase 3, randomized,double-blind EDGE trial

Eliglustat is a first-line oral therapy for adults with Gaucher disease type 1 (GD1) with compatible CYP2D6-metabolizer phenotypes (> 90% of patients). The randomized, double-blind EDGE trial (NCT01074944, Sanofi Genzyme) evaluated once-daily eliglustat dosing compared with the approved twice-daily regimen at the same total daily dose in adults with GD1. Subjects received twice-daily dosing during a 6- to 18-month lead-in period. Only subjects who attained prespecified treatment goals for hemoglobin, platelet count, spleen and liver volumes, and bone symptoms during the lead-in period were randomized to once- or twice-daily dosing. Of 170 enrolled patients, 156 completed the lead-in period and 131 met all requirements to enter the double-blind treatment period. To achieve the composite primary endpoint in the double-blind period, patients had to maintain clinical stability relative to baseline on all five endpoints (hemoglobin, platelet count, spleen and liver volumes, and bone symptoms) and meet pharmacokinetic and other tolerability requirements as determined by the investigator after 1 year of eliglustat treatment. After 1 year, 80.4% (95% CI: 67.6, 89.8) of once-daily patients were stable compared with 83.1% (95% CI: 71.0, 91.6) of twice-daily patients. The 95% CI for the mean difference of ? 2.7% between groups was ? 17.7, 11.9. Because the lower bound of the CI exceeded the pre-defined non-inferiority margin of ? 15%, once-daily dosing could not be declared non-inferior to twice-daily dosing. Both once-daily and twice-daily patients maintained mean values for hematologic and visceral measures within established therapeutic goals during the double-blind treatment and long-term extension periods. Eliglustat was generally well-tolerated during this long-term trial (mean treatment duration: 3.3 years), with just four withdrawals (2%) for related adverse events (AE), and similar AE profiles for both dosing regimens. Patients on twice-daily eliglustat showed more stability overall, and this dose regimen was better tolerated, confirming the dosing regimen for most patients specified in the drug label.     

Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy study

BACKGROUND: Both sublingual allergen-specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed. OBJECTIVE: To investigate the clinical efficacy of SLIT vs SCIT and secondary to compare SLIT and SCIT with placebo and to evaluate the relative clinical efficacy in relation to systemic side-effects. METHODS: A 3-year randomized, placebo-controlled, double-blind, double-dummy study including 71 adult birch pollen hay fever patients treated for two consecutive years after a baseline year. Allocation to treatment groups was based on disease severity in the baseline season, gender and age. RESULTS: Clinical efficacy was estimated in 58 patients completing the first treatment year by subtracting baseline data and by calculating the ratio first treatment season vs baseline. SLIT diminished the median disease severity to one-half and SCIT to one-third of placebo treatment. No statistical significant difference between the two groups was observed. Both for symptoms and medication scores actively treated patients showed statistically significant and clinical relevant efficacy compared with placebo. SLIT treatment only resulted in local mild side-effects, while SCIT resulted in few serious systemic side-effects. CONCLUSION: Based on the limited number of patients the clinical efficacy of SLIT was not statistically different from SCIT, and both treatments are clinically effective compared with placebo in the treatment of birch pollen rhinoconjunctivitis. The lack of significant difference between the two treatments does not indicate equivalent efficacy, but to detect minor differences necessitates investigation of larger groups. Due to the advantageous safety profile SLIT may be favored.     

国产与进口注射用头孢唑肟注射液治疗细菌性感染性疾病随机双盲多中心随机对照临床研究

目的：评价头孢唑肟国产品治疗细菌性感染的疗效和安全性。方法：采用多中心随机双盲对照临床观察，共160例患呼吸道或泌尿道感染的病人入组，国产品组和进口品组各80例。治疗方法均为头孢唑肟2g，每日二次，疗程7-14天。结果：国产品组和进口品组的痊愈率分别为62．5％（50／80）、56．25％（45／80），有效率均为90％（72／80），细菌清除率分别为87．1％（54／62）和90．3％（56／62），不良反应发生率分别为8．75％（7／80）和7．50％（6／80）。经统计学分析均无显著差异（P〉0．05）。结论：国产注射用头孢唑肟治疗呼吸道感染和泌尿道感染的疗效和安全性与进口头孢唑肟相仿。     

Low-dose interferon in chronic hepatitis non-A/non-B: effects on quantitative liver function and structure in a randomized,controlled multicenter trial

Summary In this randomized, controlled multicenter trial we evaluated the effects of recombinant interferon-_2b on galactose elimination capacity and histological activity index in 88 patients with chronic active hepatitis non-A/non-B. Forty-five patients were randomly assigned to treatment with interferon at 1.5 × 10⁶ U three times per for 1 year; 43 patients were assigned to no treatment. A complete response (normalization of alanine aminotransferase) was observed, respectively, in 47% and 5% of the two groups (P<0.006); 47% of these patients suffered a relapse. Thus 22% of patients had a sustained response. Histological activity decreased significantly in responders (P<0.04) while the biopsy score did not change significantly in nonresponders. In contrast, galactose elimination capacity — a surrogate marker for survival in chronic active hepatitis — was not affected by response to treatment. None of the parameters evaluated, including hepatitis C virus RNA, was able to predict response or relapse. We conclude that low-dose interferon treatment for 1 year is as effective as the recommended treatment schedule.Abbreviations ALT alanine aminotransferase - HCV hepatitis C virus Dedicated to Prof. Dr. G. Paumgartner on the occasion of his 60th birthday by the Swiss hepatologists and his Swiss friends     

Effect of multimodality chest physiotherapy in prevention of ventilator-associated pneumonia: A randomized clinical trial

Background:

Despite remarkable progress that has been achieved in the recent years in the diagnosis, prevention, and therapy for ventilator-associated pneumonia (VAP), this disease continues to create complication during the course of treatment in a significant proportion of patients while receiving mechanical ventilation.

