Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II

Objectives

Type II glycogenosis (GSDII) is a lysosomal storage disorder due to acid alpha-glucosidase (GAA) deficiency. Enzyme replacement therapy (ERT) with human recombinant alpha-glucosidase (rhGAA) has been demonstrated to be effective in the treatment of infantile forms of GSDII, but little information is available concerning late-onset phenotypes. Long-term follow-up studies are not available at present. The aim of this study was to evaluate the ERT long-term effects in late-onset GSDII.

Methods

Twenty-four patients, including 7 juveniles and 17 adults, received bi-weekly infusion of rhGAA (20 mg/kg) for at least 36 months. Clinical conditions, muscular function (6-min walking test, 6MWT; Walton scale, WS), respiratory function (vital capacity, VC; forced expiratory volume, FEV1; arterial pCO₂), and muscle enzymes were assessed every 6 months.

Results

The 6MWT improved in both juvenile and adult patients (p?=?0.01, p?=?0.0002, respectively), as well as in patients with moderate to severe muscle function impairment (WS?>?3.5; p?=?0.002). An overall improvement in WS was also observed (p?=?0.0003). VC and FEV1 remained unchanged, while pCO₂ decreased (p?=?0.017). Muscle enzymes decreased significantly (p?<?0.0001). Two patients (8%) showed transient secondary events during ERT.

Conclusions

Long-term ERT with rhGAA was shown to be safe, well tolerated, and effective in improving motor function and in stabilizing respiratory function in late-onset GSDII. The response pattern showed a progressive clinical improvement during the follow-up period in juvenile patients, while in adults it reached and maintained a plateau after the first year of treatment.     

Effectiveness of enzyme replacement therapy in adults with late-onset Pompe disease: results from the NCS-LSD cohort study

Objectives

To determine the effectiveness of enzyme replacement therapy (ERT) for adults with late-onset Pompe disease.

Design

A longitudinal cohort study including prospective and retrospective clinical outcome data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment. Untreated patients contributed natural history data.

Participants

Consenting adults (N?=?62) with a diagnosis of late-onset Pompe disease who attended a specialist treatment centre in England. This cohort represented 83 % of all patients in the UK with a confirmed diagnosis of this rare condition. At study entry, all but three patients were receiving ERT (range of treatment duration, 0 to 3.1 years).

Outcome measures

Percent predicted forced vital capacity (%FVC); ventilation dependency; mobility; 6 min walk test (6MWT); muscle strength and body mass index (BMI).

Results

An association was found between time on ERT and significant increases in the distance walked in the 6MWT (p?p?Conclusions These data provide some further evidence of the effectiveness of ERT in adults with late-onset Pompe disease.

Synopsis

The results of this longitudinal cohort study of 62 adults with late-onset Pompe disease, provide further evidence on the effectiveness of ERT in this rare condition.     

Dynamic changes of lipid profile in Romanian patients with Gaucher disease type 1 under enzyme replacement therapy: a prospective study

Background

Dyslipidemia in Gaucher disease includes reduced total, low-density lipoprotein (LDL)-, and high-density lipoprotein (HDL)-cholesterol (C). No prospective analysis of lipid profile changes in treatment-naïve patients under enzyme replacement therapy (ERT) is available.

Methods

We analyzed lipid profile changes during ERT in a prospective controlled manner. Twelve treatment-naïve patients, Gaucher disease type 1 (GD1), 29.5 ± 12.9 years, 4M/8F. Diagnosis was made by enzymatic measurement and mutational analysis. Total-, LDL-, and HDL-C, triglycerides (TG), and LDL subfractions were assessed before the start of ERT with imiglucerase and biannually for 3 years. Patients were matched with healthy controls before and after 3 years of ERT.

