Filter
5644
Text search:
therapy
Featured
536
1394
Language
5130
173
166
143
51
46
45
35
15
13
8
6
6
5
5
4
4
4
4
4
4
3
3
3
2
2
2
2
2
2
2
2
2
1
1
1
1
1
1
1
1
Document type
3354
833
755
262
125
120
93
28
24
17
14
9
5
1
Countries / Regions
327
195
158
140
125
107
107
107
98
97
94
90
76
70
66
65
65
65
64
63
62
59
55
55
49
49
46
45
39
39
35
32
31
27
25
24
24
24
24
23
17
17
15
14
14
14
13
13
13
12
12
11
11
11
10
10
10
10
10
9
9
9
9
9
8
8
8
8
7
7
7
7
6
6
6
6
6
5
5
5
5
5
5
5
4
4
4
4
4
4
4
4
4
3
3
3
3
3
3
3
3
3
3
2
2
2
2
2
2
2
2
2
2
2
2
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
Authors & Publishers
658
312
281
201
167
110
99
94
94
86
41
38
32
29
28
28
28
26
25
24
24
23
22
22
21
21
21
21
21
20
19
19
18
18
18
18
17
17
17
16
16
16
16
16
16
16
15
14
14
14
14
14
13
13
13
13
13
12
12
12
11
11
11
11
11
10
10
10
10
10
10
10
9
9
9
9
9
9
9
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
7
7
7
7
7
7
7
7
7
7
7
7
7
7
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
Publication Years
1339
3715
563
24
3
Category
2191
526
298
242
107
98
47
2
Toolboxes
613
574
514
303
206
197
176
167
158
114
84
84
74
67
45
38
33
31
30
24
21
18
17
15
15
Asthma is a heterogeneous condition characterised by chronic inflammation and variable expiratory airflow limitation, with airway reversibility. Management of chronic inflammation with anti-asthma medication improves asthma control and quality of life. The aim of this journal is to provide an eviden
...
ce-based approach for chronic asthma management in young children and adolescents and provide guidance on the use of new asthma drugs in children.
For that, the South African Childhood Asthma Working Group (SACAWG) convened in January 2017. The asthma treatment task group reviewed the available scientific literature and international asthma treatment guidelines. The evidence was then graded according to the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system and recommendations were made based on scientific evidence and local context. Asthma management recommendations were made for children ˂6 years of age and older children and adolescents, as well as for stepping up and stepping down of therapy. This review does not include biologics or novel asthma drugs, which are covered in another CME article in this edition of SAMJ.
The final conclusions are that it is important to ensure good response, treatment and adherence, type of medication, device and checking of technique are all critical. Stepping up of therapy should be done only after ensuring good adherence and technique. Once therapeutic response is achieved, medication administration has to be stepped down to improve ease of use and avoid unnecessary side-effects.
more
BMC Infectious Diseases volume 23, Article number: 342 (2023).
Tuberculosis (TB) is among the leading causes of death globally. The disease has a huge burden in Namibia, with a case notification rate of at least 442 per 100,000. To date, Namibia is among the countries with the highest global TB bur
...
den, despite all efforts to reduce it. This study aimed to determine the factors associated with the unsuccessful treatment outcomes of the Directly Observed Therapy Short course (DOTS) programme in the Kunene and Oshana regions.
more
Malaria in pregnancy is a significant health problem in malaria-endemic areas. It not only causes substantial childhood morbidity and mortality but also increases the risks of adverse events for pregnant women and their developing fetuses. Most of the burden in these areas is due to infection with P
...
lasmodium falciparum. Artemisinin-based combination therapy (ACT) has been recommended as first-line treatment for uncomplicated P. falciparum malaria in all populations, including pregnant women in their second and third trimesters, since 2006. However, for women in their first trimester of pregnancy, WHO recommended as first-line treatment a combination of quinine and clindamycin.
