P

#

Gecontroleerde zoektermen

A

"amyotrophic lateral sclerosis"[MeSH Terms]

B

32277

"amyotrophic lateral sclerosis"[MeSH Terms] OR ("amyotrophic"[All Fields] AND "lateral"[All Fields] AND "sclerosis"[All Fields]) OR "amyotrophic lateral sclerosis"[All Fields] OR ALS[All Fields] OR "progressive spinal muscular atrophy"[All Fields] OR "Motorneuron disease"[All Fields]

I

"noninvasive ventilation"[MeSH Terms]

C

9076

"noninvasive ventilation"[MeSH Terms] OR ("noninvasive"[All Fields] AND "ventilation"[All Fields]) OR "noninvasive ventilation"[All Fields] OR "non-invasive ventilation"[All Fields] OR "non invasive ventilation"[All Fields] OR "noninvasive ventilations"[All Fields] OR "non-invasive ventilations"[All Fields] OR "non invasive ventilations"[All Fields] OR "Ventilation, Noninvasive"[All Fields] OR "Ventilation, Non-invasive"[All Fields] OR "Ventilation, Non invasive"[All Fields] OR "noninvasive ventilatory support"[All Fields] OR "non-invasive ventilatory support"[All Fields] OR "non invasive ventilatory support"[All Fields] OR "home mechanical ventilation"[All Fields] OR "nocturnal ventilation"[All Fields] OR "non-invasive positive pressure ventilation"[All Fields] OR "noninvasive positive pressure ventilation"[All Fields] OR "non invasive positive pressure ventilation"[All Fields]

D

Initiation OR Adaptation OR implementation OR early

PICO

b+c

490*

b+c+d

allocation concealment (selection bias)

blinding (performance bias and detection bias)

incomplete outcome data (attrition bias)

selective reporting (reporting bias)

Bourke, 2006

Low risk

High risk

Low risk

Low risk

Jacobs, 2016

Low risk

Low risk

Low risk

Low risk

Failure to apply appropriate eligibility criteria

Flawed measurement of exposure and outcome

Failure to control for confounding

Incomplete follow-up

Pinto, 1995

Low risk

Low risk

Low risk

Low risk

Mustfa, 2006

Low risk

Low risk

Low risk

High risk

Sancho, 2017

High risk

Low risk

Low risk

Low risk

Lyall, 2001

High risk

Low risk

High risk

High risk

Newsom-Davies, 2001

High risk

Low risk

Low risk

Low risk

Chio, 2011

High risk

Low risk

Low risk

Low risk

Burkhardt, 2017

High risk

Low risk

Low risk

Low risk

Dreyer, 2013

High risk

Low risk

Low risk

Low risk

Hirose, 2018

High risk

Low risk

Low risk

Low risk

Sanjuan-Lopez, 2017

High risk

Low risk

Low risk

Low risk

Siirala, 2013

Low risk

Low risk

Low risk

Low risk

Zamietra, 2011

High risk

Low risk

Low risk

Low risk

Berlowitz, 2016

Not clear

Low risk

Low risk

Low risk

Cedarbaum, 2001

Not clear

Not clear

High risk

Not clear

Kleopa, 1999

Low risk

Low risk

High risk

Low risk

Shoesmith, 2007

Not clear

Low risk

High risk

Low risk

Carratu, 2009

Low risk

Low risk

High risk

Low risk

Quality assessment

No. of patients

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

NIV

No NIV

Quality

Survival

2

RCT

Serious¹

Not serious

Not serious

Serious²

50

45

ÅÅ¡¡

13

OBS

Serious³

Not serious

Not Serious

Not serious

854

1874

Å¡¡¡

Quality of life

1

RCT

Serious¹

Not serious

Not serious

Serious²

22

19

ÅÅ¡¡

3

OBS

Serious³

Not serious

Not serious

Serious²

53

50

Å¡¡¡

Study reference

Study characteristics

Patient characteristics

Measures

Conclusion

Comments

Bourke, 2006

Country: UK

Type of study: RCT

Type of patients: Patients were subsequently randomly assigned to NIV or standard care if and when they met one or both of the predefined criteria: orthopnoea with PImax less than 60% of that predicted or symptomatic daytime hypercapnia

N in analysis: 41

NIV: 22

No NIV: 19

Age and gender:

Age (yrs) 63·7 (10·3) vs 63·0 (8·1)

Sex (male) 14 (64%) vs 10 (53%)

Intervention: NIV versus standard care

Follow-up: at least 12 months or until death

Outcome measures:

• Quality of life (SF36 MCS and SAQLI symptoms domain)
• Survival

In patients with amyotrophic lateral sclerosis without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy. In patients with severe bulbar impairment, NIV improves sleep-related symptoms, but is unlikely to confer a large survival advantage.