Results

At baseline, we found severely reduced HDL-C concentrations (23.6 ± 5.4 mg/dl) and enhanced LDL/HDL ratios (3.1 ± 0.7). HDL-C increased after 6 months (29.2 ± 5.7, p?=?0.023), LDL/HDL ratio decreased after 30 months (2.5 ± 0.5, p?=?0.039). TG, even not consistently enhanced at baseline (128 ± 31.3 mg/dl), yet higher than in controls (p?<?0.001), decreased after 18 months, being comparable with controls after 3 years of ERT. Small, dense LDL (mg/dl) increased continuously without significant difference to controls. After 3 years of ERT, only reduced HDL-C concentrations persisted as a potentially atherogenic alteration; however, mean concentrations markedly improved (42.9 ± 8.3 mg/dl, p?<?0.001). Lipid parameters correlated with six markers of disease severity.

Conclusions

This is the first prospective controlled study regarding lipid profile dynamics during ERT (glucocerebrosidase) in initially treatment-naïve GD1 patients. The most important changes were reduced HDL-C and enhanced LDL/HDL ratio. Their dynamics during ERT and correlations with markers of disease activity suggest that they can be considered markers of disease severity and follow-up in Gaucher patients under treatment.     

Clinical profile of early-onset and late-onset idiopathic chronic pancreatitis in South India

Background and Aim

Idiopathic chronic pancreatitis (ICP) is the most common form of chronic pancreatitis reported in India. There is paucity of literature on the prevalence and profiles of early- and late-onset forms of ICP in India.

Material and Methods

We compared the profile of early- and late-onset ICP in a patient population attending a tertiary care hospital in South India.

Results

Pain was the characteristic feature as more than 90 % with both early-onset and late-onset ICP had pain as the most significant symptom. Onset of pain was at age 14.9?±?7.7 years in early-onset and at 38.1?±?9.9 in late-onset ICP (p?<?0.001). There was considerable delay between onset of pain in early onset as compared to late-onset ICP. Diabetes was seen in 41.4 % in early-onset as compared to 69.1 % in late-onset ICP (p?<?0.001). Pancreatic exocrine insufficiency was seen in 34.4 % in early-onset as compared to 53.2 % in late-onset ICP (p?<?0.001). Increased prevalence of exocrine insufficiency and diabetes was observed in late-onset as compared to early-onset ICP. Univariate analysis showed that alcohol use, smoking, age, and family history of diabetes were significantly associated with diabetes. Multivariate analysis showed strong associations for diabetes with smoking (odds ratio (OR)?=?4.2), calcification (OR?=?7.7), as well as family history and age >40 years.

Conclusions

There were differences between early-onset and late-onset ICP in southern Indian patients. Diabetes was strongly associated with smoking and pancreatic calcification.     

Long-term effectiveness of enzyme replacement therapy in adults with Gaucher disease: results from the NCS-LSD cohort study

Objectives

To determine the effectiveness of enzyme replacement therapies (ERT) for adults with Gaucher disease (GD).

Design

A longitudinal, multi-centre cohort study, including prospective and retrospective clinical data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment. Untreated patients contributed natural history data.

Participants

Consenting adults (N?=?150, aged 16 to 83 years) with a diagnosis of GD who attended a specialist treatment centre in England. At recruitment, 131 patients were receiving ERT (mean treatment duration, 10.8 years; range 0–18 years).

Outcome measures

Clinical outcomes chosen to reflect disease progression, included platelet count; haemoglobin; absence/presence of bone pain; spleen and liver volumes and AST levels.

Results

One hundred and fifty adults were recruited. Duration of ERT was associated with statistically significant improvements in platelet count (p?p?p?p?=?0.02).

Conclusions

These data provide further evidence of the long-term effectiveness of ERT in adults with GD.     

Long-term effectiveness of enzyme replacement therapy in children with Gaucher disease: results from the NCS-LSD cohort study

Objectives

To determine the effectiveness of enzyme replacement therapies (ERT) for children with Gaucher disease (GD).

Design

A longitudinal cohort study including prospective and retrospective clinical data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Children on treatment contributed data before and during treatment. Children not on treatment contributed natural history data.