Based on a review of the evidence conducted in 2022, WHO now recommends artemether–lumefantrine, the ACT with the most human safety data available, as the preferred treatment for uncomplicated P. falciparum malaria in the first trimester of pregnancy. This document presents all relevant evidence on the effects and safety in early pregnancy of artemisinins and partner medicines used in ACTs from both studies in experimental animals and observational studies in humans.
more
WHO guideline on balanced national controlled medicines policies to ensure medical access and safety
Access to medicines is essential for attainment of universal health coverage, which is central to achievement of the health-related Sustainable Development Goals. Controlled medicines include those such as opioids, benzodiazepines, barbiturates, amphetamines and others with identified or emergent cl
...
inical indications. WHO recognizes that these medicines are necessary for pre- and post-operative care, for sedation, for the management of both acute and chronic pain, for palliative care, as anticonvulsants (anti-epileptics), for the management of anxiety disorders and for the management of substance use disorders, including as opioid agonist therapy (OAT).
more
This publication is based on the list of clinical interventions selected from clinical guidelines on prevention, screening, diagnosis, treatment, palliative care, monitoring and end of life care. This publication addresses medical devices for six types of cancer: breast, cervical, colorectal, leukem
...
ia, lung and prostate. The first section defines the global increase in cancer cases, the global goals to manage NCDs and the WHO activities related to these goals. The second section presents the methodology used for the selection of medical devices that support clinical interventions required to screen, diagnose, treat and monitor cancer stages, as well as the provision of palliative care, based on evidence-based information. The third section lists the priority medical devices required to manage cancer in seven different units of health care services: 1. Vaccination, clinical assessment and endoscopy, 2. Medical imaging and nuclear medicine, 3. Surgery, 4. Laboratory and pathology, 5. Radiotherapy, 6. Systemic therapy and 7. Palliative and end of life care
more
The Western Pacific Region is the largest and most diverse region in the world, made up of 37 countries and territories in the Pacific, Oceania and parts of Asia, with a population of more than 1.9 billion people stretching over an area from China and Mongolia in the north to New Zealand in the sout
...
h. In 1999, 22 countries and territories in the Pacific joined together and launched the Pacific Programme to Eliminate Lymphatic Filariasis. Shortly after, the Global Programme to Eliminate Lymphatic Filariasis was launched in 2000. In 2004, 12 countries in the Asia subregion of the Western Pacific Region and Southeast Asian Region joined and developed the Mekong-Plus Strategic Plan for Elimination of Lymphatic Filariasis. Since then, significant efforts have been made by all endemic countries, with annual mass drug administration (MDA) as a principal strategy, through strong partnership with the WHO and other donors and partners. As a result, by the end of 2019, 10 of 22 endemic countries in the region, including 8 of 16 countries in the Pacific and 2 countries in the Asia subregion, achieved WHO validation for elimination of lymphatic filariasis (LF) as a public health problem. All the other countries are either progressing with post-MDA surveillance or accelerating efforts by adoption of the new triple drug therapy strategy and enhancement of MDA campaigns to tackle persistent transmission. Some 85% of the originally endemic implementation units have stopped MDA and the number of people requiring MDA for LF in the Western Pacific Region was reduced by 72% from 2000 to 2018. This paper reviews the progress, key success factors and remaining challenges and indicates the way forward to achieve LF elimination in the Western Pacific Region.
more
After 100 years of chemotherapy with impractical and toxic drugs, an oral cure for human African trypanosomiasis (HAT) is available: Fexinidazole. In this case, we review the history of drug discovery for HAT with special emphasis on the discovery, pre-clinical development, and operational challenge
...