Jacobs, 2016

Country: USA

Type of study: RCT

Type of patients: Eligible participants were 18 years of age or older and diagnosed with probable or definite ALS by El Escorial criteria. Exclusion criteria were forced vital capacity (FVC),50% predicted, current involvement in a clinical treatment trial, previous or current use of positive pressure ventilation equipment (as this could unmask participants), oxygen therapy, previous pneumothorax, and bullous emphysema.

N in analysis: n=54 (active NIV: n=28, sham NIV: n=26)

Age and gender:

Active NIV: median age 57.5, 15 male

Sham NIV: median age 61, 14 male

Intervention: Patients with ALS were randomized to receive either sham NIV or active NIV and underwent active surveillance approximately every 3 months until they reached a forced vital capacity (FVC),50% or required NIV for clinical symptom management.

Outcome measures:

• NIV use
• FVC
• Survival
• maximal inspiratory or expiratory pressure

While our study was not powered to detect differences in clinical outcome by treatment group, better respiratory function outcomes in the active NIV group were suggested, specifically with a significant attenuation of the monthly decline in FVC% for the active NIV group compared to sham NIV group.

Study

Relevant results

Bourke, 2006

NIV improved TiMCS, Tisym, _MCS, _sym, and survival in all patients and in the subgroup with better bulbar function (n=20). This subgroup showed improvement in several measures of quality of life and a median survival benefit of 205 days (p=0·006) with maintained quality of life for most of this period. NIV improved some quality-of-life indices in those with poor bulbar function, including _sym (p=0·018), but conferred no survival benefit.

Jacobs, 2016

The mean NIV use was 2.0 hours (95% confidence interval [CI] 1.1–3.0) per day in the sham NIV treatment group and 3.3 hours (CI 2.0–4.6) per day in the active NIV group, which did not differ by treatment group (p 5 0.347). The majority of sham NIV participants (88%) and active NIV participants (73%) reported only mild or no problem with NIV use. Difference of change in FVC through the treatment period by group (0.44 per month) favored active NIV (p 5 0.049). Survival and changes in maximal inspiratory or expiratory pressure did not differ between treatment groups.

Study reference

Study characteristics

Patient characteristics

Measures

Conclusion

Comments

Pinto, 1995

Country: Portugal

Type of study:

non-randomised prospective observational

study

Type of patients:

ALS bulbar patients

N in analysis:

20 (2 were excluded in a later stage)

(I: 10 palliative management,

II: 10 Bipap support)

Age and gender:

11 males and 9 females

age ranged from 51-69 years (mean age 57 years).

Intervention:

20 ALS consecutive patients with bulbar features and with definite or probable disease according to El Escorial criteria. After the onset of abnormalities in diurnal gas exchanges:

• The first 10 patients were treated with oxygen, bronchodilators and other palliative measures, control group.
• The following 10 patients were submitted to Bipap.

Outcome measures:

Survival

In spite of the small number of patients, preliminary results strongly support the importance of BIPAP in ALS patients, though further studies must go on in order to optimize the best time for introducing Bipap.

Mustfa, 2006

Country:

UK

Type of study:

Prospective observational study

Type of patients: patients with clinical and electrophysiologic evidence fulfilling El Escorial criteria for definite, probable, or possible ALS

N in analysis:

Twenty-six were established on NIV, 13 declined or could not tolerate NIV (untreated group). 15 patients without respiratory muscle weakness (RMW) but with similar ALS severity and age were studied in parallel (control)

Age and gender:

The mean age and range

• NIV: 60 yrs; 41 to 76 yrs
• unable to tolerate or declining NIV: 67yrs; 46 to 82 yrs
• without RMW: 60 years; 40 to 77 yrs.

Intervention:

Criteria for NIV were symptoms characteristic of severe RMW, such as orthopnea, unrefreshing sleep, daytime somnolence, and reduced appetite

Outcome measures:

• survival
• Quality of life
• Quality of life of caregivers

Noninvasive ventilation (NIV) improves QoL despite ALS progression. NIV has no impact on most aspects of caregiver QoL and does not significantly increase caregiver burden or stress.