Participants

Consenting children (N?=?25, aged 1.1 to 15.6 years) with a diagnosis of GD (14 with GD1 and 11 with GD3) who attended a specialist treatment centre in England. At recruitment, 24 patients were receiving ERT (mean treatment duration, 5.57 years; range 0-13.7 years).

Outcome measures

Clinical outcomes chosen to reflect disease progression, included platelet count; haemoglobin and absence/presence of bone pain.

Results

Duration of ERT was associated with statistically significant improvements in platelet count (p?p?p?=?0.02). The magnitude of effect on haematological parameters was greater in children with GD3 than in those with GD1.

Conclusions

These data provide further evidence of the long-term effectiveness of ERT in children with GD.     

Duration of treatment for candidemia and risk for late-onset ocular candidiasis

Purpose

Few reports have been published on the optimal duration of treatment of ocular candidiasis. We have investigated the incidence of late-onset Candida chorioretinitis and endophthalmitis in patients with candidemia who did not initially receive an ophthalmologic examination. The aim was to determine the duration of initial antifungal treatment that may be sufficient to avoid this complication.

Methods

This was a long-term follow-up study of 144 patients with candidemia who survived for at least 60 days after the onset of candidemia. The frequency of early- and late-onset ocular complications due to candida infection and factors associated with ocular candidiasis were investigated.

Results

Fundoscopy was performed on 60 patients, revealing 12 cases of ocular candida infection (20 %). Risk factors were infection with Candida albicans compared to other Candida species (p = 0.021) and surgery due to solid tumor (p = 0.004). Only one case of late-onset ocular candidiasis occurred among the 84 candidemic patients who did not receive an initial ophthalmologic examination. For unknown reasons, this patient had received only 2 days of systemic antifungal treatment initially.

Conclusions

No case of late-onset ocular candidiasis was detected in unexamined patients who received at least 14 days of antifungal treatment. Based on our results, it would appear that the recommended 2 weeks of treatment after the first negative blood culture are sufficient to avoid late-onset complications due to undiscovered Candida chorioretinitis in patients surviving for more than 60 days after the onset of candidemia.     

Enzyme replacement therapy for alpha-mannosidosis: 12 months follow-up of a single centre, randomised, multiple dose study

Background

Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly intravenous enzyme replacement therapy (ERT). We present the preliminary data after 12 months of treatment.

Methods

This is a phase I-II study to evaluate safety and efficacy of rhLAMAN. Ten patients (7–17 y) were treated. We investigated efficacy by testing motor function (6-minutes-Walk-Test (6-MWT), 3-min-Stair-Climb-Test (3-MSCT), The Bruininks-Oseretsky Test of Motor Proficiency (BOT2), cognitive function (Leiter-R), oligosaccharides in serum, urine and CSF and Tau- and GFA-protein in CSF.

Results

Oligosaccharides: S-, U- and CSF-oligosaccharides decreased 88.6 % (CI ?92.0 ?85.2, p?<?0.001), 54.1 % (CI ?69.5- ?38.7, p?<?0,001), and 25.7 % (CI ?44.3- ?7.1, p?<?0.05), respectively. Biomarkers: CSF-Tau- and GFA-protein decreased 15 %, p?<?0.009) and 32.5, p?<?0.001 respectively. Motor function: Improvements in 3MSCT (31 steps (CI 6.8-40.5, p?<?0.01) and in 6MWT (60.4 m (CI ?8.9 ?51.1, NS) were achieved. Cognitive function: Improvement in the total Equivalence Age of 4 months (0.34) was achieved in the Leiter R test (CI ?0.2-0.8, NS).

Conclusions

These data suggest that rhLAMAN may be an encouraging new treatment for patients with alpha-mannosidosis.The study is designed to continue for a total of 18 months. Longer-term follow-up of patients in this study and the future placebo-controlled phase 3 trial are needed to provide greater support for the findings in this study.     

