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وَحَدَّثَنَا إِسْحَاقُ بْنُ إِبْرَاهِيمَ الْحَنْظَلِيُّ، وَمُحَمَّدُ بْنُ أَبِي عُمَرَ، - وَتَقَارَبَا فِي لَفْظِ الْحَدِيثِ - قَالَ ابْنُ أَبِي عُمَرَ حَدَّثَنَا وَقَالَ، إِسْحَاقُ أَخْبَرَنَا عَبْدُ الرَّزَّاقِ، أَخْبَرَنَا مَعْمَرٌ، عَنِ الزُّهْرِيِّ، عَنْ عُبَيْدِ اللَّهِ بْنِ عَبْدِ اللَّهِ بْنِ أَبِي ثَوْرٍ، عَنِ ابْنِ عَبَّاسٍ، قَالَ لَمْ أَزَلْ حَرِيصًا أَنْأَسْأَلَ عُمَرَ عَنِ الْمَرْأَتَيْنِ مِنْ أَزْوَاجِ النَّبِيِّ صلى الله عليه وسلم اللَّتَيْنِ قَالَ اللَّهُ تَعَالَى ‏{‏إِنْ تَتُوبَا إِلَى اللَّهِ فَقَدْ صَغَتْ قُلُوبُكُمَا‏}‏ حَتَّى حَجَّ عُمَرُ وَحَجَجْتُ مَعَهُ فَلَمَّا كُنَّا بِبَعْضِ الطَّرِيقِ عَدَلَ عُمَرُ وَعَدَلْتُ مَعَهُ بِالإِدَاوَةِ فَتَبَرَّزَ ثُمَّ أَتَانِي فَسَكَبْتُ عَلَى يَدَيْهِ فَتَوَضَّأَ فَقُلْتُ يَا أَمِيرَ الْمُؤْمِنِينَ مَنِ الْمَرْأَتَانِ مِنْ أَزْوَاجِ النَّبِيِّ صلى الله عليه وسلم اللَّتَانِ قَالَ اللَّهُ عَزَّ وَجَلَّ لَهُمَا ‏{‏ إِنْ تَتُوبَا إِلَى اللَّهِ فَقَدْ صَغَتْ قُلُوبُكُمَا‏}‏ قَالَ عُمَرُ وَاعَجَبًا لَكَ يَا ابْنَ عَبَّاسٍ - قَالَ الزُّهْرِيُّ كَرِهَ وَاللَّهِ مَا سَأَلَهُ عَنْهُ وَلَمْ يَكْتُمْهُ - قَالَ هِيَ حَفْصَةُ وَعَائِشَةُ ‏.‏ ثُمَّ أَخَذَ يَسُوقُ الْحَدِيثَ قَالَ كُنَّا مَعْشَرَ قُرَيْشٍ قَوْمًا نَغْلِبُ النِّسَاءَ فَلَمَّا قَدِمْنَا الْمَدِينَةَ وَجَدْنَا قَوْمًا تَغْلِبُهُمْ نِسَاؤُهُمْ فَطَفِقَ نِسَاؤُنَا يَتَعَلَّمْنَ مِنْ نِسَائِهِمْ - قَالَ - وَكَانَ مَنْزِلِي فِي بَنِي أُمَيَّةَ بْنِ زَيْدٍ بِالْعَوَالِي فَتَغَضَّبْتُ يَوْمًا عَلَى امْرَأَتِي فَإِذَا هِيَ تُرَاجِعُنِي فَأَنْكَرْتُ أَنْ تُرَاجِعَنِي ‏.‏ فَقَالَتْ مَا تُنْكِرُ أَنْ أُرَاجِعَكَ فَوَاللَّهِ إِنَّ أَزْوَاجَ النَّبِيِّ صلى الله عليه وسلم لَيُرَاجِعْنَهُ وَتَهْجُرُهُ إِحْدَاهُنَّ الْيَوْمَ إِلَى اللَّيْلِ ‏.‏ فَانْطَلَقْتُ فَدَخَلْتُ عَلَى حَفْصَةَ فَقُلْتُ أَتُرَاجِعِينَ رَسُولَ اللَّهِ صلى الله عليه وسلم فَقَالَتْ نَعَمْ ‏.‏ فَقُلْتُ أَتَهْجُرُهُ إِحْدَاكُنَّ الْيَوْمَ إِلَى اللَّيْلِ قَالَتْ نَعَمْ ‏.‏ قُلْتُ قَدْ خَابَ مَنْ فَعَلَ ذَلِكَ مِنْكُنَّ وَخَسِرَ أَفَتَأْمَنُ إِحْدَاكُنَّ أَنْ يَغْضَبَ اللَّهُ عَلَيْهَا لِغَضَبِ رَسُولِهِ صلى الله عليه وسلم فَإِذَا هِيَ قَدْ هَلَكَتْ لاَ تُرَاجِعِي رَسُولَ اللَّهِ صلى الله عليه وسلم وَلاَ تَسْأَلِيهِ شَيْئًا وَسَلِينِي مَا بَدَا لَكِ وَلاَ يَغُرَّنَّكِ أَنْ كَانَتْ جَارَتُكِ هِيَ أَوْسَمَ وَأَحَبَّ إِلَى رَسُولِ اللَّهِ صلى الله عليه وسلم مِنْكِ - يُرِيدُ عَائِشَةَ - قَالَ وَكَانَ لِي جَارٌ مِنَ الأَنْصَارِ فَكُنَّا نَتَنَاوَبُ النُّزُولَ إِلَى رَسُولِ اللَّهِ صلى الله عليه وسلم فَيَنْزِلُ يَوْمًا وَأَنْزِلُ يَوْمًا فَيَأْتِينِي بِخَبَرِ الْوَحْىِ وَغَيْرِهِ وَآتِيهِ بِمِثْلِ ذَلِكَ وَكُنَّا نَتَحَدَّثُ أَنَّ غَسَّانَ تُنْعِلُ الْخَيْلَ لِتَغْزُوَنَا فَنَزَلَ صَاحِبِي ثُمَّ أَتَانِي عِشَاءً فَضَرَبَ بَابِي ثُمَّ نَادَانِي فَخَرَجْتُ إِلَيْهِ فَقَالَ حَدَثَ أَمْرٌ عَظِيمٌ ‏.‏ قُلْتُ مَاذَا أَجَاءَتْ غَسَّانُ قَالَ لاَ بَلْ أَعْظَمُ مِنْ ذَلِكَ وَأَطْوَلُ طَلَّقَ النَّبِيُّ صلى الله عليه وسلم نِسَاءَهُ ‏.‏ فَقُلْتُ قَدْ خَابَتْ حَفْصَةُ وَخَسِرَتْ قَدْ كُنْتُ أَظُنُّ هَذَا كَائِنًا حَتَّى إِذَا صَلَّيْتُ الصُّبْحَ شَدَدْتُ عَلَىَّ ثِيَابِي ثُمَّ نَزَلْتُ فَدَخَلْتُ عَلَى حَفْصَةَ وَهْىَ تَبْكِي فَقُلْتُ أَطَلَّقَكُنَّ رَسُولُ اللَّهِ صلى الله عليه وسلم فَقَالَتْ لاَ أَدْرِي هَا هُوَ ذَا مُعْتَزِلٌ فِي هَذِهِ الْمَشْرُبَةِ ‏.‏ فَأَتَيْتُ غُلاَمًا لَهُ أَسْوَدَ فَقُلْتُ اسْتَأْذِنْ لِعُمَرَ ‏.‏ فَدَخَلَ ثُمَّ خَرَجَ إِلَىَّ فَقَالَ قَدْ ذَكَرْتُكَ لَهُ فَصَمَتَ فَانْطَلَقْتُ حَتَّى انْتَهَيْتُ إِلَى الْمِنْبَرِ فَجَلَسْتُ فَإِذَا عِنْدَهُ رَهْطٌ جُلُوسٌ يَبْكِي بَعْضُهُمْ فَجَلَسْتُ قَلِيلاً ثُمَّ غَلَبَنِي مَا أَجِدُ ثُمَّ أَتَيْتُ الْغُلاَمَ فَقُلْتُ اسْتَأْذِنْ لِعُمَرَ ‏.‏ فَدَخَلَ ثُمَّ خَرَجَ إِلَىَّ ‏.‏ فَقَالَ قَدْ ذَكَرْتُكَ لَهُ فَصَمَتَ ‏.‏ فَوَلَّيْتُ مُدْبِرًا فَإِذَا الْغُلاَمُ يَدْعُونِي فَقَالَ ادْخُلْ فَقَدْ أَذِنَ لَكَ فَدَخَلْتُ فَسَلَّمْتُ عَلَى رَسُولِ اللَّهِ صلى الله عليه وسلم فَإِذَا هُوَ مُتَّكِئٌ عَلَى رَمْلِ حَصِيرٍ قَدْ أَثَّرَ فِي جَنْبِهِ فَقُلْتُ أَطَلَّقْتَ يَا رَسُولَ اللَّهِ نِسَاءَكَ فَرَفَعَ رَأْسَهُ إِلَىَّ وَقَالَ ‏"‏ لاَ ‏"‏ ‏.‏ فَقُلْتُ اللَّهُ أَكْبَرُ لَوْ رَأَيْتَنَا يَا رَسُولَ اللَّهِ وَكُنَّا مَعْشَرَ قُرَيْشٍ قَوْمًا نَغْلِبُ النِّسَاءَ فَلَمَّا قَدِمْنَا الْمَدِينَةَ وَجَدْنَا قَوْمًا تَغْلِبُهُمْ نِسَاؤُهُمْ فَطَفِقَ نِسَاؤُنَا يَتَعَلَّمْنَ مِنْ نِسَائِهِمْ فَتَغَضَّبْتُ عَلَى امْرَأَتِي يَوْمًا فَإِذَا هِيَ تُرَاجِعُنِي فَأَنْكَرْتُ أَنْ تُرَاجِعَنِي ‏.‏ فَقَالَتْ مَا تُنْكِرُ أَنْ أُرَاجِعَكَ فَوَاللَّهِ إِنَّ أَزْوَاجَ النَّبِيِّ صلى الله عليه وسلم لَيُرَاجِعْنَهُ وَتَهْجُرُهُ إِحْدَاهُنَّ الْيَوْمَ إِلَى اللَّيْلِ ‏.‏ فَقُلْتُ قَدْ خَابَ مَنْ فَعَلَ ذَلِكَ مِنْهُنَّ وَخَسِرَ أَفَتَأْمَنُ إِحْدَاهُنَّ أَنْ يَغْضَبَ اللَّهُ عَلَيْهَا لِغَضَبِ رَسُولِهِ صلى الله عليه وسلم فَإِذَا هِيَ قَدْ هَلَكَتْ فَتَبَسَّمَ رَسُولُ اللَّهِ صلى الله عليه وسلم فَقُلْتُ يَا رَسُولَ اللَّهِ قَدْ دَخَلْتُ عَلَى حَفْصَةَ فَقُلْتُ لاَ يَغُرَّنَّكِ أَنْ كَانَتْ جَارَتُكِ هِيَ أَوْسَمُ مِنْكِ وَأَحَبُّ إِلَى رَسُولِ اللَّهِ صلى الله عليه وسلم مِنْكِ ‏.‏ فَتَبَسَّمَ أُخْرَى فَقُلْتُ أَسْتَأْنِسُ يَا رَسُولَ اللَّهِ ‏.‏ قَالَ ‏"‏ نَعَمْ ‏"‏ ‏.‏ فَجَلَسْتُ فَرَفَعْتُ رَأْسِي فِي الْبَيْتِ فَوَاللَّهِ مَا رَأَيْتُ فِيهِ شَيْئًا يَرُدُّ الْبَصَرَ إِلاَّ أُهُبًا ثَلاَثَةً فَقُلْتُ ادْعُ اللَّهَ يَا رَسُولَ اللَّهِ أَنْ يُوَسِّعَ عَلَى أُمَّتِكَ فَقَدْ وَسَّعَ عَلَى فَارِسَ وَالرُّومِ وَهُمْ لاَ يَعْبُدُونَ اللَّهَ فَاسْتَوَى جَالِسًا ثُمَّ قَالَ ‏"‏ أَفِي شَكٍّ أَنْتَ يَا ابْنَ الْخَطَّابِ أُولَئِكَ قَوْمٌ عُجِّلَتْ لَهُمْ طَيِّبَاتُهُمْ فِي الْحَيَاةِ الدُّنْيَا ‏"‏ ‏.‏ فَقُلْتُ اسْتَغْفِرْ لِي يَا رَسُولَ اللَّهِ ‏.‏ وَكَانَ أَقْسَمَ أَنْ لاَ يَدْخُلَ عَلَيْهِنَّ شَهْرًا مِنْ شِدَّةِ مَوْجِدَتِهِ عَلَيْهِنَّ ‏.‏ حَتَّى عَاتَبَهُ اللَّهُ عَزَّ وَجَلَّ ‏.‏ قَالَ الزُّهْرِيُّ فَأَخْبَرَنِي عُرْوَةُ، عَنْ عَائِشَةَ، قَالَتْ لَمَّا مَضَى تِسْعٌ وَعِشْرُونَ لَيْلَةً دَخَلَ عَلَىَّ رَسُولُ اللَّهِ صلى الله عليه وسلم بَدَأَ بِي فَقُلْتُ يَا رَسُولَ اللَّهِ إِنَّكَ أَقْسَمْتَ أَنْ لاَ تَدْخُلَ عَلَيْنَا شَهْرًا وَإِنَّكَ دَخَلْتَ مِنْ تِسْعٍ وَعِشْرِينَ أَعُدُّهُنَّ ‏.‏ فَقَالَ ‏"‏ إِنَّ الشَّهْرَ تِسْعٌ وَعِشْرُونَ - ثُمَّ قَالَ - يَا عَائِشَةُ إِنِّي ذَاكِرٌ لَكِ أَمْرًا فَلاَ عَلَيْكِ أَنْ لاَ تَعْجَلِي فِيهِ حَتَّى تَسْتَأْمِرِي أَبَوَيْكِ ‏"‏ ‏.‏ ثُمَّ قَرَأَ عَلَىَّ الآيَةَ ‏{‏ يَا أَيُّهَا النَّبِيُّ قُلْ لأَزْوَاجِكَ‏}‏ حَتَّى بَلَغَ ‏{‏ أَجْرًا عَظِيمًا‏}‏ قَالَتْ عَائِشَةُ قَدْ عَلِمَ وَاللَّهِ أَنَّ أَبَوَىَّ لَمْ يَكُونَا لِيَأْمُرَانِي بِفِرَاقِهِ قَالَتْ فَقُلْتُ أَوَفِي هَذَا أَسْتَأْمِرُ أَبَوَىَّ فَإِنِّي أُرِيدُ اللَّهَ وَرَسُولَهُ وَالدَّارَ الآخِرَةَ ‏.‏ قَالَ مَعْمَرٌ فَأَخْبَرَنِي أَيُّوبُ أَنَّ عَائِشَةَ قَالَتْ لاَ تُخْبِرْ نِسَاءَكَ أَنِّي اخْتَرْتُكَ فَقَالَ لَهَا النَّبِيُّ صلى الله عليه وسلم ‏"‏ إِنَّ اللَّهَ أَرْسَلَنِي مُبَلِّغًا وَلَمْ يُرْسِلْنِي مُتَعَنِّتًا ‏"‏ ‏.‏ قَالَ قَتَادَةُ صَغَتْ قُلُوبُكُمَا مَالَتْ قُلُوبُكُمَا‏.‏