Comparison between NIV patients (n=13) and no RMW patients (n=15). No comparison between NIV and group that refused/not tolerated NIV

Sancho, 2017

Country: Spain

Type of study: prospective observational

Type of patients: patients diagnosed with definitive or probable ALS were included, according to the revised El Escorial criteria, in whom NIV was initiated. Those patients who refused NIV were taken as the control group.

N in analysis: 140 (120 NIV, 20 controls

Age and gender:

Age NIV: 64.05±9.11 No NIV: 66.05±10.27

Males/females NIV:56/64 No NIV: 6/14

Intervention: NIV was indicated in the presence of any of the following criteria: presence of hypoventilation symptoms (dyspnoea, orthopnoea, fatigue, morning headache, daytime hypersomnolence and decreased cognitive function), arterial carbon dioxide tension (Pa_CO2) >45 mmHg, time spent with oxygen saturation measured by pulse oximetry (SpO2) <90% at night (%sleepSpO2<90) being >5% and forced vital capacity <50% of predicted.

Outcome measures:

• Survival

The findings of the present study show that volume-cycled NIV prolongs survival not only in ALS patients with no or moderate bulbar dysfunction, but also in some with severe bulbar impairment, demonstrating the usefulness of these procedures if the relevant expertise is available.

Lyall, 2001

Country: UK

Type of study: prospective observational

Type of patients: patients with ALS with symptoms of sleep-disordered breathing (daytime somnolence, poor appetite, morning headache, orthopnea, and dyspnea) in whom investigations had established the presence of respiratory muscle weakness, hypoventilation, and sleep-disordered breathing.

Control subjects were patients with ALS identified as having normal diaphragm function. Control subjects were selected if they had similar levels of generalized disability

but no evidence of sleep-disordered breathing

N in analysis: NIPPV group: n=16, control: n=11

Age and gender: NIPPV: 61.3 (SD, 6.8) years, control group: 61.2 (7.6) years.

NIPPV: 2 women, control: 1 women

Intervention: Patients initially used ventilation at night, but as respiratory muscle strength declined it was used to treat daytime dyspnea, with several patients eventually requiring continuous ventilation.

Outcome measures:

• vitality function
• quality of life

Noninvasive positive pressure ventilation improved scores in the “Vitality” domain by as much as 25%, for periods of up to 15 months, despite disease progression. Noninvasive positive pressure ventilation did not cause reduced quality of life, as any fall in scores in the ventilated group were comparable to those seen in a control group. In conclusion, noninvasive positive pressure ventilation enhances quality of life when used to treat sleep-disordered breathing in patients with ALS.

Control group not comparable with NIPPV group in sleep-disordered breathing

Newsom-Davies, 2001

Country: UK

Type of study: prospective observational

Type of patients: The NIPPV group consisted of nine patients with a diagnosis of possible, probable, or definite ALS, as defined by the El Escorial criteria, and evidence of hypoventilation and sleep disturbance.

control group: patients with ALS without any evidence of respiratory difficulty or sleep disturbance

N in analysis: NIPPV: n=9, control: n=10

Age and gender: NIPPV: 61.11 (7.83), control: 61.90 (6.97)

NIPPV: 0 women, control: 3 women

Intervention: 6 weeks NIPPV during the night

Outcome measures:

• cognitive function

Nocturnal hypoventilation and sleep disturbance may cause cognitive dysfunction in ALS. These deficits may be partially improved by NIPPV over a 6-week period.

Control group no respiratory difficulty

Study reference

Study characteristics

Patient characteristics

Measures

Conclusion

Comments

Chio, 2011

Country: Italy

Type of study: registry

Type of patients: ALS incident cases in two Italian regions

N in analysis: 1260 cases

NIV: 259

No NIV: 1001

Age and gender: 687 men and 573 women, mean age: 64.9 years (SD 11.2; range 20-90)

Intervention: In 1995, criteria for the prescription of NIV were presence of respiratory signs and symptoms (dyspnoea at rest or during exertion, orthopnoea, morning headache, disturbed sleep, daytime hypersomnolence, weak cough) and/or vital capacity <50% or 1 l and/or arterial blood gas analysis showing morning pCO2 ³45 mm Hg (6 kPa).11 In 1999, we also considered nocturnal oxygen desaturation for more than 5 consecutive minutes. It should be noted that during the first 5 years of the study, only three hospitals in Piemonte had services for NIV. Each neurologist in the region could refer his/her patients to these services. After 2000, a regional network for NIV was implemented, and more than 10 centres for NIV were established.