Half-Dose Rabeprazole Has an Equal Efficacy to Standard-Dose Rabeprazole on Endoscopic Submucosal Dissection-Induced Ulcer

Background

Although endoscopic submucosal dissection (ESD)-induced ulcers heal faster and recur less often than non-iatrogenic gastric ulcers, the optimal dosage and duration of proton pump inhibitor treatment for ESD-induced ulcers remain unclear.

Aims

To evaluate the efficacy of half-dose rabeprazole on endoscopic submucosal dissection-induced ulcer compared with standard dose rabeprazole.

Methods

The study was a prospective randomized controlled double-blind trial at a single tertiary hospital. A total of 80 patients who underwent ESD for gastric neoplasia were enrolled. Of these patients, 10 were not followed to completion. Final analysis included the remaining 70 patients. Rabeprazole 20 or 10 mg, depending on randomization, was given orally for 4 weeks after ESD.

Results

Of the 70 patients, 45 (64 %) were men, and the median age was 65.2 ± 9.7 years. The mean ESD-induced ulcer area was 673 mm². No significant differences in ulcer area reduction ratio (p = 0.49) or ulcer-related symptoms (p = 0.91) were observed between the two groups at 4 weeks after ESD.

Conclusion

For ESD-induced ulcers, treatment with 10 mg of rabeprazole daily produces a similar outcome as 20 mg of rabeprazole with regard to healing efficacy and symptom resolution.     

Long-term effectiveness of enzyme replacement therapy in Fabry disease: results from the NCS-LSD cohort study

Objectives

To determine the effectiveness of enzyme replacement therapy (ERT) for adults and children with Fabry disease.

Design

Cohort study including prospective and retrospective clinical data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment and untreated patients contributed natural history data.

Participants

Consenting adults (N?=?289) and children (N?=?22) with a confirmed diagnosis of Fabry disease attending a specialist Lysosomal Storage Disorder treatment centre in England. At recruitment 211 adults and seven children were on ERT (range of treatment duration, 0 to 9.7 and 0 to 4.2 years respectively).

Outcome measures

Clinical outcomes chosen to reflect disease progression included left ventricular mass index (LVMI); proteinuria; estimated glomerular filtration rate (eGFR); pain; hearing and transient ischaemic attacks (TIA)/stroke.

Results

We found evidence of a statistically significant association between time on ERT and a small linear decrease in LVMI (p?=?0.01); a reduction in the risk of proteinuria after adjusting for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (p?p?=?0.01 and p?Conclusions These data provide some further evidence on the long-term effectiveness of ERT in adults with Fabry disease, but evidence of effectiveness could not be demonstrated in children.     

Predictors of left atrium appendage clot detection despite on-target warfarin prevention for atrial fibrillation

Background and purpose

The antithrombotic management of atrial fibrillation (AF) is currently based on clinical scores (CHADS₂ or CHA₂DS₂VASc). The prevalence of left atrium (LA) thrombi in effectively anticoagulated AF patients has been reported as being up to 7.7 %. We tried to correlate LA/LA appendage (LAA) thrombus detection with possible clinical predictors in warfarin-treated patients.

Methods

We performed trans-esophageal echocardiography on 430 patients (mean age, 60.3?±?9.8 years) receiving oral anticoagulant (OAC) therapy and undergoing pulmonary vein isolation. In 10/430 (2.3 %), an LA thrombus was found despite therapeutic OAC (mean INR 2.6?±?0.6; range, 2.0–3.8) over the previous 4 weeks.