Ibn 'Abbas (Allah be pleased with them) reported. I had always been anxious to ask 'Umar (Allah be pleased with him) about the two ladies amongst the wives of Allah's Prophet (may peace be upon Lim) about whom Allah, the Exalted, said:" If you both turn in repentance to Allah, then indeed your hearts are inclined (to this)" (Ixvi. 4), until 'Umar (Allah be pleased with him) set out for Hajj and I also went along with him. And as we were going along a path, 'Umar (Allah be pleased with hiyn) went aside and I also went aside with him with a jug (of water). He answered the call of nature, and then came to me and I poured water over his hands and he performed ablution I said: Commander of the Faithful, who are the two ladies amongst the wives of Allah's Prophet (ﷺ) about whom Allah, the Exalted and Majestic, said: 'If you both turn to Allah in repentance, then indeed your heart are inclined to it"? 'Umar (Allah he pleased with him) said: How strange is it for you, Ibn 'Abbas! (Zuhri said: By Allah, he disliked what he asked about, but did not keep it a secret.) He ('Umar) said: They are Hafsa and 'A'isha; and he then began to narrate the hadith and said: We were such people among the Quraish who dominated women, and as we reached Medina we found there people who were dominated by their women, and our women began to learn (the habits) of their women. He further said: And my house was situated in the suburb of Aledina in the tribe of Banu Umayya b. Zaid. One day I became angry with my wife and she retorted upon me. I did not like that she should retort upon me. She said: You disapprove of my retorting upon you By Allah, the wives of Allah's Apostle (ﷺ) retort upon him, and one of them detaches herself from him for the day until the night. So I ('Umar) went out and visited Hafsa and said: Do you retort upon Allah's Messenger (ﷺ)? She said: Yes. I said; Does any one of you detach herself from him from the day to the night? She said: Yes. He said: She who did like it amongst you in fact failed and incurred loss. Does everyone amongst you not fear the wrath of Allah upon her due to the wrath of His Messenger (ﷺ), and (as a result thereof) she may perish? So do not retort upon Allah's Messenger (ﷺ) and do not ask him for anything, but ask me that which you desire, (and the frank behaviour) of your companion may not mislead you, if she is more graceful and is dearer to Allah's Messenger (ﷺ) than you (meaning 'A'isha) (Allah be pleased with her). He (Hadrat 'Umar further) said: I had a compalaion from the Ansar and, we used to remain in the company of the Messenger (ﷺ) turn by turn. He remained there for a day while I remained there on the other day, and he brought me the news about the revelation and other (matter), and I brought him (the news) like this. And we discussed that the Ghassanids were shoeing the horses in order to attack us. Id y companion once attended (the Apostle). and then came to me at night and knocked at my door and called me, and I came out to him, and he said: A matter of great importance has happened. I said: What is that? Have the Ghassanids come? He said: No, but even more serious and more significant than that: the Prophet (ﷺ) has divorced his wives. I said: Hafsa has failed and has incurred loss. and I feared that it would happen. When it was dawn I observed the dawn prayer and dressed myself, and then came there (in the house of the Holy Prophet) and visited Hafsa, and she was weeping. I said: Has Allah's Messenger (ﷺ) divorced you (all)? She said: I do not know. He has, however, separated himself in his attic. I came to a black servant and said to him: Seek permission for 'Umar. He went in and then came to me and said: I made mention of you to him, but he kept quiet. I then went to the pulpit and sat there, and there was a group of people sitting by it and some of then were weeping. I sat there for some time, until I was overpowered (by that very idea) which was in my mind. I then came back to the boy and said to him: Seek permission for Umar. He went in and came to me and said: I made mention of you to him but he kept quiet. I was about to turn back when the boy called me and said: Go in; permission has been granted to you. I went in and greeted Allah's Messenger (ﷺ) and he was reclining against the couch of mat and it had left its marks upon his side. I said: Messenger of Allah, have you divorced your wives? He raised his head towards me and said: No. I said: Allah is the Greatest. Messenger of Allah, I wish if you had seen how we the people of Quraish had domination over women but when we came to Medina we found people whom their women dominated. So our women began to learn from their women. One dily I became angry with my wife and she began to retort upon me. I did not approve that she should retort upon me. She said: You do not like that I should retort upon you, but, by Allah. the wives of Allah's Apostle (ﷺ) retort upon him and any one of them separates herself from him for a day until night. I said: He who did that amongst them in fact failed and incurred loss. Does any of them feel sate from the wrath of Allahupon her due to the wrath of Allah's Messenger (ﷺ), and she has certainly perished. Allah's Messtnger (ﷺ) smiled, I said: Messenger of Allah, I visited Hafsa and said: (The behaviour) of your companion ('A'isha) may not mislead you, If she is more graceful than you and is dearer to Allah's Messenger (ﷺ) than you. Allah's Messenger (ﷺ) smiled for the second time. I said: Allah's Messenger, way I talk to you about agreeable things? He said: Yes. I sat down and lifted my head (to see things) in the house and, by Allah, I did not see anything significant besides three hides. I said: Messenger of Allah, supplicate the Lord that He should make (life) prosperous for your Ummah as He has made plentiful for the people of Persia and Rome (in spite of the fact) that they do no, worship Allah, the Exalted and Majestic, whereupon he (Allah's Messenger) sat up an I then said: Ibn Khattab, do you doubt that they are a nation whom their nice things have been given immediately in the life of this world. I said: Allah's Messenger! seek pardon for me. And he (Allah's Messenger) had taken an oath that he would not visit them for a month due to extreme annoyance with them until Allah showed His displeasure to him (Allah's Messenger). Zuhri said: 'Urwa informed me that 'A'Isha (Allah be pleased with her) said: When twenty-nine nights were over, Allah's Messenger (ﷺ) visited me, and he began (his visit) with me. I said: Messenger of Allah, you had taken an oath that you would not visit us for a month, while you have visited after I have counted only twenty-nine (nights). Thereupon he said: The month may also be of twenty-nine (days). He then said: 'A'isha, I am going to talk to you about a matter, and you should not be hasty in it (and do not give your final decision) until you have consulted your parents. He then recited this verse to me:" O Prophet, say to your wives" till he reached" mighty reward" (xxxiii. 28). 'A'isha (Allah be pleased with her) said: By Allah, he knew that my parents would not allow me to separate from him. I said: Is there any need to consult my parents in this matter? I in fact choose Allah and His Messenger (ﷺ) and the abode in the Hereafter. Ma'mar said: Ayyub reported to me that 'A'isha said: Don't inform your wives that I have chosen you, whereupon Allah's Apostle (ﷺ) said: Verily Allah has sent me as a conveyer of message, and He has not sent me as a source of hardship (to others). Qatada said:" Saghat qulubukum" means" Your hearts have inclined

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An online healthy relationship tool and safety decision aid for women experiencing intimate partner violence (I-DECIDE): a randomised controlled trial.

Background: Evidence for online interventions to help women experiencing intimate partner violence is scarce. We assessed whether an online interactive healthy relationship tool and safety decision aid (I-DECIDE) would increase women's self-efficacy and improve depressive symptoms compared with an intimate partner violence information website. Methods: In this two-group pragmatic randomised controlled trial, we enrolled women who had screened positive for any form of intimate partner violence or fear of a partner in the 6 months before recruitment. Women aged 16-50 years currently residing in Australia, who had safe access to a computer and an internet connection, and who answered positively to one of the screening questions in English were eligible for inclusion. Participants were randomly assigned (1:1) by computer to receive either the intervention or control website. The intervention website consisted of modules on healthy relationships, abuse and safety, and relationship priority setting, and a tailored action plan. The control website was a static intimate partner violence information website. As the initial portion of the website containing the baseline questions was identical for both groups, there was no way for women to tell which group they had been allocated to, and the research team were also masked to participant allocation until after analysis of the 12-month data. Data were collected at baseline, immediately after completion of the website, at 6 months, and 12 months. Primary outcomes were mean general self-efficacy score (immediately after website completion, and at 6 months and 12 months) and mean depression score (at 6 months and 12 months). Data analyses were done according to intention-to-treat principles, accounting for missing data, and adjusted for outcome baseline scores. This trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN 12614001306606. Findings: Between Jan 16, and Aug 28, 2015, 584 patients registered for the study and were assessed for eligibility. 422 eligible participants were randomly allocated to the intervention group (227 patients) or control group (195 patients). 179 (79%) participants in the intervention group and 156 (80%) participants in the control group completed 12-month follow-up. Mean self-efficacy at 6 months and 12 months was lower for participants in the intervention group than for participants in the control group, although this did not meet the prespecified mean difference (6 months: 27·5 [SD 5·1] vs 28·1 [4·4], imputed mean difference 1·3 [95% CI 0·3 to 2·3]; 12 months: 27·8 [SD 5·4] vs 29·0 [5·0], imputed mean difference 1·6 [95% CI 0·5 to 2·7]). We found no difference between groups in depressive symptoms at 6 months or 12 months (6 months: 22·5 [SD 17·1] vs 24·2 [17·2], imputed mean difference -0·3 [95% CI -3·5 to 3·0]; 12 months: 21·9 [SD 19·3] vs 21·5 [19·3], imputed mean difference -1·9 [95% CI -5·6 to 1·7]). Qualitative findings indicated that participants found the intervention supportive and a motivation for action. Interpretation: Our findings highlight the need for further research, development, and refinement of online interventions for women experiencing intimate partner violence, particularly into the duration needed for interventions. Although we detected no meaningful differences between groups, our qualitative results indicated that some women find an online tool a helpful source of motivation and support. Funding: Australian Research Council.

The Lancet. Public health · randomised controlled trial · 43 citationsread the source →

An observational study protocol to explore loneliness and systemic inflammation in an older adult population with chronic venous leg ulcers.