Outcome measures:

• survival
• factors affecting survival (multivariate)

In an epidemiological setting, NIV represents an increasingly utilised option for the treatment of respiratory disturbances in ALS and has favourable effects on survival, in particular among patients followed by tertiary ALS centres. Sociocultural factors, such as age, gender and marital status, strongly influence the probability of undergoing NIV. Efforts should be made to remove these obstacles in order to spread the use of NIV in all ALS patients with respiratory

failure.

There are different reasons for not using NIV in control group (depends on center, criteria, etc)

Difference between respiratory insuffiency between cases and controls not known

Burkhardt, 2017

Country:

Switzerland

Type of study:

retrospective

Type of patients: deceased ALS patients

N in analysis: 71 (33 NIV-, 38 NIV+)

Age and gender:

NIV- 64.4 yrs

NIV+ 61.3 yrs

Intervention: The indication for initiation of NIV was, as recommended by the guidelines based on clinical signs of respiratory insufficiency in combination with respiratory parameters (forced vital capacity and sniff nasal pressure) with subsequent, nocturnal polysomnography

Outcome measures: survival

The use of NIV and PEG prolongs survival in ALS.

Dreyer, 2013

Country:

Denmark

Type of study:

retrospective single-centre study

Type of patients: all patients in whom ALS had been diagnosed according to standard criteria and who were referred

to Respiratory Centre West (west Denmark)

N in analysis: 409 patients were included in the study, divided into four groups: 1) no treatment (n=146); 2) treatment with non-invasive HMV (n=173); 3) treatment with non-invasive HMV followed by invasive HMV by tracheostomy (n=69); and 4) treatment with invasive HMV by tracheostomy (n=21).

Age and gender: 164 females and 245 males with an average age of 62.0 (range 23 – 97) years

Intervention: The

criteria for HMV were presence of respiratory signs and symptoms and/or vital capacity < 50% and/or morning pCO₂ ³ 45 mmHg (6 kPa) and/or nocturnal oxygen desaturation for more than 5 consecutive min.

Outcome measures:

• survival
• factors influencing survival

Non-invasive HMV followed by invasive HMV is a possible treatment of respiratory symptoms in ALS and has a significant effect on survival.

Also effect of invasive ventilation was studied

Hirose, 2018

Country:

Japan

Type of study: retrospective

Type of patients: patients followed at the Osaka Medical College Hospital

N in analysis:

197 in total, 114 from year 2000

59 of 114 patients used NIV

Age and gender: -

Intervention: Since 2000, NIV therapy has been offered to all participants who presented clear evidence of respiratory muscle involvement related to hypoventilation with at least 1 criterion (pCO2 ≥45 mm Hg, dyspnea at night, or %FVC <50). All patients were followed until death from natural causes or at the time of TIV (first end point), death following NIV, at the time when NIV was transitioned to TIV (second end point), or at death following TIV (third end point).

Outcome measures:

• Survival
• Characteristics of patients transitioning to TIV

This study confirmed a positive survival effect with NIV, which was less effective in patients with bulbar dysfunction.

Sanjuan-Lopez, 2017

Country: Spain

Type of study: retrospective

Type of patients: Patients with a definitive or probable diagnosis of ALS determined by a neurologist according to the revised El Escorial criteria were included.

N in analysis: 114

43 NIV (37 only NIV)

7 IV (6 of them first NIV)

Age and gender:

57 (50%) men and 57 (50%) women

67.3±10.8 years

Intervention:

After respiratory assessment by the treating pulmonologist, all patients with respiratory failure, according to established criteria, were offered a mechanical ventilation device.

Outcome measures:

• survival

Long-term mechanical ventilation prolongs survival in ALS.

Also effect of invasive ventilation was studied

Siirala, 2013

Country:

Finland

Type of study: retrospective

Type of patients: patients fulfilling the El Escorial World Federation criteria for probable or definitive ALS

N in analysis: 84

Group 1 (£ 65): 23 NIV, 19 no NIV

Group 2 (> 65): 18 NIV, 24 no NIV

Age and gender:

Group 1 (male/female): NIV 10/13, no NIV 10/9

Median age 59 years (range 49 – 65)

Group 2 (male/female): NIV 9/9, no NIV 8/16

Median age 76 years (66 – 85)

Intervention: NIV and other palliative treatments were offered to all the patients. 84 patients were included and retrospectively divided into two groups based on their age at the time of the diagnosis: Group 1 (age ≤ 65 years) and Group 2 (age > 65 years). Both groups were then subdivided further based on patients´ ability to tolerate the NIV. These were designated as the NIV Group and the Conventional Group

Outcome measures:

• survival

This retrospective study found that NIV use was associated with improved survival outcomes in ALS

patients older than 65 years.