Results

Two study groups were identified:

1. T-positive group?=?with LAA thrombus (10 patients)
2. T-negative group?=?without LAA thrombus (420 patients)

The T-positive patients had a higher CHADS₂ score (1.5?±?0.7 versus 0.7?±?0.8; p?=?0.004), a lower LVEF (54.7?±?9.5 % versus 60.2?±?7.4; p?=?0.02), and a larger LA size (LA diameter, 56?±?12.2 mm versus 46?±?6.5 mm; p? <?0.001and normalized LA volume: 140.2?±?66 ml/m² vs. 67?±?39 ml/m²; p?<?0.05). On multivariate analysis, a larger LA diameter and normalized LA volume (OR, 1.14; 95 % C.I., 1.04–1.26; p?=?0.006 and OR, 1.02; 95 % C.I., 1.01–1.03; p?=?0.001, respectively) and a higher CHA₂DS₂VASc score (OR, 2.4; 95 % C.I., 1.4–4.2; p?=?0.001) predicted left atrium appendage (LAA) thrombus. In another 42/430 (9.8 %) patients, an LA spontaneous echo-contrast (SEC) was detected. Thus, cumulatively, 52/430 (12.1 %) patients had either LAA thrombi (10 patients) or SEC (42 patients). LA diameter continued to predict the presence of either thrombi or SEC (OR, 1.14; 95 % C.I., 1.07–1.2; p?<?0.05).

Conclusions

We found a 2.3 % prevalence of LA thrombus (12.1 % when SEC was also considered). The thrombus was present despite on-target warfarin prevention. In addition to a higher CHA₂DS₂VASc score, a larger LA size was a strong predictor of clot detection.     

Robotic ablation of atrial fibrillation with a new remote catheter system

Purpose

Pulmonary vein isolation (PVI) is widely established as a curative treatment option for atrial fibrillation (AF). A wide range of techniques to improve catheter manipulation and steerability has been developed over the past years. A new remote catheter system (RCS) has recently become available (Amigo Remote Catheter System, Catheter Robotics, Budd Lake, NJ, USA). Here, we present a dual-center study on the RCS for left atrial mapping and PVI in patients with paroxysmal AF compared to a control group undergoing conventional PVI.

Methods

One hundred nineteen patients who underwent PVI for paroxysmal AF were studied. Forty patients underwent PVI with the use of the RCS. Seventy-nine patients, who underwent conventional PVI, served as control group. Procedural data were compared between the two groups.

Results

PVI was achieved in all patients. In the RCS group compared to standard ablation group, there were no significant differences in procedure duration (159.1?±?45.4 vs. 146?±?30.1 min, p?=?0.19), total energy delivery (78,146.3?±?26,992.4 vs. 87,963.9?±?79,202.1 Ws, p?=?0.57), and total fluoroscopy time (21.2?±?8.6 vs. 23.9?±?5.4 min, p?=?0.15). Operator fluoroscopy exposure was significantly reduced in the RCS group (13.4?±?6.1 vs. 23.9?±?5.4 min, p?Conclusions These initial results suggest that left atrial mapping and PVI are feasible with the use of the Amigo RCS. Acute procedural efficacy is comparable to the standard approach. The use of the Amigo RCS leads to a significant reduction of operator fluoroscopy exposure.     

Ulcerative Colitis: Comparison Between Elderly and Young Adult Patients and Between Elderly Patients with Late-Onset and Long-Standing Disease

Background and Aim

We examined the pathologies, treatment characteristics, and clinical course of elderly ulcerative colitis (UC) patients.

Methods

Among 222 UC patients (127 men, 95 women; average age, 34 ± 16 years), we selected 109 with UC diagnosed between 20 and 39 years of age (young adult group) and 23 diagnosed at ≥60 years of age (elderly group). Moreover, 12 patients diagnosed between 60 and 64 years of age (late-onset group) and 6 patients aged ≥60 years diagnosed under 50 years old (long-standing group) were also extracted for sub-analysis. The clinical characteristics and course were compared among the groups.

Results

The average age at onset was 29 ± 6 years in the young adult group and 66 ± 5 years in the elderly group. The frequency of immunomodulator or steroid use did not differ between the two groups. The comorbidity rate was 14.7 % in the young adult group and 69.6 % in the elderly group (P < .0001). Seven patients (58.3 %) in the late-onset UC group and none of the patients in the long-standing UC group were on steroid treatment. None of the patients in the long-standing UC group required hospitalization/surgery for UC exacerbation, while 3 (25.0 %) and 2 patients (16.7 %) in the late-onset group required hospitalization and surgery, respectively.