s of the clinical trials of fexinidazole. The screening of the Drugs for Neglected Diseases initiative (DNDi) HAT-library by the Swiss TPH had singled out fexinidazole, originally developed by Hoechst (now Sanofi), as the most promising of a series of over 800 nitroimidazoles and related molecules. In cell culture, fexinidazole has an IC50 of around 1 µM against Trypanosoma brucei and is more than 100-fold less toxic to mammalian cells. In the mouse model, fexinidazole cures both the first, haemolymphatic, and the second, meningoencephalitic stage of the infection, the latter at 100 mg/kg twice daily for 5 days. In patients, the clinical trials managed by DNDi and supported by Swiss TPH mainly conducted in the Democratic Republic of the Congo demonstrated that oral fexinidazole is safe and effective for use against first- and early second-stage sleeping sickness. Based on the positive opinion issued by the European Medicines Agency in 2018, the WHO has released new interim guidelines for the treatment of HAT including fexinidazole as the new therapy for first-stage and non-severe second-stage sleeping sickness caused by Trypanosoma brucei gambiense (gHAT). This greatly facilitates the diagnosis and treatment algorithm for gHAT, increasing the attainable coverage and paving the way towards the envisaged goal of zero transmission by 2030.
more
Integrated community-based intervention for urinary schistosomiasis and soil-transmitted helminthiasis in children from Caxito, Angola
Lemosa, M.; Fançonya, C.; Moura, S. et al
The royal society of tropical medicine and hygiene
(2020)
C2
Schistosomiasis and soil-transmitted helminths (STH) infections are major public health problems. We aimed to study the 6-mo impact of mass drug administration with praziquantel and albendazole on urinary schistosomiasis and STH.We examined children (aged 2–15 y) from one hamlet, who provided urin
...
e and faeces samples at baseline (n=197), 1 mo (n=102) and 6 mo (n=92); 67 completed the protocol.At baseline, 47/67 (70.1%) children presented Schistosoma haematobium (75.8% in the baseline total sample) and 12/67 (17.9%) with STH (30.5% in the initial sample, p=0.010). Among the children, 47.3% had heavy Schistosoma haematobium infection. The most frequent STH was Trichuris trichiura in 9.0%. We also found Hymenolepis nana (13.2%) and Plasmodium falciparum (9.1%) infections and anaemia (82.1%). One mo after chemotherapy there was a significant (p=0.013) reduction of Schistosoma haematobium prevalence (23.5%) and a high egg reduction rate (86.9%). Considering the sample of 67 children, the mean egg concentration was 498 at baseline, 65 at 1 mo and 252 at 6 mo (p<0.05). We also observed a reduction in STH infections, 50% in Ascaris lumbricoides, 33.3% in T. trichiura and 50% in hookworms. At 6 mo, the prevalence of Schistosoma haematobium (76.1%) was similar to the baseline and the STH reduction was not significant.Longitudinal studies have reported many losses in these settings, but we were able to show that mass drug administration for control of schistosomiasis and STH present low effectiveness, that reinfections occur rapidly and that stand alone anthelmintic therapy is not a sustainable choice.
more
WHO has updated its guidelines for COVID-19 therapeutics, with revised recommendations for patients with non-severe COVID-19. This is the 13th update to these guidelines.
Updated risk rates for hospital admission in patients with non-severe COVID-19
The guidance includes updated risk rates for
...
hospital admission in patients with non-severe COVID-19.
The current COVID-19 virus variants tend to cause less severe disease while immunity levels are higher due to vaccination, leading to lower risks of severe illness and death for most patients.
This update includes new baseline risk estimates for hospital admission in patients with non-severe COVID-19. The new ‘moderate risk’ category now includes people previously considered to be high risk including older people and/or those with chronic conditions, disabilities, and comorbidities of chronic disease. The updated risk estimates will assist healthcare professionals to identify individuals at high, moderate or low risk of hospital admission, and to tailor treatment according to WHO guidelines:
**High: **People who are immunosuppressed remain at higher risk if they contract COVID-19, with an estimated hospitalization rate of 6%.
**Moderate: **People over 65 years old, those with conditions like obesity, diabetes and/or chronic conditions including chronic obstructive pulmonary disease, kidney or liver disease, cancer, people with disabilities and those with comorbidities of chronic disease are at moderate risk, with an estimated hospitalization rate of 3%.
Low: Those who are not in the high or moderate risk categories are at low risk of hospitalization (0.5%). Most people are low risk.