Objective:

This study was designed to evaluate the effect of multimodality chest physiotherapy in intubated and mechanically ventilated patients undergoing treatment in the intensive care units (ICUs) for prevention of VAP.

Patients and Methods:

A total of 101 adult intubated and mechanically ventilated patients were included in this study. Manual hyperinflation (MH) and suctioning were administered to patients in the control group (n = 51), and positioning and chest wall vibrations in addition to MH plus suctioning (multimodality chest physiotherapy) were administered to patients in the study group (n = 50) till they were extubated. Both the groups were subjected to treatment twice a day. Standard care in the form of routine nursing care, pharmacological therapy, inhalation therapy, as advised by the concerned physician/surgeon was strictly implemented throughout the intervention period.

Results:

Data were analyzed using SPSS window version 9.0. The Clinical Pulmonary infection Score (CPIS) Score showed significant decrease at the end of extubation/successful outcome or discharge in both the groups (P = 0.00). In addition, significant decrease in mortality rate was noted in the study group (24%) as compared to the control group (49%) (P = 0.007).

Conclusions:

It was observed in this study that twice-daily multimodality chest physiotherapy was associated with a significant decrease in the CPIS Scores in the study group as compared to the control group suggesting a decrease in the occurrence of VAP. There was also a significant reduction in the mortality rates with the use of multimodality chest physiotherapy in mechanically ventilated patients.     

Cooperative group of additional immunoglobulin therapy in severe bacterial infections: Results of a multicenter randomized controlled trial in cases of diffuse fibrinopurulent peritonitis

Summary A multicenter randomized controlled clinical trial, which was carried out in 10 hospitals in the Federal Republic of Germany between 1979 and 1983, studied the influence of i.v. immunoglobulin G on the mortality in patients with diffuse acute fibrinopurulent peritonitis. Altogether 288 patients were enrolled in the trial. There was no statistically significant difference in the mortality rates within the treated group (46%) vs the control group (41%). The power of the statistical test to detect a decrease of the mortality by 20% was calculated to be 0.93. This result did not change when we eliminated 50 patients not strictly obeying the entrance criteria of the analysis, or when we focused on a subgroup of patients with initial deficiency of immunoglobulin G. Factors influencing mortality were a preceding laparotomy, serum creatinine level above 2 mg/100 ml, and necessity for artificial respiration. These factors, reflecting the surgical situation and the severity of shock, essentially explain the mortality differences observed between the participating hospitals.Abbreviations DAFPP diffuse acute fibrinopurulent peritonitis Names and addresses see Table 5In memoriam H.J. Jesdinsky     

Effectiveness of shared decision-making intervention in patients with lumbar degenerative diseases: A randomized controlled trial

ObjectiveTo evaluate the efficacy of shared decision-making (SDM) intervention among patients with lumbar degenerative diseases (LDDs) in terms of decision self-efficacy, control preferences, SDM process, decision satisfaction, and conflict.MethodsA total of 130 outpatients with LDDs recruited from orthopedic or rehabilitation clinics were randomly assigned to the SDM intervention (n = 67) or comparison (n = 63) groups. Patients in the intervention group received decision aids (DAs) with decision coaching and those in controlled group received standard educational materials from a health educator. The primary outcome was decision self-efficacy, and secondary outcomes were control preference, SDM process, conflict, and satisfaction.ResultsThe SDM intervention significantly improved decision self-efficacy (mean difference [MD] = 7.1, 95% confidence interval [CI]: 1.7–12.5, partial η² = 0.05) and reduced conflict (MD = −7.0, 95% CI: −12.2 to −1.9, partial η² = 0.06), especially in patients without family involvement, compared with the health education group. However, no significant between-group differences were observed in other outcomes.ConclusionSDM intervention improved SDM self-efficacy and reduced conflict in patients with LDDs.Practice ImplicationsClinicians can integrate DAs and decision coaching in SDM conversations. SDM intervention seems to engage patients in decision-making, especially those without family involvement.     

Effectiveness of question prompt lists in patients with breast cancer: A randomized controlled trial

ObjectivesTo evaluate the effectiveness of a question prompt list (QPL) in decision self-efficacy, decision-making participation, patient–physician communication, decisional conflict or regret, and health status in patients with breast cancer.MethodsA total of 240 patients with breast cancer were randomly assigned to a QPL group or control group (n = 120 each). The intervention and control groups received an additional educational QPL booklet and routine care, respectively.ResultsThe intervention group exhibited significant improvements in decision self-efficacy, perceived patient–physician interactions, and patient–physician communication compared with the control group. Multilevel modeling analyses revealed significant group–time interaction effects on decision self-efficacy (β = 9.99, P < 0.01), perceived patient–physician interactions (β = 8.10, P < 0.01), patient–physician communication (β = 5.02, P < 0.01), and anxiety status (β = ?3.78, P < 0.05). The QPL intervention exerted more favorable effects than routine care, with repeated measurements of the same patients and the data of patients under the care of the same surgeons accounted for.ConclusionsThe QPL intervention exerted multidimensional effects on decision-making outcomes among patients with breast cancer.Practical implicationsClinicians can integrate a QPL into routine care for patients with breast cancer.