Background: Chronic venous leg ulcers (CVLUs) are the most common type of lower extremity wound. Even when treated with evidenced-based care, 30-50% of CVLUs fail to heal. A specific gap exists about the association between psychosocial stressors, particularly loneliness, and biomarkers of inflammation and immunity. Loneliness is highly prevalent in persons with CVLUs, has damaging effects on health, and contributes to the development of multiple chronic conditions, promotes aberrant inflammation, and diminishes healing. However, the confluence of loneliness, inflammation and the wound healing trajectory has not been elucidated; specifically whether loneliness substantially mediates systemic inflammation and alters healing over time. This study seeks to address whether there is a specific biomarker profile associated with loneliness, CVLUs, and wound healing that is different from non-lonely persons with CVLUs. Methods: An observational prospective study will identify, characterize and explore associations among psychosocial stressors, symptoms and biomarkers between 2 CVLU groups, with loneliness+ (n = 28) and without loneliness- (n = 28) during 4 weeks of wound treatment, measured at 3 time points. We will examine psychosocial stressors and symptoms using psychometrically-sound measures include PROMIS® and other questionnaires for loneliness, social isolation, depression, anxiety, stigma, sleep, fatigue, pain, quality of life, cognition, and function. Demographics data including health history, sex, age, wound type and size, wound age, and treatment will be recorded from the electronic health record. We will characterize a biomarker panel of inflammatory genes including chemotaxic and growth factors, vascular damage, and immune regulators that express in response to loneliness to loneliness and CVLUs using well-established RNA sequence and PCR methods for whole blood samples. In an exploratory aim we will explore whether age and sex/psychological stressors and symptoms indicate potential moderation/mediation of the effect of loneliness on the biomarker profile over the study period. Discussion: This study will provide insight into the influence of psychosocial stressors, symptoms, and biological mechanisms on wound healing, towards advancing a future healing prediction model and interventions to address these stressors and symptoms experienced by persons with CVLUs.

BMC geriatrics · clinical trial · 10 citationsread the source →

Long-term outcomes of childhood sexual abuse: an umbrella review.

Background: Although many meta-analyses have examined the association between childhood sexual abuse and subsequent outcomes, the scope, validity, and quality of this evidence has not been comprehensively assessed. We aimed to systematically review existing meta-analyses on a wide range of long-term psychiatric, psychosocial, and physical health outcomes of childhood sexual abuse, and evaluate the quality of the literature. Methods: In this umbrella review, we searched four databases (PsycINFO, PubMed, Cumulative Index to Nursing and Allied Health Literature, and Global Health) from inception to Dec 31, 2018, to identify meta-analyses of observational studies that examined the association between childhood sexual abuse (before 18 years of age) and long-term consequences (after 18 years). We compared odds ratios (ORs) across different outcomes. We also examined measures of quality, including heterogeneity between studies and evidence for publication bias. This study is registered with PROSPERO, CRD42016049701. Findings: We identified 19 meta-analyses that included 559 primary studies, covering 28 outcomes in 4 089 547 participants. Childhood sexual abuse was associated with 26 of 28 specific outcomes: specifically, six of eight adult psychiatric diagnoses (ORs ranged from 2·2 [95% CI 1·8-2·8] to 3·3 [2·2-4·8]), all studied negative psychosocial outcomes (ORs ranged from 1·2 [1·1-1·4] to 3·4 [2·3-4·8]), and all physical health conditions (ORs ranged from 1·4 [1·3-1·6] to 1·9 [1·4-2·8]). Strongest psychiatric associations with childhood sexual abuse were reported for conversion disorder (OR 3·3 [95% CI 2·2-4·8]), borderline personality disorder (2·9 [2·5-3·3]), anxiety (2·7 [2·5-2·8]), and depression (2·7 [2·4-3·0]). The systematic reviews for two psychiatric outcomes (post-traumatic stress disorder and schizophrenia) and one psychosocial outcome (substance misuse) met high quality standards. Quality was low for meta-analyses on borderline personality disorder and anxiety, and moderate for conversion disorder. Assuming causality, population attributable risk fractions for outcomes ranged from 1·7% (95% CI 0·7-3·3) for unprotected sexual intercourse to 14·4% (8·8-19·9) for conversion disorder. Interpretation: Although childhood sexual abuse was associated with a wide range of psychosocial and health outcomes, systematic reviews on only two psychiatric disorders (post-traumatic stress disorder and schizophrenia) and one psychosocial outcome (substance misuse) were of a high quality. Whether services should prioritise interventions that mitigate developing certain psychiatric disorders following childhood abuse requires further review. Higher-quality meta-analyses for specific outcomes and more empirical studies on the developmental pathways from childhood sexual abuse to later outcomes are necessary. Funding: Wellcome Trust.

The lancet. Psychiatry · systematic review · 459 citationsread the source →

Role of Physical Activity and Sedentary Behavior in the Mental Health of Preschoolers, Children and Adolescents: A Systematic Review and Meta-Analysis.

Background: Evidence suggests that participation in physical activity may support young people's current and future mental health. Although previous reviews have examined the relationship between physical activity and a range of mental health outcomes in children and adolescents, due to the large increase in published studies there is a need for an update and quantitative synthesis of effects. Objectives: The objectives of this study were to determine the effect of physical activity interventions on mental health outcomes by conducting a systematic review and meta-analysis, and to systematically synthesize the observational evidence (both longitudinal and cross-sectional studies) regarding the associations between physical activity and sedentary behavior and mental health in preschoolers (2-5 years of age), children (6-11 years of age) and adolescents (12-18 years of age). Methods: A systematic search of the PubMed and Web of Science electronic databases was performed from January 2013 to April 2018, by two independent researchers. Meta-analyses were performed to examine the effect of physical activity on mental health outcomes in randomized controlled trials (RCTs) and non-RCTs (i.e. quasi-experimental studies). A narrative synthesis of observational studies was conducted. Studies were included if they included physical activity or sedentary behavior data and at least one psychological ill-being (i.e. depression, anxiety, stress or negative affect) or psychological well-being (i.e. self-esteem, self-concept, self-efficacy, self-image, positive affect, optimism, happiness and satisfaction with life) outcome in preschoolers, children or adolescents. Results: A total of 114 original articles met all the eligibility criteria and were included in the review (4 RCTs, 14 non-RCTs, 28 prospective longitudinal studies and 68 cross-sectional studies). Of the 18 intervention studies, 12 (3 RCTs and 9 non-RCTs) were included in the meta-analysis. There was a small but significant overall effect of physical activity on mental health in children and adolescents aged 6-18 years (effect size 0.173, 95% confidence interval 0.106-0.239, p < 0.001, percentage of total variability attributed to between-study heterogeneity [I2] = 11.3%). When the analyses were performed separately for children and adolescents, the results were significant for adolescents but not for children. Longitudinal and cross-sectional studies demonstrated significant associations between physical activity and lower levels of psychological ill-being (i.e. depression, stress, negative affect, and total psychological distress) and greater psychological well-being (i.e. self-image, satisfaction with life and happiness, and psychological well-being). Furthermore, significant associations were found between greater amounts of sedentary behavior and both increased psychological ill-being (i.e. depression) and lower psychological well-being (i.e. satisfaction with life and happiness) in children and adolescents. Evidence on preschoolers was nearly non-existent. Conclusions: Findings from the meta-analysis suggest that physical activity interventions can improve adolescents' mental health, but additional studies are needed to confirm the effects of physical activity on children's mental health. Findings from observational studies suggest that promoting physical activity and decreasing sedentary behavior might protect mental health in children and adolescents. PROSPERO Registration Number: CRD42017060373.

Sports medicine (Auckland, N.Z.) · meta-analysis · 693 citationsread the source →

The prevalence of posttraumatic stress disorder in pregnancy and after birth: A systematic review and meta-analysis.

Background: Previous reviews have provided preliminary insights into risk factors and possible prevalence of Post-traumatic Stress Disorder (PTSD) postpartum with no attempt to examine prenatal PTSD. This study aimed to assess the prevalence of PTSD during pregnancy and after birth, and the course of PTSD over this time. Methods: PsychINFO, PubMed, Scopus and Web of Science were searched using PTSD terms crossed with perinatal terms. Studies were included if they reported the prevalence of PTSD during pregnancy or after birth using a diagnostic measure. Results: 59 studies (N =24267) met inclusion criteria: 35 studies of prenatal PTSD and 28 studies of postpartum PTSD (where 4 studies provided prevalence of PTSD in pregnancy and postpartum). In community samples the mean prevalence of prenatal PTSD was 3.3% (95%, CI 2.44-4.54). The majority of postpartum studies measured PTSD in relation to childbirth with a mean prevalence of 4.0% (95%, CI 2.77-5.71) in community samples. Women in high-risk groups were at more risk of PTSD with a mean prevalence of 18.95% (95%, CI 10.62-31.43) in pregnancy and 18.5% (95%, CI 10.6-30.38) after birth. Using clinical interviews was associated with lower prevalence rates in pregnancy and higher prevalence rates postpartum. Limitations: Limitations include use of stringent diagnostic criteria, wide variability of PTSD rates, and inadequacy of studies on prenatal PTSD measured in three trimesters. Conclusions: PTSD is prevalent during pregnancy and after birth and may increase postpartum if not identified and treated. Assessment and treatment in maternity services is recommended.

Journal of affective disorders · meta-analysis · 461 citationsread the source →

A randomized controlled trial of a couple relationship and coparenting program (Couple CARE for Parents) for high- and low-risk new parents.

Objective: This study evaluated the effectiveness of couple relationship education in assisting couples to sustain relationship functioning and parenting sensitivity, and whether benefits were moderated by risk of maladjustment in the transition to parenthood ("risk"). Method: Two hundred fifty couples expecting their first child were assessed on risk and randomly assigned to either the Couple CARE for Parents (CCP), a couple relationship- and coparenting-focused education program (n = 125), or the Becoming a Parent Program (BAP), a mother-focused parenting program (n = 125). Couples completed assessments of their couple relationship during pregnancy, after intervention at 4 months postpartum, and at 16 and 28 months postpartum. Observed parenting and self-report parenting stress were assessed at 4 months postpartum, and parenting stress was assessed again at 16 and 28 months postpartum. Results: Risk was associated with greater relationship and parenting adjustment problems. Relative to BAP, CCP women decreased their negative communication and showed a trend to report less parenting stress irrespective of risk level. High-risk women receiving CCP reported higher relationship satisfaction, and were less intrusive in their parenting, than high-risk women receiving BAP. There were no effects of CCP on sensitive parenting and parenting intrusiveness for women. High-risk men in CCP showed a trend for higher relationship satisfaction than high-risk BAP men, but there were no effects of CCP for men on any parenting outcomes. Conclusions: CCP is a potentially useful intervention, but benefits are primarily for high-risk women.

Journal of consulting and clinical psychology · randomised controlled trial · 38 citationsread the source →

Clinician-led, peer-led, and internet-delivered dissonance-based eating disorder prevention programs: Effectiveness of these delivery modalities through 4-year follow-up.

Objective: Independent trials have found that the dissonance-based Body Project eating disorder prevention program is efficacious and effective; the present trial provided the first test of whether delivery could be task-shifted from clinician-delivery to peer educator-delivery or Internet-delivery without loss of effectiveness through 4-year follow-up. Method: Young women at high-risk for eating disorders because of body image concerns (N = 680, Mage = 22.2) recruited at 3 colleges were randomized to clinician-led Body Project groups, peer-led Body Project groups, the Internet-based eBody Project, or educational video control. Results: Participants in clinician- and peer-led Body Project groups and the eBody Project generally showed larger reductions in risk factors and eating disorder symptoms versus controls through 1- and 2-year follow-up (d = .16-.59), with some effects persisting through 3- and 4-year follow-ups (d = .28-.58). Peer-led Body Project participants showed greater reductions in some risk factors than eBody Project participants (d = .18-.19), but no other contrasts between Body Project interventions differed. Eating disorder onset over 4-year follow-up was significantly lower for peer-led Body Project participants (8.1%) than control participants (17.6%) and clinician-led Body Project participants (19.3%), and marginally lower than eBody Project participants (15.5%). Conclusions: The evidence that all three Body Project interventions outperformed educational video controls, peer-led groups outperformed the Internet-based intervention, and peer-led groups showed lower eating disorder onset over 4-year follow-up than the other conditions are novel. Results imply that it might be optimal to task-shift Body Project delivery to peer-leaders to address implementation barriers associated with clinician-led delivery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Journal of consulting and clinical psychology · randomised controlled trial · 68 citationsread the source →

The effects of social group interventions for depression: Systematic review.