Conclusions

The comorbidity rate was significantly higher in the elderly group. Treatments did not differ significantly between the young adult and elderly groups. Therefore, it appears that the inflammation tends to subside with age in elderly patients with long-standing UC.     

Effect of musculoskeletal pain on sleep architecture in patients with obstructive sleep apnea

Rationale

Obstructive sleep apnea and chronic musculoskeletal pain both affect sleep. Sleep architecture of patients suffering from both is largely unknown.

Objectives

This study seeks to define the sleep architecture of patients with chronic musculoskeletal pain and obstructive sleep apnea.

Methods

Patients with obstructive sleep apnea diagnosed by sleep study during the past 3 years were included. Patients with clinical documentation of chronic musculoskeletal pain constituted cases, while others were classified as controls.

Measurements

Demographics, clinical factors affecting sleep, medications affecting sleep, Epworth sleepiness scores, and polysomnographic parameters; total sleep time, sleep efficiency, sleep stages, rapid eye movement (REM) sleep onset, apnea–hypopnea index, arousal index, and periodic leg movements were recorded.

Results

There were 393 subjects: 200 cases (obstructive sleep apnea and chronic musculoskeletal pain) and 193 controls (obstructive sleep apnea alone). There was significant difference in total sleep time (274.5?±?62.5 vs. 302.2?±?60.1 min, p?=?0.0001), sleep efficiency (73.54?±?15.8 vs. 78.76?±?14.3 %, p?=?0.0003), and REM sleep onset (148.18?±?80.5 vs. 124.8?±?70.9 min, p?=?0.006). Subgroup analysis within the obstructive sleep apnea with chronic musculoskeletal pain group revealed that subjects had better total sleep time and sleep efficiency if they were on REM sleep affecting medications (suppressants and stimulants). Those on REM sleep suppressants slept 25.7 min longer and had 6.4 % more efficient sleep than those not on REM suppressants (p?=?0.0034 and p?=?0.0037).

Conclusion

Patients with obstructive sleep apnea and chronic musculoskeletal pain sleep not only significantly less but also with inferior sleep quality. Their REM sleep is also less in duration and its onset is delayed. Despite low TST and SE, these patients may not exhibit sleepiness.     

The Efficacy of Adefovir Plus Entecavir Combination Therapy in Patients with Chronic Hepatitis B Refractory to Both Lamivudine and Adefovir

Background

The efficacy of adefovir (ADV) plus entecavir (ETV) combination in patients with chronic hepatitis B (CHB) who developed multidrug refractoriness had not been fully evaluated. We aimed to evaluate the efficacy of ADV plus ETV as compared to that of lamivudine (LAM) plus ADV in the patients with antiviral refractoriness to sequential LAM monotherapy and then ADV monotherapy.

Methods

Twenty-seven patients were treated with a combination of ADV plus ETV and 63 patients were treated with a combination of LAM plus ADV. The virological and biochemical parameters were compared between the two groups, retrospectively.

Results

Treatment with a combination of ADV plus ETV produced significantly superior virological response than that of a combination of LAM plus ADV. At 12 months, the HBV DNA declined more in the ADV plus ETV group than in the LAM plus ADV (?4.52 ± 1.956 vs. ?2.65 ± 1.723 log₁₀IU/mL; p = 0.001). The rate of a complete response at 12 months was greater in the ADV plus ETV group than that in the LAM plus ADV group (63.16 vs. 14.81 %, p < 0.001).

Conclusion

In the patients with CHB refractory to both LAM and ADV, the response to ADV plus ETV was significantly superior compared to that of the LAM plus ADV in suppressing HBV DNA. The result indicates that ADV plus ETV can be used as a bridging therapy in the patients with refractoriness to both LAM and ADV, especially in the areas where tenofovir is not yet available.     