Review of COVID-19 treatments for people with non-severe COVID-19
WHO continues to strongly recommend nirmatrelvir-ritonavir (also known by its brand name ‘Paxlovid’) for people at high-risk and moderate risk of hospitalization. The recommendations state that nirmatrelvir-ritonavir is considered the best choice for most eligible patients, given its therapeutic benefits, ease of administration and fewer concerns about potential harms. Nirmatrelvir-ritonavir was first recommended by WHO in April 2022.
If nirmatrelvir-ritonavir is not available to patients at high-risk of hospitalization, WHO suggests the use of molnupiravir or remdesivir instead.
WHO suggests against the use of molnupiravir and remdesivir for patients at moderate risk, judging the potential harms to outweigh the limited benefits in patients at moderate risk of hospital admission.
For people at low risk of hospitalization, WHO does not recommend any antiviral therapy. Symptoms like fever and pain can continue to be managed with analgesics like paracetamol.
WHO also recommends against use of a new antiviral (VV116) for patients, except in clinical trials.
The update also includes a strong recommendation against the use of ivermectin for patients with non-severe COVID-19. WHO continues to advise that in patients with severe or critical COVID-19, ivermectin should only be used in clinical trials.
more
Cardiovascular disease (CVD) is the leading cause of global deaths, with the majority occurring in low- and middle-income countries (LMIC). The primary and secondary prevention of CVD is suboptimal throughout the world, but the evidence-practice gaps are much more pronounced in LMIC. Barriers at the
...
patient, health-care provider, and health system level prevent the implementation of optimal primary and secondary prevention. Identification of the particular barriers that exist in resource-constrained settings is necessary to inform effective strategies to reduce the identified evidence-practice gaps. Furthermore, targeting modifiable factors that contribute most significantly to the global burden of CVD, including tobacco use, hypertension, and secondary prevention for CVD will lead to the biggest gains in mortality reduction. We review a select number of novel, resource-efficient strategies to reduce premature mortality from CVD, including: (1) effective measures for tobacco control; (2) implementation of simplified screening and management algorithms for those with or at risk of CVD, (3) increasing the availability and affordability of simplified and cost-effective treatment regimens including combination CVD preventive drug therapy, and (4) simplified delivery of health care through task-sharing (non-physician health workers) and optimizing self-management (treatment supporters). Developing and deploying systems of care that address barriers related to the above, will lead to substantial reductions in CVD and related mortality.
more
Non-communicable diseases (NCDs) pose a substantial threat to many health systems, especially in low-income and middle-income countries (LMICs) where they are already overstretched. In the past few decades, deaths from NCDs in LMICs have spiked, whereas numbers in high-income countries have stabilis
...
ed. Worryingly, a large proportion of deaths from NCDs (29%) in LMICs occur among people younger than 60 years compared with the proportion in high-income countries (13%). This finding has been attributed to poor access to effective and equitable health-care services in most LMICs. The threat of NCDs in LMICs was recognised by the UN 2011 High-Level Meeting, and is now featured in Sustainable Development Goal 3 in the form of reducing premature mortality from NCDs by one-third before 2030. Cardiovascular diseases (CVDs) are the leading cause of deaths from NCDs (ie, 48% of all NCDs deaths). Therefore, substantial reductions in CVDs will have a major impact on reducing the overall burden of NCDs globally. The good news is that most CVDs can be prevented by addressing the key underlying behavioural risk factors, such as physical inactivity, unhealthy diet, tobacco use, and harmful use of alcohol, through population-wide approaches. Among individuals with or at high risk of CVD, early detection and effective management with appropriate counselling and medicines can reduce cardiovascular deaths substantially.