Background: There is a growing prevalence of prolonged antidepressant use globally. Social group interventions may be an effective way to manage mild to moderate depression, especially with patients seeking to discontinue antidepressant use. This systematic review evaluates studies that used social group interventions to manage depression. Methods: Studies published up to June 2019 in nine bibliographic databases were identified using search terms related to depression, social interventions, and social participation. Formal therapies for depression (cognitive behaviour therapy, music therapy) were excluded as they have been reviewed elsewhere. Results: 24 studies met inclusion criteria; 14 RCTs, 6 non-randomised controlled trials and 4 pre-post evaluations. In total, 28 social group programs were evaluated, 10 arts-based groups, 13 exercise groups and 5 others. Programs ranged in 'dose' from 5 to 150 hours (M = 31 hours) across 4 to 75 weeks (M = 15 weeks) and produced effect sizes on depression in the small to very large range (Hedge's g = .18 to 3.19, M = 1.14). A regression analysis revealed no participant variables, study variables or intervention variables were related to effect size on depression. Limitations: Risks of bias were found, primarily in the non-randomised studies, which means the findings must be regarded as preliminary until replicated. Conclusion: These findings indicate that social group interventions are an effective way to manage mild to moderate depression symptoms in a variety of populations. This approach may also help to prevent relapse among patients tapering off antidepressant medication.

Journal of affective disorders · systematic review · 34 citationsread the source →

Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress.

Context: We recently demonstrated that 28-d bed rest in healthy volunteers results in a moderate loss of lean leg mass and strength. Objective: The objective of this study was to quantify changes in muscle protein kinetics, body composition, and strength during a clinical bed rest model reflecting both physical inactivity and the hormonal stress response to injury or illness. Design: Muscle protein kinetics were calculated during a primed, continuous infusion (0.08 micromol/kg.min) of 13C6-phenylalanine on d 1 and 28 of bed rest. Setting: The setting for this study was the General Clinical Research Center at the University of Texas Medical Branch. Participants: Participants were healthy male volunteers (n = 6, 28 +/- 2 yr, 84 +/- 4 kg, 178 +/- 3 cm). Intervention: During bed rest, hydrocortisone sodium succinate was administered iv (d 1 and 28) and orally (d 2-27) to reproduce plasma cortisol concentrations consistent with trauma or illness (approximately 22 microg/dl). Main outcome measures: We hypothesized that inactivity and hypercortisolemia would reduce lean muscle mass, leg extension strength, and muscle protein synthesis. Results: Volunteers experienced a 28.4 +/- 4.4% loss of leg extension strength (P = 0.012) and a 3-fold greater loss of lean leg mass (1.4 +/- 0.1 kg) (P = 0.004) compared with our previous bed rest-only model. Net protein catabolism was primarily due to a reduction in muscle protein synthesis [fractional synthesis rate, 0.081 +/- 0.004 (d 1) vs. 0.054 +/- 0.007%/h (d 28); P = 0.023]. There was no change in muscle protein breakdown. Conclusion: Prolonged inactivity and hypercortisolemia represents a persistent catabolic stimulus that exacerbates strength and lean muscle loss via a chronic reduction in muscle protein synthesis.

The Journal of clinical endocrinology and metabolism · clinical trial · 177 citationsread the source →

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

Background: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings: In 2019, there were 12·2 million (95% UI 11·0-13·6) incident cases of stroke, 101 million (93·2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6·55 million (6·00-7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8-12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1-6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0-73·0), prevalent strokes increased by 85·0% (83·0-88·0), deaths from stroke increased by 43·0% (31·0-55·0), and DALYs due to stroke increased by 32·0% (22·0-42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0-18·0), mortality decreased by 36·0% (31·0-42·0), prevalence decreased by 6·0% (5·0-7·0), and DALYs decreased by 36·0% (31·0-42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0-24·0) and incidence rates increased by 15·0% (12·0-18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5-3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5-3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57-8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97-3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01-1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7-90·8] DALYs or 55·5% [48·2-62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3-48·6] DALYs or 24·3% [15·7-33·2]), high fasting plasma glucose (28·9 million [19·8-41·5] DALYs or 20·2% [13·8-29·1]), ambient particulate matter pollution (28·7 million [23·4-33·4] DALYs or 20·1% [16·6-23·0]), and smoking (25·3 million [22·6-28·2] DALYs or 17·6% [16·4-19·0]). Interpretation: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding: Bill & Melinda Gates Foundation.

The Lancet. Neurology · 5441 citationsread the source →

Geriatric assessment-identified deficits in older cancer patients with normal performance status.

Background: We investigated whether a brief geriatric assessment (GA) would identify important patient deficits that could affect treatment tolerance and care outcomes within a sample of older cancer patients rated as functionally normal (80%-100%) on the Karnofsky performance status (KPS) scale. Methods: Cancer patients aged ≥65 years were assessed using a brief GA that included both professionally and patient-scored KPS and measures of comorbidity, polypharmacy, cognition, function, nutrition, and psychosocial status. Data were analyzed using descriptive statistics and multivariable logistic regression. Results: The sample included 984 patients: mean age was 73 years (range: 65-99 years), 74% were female, and 89% were white. GA was conducted before (23%), during (41%), or after (36%) treatment. Overall, 54% had a breast cancer diagnosis (n = 528), and 46% (n = 456) had cancers at other sites. Moreover, 81% of participants (n = 796) had both professionally and self-rated KPS ≥80, defined as functionally normal, and those patients are the focus of analysis. In this subsample, 550 (69%) had at least 1 GA-identified deficit, 222 (28%) had 1 deficit, 140 (18%) had 2 deficits, and 188 (24%) had ≥3 deficits. Specifically, 43% reported taking ≥9 medications daily, 28% had decreased social activity, 25% had ≥4 comorbidities, 23% had ≥1 impairment in instrumental activities of daily living, 18% had a Timed Up and Go time ≥14 seconds, 18% had ≥5% unintentional weight loss, and 12% had a Mental Health Index score ≤76. Conclusion: Within this sample of older cancer patients who were rated as functionally normal by KPS, GA identified important deficits that could affect treatment tolerance and outcomes.

The oncologist · clinical trial · 171 citationsread the source →

How effects on health equity are assessed in systematic reviews of interventions.

Background: Enhancing health equity is endorsed in the Sustainable Development Goals. The failure of systematic reviews to consider potential differences in effects across equity factors is cited by decision-makers as a limitation to their ability to inform policy and program decisions.  OBJECTIVES: To explore what methods systematic reviewers use to consider health equity in systematic reviews of effectiveness. Search methods: We searched the following databases up to 26 February 2021: MEDLINE, PsycINFO, the Cochrane Methodology Register, CINAHL, Education Resources Information Center, Education Abstracts, Criminal Justice Abstracts, Hein Index to Foreign Legal Periodicals, PAIS International, Social Services Abstracts, Sociological Abstracts, Digital Dissertations and the Health Technology Assessment Database. We searched SCOPUS to identify articles that cited any of the included studies on 10 June 10 2021. We contacted authors and searched the reference lists of included studies to identify additional potentially relevant studies. Selection criteria: We included empirical studies of cohorts of systematic reviews that assessed methods for measuring effects on health inequalities. We define health inequalities as unfair and avoidable differences across socially stratifying factors that limit opportunities for health. We operationalised this by assessing studies which evaluated differences in health across any component of the PROGRESS-Plus acronym, which stands for Place of residence, Race/ethnicity/culture/language, Occupation, Gender or sex, Religion, Education, Socioeconomic status, Social capital. "Plus" stands for other factors associated with discrimination, exclusion, marginalisation or vulnerability such as personal characteristics (e.g. age, disability), relationships that limit opportunities for health (e.g. children in a household with parents who smoke) or environmental situations which provide limited control of opportunities for health (e.g. school food environment). Data collection and analysis: Two review authors independently extracted data using a pre-tested form. Risk of bias was appraised for included studies according to the potential for bias in selection and detection of systematic reviews.  MAIN RESULTS: In total, 48,814 studies were identified and the titles and abstracts were screened in duplicate. In this updated review, we identified an additional 124 methodological studies published in the 10 years since the first version of this review, which included 34 studies. Thus, 158 methodological studies met our criteria for inclusion. The methods used by these studies focused on evidence relevant to populations experiencing health inequity (108 out of 158 studies), assess subgroup analysis across PROGRESS-Plus (26 out of 158 studies), assess analysis of a gradient in effect across PROGRESS-Plus (2 out of 158 studies) or use a combination of subgroup analysis and focused approaches (20 out of 158 studies). The most common PROGRESS-Plus factors assessed were age (43 studies), socioeconomic status in 35 studies, low- and middle-income countries in 24 studies, gender or sex in 22 studies, race or ethnicity in 17 studies, and four studies assessed multiple factors across which health inequity may exist. Only 16 studies provided a definition of health inequity. Five methodological approaches to consider health equity in systematic reviews of effectiveness were identified: 1) descriptive assessment of reporting and analysis in systematic reviews (140 of 158 studies used a type of descriptive method); 2) descriptive assessment of reporting and analysis in original trials (50 studies); 3) analytic approaches which assessed differential effects across one or more PROGRESS-Plus factors (16 studies); 4) applicability assessment (25 studies) and 5) stakeholder engagement (28 studies), which is a new finding in this update and examines the appraisal of whether relevant stakeholders with lived experience of health inequity were included in the design of systematic reviews or design and delivery of interventions. Reporting for both approaches (analytic and applicability) lacked transparency and was insufficiently detailed to enable the assessment of credibility. Authors' conclusions: There is a need for improvement in conceptual clarity about the definition of health equity, describing sufficient detail about analytic approaches (including subgroup analyses) and transparent reporting of judgments required for applicability assessments in order to consider health equity in systematic reviews of effectiveness.

The Cochrane database of systematic reviews · systematic review · 38 citationsread the source →

Trajectories of psychological distress in adolescent and young adult patients with cancer: a 1-year longitudinal study.

Purpose: To examine prevalence and changes in symptoms of psychological distress over 1 year after initial cancer diagnosis in adolescent and young adult (AYA) patients with cancer. Sociodemographic and clinical predictors of changes in distress were examined. Patients and methods: In this multisite, longitudinal, prospective study of an ethnically diverse sample, 215 patients age 14 to 39 years were assessed for psychological distress within the first 4 months of diagnosis and again 6 and 12 months later. Linear mixed models with random intercept and slope estimated changes in distress, as measured by the Brief Symptom Inventory-18 (BSI-18). Results: Within the first 4 months of diagnosis, 60 respondents (28%) had BSI-18 scores suggesting caseness for distress. On average, distress symptoms exceeded population norms at the time of diagnosis, dipped at the 6-month follow-up, but increased to a level exceeding population norms at the 12-month follow-up. A statistically significant decline in distress over 1 year was observed; however, the gradient of change was not clinically significant. Multivariate analyses revealed that the reduction in distress over time was primarily a function of being off treatment and involved in school or work. Notably, cancer type or severity was not associated with distress. Conclusion: Findings emphasize the importance of early psychosocial intervention for distress in AYAs as well as the need to manage treatment-related symptoms and facilitate AYAs' involvement in work or school to the extent possible. Continued research is needed to understand how distress relates to quality of life, functional outcomes, treatment, and symptom burden throughout the continuum of care.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · cohort or longitudinal · 184 citationsread the source →

Tadalafil for prevention of erectile dysfunction after radiotherapy for prostate cancer: the Radiation Therapy Oncology Group [0831] randomized clinical trial.

Importance: Tadalafil is used to treat erectile dysfunction after prostate cancer treatment, but its role as a preventive agent is undefined. Objectives: To determine primarily whether tadalafil preserved erectile function in men treated with radiotherapy for prostate cancer, and secondarily to determine whether participant- or partner-reported overall sexual function and sexual and marital satisfaction were affected. Design, setting, and participants: Stratified, placebo-controlled, double-blind, parallel-group study with 1:1 randomization at 76 community-based and tertiary medical sites in the United States and Canada. Two hundred forty-two participants with intact erectile function scheduled to receive radiotherapy for prostate cancer were recruited between November 2009 and February 2012 with follow-up through March 2013. Interventions: One hundred twenty-one participants were assigned 5 mg of tadalafil daily and 121 were assigned placebo for 24 weeks starting with external radiotherapy (63%) or brachytherapy (37%). Participant-reported International Index of Erectile Function response before radiotherapy and at weeks 2 and 4, between weeks 20 and 24, between weeks 28 and 30, and 1 year thereafter. Participants and partners could respond also to the Sexual Adjustment Questionnaire and to the Locke Marital Adjustment Test before radiotherapy, between weeks 20 and 24 and weeks 28 and 30, and at 1 year. Main outcomes and measures: Primary outcome was off-drug spontaneous erectile function 28 to 30 weeks after radiotherapy started. Secondary end points were spontaneous erection at 1 year; overall sexual function and satisfaction; marital adjustment; and partner-reported satisfaction and marital adjustment at 28 to 30 weeks and 1 year, predictors of tadalafil response; and adverse events. Results: Among 221 evaluable participants, 80 (79%; 95% CI, 70%-88%) assigned to receive tadalafil retained erectile function between weeks 28 and 30 compared with 61 (74%; 95% CI, 63%-85%) assigned to receive placebo (P = .49); an absolute difference of 5% (95% CI, -9% to 19%). A significant difference was also not observed at 1 year (72%; 95% CI, 60%-84% vs 71%; 95% CI, 59%-84%; P = .93). Tadalafil was not associated with significantly improved overall sexual function or satisfaction; a significant difference was not observed in any domain subscale. Partners of men assigned tadalafil noted no significant effect on sexual satisfaction, and marital adjustment was not significantly improved in participants or partners. Conclusions and relevance: Among men undergoing radiotherapy for prostate cancer, daily use of tadalafil compared with placebo did not result in improved erectile function. These findings do not support daily use of tadalafil to prevent erectile dysfunction in these patients. Trial registration: clinicaltrials.gov Identifier: NCT00931528.