Risk factors associated with early- versus late-onset implantable cardioverter-defibrillator infections

Aims

The infection rates of implantable cardioverter-defibrillators systems (ICDs) are higher than that of permanent pacemaker. Risk factors associated with ICD infection have not been characterized and are the subject of the current investigation.

Methods

All patients who had an ICD implanted at Mayo Clinic Rochester between 1991 and 2008 were retrospectively reviewed. Each case of ICD infection was matched with two non-infected controls. Cases of ICD infection were further stratified by early- (??6 months) versus late-onset (>6 months) infection. Multivariable analysis was performed to identify significant risk factors for ICD infection.

Results

Sixty-eight patients with ICD infection and 136 matched controls met the inclusion criteria. Thirty-five cases presented with early-onset infection and 33 had late-onset device infection. Staphylococcal species were the most common pathogens in both groups of patients. Patients with early-onset infection were more likely to present with generator pocket infection (p?=?0.02). Patients with multiple comorbid conditions (high Charlson index) tended to have longer hospital stay during implantation admission (p?=?0.009). In a multivariable logistic regression model, the presence of epicardial leads (odds ratio (OR)?=?9.7, p?=?0.03) and postoperative complications at the generator pocket (OR?=?27.2, p?<?0.001) were significant risk factors for early-onset ICD infection, whereas longer duration of hospitalization at the time of implantation (2 days versus 1 day: OR?=?33.1, p?<?0.001; ??3 days versus 1 day: OR?=?49.0, p?<?0.001) and chronic obstructive pulmonary disease (OR?=?9.8, p?=?0.02) were associated with late-onset infections.

Conclusions

Our study findings suggest that risk factors associated with early- and late-onset ICD infection are different. While circumstances that may increase the chances of pocket contamination in the perioperative period are more likely to be associated with early-onset ICD infection, overall poor health of the host may increase the likelihood of late-onset ICD infection. These factors should be considered when developing strategies to minimize risk of device infection.     

The effect of continuous positive airway pressure therapy on blood pressure and arterial stiffness in hypertensive patients with obstructive sleep apnea

Aim

We aimed to evaluate the effect of continuous positive airway pressure (CPAP) therapy on blood pressure (BP) and arterial stiffness in hypertensive patients with obstructive sleep apnea (OSA).

Patients and methods

We studied 38 hypertensive patients who suffered from severe OSA. Ambulatory BP measurement was performed at baseline and after at least 3 months of uninterrupted CPAP therapy. In 19 of these patients, we also measured pulse wave velocity (PWV) at baseline, after the first night of CPAP therapy and at 3 months. Fifteen normotensive subjects without OSA comprised the control group.

Results

CPAP therapy reduced systolic BP from 141.5?±?12.1 to 133.5?±?9.7 mmHg (p?=?0.007) and diastolic BP from 87.8?±?6.8 to 83?±?5.4 mmHg (p?=?0.004). CPAP also reduced the PWV from 8.81?±?1.4 to 8.18?±?1 m/s after the first night of CPAP therapy (p?=?0.003) and to 7.37?±?1 m/s at 3 months (p?=?0.007).

Conclusions

To the best of our knowledge, this is the first study demonstrating that CPAP therapy in hypertensive patients with OSA improves arterial stiffness from the first night and that this favorable effect is maintained for at least 3 months of CPAP use. A reduction in BP was also observed, even though BP control was not always achieved.     

Endoscopic Minor Papilla Sphincterotomy in Patients with Santoriniceles Reduces Pain and Improves Quality of Life

Background

Pancreas divisum patients with focal obstruction of the minor papilla and resulting dilation of the dorsal pancreatic duct [a santorinicele (SC)] have been reported to improve with endoscopic sphincterotomy of the minor papilla (ESMP). In this study, we assess the long-term efficacy of ESMP in SC patients.

Methods

A retrospective review of the endoscopic database was performed. Fifteen patients with SCs were identified. A follow-up questionnaire was mailed to patients to assess for changes in quality of life (QOL), narcotic use, hospital admissions, and pain after ESMP.