Zamietra, 2011

Country: USA

Type of study: retrospective

Type of patients: patients seen at a multidisciplinary ALS clinic between July 2008 and December 2010 with clinically definite, probable, probable laboratory supported,

or possible ALS who had received NIPPV or PEG and in whom QoL assessments and measures of physical function were obtained at the last routine ALS clinic visit prior to intervention

(pre-intervention assessment), and for two consecutive visits post-intervention (post-intervention 1 and 2 assessments).

N in analysis: 22 patients: 6 in the NIPPV group, 11 in the PEG group, and 5 in the NIPPV/PEG group

Age and gender:

N=12 male

58.9 ± 12.7,

Intervention: Patients were divided into three groups: 1) NIPPV alone; 2) PEG alone; 3) NIPPV and PEG during the time-interval between the pre-intervention and post-intervention 1 assessments

Outcome measures:

• Quality of life (ALSSQoL-R)

In conclusion, overall QoL in ALS does not appear to change after NIPPV or PEG. This may reflect the impact of non-health-related factors or may be due to a response shift.

Berlowitz, 2016

Country: Australia

Type of study: retrospective analysis

Type of patients: Data from all patients with ALS/MND included in the Bethlehem Hospital ALS/MND database between 1991 and 2011 were included.

N in analysis: n=929

NIV: 219

No NIV 711

Age and gender:

NIV: 58.3 ±11.5, % male 71.7

No NIV: 64.0 ±11.9, % male 52.8

Intervention: Patients were categorised into four clinical phenotypes (ALS, flail arm, flail leg and PLS) according to site of presenting symptom and the pattern of upper versus LMN involvement. NIV was not routinely prescribed until 2002.

After 1999, criteria for offering NIV initiation followed the recommendations by the American Academy of Neurology ALS Practice Parameter. If the team determines that ventilation is not required at the time of referral, patients are reviewed and offered ventilation when indicated.

Outcome measures:

• Tracheostomy-free survival
• Decline in pulmonary function

These data

confirm that NIV improves survival in MND/ALS. The overall magnitude of benefit is 13 months and was largest in those with ALS-bulbar disease.

Bulbar subgroup

Cedarbaum, 2001

Country: USA

Type of study: retrospective analysis

Type of patients: 387 placebo patients in a Phase III trial of r-metHuBDNF were followed

for 9 months.

N in analysis: MV 35 (28 bipap, 7 TIV)

No MV: 352

Age and gender: ?

Intervention: Data pertaining to ventilatory support were not a prospectively defined end-point for the trial. To generate the data used for this analysis, information captured on adverse event and health resource utilization case report forms was combined retrospectively after the end of the trial.

Outcome measures:

• survival

Of the 9% of placebo patients who received MV, BiPAP patients were more rapidly progressing than non-BIPAP patients, and showed a greater eventual mortality rate.

There is no (randomized) control group of patients with similar baseline characteristics, large difference in baseline FVC

Kleopa, 1999

Country: USA

Type of study: retrospective analysis

Type of patients: Patients diagnosed with ALS according to the El Escorial criteria who were followed in the ALS Clinical Center at Hahnemann University Hospital between 1993 and 1997. The patients were divided retrospectively into three groups: Group 1 accepted Bipap and was able to tolerate it well, using it 4 or more h per day. Group 2 also accepted Bipap but did not tolerate it well and used it less than 4 h per day. Finally, Group 3 refused to try Bipap.

N in analysis: group 1: n=38, group 2: n=32, group 3: n=52

Age and gender: 62.2±11.8, male=52, female=70

Pulmonary function at baseline comparable

Intervention: Bipap was offered to all patients in our clinic when they presented with symptoms of respiratory insufficiency when their FVC dropped below 50% of predicted, or if their FVC dropped more than 15% within a three month period

Outcome measures:

• survival
• pulmonary function

We conclude that Bipap can significantly prolong survival and slow the decline of FVC in ALS. Our results suggest that all patients with ALS be offered Bipap when their FVC drops below 50%, at the onset of dyspnea, or when a rapid drop in %FVC is noted.