JAMA · randomised controlled trial · 44 citationsread the source →

Risk of late effects of treatment in children newly diagnosed with standard-risk acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study cohort.

Background: Treatment of patients with paediatric acute lymphoblastic leukaemia has evolved such that the risk of late effects in survivors treated in accordance with contemporary protocols could be different from that noted in those treated decades ago. We aimed to estimate the risk of late effects in children with standard-risk acute lymphoblastic leukaemia treated with contemporary protocols. Methods: We used data from similarly treated members of the Childhood Cancer Survivor Study cohort. The Childhood Cancer Survivor Study is a multicentre, North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986. We included cohort members if they were aged 1·0-9·9 years at the time of diagnosis of acute lymphoblastic leukaemia and had received treatment consistent with contemporary standard-risk protocols for acute lymphoblastic leukaemia. We calculated mortality rates and standardised mortality ratios, stratified by sex and survival time, after diagnosis of acute lymphoblastic leukaemia. We calculated standardised incidence ratios and absolute excess risk for subsequent neoplasms with age-specific, sex-specific, and calendar-year-specific rates from the Surveillance, Epidemiology and End Results Program. Outcomes were compared with a sibling cohort and the general US population. Findings: We included 556 (13%) of 4329 cohort members treated for acute lymphoblastic leukaemia. Median follow-up of the survivors from 5 years after diagnosis was 18·4 years (range 0·0-33·0). 28 (5%) of 556 participants had died (standardised mortality ratio 3·5, 95% CI 2·3-5·0). 16 (57%) deaths were due to causes other than recurrence of acute lymphoblastic leukaemia. Six (1%) survivors developed a subsequent malignant neoplasm (standardised incidence ratio 2·6, 95% CI 1·0-5·7). 107 participants (95% CI 81-193) in each group would need to be followed-up for 1 year to observe one extra chronic health disorder in the survivor group compared with the sibling group. 415 participants (376-939) in each group would need to be followed-up for 1 year to observe one extra severe, life-threatening, or fatal disorder in the group of survivors. Survivors did not differ from siblings in their educational attainment, rate of marriage, or independent living. Interpretation: The prevalence of adverse long-term outcomes in children treated for standard risk acute lymphoblastic leukaemia according to contemporary protocols is low, but regular care from a knowledgeable primary-care practitioner is warranted. Funding: National Cancer Institute, American Lebanese-Syrian Associated Charities, Swiss Cancer Research.

The Lancet. Oncology · cohort or longitudinal · 102 citationsread the source →

Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial.

Background: Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control. Methods: In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within 5 weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5 × 5 Gy over a maximum of 8 days) followed by six cycles of CAPOX chemotherapy (capecitabine 1000 mg/m2 orally twice daily on days 1-14, oxaliplatin 130 mg/m2 intravenously on day 1, and a chemotherapy-free interval between days 15-21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin [folinic acid] 200 mg/m2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m2 intravenously and fluorouracil 600 mg/m2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3-14) followed by total mesorectal excision. Choice of CAPOX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1·8 Gy up to 50·4 Gy or 25 fractions of 2·0 Gy up to 50·0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m2 followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPOX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov, NCT01558921, and is now complete. Findings: Between June 21, 2011, and June 2, 2016, 920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4·6 years (IQR 3·5-5·5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23·7% (95% CI 19·8-27·6) in the experimental group versus 30·4% (26·1-34·6) in the standard of care group (hazard ratio 0·75, 95% CI 0·60-0·95; p=0·019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression). Interpretation: The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer. Funding: Dutch Cancer Foundation, Swedish Cancer Society, Spanish Ministry of Economy and Competitiveness, and Spanish Clinical Research Network.

The Lancet. Oncology · randomised controlled trial · 1212 citationsread the source →

Efficacy of 12-step mutual-help groups other than Alcoholics Anonymous: a systematic review and meta-analysis.

This paper offers a systematic review of quantitative and qualitative studies on the main twelve-step mutual-help (TSMH) groups (excluding Alcoholics Anonymous) and four meta-analyses exploring the correlation between (i) duration or involvement in TSMH groups and; (ii) severity of symptoms or quality of life. Systematic review was conducted following PRISMA guidelines. Searches of databases (MEDLINE, PsychInfo), a register (ClinicalTrials) and citations were conducted, from inception through November 01 2022. Fifty five articles were included (24 quantitative, 27 qualitative, 4 mixed-methods), corresponding to 47 distinctive studies. 68% of these studies were conducted in North America, 17% in Middle East, 11% in the European Union and 4% in Australia. The most studied TSMH group were Gamblers Anonymous (28% of the 47 studies), Narcotics Anonymous (26%), Double Trouble in Recovery (15%), Overeaters Anonymous (19%) and TSMH groups for compulsive sexual behaviors (11%). The four meta-analyses pooled data from 9 studies. Pooled mean age ranged from 36.5 to 40.5. 80-81% of participants were male. TSMH attendance and involvement were negatively correlated with severity of symptoms (high and medium levels of evidence) and positively correlated with quality of life (low levels of evidence). Twenty-one qualitative papers reported factors influencing recovery: Social (n = 15), emotional (n = 9), spiritual (n = 8), self-identification or psychological (n = 6) factors. Review provides characteristics of TSMH groups others than Alcoholics Anonymous, with implications for both research and healthcare practice. The perspective to implement TSMH groups targeting ontological addiction, at the root of all addiction, is discussed. Protocol registration: Prospero registration number: CRD42022342605.

European archives of psychiatry and clinical neuroscience · meta-analysis · 5 citationsread the source →

Association of depressive and/or pregnancy-related anxiety symptoms in pregnancy with maternal and neonatal biologic aging.

BACKGROUND: Prenatal depression and anxiety affect nearly 20% of individuals, and emerging evidence links psychological distress to accelerated biological aging. However, the joint effects of depressive and anxiety symptoms on biological aging in mother-infant dyads are understudied. We investigated associations of prenatal maternal depressive and/or pregnancy-related anxiety symptoms with two markers of biological aging [leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn)], in maternal blood and neonatal cord blood. METHODS: This was a secondary analysis of a prospective cohort of mother-infant dyads enrolled 1999–2002 during their first prenatal visit to a multispecialty practice in Massachusetts. Participants were eligible if they were carrying a singleton gestation, English-speaking, and under 22 weeks gestational age. The exposure was prenatal depressive symptoms (Edinburgh Postnatal Depression Scale [EPDS] ≥ 13) and/or pregnancy-related anxiety (PrAS moderate-high), grouped into four mutually exclusive categories: 1) low anxiety and low depressive symptoms (referent); 2) high depressive symptoms alone; 3) moderate-high PrAS alone; 4) and both. The primary outcome was maternal and neonatal markers of biological aging and oxidative stress (LTL and mtDNAcn), measured from maternal (1st or 2nd trimester) and neonatal (cord) blood and calculated using quantitative PCR. Multivariable linear generalized estimating equation regression models were used to assess the relationship between prenatal mental health symptoms and maternal/neonatal biological aging/oxidative stress, adjusting for confounders. RESULTS: Among 751 pregnancies, 479 (64%) had low pregnancy-related anxiety and low depressive symptoms, 33 (4%) had high depressive symptoms alone, 209 (28%) had moderate-high PrAS alone, and 30 (4%) had both. High depressive symptoms alone and moderate-high PrAS were each associated with shorter maternal LTL [ß = -0.07, 95% Confidence Interval (CI) -0.13, -0.02 for depressive; ß = -0.04, 95% CI -0.08, -0.01 for PrAS]. Mothers with depressive symptoms alone also had higher neonatal cord blood mtDNAcn (ß = 0.11, 95% CI 0.01, 0.21). CONCLUSIONS: Prenatal symptoms of depression or pregnancy-related anxiety were independently associated with molecular signatures of accelerated biologic aging in mothers and their neonates. These findings underscore that perinatal mental health symptoms exert measurable biological effects that could influence long-term health trajectories, and reinforce the urgent need for comprehensive mental health care during pregnancy.

BMC pregnancy and childbirthread the source →

Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study.

Background: Bivalent oral poliovirus vaccine (bOPV; types 1 and 3) is expected to replace trivalent OPV (tOPV) globally by April, 2016, preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus. Because data are needed on sequential IPV-bOPV schedules, we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants. Methods: We did a randomised, controlled, open-label, non-inferiority trial with healthy, full-term (>2·5 kg birthweight) infants aged 8 weeks (± 7 days) at six well-child clinics in Santiago, Chile. We used supplied lists to randomly assign infants (1:1:1) to receive three polio vaccinations (IPV by injection or bOPV as oral drops) at age 8, 16, and 24 weeks in one of three sequential schedules: IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV. We did the randomisation with blocks of 12 stratified by study site. All analyses were done in a masked manner. Co-primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion (within a 10% margin) and antibody titres (within two-thirds log2 titres) to poliovirus serotypes 1 and 3 at age 28 weeks, analysed in the per-protocol population. Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks. Safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01841671, and is closed to new participants. Findings: Between April 25 and August 1, 2013, we assigned 570 infants to treatment: 190 to IPV-bOPV-bOPV, 192 to IPV-IPV-bOPV, and 188 to IPV-IPV-IPV. 564 (99%) were vaccinated and included in the intention-to-treat cohort, and 537 (94%) in the per-protocol analyses. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, the proportions of children with seroconversion to type 1 poliovirus were 166 (98·8%) of 168, 95% CI 95·8-99·7; 178 (100%), 97·9-100·0; and 175 (100%), 97·9-100·0. Proportions with seroconvsion to type 3 poliovirus were 163 (98·2%) of 166, 94·8-99·4; 177 (100%), 97·9-100·0, and 172 (98·9%) of 174, 95·9-99·7. Non-inferiority was thus shown for the bOPV-containing schedules compared with the all-IPV schedule, with no significant differences between groups. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, the proportions of children with seroprotective antibody titres to type 1 poliovirus were 168 (98·8%) of 170, 95% CI 95·8-99·7; 181 (100%), 97·9-100·0; and 177 (100%), 97·9-100·0. Proportions to type 3 poliovirus were 166 (98·2%) of 169, 94·9-99·4; 180 (100%), 97·9-100·0; and 174 (98·9%) of 176, 96·0-99·7. Non-inferiority comparisons could not be done for this outcome because median titres for the groups receiving OPV were greater than the assay's upper limit of detection (log2 titres >10·5). The proportions of children seroconverting to type 2 poliovirus in the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, were 130 (77·4%) of 168, 95% CI 70·5-83·0; 169 (96·0%) of 176, 92·0-98·0; and 175 (100%), 97·8-100. IPV-bOPV schedules resulted in almost a 0·3 log reduction of type 2 faecal shedding compared with the IPV-only schedule. No participants died during the trial; 81 serious adverse events were reported, of which one was thought to be possibly vaccine-related (intestinal intussusception). Interpretation: Seroconversion rates against polioviruses types 1 and 3 were non-inferior in sequential schedules containing IPV and bOPV, compared with an all-IPV schedule, and proportions of infants with protective antibodies were high after all three schedules. One or two doses of bOPV after IPV boosted intestinal immunity for poliovirus type 2, suggesting possible cross protection. Additionally, there was evidence of humoral priming for type 2 from one dose of IPV. Our findings could give policy makers flexibility when choosing a vaccination schedule, especially when trying to eliminate vaccine-associated and vaccine-derived poliomyelitis. Funding: Bill & Melinda Gates Foundation.

The Lancet. Infectious diseases · randomised controlled trial · 60 citationsread the source →

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial.