Results

Fifteen patients were mailed questionnaires and 11 responses were obtained. The average pain score prior to ESMP was 8.6/10 (SD ± 1.7) and significantly decreased to 2.7/10 (SD ± 2.0) (p < 0.05) after treatment. Six patients required narcotics before ESMP and none used narcotics for recurrent pancreatic type pain after. Nine patients had recurring admissions for pancreatitis prior to ESMP while only two were admitted after treatment. Mean QOL score prior to ESMP was 4.5/10 (SD ± 2.7) and increased significantly to 8.4/10 (SD ± 1.3) (p < 0.05) with two patients rating their QOL at 10/10.

Conclusions

QOL, narcotic use, hospital admissions, and pain scores all improved with ESMP. Endoscopic therapy for this uncommon condition appears both justified and potentially curative.     

Exercise Capacity and Ventilatory Response During Exercise in COPD Patients With and Without β Blockade

Background

Although β blockade (BB) in patients with chronic obstructive pulmonary disease (COPD) does not show signs of worsening pulmonary function or respiratory symptoms, the effects on cardiopulmonary exercise testing (CPET) remain unclear. The aim of this study was to determine whether BB affects exercise capacity, gas exchange, and hemodynamic responses in patients with COPD.

Methods

Twenty-four COPD subjects on BB were matched to 24 COPD subjects without BB according to age, gender, body mass index, and severity of COPD. All subjects underwent resting pulmonary function and symptom-limited CPET.

Results

Comparing COPD patients with and without BB revealed that percent peak oxygen consumption and VE/VCO₂ nadir were not significantly different (45 ± 16 vs. 51 ± 23 %, p = 0.30, and 35.1 ± 8.5 vs. 36.2 ± 11.6 %, p = 0.69). Systolic blood pressure and heart rate at peak exercise were significantly decreased in COPD patients with BB (168 ± 16 vs. 185 ± 20 mmHg, and 109 ± 16 vs. 122 ± 14 bpm, respectively, p < 0.05).

Conclusion

Exercise capacity and gas exchange remain unaffected in patients with COPD in the presence of BB, although heart rate and blood pressure are lower. These findings imply that BB does not adversely affect functional capacity in patients with COPD.     

Sacral nerve stimulation for fecal incontinence improves symptoms, quality of life and patients' satisfaction: results of a monocentric series of 119 patients

Purpose

Sacral nerve stimulation (SNS) is validated as an efficient treatment for fecal incontinence (FI). However, long-term results are scarce in the literature. The goal of this study was to assess the impact of SNS on FI symptoms and quality of life, based on a retrospective analysis of prospectively collected data.

Methods

From 2001 to 2009, 119 patients (six men, mean age 61 years) underwent SNS testing for FI after an extensive diagnostic workup. Permanent implantation was realized when FI symptoms improved during testing, and follow-up visits were performed every 12 months thereafter. This follow-up evaluated morbidity and efficacy, based on clinical data and self-administered questionnaires including Jorge and Wexner FI score, urinary incontinence score (urinary distress inventory-6, UDI-6), gastrointestinal quality of life index (GIQLI), and auto-evaluation scale.

Results

A permanent stimulator was implanted after a positive test in 102 patients (91 %). Ten patients were explanted during follow-up (pain in one case and absence of efficacy in nine), and 29 had the stimulator and/or the electrode changed. The mean follow-up was 48 months (range 12–84): there was a significant improvement of FI score (9?±?1 vs 14?±?3, p?<?0.0001), UDI-6 score (8?±?4 vs 11?±?5, p?<?0.05), and GIQLI index (p?<?0.002). The improvement was present at 12 months follow-up and remained stable. Eighty percent of patients were satisfied with the treatment at the last point of follow-up. None of the pretreatment variables were predictive of SNS efficacy.

Conclusions

SNS improved FI and quality of life, and this efficacy remained over time. Although a complete disappearance of FI was rare, most patients were satisfied.