Bulbar subgroup

Shoesmith, 2007

Country: Canada

Type of study:

Retrospective analysis

Type of patients: ALS patients with respiratory onset

N in analysis: n=21 (NIPPV: n=9, no NIPPV: n=13)

Age and gender: mean: 65.7±7.1. 16 men, 5 women

Intervention: NIPPV in the form of bilevel NIPPV

Outcome measures:

• survival

Non-invasive positive pressure ventilation (NIPPV) significantly improved survival compared with those who did not use NIPPV.

Effect of NIPPV was not the primary aim of the study

Carratu, 2009

Country: Italy

Type of study: retrospective analysis

Type of patients: Twenty-eight patients presented a FVC < 75% and nocturnal respiratory insufficiency at polysomnography, requiring NPPV. Sixteen were treated with NPPV, while twelve refused or were intolerant to NPPV.

N in analysis: n=28 NIV: 16, no NIV: 12

Age and gender:

NIV: age 55.93 (5.09), male: 9

No NIV: 57.54 (6.54), male 7

Intervention: Patients were instructed to use noninvasive positive-pressure ventilation nightly as tolerated and as necessary in the daytime, according to previous reports. Tolerance was defined as the ability to sleep nightly while receiving noninvasive positive-pressure ventilation for at least 4 consecutive hours.

Outcome measures:

• survival

This report demonstrates that early treatment with NPPV prolongs survival and reduces decline of FVC% in ALS

P

#

Gecontroleerde zoektermen

A

"amyotrophic lateral sclerosis"[MeSH Terms]

B

32277

"amyotrophic lateral sclerosis"[MeSH Terms] OR ("amyotrophic"[All Fields] AND "lateral"[All Fields] AND "sclerosis"[All Fields]) OR "amyotrophic lateral sclerosis"[All Fields] OR ALS[All Fields] OR "progressive spinal muscular atrophy"[All Fields] OR "Motorneuron disease"[All Fields]

I

"noninvasive ventilation"[MeSH Terms]

C

9076

"noninvasive ventilation"[MeSH Terms] OR ("noninvasive"[All Fields] AND "ventilation"[All Fields]) OR "noninvasive ventilation"[All Fields] OR "non-invasive ventilation"[All Fields] OR "non invasive ventilation"[All Fields] OR "noninvasive ventilations"[All Fields] OR "non-invasive ventilations"[All Fields] OR "non invasive ventilations"[All Fields] OR "Ventilation, Noninvasive"[All Fields] OR "Ventilation, Non-invasive"[All Fields] OR "Ventilation, Non invasive"[All Fields] OR "noninvasive ventilatory support"[All Fields] OR "non-invasive ventilatory support"[All Fields] OR "non invasive ventilatory support"[All Fields] OR "home mechanical ventilation"[All Fields] OR "nocturnal ventilation"[All Fields] OR "non-invasive positive pressure ventilation"[All Fields] OR "noninvasive positive pressure ventilation"[All Fields] OR "non invasive positive pressure ventilation"[All Fields]

D

Initiation OR Adaptation OR implementation OR early

PICO

b+c

490*

allocation concealment (selection bias)

blinding (performance bias and detection bias)

incomplete outcome data (attrition bias)

selective reporting (reporting bias)

Jackson, 2001

Low risk

Low risk

High risk

Low risk

Failure to apply appropriate eligibility criteria

Flawed measurement of exposure and outcome

Failure to control for confounding

Incomplete follow-up

Pinto, 2003

Not clear

Low risk

Low risk

Low risk

Terzano, 2015

Low risk

Low risk

High risk

Low risk

Khamankar, 2018

Low risk

Low risk

Low risk

Low risk

Lechtzin, 2007

Low risk

Low risk

Low risk

Low risk

Vitacca, 2017

Not clear

Low risk

Low risk

Low risk

Quality assessment

No. of patients

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

NIV

No NIV

Quality

Survival

3

OBS

Not serious

Not serious

Not Serious

Serious

114

214

Å¡¡¡

Quality of life

1

RCT

Serious¹

Not serious

Not serious

Serious²

7

6

ÅÅ¡¡

Study reference

Study characteristics

Patient characteristics

Measures

Conclusion

Comments

Jackson, 2001

Country:

Type of study:

RCT

Type of patients:

Patients recruited from ALS centers

N in analysis:

7 participants with ALS in early NIPPV group and 6 participants in late NIPPV group

Age and gender: not provided

Intervention: Early NIPPV (FVC 70% to 100%) and late (“standard of care”) NIPPV (FVC < 50%)

Outcome measures:

• survival at 3 months,
• Quality of life (SF-36, ALSFRS-R, and SAQLI)

Follow-up: 3 months

Our data suggest that initiation of NPPV earlier than our current standard of care may result in improved quality of life.