Background: Post-traumatic stress disorder (PTSD) is prevalent in military personnel and first responders, many of whom do not respond to currently available treatments. This study aimed to assess the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treating chronic PTSD in this population. Methods: We did a randomised, double-blind, dose-response, phase 2 trial at an outpatient psychiatric clinic in the USA. We included service personnel who were 18 years or older, with chronic PTSD duration of 6 months or more, and who had a Clinician-Administered PTSD Scale (CAPS-IV) total score of 50 or greater. Using a web-based randomisation system, we randomly assigned participants (1:1:2) to three different dose groups of MDMA plus psychotherapy: 30 mg (active control), 75 mg, or 125 mg. We masked investigators, independent outcome raters, and participants until after the primary endpoint. MDMA was administered orally in two 8-h sessions with concomitant manualised psychotherapy. The primary outcome was mean change in CAPS-IV total score from baseline to 1 month after the second experimental session. Participants in the 30 mg and 75 mg groups subsequently underwent three 100-125 mg MDMA-assisted psychotherapy sessions in an open-label crossover, and all participants were assessed 12 months after the last MDMA session. Safety was monitored through adverse events, spontaneously reported expected reactions, vital signs, and suicidal ideation and behaviour. This study is registered with ClinicalTrials.gov, number NCT01211405. Findings: Between Nov 10, 2010, and Jan 29, 2015, 26 veterans and first responders met eligibility criteria and were randomly assigned to receive 30 mg (n=7), 75 mg (n=7), or 125 mg (n=12) of MDMA plus psychotherapy. At the primary endpoint, the 75 mg and 125 mg groups had significantly greater decreases in PTSD symptom severity (mean change CAPS-IV total scores of -58·3 [SD 9·8] and -44·3 [28·7]; p=0·001) than the 30 mg group (-11·4 [12·7]). Compared with the 30 mg group, Cohen's d effect sizes were large: 2·8 (95% CI 1·19-4·39) for the 75 mg group and 1·1 (0·04-2·08) for the 125 mg group. In the open-label crossover with full-dose MDMA (100-125 mg), PTSD symptom severity significantly decreased in the group that had previously received 30 mg (p=0·01), whereas no further significant decreases were observed in the group that previously achieved a large response after 75 mg doses in the blinded segment (p=0·81). PTSD symptoms were significantly reduced at the 12-month follow-up compared with baseline after all groups had full-dose MDMA (mean CAPS-IV total score of 38·8 [SD 28·1] vs 87·1 [16·1]; p<0·0001). 85 adverse events were reported by 20 participants. Of these adverse events, four (5%) were serious: three were deemed unrelated and one possibly related to study drug treatment. Interpretation: Active doses (75 mg and 125 mg) of MDMA with adjunctive psychotherapy in a controlled setting were effective and well tolerated in reducing PTSD symptoms in veterans and first responders. Funding: Multidisciplinary Association for Psychedelic Studies.

The lancet. Psychiatry · randomised controlled trial · 258 citationsread the source →

The Management of Preoperative Anxiety in Children: An Update

Anxiety in children undergoing surgery is characterized by subjective feelings of tension, apprehension, nervousness, and worry that may be expressed in various forms (1). Postoperative maladaptive behaviors, such as new onset enuresis, feeding difficulties, apathy and withdrawal, and sleep disturbances, may also result from anxiety before surgery. In fact, studies have indicated that up to 60% of all children undergoing surgery may present with negative behavioral changes at 2 wk postoperatively (1,2). Variables such as age, temperament, and anxiety of the child and parent in the preoperative holding area have been identified as predictors for these behavioral changes (1). Extreme anxiety during induction of anesthesia is also associated with an increase of these postoperative negative behavioral changes (3). In addition to behavioral manifestations, preoperative anxiety activates the human stress response, leading to increased serum cortisol, epinephrine, and natural killer cell activity (4,5). This stress response can be activated by many different noxious stimuli including fear, anxiety, pain, cold, major surgery, and infection. The main components of the stress system are the corticotropin-releasing hormone and the locus ceruleus-norepinephrine/autonomic systems and their peripheral effectors, the hypothalamic pituitary-adrenal axis and the limbs of the autonomic system (5). There is also evidence for a bidirectional communication between the neuroendocrine system and the immune system. Stress activates the hypothalamic pituitary-adrenal axis, increases circulating glucocorticoids, and is associated with alterations of immune function and susceptibility to infection and neoplastic disease (6). The human response to surgical stress is characterized by a series of hormonal, immunological, and metabolic changes that together constitute the global surgical stress response (7,8). This perioperative response is considered a homeostatic mechanism for adapting to the perioperative injury. The effects of the surgical stress response, however, may be detrimental: neuroendocrine hormones (e.g., cortisol, catecholamines) and cytokines (e.g., interleukin-6) provoke a negative nitrogen balance and catabolism, delay wound healing, and cause postoperative immunosuppression (7,8). Children are particularly vulnerable to the global surgical stress response because of limited energy reserves, larger brain masses, and obligatory glucose requirements (9). Because acute psychological stress, such as preoperative anxiety, is associated with immediate stress hormone release, the contribution of perioperative psychological factors to the global perioperative stress response cannot be ignored. In adults, increased preoperative anxiety is associated with poor postoperative behavioral and clinical recovery (10,11). As an indicator of the importance of preoperative anxiety, a panel of 72 anesthesiologists recently ranked various anesthesia low-morbidity clinical outcomes based on importance and frequency. The five clinical outcomes with the highest combined score were incisional pain, nausea, vomiting, preoperative anxiety, and discomfort from IV insertion (12). Thus, consensus is evident among anesthesiologists about the need to treat anxiety before surgery. In a modern epidemiological framework, diseases can be characterized in terms of risk factors, interventions, and outcomes. In this update, we will review preoperative anxiety in children using this conceptual framework (Fig. 1).Figure 1: Conceptual framework of perioperative anxiety. Revised from (72).The Psychobiology of Separation Learning to cope with separation from a parent is necessary for a child’s normal development (13). Separation experiences such as going to school facilitate normal psychological development and personality organization. Other separation experiences, such as perioperative separation, may precipitate confusion and anxiety. Between these two extremes, there are many separation experiences with varying degrees of psychobiological stress. In the first weeks of life, infants are able to discriminate among people, but will accept care and comfort from adults other than their parents (14). By 3 mo of age, however, infants begin to respond differently to familiar and unfamiliar people. Older infants smile more at familiar people and may even try to engage their attention (14). Separation anxiety usually begins at 7–8 mo of age and peaks around 1 yr of age. In part, separation anxiety represents the infant’s acquisition of new cognitive abilities and object permanence. The intensity of separation anxiety declines with age, largely because of increasing cognitive abilities and memory capacity. Frequently, however, the increase in abilities does not immunize toddlers and preschoolers against the stress and distress of separations. The extent to which separation is traumatic or evokes adaptive responses reflects an individual child’s developmental age, parenting experiences, genetic endowment, and environmental stability. For children with biologically based vulnerabilities, such as a sensitivity to novelty and transitions, even expected separations may impose a greater degree of stress than for less sensitive children (13). How parents help the child mediate a separation experience play a crucial role in the child’s acute and long-term responses. In the extreme, the parent may be unable to mediate the experience for the child because of limitations such as severe anxiety. How well children have been cared for up to the time of the separation also influences their response to the stressor. Children deprived of attention in the home are at increased risk for stress in response to separations. Thus, the extent to which separations evoke adaptive responses reflects an individual child’s genetics, personality, parenting, and previous life experiences. Preoperative Anxiety: Identification Identifying risk factors for development of preoperative anxiety is important, as more resources can be directed toward vulnerable children. Children 1–5 yr old are at the highest risk for developing extreme anxiety (1). This is not surprising considering the psychobiology of separation anxiety. Children who are shy or inhibited and those who have a high intelligence quotient and lack good adaptive abilities are also at increased risk (15). Previous surgery or hospitalization and poor response to visits to the pediatrician’s office are also predictors for the development of preoperative anxiety. Finally, parental anxiety has been identified as a predictor for increased child’s anxiety. Preoperative Anxiety: Behavioral Modalities Preoperative Preparation Programs Most studies suggest that preoperative preparation programs reduce anxiety and enhance coping in children (16). These behavioral preparation programs have evolved significantly over recent decades. In the 1960s, preparation programs were designed to provide an orientation tour and narrative information and facilitate trust between the hospital staff, the child, and the parent (16). In the 1970s, modeling techniques were developed where children indirectly experienced the perioperative course by role rehearsal using dolls or by viewing a video (17). These modeling techniques were augmented in the late 1980s with child life preparation and the teaching of coping skills (17). Currently, development of coping skills is considered the most effective preoperative preparation intervention, followed by modeling, play therapy, operating room tour, and printed material (18). Although experts favor teaching of coping skills, most preparation programs in the United States consist of an orientation tour and printed information (18). Although coping preparation has been associated with reduction of anxiety in the preoperative holding area, no differences were found among the various preparation programs during induction, in the recovery room period, or postoperatively (19). Thus, the cost-effectiveness of child life specialists may or may not be justified by an associated reduction in preoperative anxiety. Psychological preparation programs should be tailored to individual needs such as age, developmental stage, and previous experience (20). The priority of the age criterion relates to both the anxiety such exposure might generate and the length of time over which children can cope with anticipation. In addition, timing of the program before surgery is an important variable (20). Children aged ≥6 yr benefit most if they participate in a preparation program ≥5 days before surgery and benefit least if the program is given only 1 day before surgery. This phenomenon is related to the way that children in this age group process new information. Finally, a child who has previously undergone surgery or has been hospitalized may develop an exaggerated emotional response to an information-based preparation program (20). As increased parental anxiety results in increased child’s anxiety (1), there is a need for interventions that are designed specifically for parents. Cassady et al. (21) demonstrated that parental preoperative anxiety decreased after viewing an educational videotape. We suggest that more parental interventions need to be developed and that a child’s anxiety should be evaluated as an outcome. Preoperative Anxiety: Behavioral Modalities Parental Presence during Induction of Anesthesia. Parents and children prefer to stay together during medical procedures such as immunizations, dental treatment, and induction of anesthesia (22). Some data indicate, however, that parental presence during induction of anesthesia (PPIA) is allowed in 26% of US hospitals and is encouraged in only 8% of hospitals (23). In contrast, 28% of hospitals have no formal hospital policy and parental presence is against hospital policy for 32% of hospitals in the US. The smallest use of this induction technique was reported in the South-Central region and the highest in the Northwest and the Northeast (23). Interestingly, anesthesiologists from Great Britain (GB) encourage PPIA significantly more than anesthesiologists from the US (23,24). The reasons for these differences may include the use of different induction techniques, less concern about legal ramifications in GB, and a stronger demand for parental presence in GB. Economic issues such as operating room (OR) efficiency, infrastructure issues, lack of induction rooms and patchy preoperative educational programs, probably limit the availability of PPIA in the US. Potential benefits from PPIA include reducing the need for preoperative sedatives and avoiding the fear and anxiety that may occur on separation to the OR. Other benefits, such as increasing the child’s compliance during induction, remain controversial. Objections to PPIA include concern about disruption of the OR routine, crowded ORs, and a possible adverse reaction of parents. In addition, increased parental anxiety can increase a child’s anxiety, prolong anesthetic induction, and place additional stress on the anesthesiologist. Although early observational studies suggested reduced anxiety if parents were present during induction (25), more recent randomized controlled trials indicate that routine parental presence is not beneficial (26–28). One study demonstrated that only children >4 yr of age, those who have a “calm” baseline personality, or those who have a parent with a “calm” baseline personality benefit from this intervention (26). When interpreting the results of these studies, however, it should be noted that the design of a randomized controlled study does not reflect the practice of all anesthesiologists. When data of survey studies are reviewed (23,24), it is noticed that most anesthesiologists use either PPIA or sedative premedication to treat preoperative anxiety. When sedative premedications were directly compared with PPIA, however, it was found that children receiving oral midazolam were significantly less anxious and more compliant during the induction process (27). A recent study examined whether a combination of PPIA and oral midazolam is more effective than oral midazolam alone (28). The investigators found that PPIA has no additive anxiolytic effects for children who received oral midazolam preoperatively. Parents who accompany their sedated children into the ORs, however, are significantly less anxious and more satisfied both with the separation process and with the overall anesthetic, nursing and surgical care provided (28). PPIA is also associated with important legal implications. Lewyn (29) described a case in which a mother was invited to accompany her son into an emergency treatment room. According to the court, the mother fainted and suffered an injury to the head. In its verdict the Illinois Supreme Court stated that a hospital, which allows a nonpatient to accompany a patient during treatment, does not have a duty to protect the nonpatient from fainting. However, if medical personnel invite the nonpatient to participate in the treatment, then the hospital has a legal responsibility toward the nonpatient. Interestingly, some hospitals in the US now require the parents to sign a written informed consent acknowledging the risk of being present during induction of anesthesia. We believe that future research interests should shift towards an emphasis on what parents actually do during induction of anesthesia, rather than simply on their presence. Allowing a parent into an OR without significant preparation may be counterproductive because some parent behaviors, such as criticism and commands, are associated with increased distress. Effective methods of training such as parental preparation programs can be developed for enhancing the effects of PPIA. Preoperative Anxiety: Pharmacological Modalities The reported rate of use of pharmacological modalities for the treatment of preoperative anxiety in the US varies widely among age groups and geographical locations (24). Premedicant sedative drugs are least often used with children <3 yr of age and most often used with adults <65 yr of age (25% vs 75%). Currently, the most commonly used sedative premedicant in the preoperative holding area is midazolam (85%), followed by ketamine (4%), transmucosal fentanyl (3%), and meperidine (2%) (Fig. 2). TABLETABLE The majority of children in the US are premedicated via the oral route (80%), followed by the intranasal route (8%), the IM route (6%), and the rectal route (3%).Figure 2: Types of premedicants used in the preoperative holding area (23).Table 1: Premedications Administered by the Oral RouteTable 2: Premedications Administered Transmucosally and RectallyMidazolam. Midazolam is a short-acting benzodiazepine that is very lipophilic at physiologic pH, which accounts for its rapid onset of action. Davis et al. (30) has demonstrated that intranasally administered midazolam in a dosage of 0.2–0.3 mg/kg in patients undergoing myringotomies led to satisfactory separation from parents and a satisfactory induction over 70% of the time and did not prolong recovery time and hospital discharge time. Midazolam administered intranasally is effective in reducing anxiety in children within 10–12 min (31). A major drawback of intranasally administered midazolam, however, is that at least 50% of children cry on administration because it transiently irritates the nasal passages. Midazolam can also be given as a nasal spray, which is effective in reducing procedural anxiety in children undergoing cancer therapy (32). Midazolam can be administrated sublingually at the same dosage as intranasally. Although sublingual administration of midazolam is associated with a decreased incidence of crying (18%), it may be difficult to prevent small children from either swallowing the midazolam or spitting it out immediately (33). Rectal administration of midazolam in doses of 0.5–1.0 mg/kg effectively reduces the anxiety of children before induction of anesthesia (34). Although the incidence of hiccups after IV midazolam is <2%, the incidence noted that in a recent study involving rectally administered midazolam was more than 20%(34). The investigators had no explanation as to the increased rate of hiccups other than the young age of the children, but they found that the hiccups were easily treated by ethyl chloride nasal spray (34). Orally administered midazolam (0.5 mg/kg) has been shown to significantly reduce preoperative anxiety in young children (27,28). Orally administered midazolam can be given in a dosage of 0.25 mg to 1.0 mg/kg up to total dose of 20 mg depending on the of surgery and the anxiety of the A and and midazolam in a of 2 in et al. examined different doses of the midazolam and found that 0.25 mg/kg in satisfactory and in a majority of patients within 20 This study also found that increasing the dose in an increase in the of patients with satisfactory and a time to onset of Other that the time for premedicated children from their parents is min with a sedative between 20 and min The of administered midazolam and in the discharge of patients is controversial. Although recent studies noted that administrated midazolam is not associated with a discharge two studies involving children undergoing that and recovery are in the children who oral midazolam study involving children who myringotomies using or anesthesia indicated that children who were given oral midazolam experienced significant in recovery time but no in discharge time from the hospital Finally, et al. have the of a combination of preoperative oral midazolam and The investigators found that requirements by and discharge was in children who had been given midazolam preoperatively. The investigators suggested that the increased postoperative may have been to of and midazolam on As indicated a significant of children experiences maladaptive behavioral changes after surgery (1). In children who were premedicated with oral midazolam had a significantly decreased incidence of negative behavioral changes during the first after surgery However, this study noted that by 2 wk postoperatively there were no significant differences between the midazolam and The mechanism by which midazolam the incidence of postoperative behavioral changes is not but it may be related to of the perioperative process Children who received a benzodiazepine for dental and were about the experience dental than children who were not about their dental This may be particularly important for children undergoing surgical in children after oral midazolam as early as min and anxiolytic effects are as early as min after administration This timing to onset of is of importance in surgery where the of is very Midazolam and can be with which The dose in children is mg/kg given IV in a of up to 1.0 mg Some children who are with will experience it is to for can also be intranasally in a dose of given by from a is a that is very which the a good for administration and Oral transmucosal fentanyl administered in the of a to a and as the was the first sedative by the and in for use in children. Oral transmucosal in and dosage is in a and given to children in the dosage of for sedative is often associated with which usually min after children begin to the children before induction of anesthesia does however, to decreased or with induction in young children In a small of can cause a leading to significant a in be present this is administered in children is associated with a incidence of postoperative and that is not easily by In fact, at least study was because of a very incidence of preoperative A significant of is that it the postoperative et al. reported that preoperative is as effective as IV fentanyl given for of postoperative in children undergoing is an that a of and from the of ketamine compared with other premedicants is that it less given in sedative doses A of ketamine as compared with other premedicants is the of increased and which can to can also cause and in children, which can parents if they are not informed about this increased incidence of postoperative is associated with preoperative administration of ketamine The effects are all dose related and can be with the use of a small dose of administered ketamine mg/kg) the time of onset of the of administered ketamine is also dose related with administered ketamine mg/kg) an onset of of min and ketamine leading to within 20 min administration may be associated with and during the postoperative recent studies have found that use of a benzodiazepine given to children undergoing ketamine did not the incidence of In addition, the incidence of postoperative and is no different in children receiving midazolam, or a combination of ketamine and midazolam together The IV preparation of ketamine can be with or to an oral of which is by most children. can be also be given intranasally rectally and IM mg/kg) care discharge time of children who received administered ketamine is reported not to be compared with administered midazolam provided that of surgery is than min administered IM in an emergency room however, was found to significantly delay discharge and increase compared with midazolam administered rectally or intranasally et al. reported that the combination of midazolam and ketamine administrated had a rate of satisfactory compared with with either oral was also found to be to IM and in children undergoing The provided and and there was less need for IV as compared with the IM is an first developed as an but found to have and sedative Orally administrated in a dose of anesthetic and for postoperative requirements by 50% in children premedicated with This in may be to the of as well as a administered is also as effective as administered fentanyl for postoperative in children undergoing The recovery of children who is to the recovery of children who oral but significantly less postoperative as compared with One major drawback for the use of as a sedative premedicant is its onset of action. has to be administered as early as min before surgery In children, is at min for administered and min for rectally administered for the research should on the development of sedatives that will be well have a very time for onset of and have of action. In addition, developed preoperative sedatives should such as and should anesthetic requirements and reduce postoperative Finally, new methods of sedative premedications should also be For of should be as well as oral transmucosal methods for other than usually at least 1 for effective serum of drugs to be is can significantly the of a and has been effective in fentanyl in adults within min at 2 Finally, the of treatment modalities such as should be research is in these The to for review of this