The importance of effective treatment for CVD has been recognised in the Global NCD Action Plan 2013–20, for which one of the nine global targets is that at least 50% of eligible individuals should receive drug therapy and counselling to prevent heart attacks and strokes by 2025.5 Although admirable, this is a hard target to achieve given that secondary prevention strategies in LMICs are often unaffordable or unavailable.
more
Malaria and HIV, two of the world’s most deadly diseases, are widespread, but their distribution overlaps greatly in sub-Saharan Africa. Consequently, malaria and HIV coinfection (MHC) is common in the region. In this paper, pertinent publications on the prevalence, impact, and treatment strategie
...
s of MHC obtained by searching major electronic databases (PubMed, PubMed Central, Google Scholar, ScienceDirect, and Scopus) were reviewed, and it was found that the prevalence of MHC in SSA was 0.7%–47.5% overall. Prevalence was 0.7%–47.5% in nonpregnant adults, 1.2%–27.8% in children, and 0.94%–37% in pregnant women. MHC was associated with an increased frequency of clinical parasitemia and severe malaria, increased parasite and viral load, and impaired immunity to malaria in nonpregnant adults, children, and pregnant women, increased in placental malaria and related outcomes in pregnant women, and impaired antimalarial drug efficacy in nonpregnant adults and pregnant women. Although a few cases of adverse events have been reported in coinfected patients receiving antimalarial and antiretroviral drugs concurrently, available data are very limited and have not prompted major revision in treatment guidelines for both diseases. Artemisinin-based combination therapy and cotrimoxazole are currently the recommended drugs for treatment and prevention of malaria in HIV-infected children and adults. However, concurrent administration of cotrimoxazole and sulfadoxine–pyrimethamine in HIV-infected pregnant women is not recommended, because of high risk of sulfonamide toxicity. Further research is needed to enhance our understanding of the impact of malaria on HIV, drug–drug interactions in patients receiving antimalarials and antiretroviral drugs concomitantly, and the development of newer, safer, and more cost-effective drugs and vaccines to prevent malaria in HIV-infected pregnant women.
more
EACS produces Guidelines for the management of people living with HIV in Europe. The English version is regularly updated by the guidelines panels with major revision every other year and minor revisions in the years in between. Guidelines are published in the autumn and translated into additional l
...
anguages.e
more
En la presente publicación se formulan orientaciones sobre la respuesta de salud pública a la farmacorresistencia del VIH (FRVIH) a inhibidores no nucleosídicos de la retrotranscriptasa (INNRT), previa al tratamiento, en personas con exposición previa a los fármacos antirretrovirales (ARV) o si
...
n antecedente de esta exposición que inician o reinician un tratamiento antirretroviral (TAR) de primera línea
more
Pregnancy often results in exclusion from clinical trials of antiretroviral (ARV) drugs, resulting in limited data on pharmacokinetics (PK), drug safety, and the efficacy of new ARV drugs in pregnancy and lactation. However, pregnancy, lactation, or the potential for pregnancy should not preclude th
...
e use of drug regimens that would be chosen for people who are not pregnant, unless adequate drug levels are not likely to be attained in pregnancy or known adverse effects outweigh potential benefits
more
HIV-1 drug resistance (HIVDR) genotyping is an essential component of the WHO global HIVDR surveillance strategy. Plasma “gold standard” specimen type for HIVDR genotyping, but its use may not be feasible in rural, remote areas in low- and middle-income countries, since preparing and storing it
...
require personnel and laboratory infrastructure that are often lacking. An alternative specimen type is dried blood spots (DBS), which can be made without special laboratory processing. DBS are more easily transported than plasma because they can be shipped at ambient temperature as non-hazardous materials using regular mail or courier services.
3rd edition
more
WHO’s antiretroviral treatment (ART) clinic-based acquired drug resistance survey method yields robust estimates of HIV viral suppression and acquired HIV drug resistance in adults, children and adolescents taking both dolutegravir and non-dolutegravir based regimens.
Results are used to inform A
...
RT programme decision making regarding optimal ART regimens and support evaluation of programme quality with respect to maximizing viral load suppression and minimizing emergence of resistance in people taking ART.
more
HIV drug resistance strategies focus on prevention through adherence and treatment optimization, surveillance to monitor resistance trends, and innovation in new drugs and diagnostics. Key approaches include implementing national action plans, strengthening laboratory capacity for monitoring, and pr
...
oviding comprehensive care, especially for vulnerable populations
more
Guidelines on lenacapavir for HIV prevention and testing strategies for long-acting injectable pre-exposure prophylaxis. Web Annex G Abstract