Incomplete data, so no results on survival

Study

Relevant results

Jackson, 2001

Seven patients randomized to Group 1 have been initiated on NPPV and all have remained compliant with treatment (defined as use >4r24 h day). Six of these patients have returned for their 3-month post-randomization visit. Five out of six patients showed an increase in the “vitality” subscale of the SF-36 (mean before 10.7 vs. after 13.0, p=0.071) and 3/6 patients reported fewer respiratory symptoms. Five of the six patients randomized to NPPV showed improvement in their pulmonary symptomscore (mean before 72.7 vs. after 80.8, p=0.04). There was no significant improvement in the ALSFRS-R or the SAQLI 3 months following treatment with NPPV.

Study reference

Study characteristics

Patient characteristics

Measures

Conclusion

Comments

Pinto, 2003

Country: Portugal

Type of study: prospective observational study

Type of patients: Group 1 (historical control group): ALS patients, in whom we used NIV after detecting early signs of diurnal respiratory insufficiency (RI).

Group 2: ALS patients, for whom we started NIV after detecting more than 15 periods of nocturnal desaturation/hour by NPO.

N in analysis: n=42

Group 1: n=24

Group 2: n=18

Age and gender:

Group 1: 60±13 years, 10 bulbar onset forms. Group 2: 56±11 years, 8 bulbar onset forms

Intervention: Patients were classified as Group 1 if on follow-up they were introduced to NIV after showing partial or global signs of RI (PaO₂<80mmHg, with or without PaCO₂>45 mmHg).

Group 2 started NIV after detecting more than 15 periods of nocturnal desaturation/hour by NPO.

Outcome measures:

• survival

Total survival and survival with NIV were longer in Group 2, supporting the hypothesis that when NIV is prescribed before diurnal respiratory insufficiency develops, survival is increased.

Terzano, 2015

Country: Italy

Type of study: prospective observational study

Type of patients: Group A: patients who started NIV from Time 0.

Group B: patients who refused NIV at Time 0 and subsequently started with the worsening of symptoms and signs.

N in analysis: 36 patients, 20 patients in the Group A and 16 in the Group B.

Age and gender: 17 women and 29 men, mean age 63.7 ± 10.4 years

Intervention: 4 month intervention period

Outcome measures:

• pulmonary function tests
•  arterial blood gas analysis

Our study highlights the importance of noninvasive mechanical ventilation as a treatment for ALS patients and also shows the early start of NIV as an important approach in order to postpone the functional decline and the decrease of respiratory muscle strength.

Study reference

Study characteristics

Patient characteristics

Measures

Conclusion

Comments

Khamankar, 2018

Country: UK

Type of study: retrospective analysis

Type of patients: patients seen at a tertiary ALS specialty clinic. Only deceased ALS patients with complete clinic and Bi-PAP treatment records for all visits were included.

N in analysis: 474 patients (403 Bi-PAP users, 71 nonusers)

Age and gender:

<55 years 32.11%

55–65 years 29.91%

>65 years (37.98%

Male 59.62%

Female 40.38%

Intervention: Survival duration (time elapsed from baseline onset until death) is compared on the basis of Bi-PAP initiation threshold (FVC %predict); daily Bi-PAP usage protocol (hours/day); daily cough assist usage (users or non-users); ALS onset type; ALSFRS-R score; and time elapsed from baseline onset until Bi-PAP initiation, using Kruskal-Wallis one-way analysis of variance and Kaplan Meier.

Outcome measures:

• Survival
•  

The “optimized” NIV protocol (Bi-PAP initiation while FVC %predict ³80, Bi-PAP usage >8 h/day, daily cough assist usage) has a 30.8 month survival median, which is double that of a “standard” NIV protocol (initiation FVC %predict <50, usage >4 h/day, no cough assist). Earlier access to Bi-PAP and cough assist, prior to precipitous respiratory decline, is needed to maximize NIV synergy and associative survival benefit.