Anesthesia & Analgesia · review · 408 citationsread the source →

Meta-analysis of Functional Neuroimaging of Major Depressive Disorder in Youth.

Importance: Despite its high prevalence and morbidity, the underlying neural basis of major depressive disorder (MDD) in youth is not well understood. Objectives: To identify in youth diagnosed as having MDD the most reliable neural abnormalities reported in existing functional neuroimaging studies and characterize their relations with specific psychological dysfunctions. Data sources: Searches were conducted in PubMed and Web of Science to identify relevant studies published from November 2006 through February 2015. The current analysis took place from August 21, 2014, to March 28, 2015. Study selection: We retained articles that conducted a comparison of youth aged 4 to 24 years diagnosed as having MDD and age-matched healthy controls using task-based functional magnetic resonance imaging and a voxelwise whole-brain approach. Data extraction and synthesis: We extracted coordinates of brain regions exhibiting differential activity in youth with MDD compared with healthy control participants. Multilevel kernel density analysis was used to examine voxelwise between-group differences throughout the whole brain. Correction for multiple comparisons was performed by computing null hypothesis distributions from 10 000 Monte Carlo simulations and calculating the cluster size necessary to obtain the familywise error rate control at P < .05. Main outcomes and measures: Abnormal levels of activation in youth diagnosed as having MDD compared with control participants during a variety of affective processing and executive functioning tasks. Results: Compared with age-matched healthy control participants (n = 274), youth with MDD (n = 246) showed reliable patterns of abnormal activation, including the following task-general and task-specific effects: hyperactivation in subgenual anterior cingulate cortex (P < .05) and ventrolateral prefrontal cortex (P < .05) and hypoactivation in caudate (P < .01) across aggregated tasks; hyperactivation in thalamus (P < .03) and parahippocampal gyrus (P < .003) during affective processing tasks; hypoactivation in cuneus (P < .001), dorsal cingulate cortex (P < .05), and dorsal anterior insula (P < .05) during executive functioning tasks; hypoactivity in posterior insula (P < .005) during positive valence tasks; and hyperactivity in dorsolateral prefrontal cortex (P < .001) and superior temporal cortex (P < .003) during negative valence tasks. Conclusions and relevance: Altered activations in several distributed brain networks may help explain the following seemingly disparate symptoms of MDD in youth: hypervigilance toward emotional stimuli from the overactivation of central hubs in the subgenual anterior cingulate cortex and thalamus that lead to a cascade of other symptoms; ineffective emotion regulation despite increased activation of the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex during affective processing, which may reverse across development or the clinical course; maladaptive rumination and poor executive control from difficulties shifting from default mode network activity to task-positive network activity during cognitively demanding tasks; and anhedonia from hypoactivation of the cuneus and posterior insula during reward processing.

JAMA psychiatry · meta-analysis · 180 citationsread the source →

Long-term developmental effect of withholding parenteral nutrition in paediatric intensive care units: a 4-year follow-up of the PEPaNIC randomised controlled trial.

Background: The PEPaNIC randomised controlled trial, which recruited 1440 critically ill infants and children in 2012-15, showed that withholding parenteral nutrition for 1 week (late-parenteral nutrition), compared with early supplementation within 24 h of admission to the paediatric intensive care unit (early-parenteral nutrition), prevented infections, accelerated recovery, and improved neurocognitive development assessed 2 years later. Because several neurocognitive domains can only be thoroughly assessed from age 4 years onwards, we aimed to determine the effect of late-parenteral nutrition versus early-parenteral nutrition on physical, neurocognitive, and emotional and behavioural development 4 years after randomisation. Methods: This is a preplanned, blinded, 4-year follow-up study of participants included in the PEPaNIC trial (done at University Hospitals Leuven, Belgium; Erasmus Medical Centre Sophia Children's Hospital, Rotterdam, Netherlands; and Stollery Children's Hospital, Edmonton, AB, Canada) and of matched healthy children. Studied outcomes were anthropometrics; health status; parent-reported or caregiver-reported executive functions, and emotional and behavioural problems; and clinical tests for intelligence, visual-motor integration, alertness, motor coordination, and memory. Through multivariable linear and logistic regression analyses, after imputation for missing values (≤30%) and adjustment for risk factors, we investigated the effect of early-parenteral nutrition versus late-parenteral nutrition. This trial is registered with ClinicalTrials.gov, NCT01536275. Findings: Between March 8, 2016, and Nov 8, 2019, 684 children from the original PEPaNIC trial (356 from the late-parenteral nutrition group and 328 from the early-parenteral nutrition group) were assessed for neurocognitive development at 4-years follow-up. Compared with the control group (369 healthy children), children who had critical illness had lower height (β-estimate -2·11 [95% CI -3·15 to -1·06]; p<0·0001) and head circumference (-0·42 [-0·67 to -0·18]; p=0.00077); and worse health status (eg, hospital admission odds ratio 4·27 [95% CI 3·12 to 5·84]; p<0·0001), neurocognitive (eg, parent-reported or caregiver-reported total executive functioning β-estimate 3·57 [95% CI 1·95 to 5·18], p<0·0001; total intelligence quotient -7·35 [-9·31 to -5·39], p<0·0001), and parent-reported or caregiver-reported emotional and behavioural developmental outcomes (internalising 2·73 [1·19 to 4·28], p=0·00055; externalising 1·63 [0·19 to 3·08], p=0·027; and total behavioural problems 2·95 [1·44 to 4·46], p=0·00013), adjusted for risk factors. Outcomes were never worse in the late-parenteral nutrition group compared with the early-parenteral nutrition group, but patients in the late-parenteral nutrition group had fewer parent-reported or caregiver-reported internalising (β-estimate -1·88 [95% CI -3·69 to -0·07]; p=0·042), externalising (-1·73 [-3·43 to -0·03]; p=0·046), and total emotional and behavioural problems (-2·44 [-4·22 to -0·67]; p=0·0070) than patients who had received early-parenteral nutrition, after adjusting for risk factors, and were no longer different from healthy controls for these outcomes. Interpretation: Omitting early parenteral nutrition use for critically ill children did not adversely affect long-term outcomes 4 years after randomisation and protected against emotional and behavioural problems, further supporting the deimplementation of early parenteral nutrition. Funding: European Research Council, Methusalem, Flanders Institute for Science and Technology, Research Foundation Flanders, Sophia Foundation, Stichting Agis Zorginnovatie, Erasmus Trustfonds, and the European Society for Clinical Nutrition and Metabolism.