Lechtzin, 2007

Country: USA

Type of study: retrospective analysis

Type of patients: adults with probable to definite ALS, diagnosed between 1998 and 2005. It was approved by the institutional review board. Entry into the study was limited to patients who used NPPV for at least four hours per 24-h period, and had spirometry performed within three months of the time NPPV was prescribed.

N in analysis: early group: n=25

Standard group: n=67

Age and gender:

Age Early: 59.4±2.7

Age Standard: 63.2±1.1

% Male Early: 64.0

% Male standard: 56.7

Intervention: comparing survival from time of diagnosis in subjects who started NPPV use when their FVC was >65% predicted (Early NPPV) with subjects who started NPPV when their FVC was below 65% predicted (Standard NPPV). The Early group (n=25) and the Standard group (n=67) were similar except for pulmonary function (mean FVC in Early NPPV group=74.3±10.1% predicted and 48.3±11.3 in Standard group, p<0.001)

Outcome measures:

• survival

Until more definitive data are available from randomized trials, our findings suggest that clinicians either encourage earlier use of NPPV or use more sensitive tests for respiratory muscle impairment than upright FVC.

Vitacca, 2017

Country: Italy

Type of study: retrospective analysis

(and post hoc analysis)

Type of patients: study conducted on an institutional database derived from medical charts of ALS patients admitted to three Italian facilities, ICS Maugeri Lumezzane

(Brescia), Don Gnocchi Foundation IRCCS - Onlus (Milano) and NEMO Clinical Centre (Milano), in the period 2008–2013.

N in analysis:

2017: Later group: n=129, very early group: n=65

Age and gender:

Later group: 64.66 ± 11.33

Very early group: 62.62 ± 11.34

Intervention: 194 ALS patients, divided into a later group (LG) with FVC <80% at NIV prescription and a very early group (VEG) with FVC ≥80% at NIV prescription. Clinical and respiratory functional data and time free to death between groups over a 3-year follow-up were compared.

Outcome measures:

• survival

Very early NIV prescription prolongs the free time from diagnosis to death in NB ALS patients whilst tracheotomy reduces the mortality risk in all patients.

Also results on the effect of tracheotomy (At 3-year follow-up, tracheotomy was needed in 23.1% (15/65) of VEG vs. 41.9% (54/129) of LG (P = 0.009) patients.)

Study

Relevant results

Khamankar, 2018

Bi-PAP users’ median survival (21.03 months, IQR = 23.97, N = 403) is significantly longer (p < 0.001) than non-users (13.84 months, IQR = 11.97, N = 71). Survival consistently increases (p < 0.01) with FVC % predict Bi-PAP initiation threshold: <50% (20.3 months); ³50% (23.60 months); ³80% (25.36 months). Bi-PAP usage >8 hours/day (23.20 months) or any daily Bi-PAP usage with cough assist (25.73 months) significantly (p < 0.001) extends survival compared to Bi-PAP alone (15.0 months). Cough assist without Bi-PAP has insignificant impact (14.17 months) over no intervention (13.68 months). Except for bulbar onset Bi-PAP users, higher ALSFRS-R total scores at Bi-PAP initiation significantly correlate with higher initiation FVC %predict and longer survival duration. Time elapsed since ALS onset is not a good predictor of when NIV should be initiated.

Lechtzin, 2007

The median time from ALS diagnosis to death was significantly longer in the Early NPPV group (2.7 years vs. 1.8 years, p=0.045). This remained significant after adjustment for potential confounding factors (H.R.=0.55, 95% CI 0.31–0.98). Survival from time of diagnosis was nearly one year longer in the Early group.

Vitacca, 2017

At 36 months from diagnosis, mortality was 35% for the VEG versus 52.7% for the LG (P = 0.022). Kaplan-Meier survival curves adjusted for tracheotomy showed a lower probability of death (P = 0.001) for the VEG as a whole (P = 0.001) and for the non-bulbar (NB) subgroup (P = 0.007). Very early NIV was protective of survival for all patients [hazard ratio (HR) 0.45; 95% confidence interval (CI) 0.28–0.74; P = 0.001] and for the NB subgroup (HR 0.43; 95% CI 0.23–0.79; P = 0.007), whilst a tracheotomy was protective for all patients (HR 0.27; 95% CI 0.15–0.50; P = 0.000) and both NB (HR 0.26; 95% CI 0.12–0.56; P = 0.001) and bulbar subgroups (HR 0.29; 95% CI 0.11–0.77; P = 0.013). Survival in VEG patients on NIV without tracheotomy was three times that for the LG (43.1% vs. 14.7%).