The Lancet. Child & adolescent health · 46 citationsread the source →

Ethnoracial and social trends in breast cancer staging at diagnosis in Brazil, 2001-14: a case only analysis.

Background: Policies for early detection of breast cancer, including clinical breast examinations and mammographic screening, were introduced in Brazil in 2004, but their effect on disease stage at diagnosis is unclear. We aimed to assess whether these policies have led to a decrease in the prevalence of late-stage breast cancer at diagnosis. Methods: In this case only analysis, using an anonymised nationwide hospital based-cancer registry network, we identified women aged 18-89 years who had been diagnosed with an invasive breast cancer in Brazil during 2001-14. We extracted individual patient-level data on patient demographics, tumour variables, and health-care provider variables for the centre where the patient was diagnosed. Our objectives were to estimate the prevalence of late-stage breast cancer (TNM stage III or IV) at diagnosis overall, across age groups, and by ethnoracial and social strata (ie, self-reported ethnoracial group, as white, black, brown, Asian, or Indigenous, and educational level, marital status, and region of residence) across the study period, and compare these estimates with international data from high-income countries (Norway and the USA). We used logistic regression to estimate odds ratios (ORs) for late-stage versus early-stage (TNM stage I or II) breast cancer at diagnosis in relation to relevant exposures, either minimally adjusted (for age, year of diagnosis, and region of residence) or fully adjusted (for all patient, tumour, and health-care provider variables). Findings: We identified 247 719 women who were diagnosed with invasive breast cancer between Jan 1, 2001, and Dec 31, 2014, with a mean age at diagnosis of 55·4 years (SD 13·3), of whom 36·2% (n=89 550) identified as white, 29·8% (n=73 826) as black or brown, and 0·7% (n=1639) as Asian or Indigenous. Prevalence of late-stage breast cancer at diagnosis remained high throughout 2001-14, at approximately 40%, was inversely associated with educational level (p value for linear trend <0·0001), and was higher for women who identified as black (minimally adjusted OR 1·61, 95% CI 1·53-1·70; fully adjusted OR 1·45, 95% CI 1·38-1·54) and brown (minimally adjusted OR 1·26, 95% CI 1·22-1·30; fully adjusted OR 1·18, 1·14-1·23) than those who identified as white. The predicted prevalence of late-stage cancer at diagnosis was highest for women who were black or brown with little or no formal education (48·8%, 95% CI 48·2-49·5) and lowest for women who were white with university education (29·4%, 28·2-30·6), but both these prevalences were higher than that of all women diagnosed with breast cancer in Norway before the introduction of mammography screening (ie, 16·3%, 95% CI 15·4%-17·2% in 1970-74). Similar ethnoracial and social patterns emerged in analyses restricted to the age group targeted by screening (50-69 years). Interpretation: The persistently high prevalence of late-stage breast cancer at diagnosis across all ethnoracial and social strata in Brazil, although more substantially among the most disadvantaged populations, implies that early detection policies might have had little effect on breast cancer mortality so far, and highlights the need to focus primarily on timely diagnosis of symptomatic breast cancer rather than on screening for asymptomatic disease. Funding: Newton Fund, Research Councils UK, and Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa.

The Lancet. Global health · 56 citationsread the source →

Two‐Year Follow‐up Outcomes in Emotionally Focused Couple Therapy: An Investigation of Relationship Satisfaction and Attachment Trajectories

Emotionally Focused Couple Therapy (EFT; The practice of emotionally focused couple therapy: Creating connection. New York, NY: Brunner-Routledge) is an evidence-based couple therapy that aims to create lasting change for couples (Clinical Psychology: Science and Practice, 6(1), 67-79). Although studies have demonstrated strong results in follow-up (Journal of Marital and Family Therapy, 28(4), 391-398), less is known about relationship functioning across time after therapy has ended. We modelled change in relationship satisfaction and attachment from pre-therapy through 24 months follow-up in 32 couples. HLM results confirmed a significant growth pattern demonstrating increases in relationship satisfaction and secure base behaviour and decreases in relationship specific attachment anxiety over the course of therapy and across follow-up at a decelerated rate. These findings support the theoretical assumption that EFT helps couples engaged in therapy create lasting relationship satisfaction and attachment change.

Journal of Marital and Family Therapy · 70 citationsread the source →

Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK.

Background: A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and we examine rates of co-occurrence among autoimmune diseases. Methods: In this UK population-based study, we used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex and ethnicity. Eligible participants were men and women (no age restriction) with acceptable records, approved for Hospital Episodes Statistics and Office of National Statistics linkage, and registered with their general practice for at least 12 months during the study period. We calculated age and sex standardised incidence and prevalence of 19 autoimmune disorders from 2000 to 2019 and used negative binomial regression models to investigate temporal trends and variation by age, sex, socioeconomic status, season of onset, and geographical region in England. To characterise co-occurrence of autoimmune diseases, we calculated incidence rate ratios (IRRs), comparing incidence rates of comorbid autoimmune disease among individuals with a first (index) autoimmune disease with incidence rates in the general population, using negative binomial regression models, adjusted for age and sex. Findings: Among the 22 009 375 individuals included in the study, 978 872 had a new diagnosis of at least one autoimmune disease between Jan 1, 2000, and June 30, 2019 (mean age 54·0 years [SD 21·4]). 625 879 (63·9%) of these diagnosed individuals were female and 352 993 (36·1%) were male. Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased (IRR 2017-19 vs 2000-02 1·04 [95% CI 1·00-1·09]). The largest increases were seen in coeliac disease (2·19 [2·05-2·35]), Sjogren's syndrome (2·09 [1·84-2·37]), and Graves' disease (2·07 [1·92-2·22]); pernicious anaemia (0·79 [0·72-0·86]) and Hashimoto's thyroiditis (0·81 [0·75-0·86]) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10·2% of the population over the study period (1 912 200 [13·1%] women and 668 264 [7·4%] men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1·72 [1·64-1·81]), rheumatoid arthritis (1·52 [1·45-1·59]), Graves' disease (1·36 [1·30-1·43]), and systemic lupus erythematosus (1·35 [1·25-1·46]). Seasonal variations were observed for childhood-onset type 1 diabetes (more commonly diagnosed in winter) and vitiligo (more commonly diagnosed in summer), and regional variations were observed for a range of conditions. Autoimmune disorders were commonly associated with each other, particularly Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Individuals with childhood-onset type 1 diabetes also had significantly higher rates of Addison's disease (IRR 26·5 [95% CI 17·3-40·7]), coeliac disease (28·4 [25·2-32·0]), and thyroid disease (Hashimoto's thyroiditis 13·3 [11·8-14·9] and Graves' disease 6·7 [5·1-8·5]), and multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases. Interpretation: Autoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases. Funding: Research Foundation Flanders.

Lancet (London, England) · 508 citationsread the source →

Control of a Nosocomial Outbreak of COVID-19 in a University Hospital.

Background: Nosocomial spread of coronavirus disease 2019 (COVID-19) causes clusters of infection among high-risk individuals. Controlling this spread is critical to reducing COVID-19 morbidity and mortality. We describe an outbreak of COVID-19 in Keio University Hospital, Japan, and its control and propose effective control measures. Methods: When an outbreak was suspected, immediate isolation and thorough polymerase chain reaction (PCR) testing of patients and health care workers (HCWs) using an in-house system, together with extensive contact tracing and social distancing measures, were conducted. Nosocomial infections (NIs) were defined as having an onset or positive test after the fifth day of admission for patients and having high-risk contacts in our hospital for HCWs. We performed descriptive analyses for this outbreak. Results: Between March 24 and April 24, 2020, 27 of 562 tested patients were confirmed positive, of whom 5 (18.5%) were suspected as NIs. For HCWs, 52 of 697 tested positive, and 40 (76.9%) were considered NIs. Among transmissions, 95.5% were suspected of having occurred during the asymptomatic period. Large-scale isolation and testing at the first sign of outbreak terminated NIs. The number of secondary cases directly generated by a single primary case found before March 31 was 1.74, compared with 0 after April 1. Only 4 of 28 primary cases generated definite secondary infection; these were all asymptomatic. Conclusions: Viral shedding from asymptomatic cases played a major role in NIs. PCR screening of asymptomatic individuals helped clarify the pattern of spread. Immediate large-scale isolation, contact tracing, and social distancing measures were essential to containing outbreaks.

Open forum infectious diseases · 43 citationsread the source →

Efficacy and Moderation of Mobile App-Based Programs for Mindfulness-Based Training, Self-Compassion Training, and Cognitive Behavioral Psychoeducation on Mental Health: Randomized Controlled Noninferiority Trial.

Background: Mindfulness-based interventions, self-compassion training, and cognitive behavioral therapy have garnered much evidence in its salutary effects on mental health. With increasing application of smartphone and mobile technology on health promotion, this study investigated the efficacy and possible moderators of mindfulness, self-compassion, and cognitive behavioral psychoeducation training mobile apps in the improvement of mental health. Objective: The aim of this study was to examine the efficacy of 3 mobile app-based programs: mindfulness-based program, self-compassion program, and cognitive behavioral psychoeducation program in improving mental well-being and reducing psychological distress. Changes in mindful awareness and self-compassion were also assessed. To further delineate the suitability of each program for different types of individuals, individual difference variables (ie, discomfort with emotions and tolerance for ambiguity) were explored for potential moderation. Methods: This study was a 3-arm, randomized, controlled, noninferiority trial examining the efficacy of mindfulness-based program, self-compassion program, and cognitive behavioral psychoeducation. Participants were randomized into either 1 of the 3 conditions. Throughout the 4-week, 28-session program, participants spent 10-15 min daily reviewing the course content and practicing various related exercises. At preprogram, postprogram, and 3-month follow-up, participants also completed Web-based measures of mental well-being, psychological distress, mindful-awareness, and self-compassion as well as the proposed moderators. Results: Among the 2161 study participants, 508 and 349 completed the post- and 3-month follow-up assessment, respectively. All 3 conditions (mindfulness-based program: N=703; cognitive behavioral psychoeducation: N=753; self-compassion program: N=705) were found to be efficacious in improving mental well-being and reducing psychological distress. All conditions enhanced mindful awareness at postprogram. Significant interaction effect was found on self-compassion; cognitive behavioral psychoeducation and self-compassion program, but not mindfulness-based program, significantly enhanced self-compassion at postprogram. No significant differences regarding usage and users' satisfaction were found among the 3 conditions. None of the proposed moderators were found to be significant. Conclusions: Mindfulness-based, self-compassion, and cognitive behavioral psychoeducation mobile apps were efficacious in improving mental well-being and reducing psychological distress among adults at postprogram and 3-month follow-up. Future app-based psychological training programs should consider gamification and personalization of content or feedback to enhance engagement and mitigate the high attrition rates that are common in app-based health promotion programs. Trial registration: Chinese Clinical Trial Registry (ChiCTR) ChiCTR-TRC-13003468; http://www.chictr.org.cn/hvshowproject.aspx?id=6220 (Archived by WebCite at http://www.webcitation.org/734PlOz50).

JMIR mental health · 71 citationsread the source →

Identifying thresholds for clinically meaningful change among clients of drug and alcohol services using the Australian Treatment Outcomes Profile.

Aims: The Austraian Treatment Outcomes Profile (ATOP) is a brief clinical outcomes tool used widely in the Australian alcohol and other drugs treatment sector to monitor clients' substance use, health, wellbeing and clinical risk factors. It has demonstrated reliability and validity, and has recommended clinical cut-offs for assessing single-occasion client-rated health scores. This study determined clinically meaningful change thresholds for ATOP substance use and health and wellbeing variables for use by clinicians in monitoring client progress, and for quality improvement and service evaluation. Design, setting and participants: A framework for assessing clinically meaningful changes scores was developed by (1) calculating statistically reliable change thresholds using data-driven techniques with a reference sample of clinical ATOP data and (2) conducting a multi-disciplinary subject matter expert group to review the utility and validity of data-derived clinically meaningful change. The study was conducted within Outpatient Alcohol and Other Drug treatment services in New South Wales, Australia. The reference sample comprised 6100 ATOPs from clients at entry to public outpatient Alcohol and Other Drug treatment services; the subject matter expert group comprised 29 key stakeholders from the specialist alcohol and other drug treatment sector. Measurements and findings: We used the Reliable Change Index method to calculate clinically meaningful change thresholds for ATOP variables. For substance use variables, a change of 30% in days of use in the last 28 (minimum 4 days) was the threshold for clinically meaningful change for substance use; for health and wellbeing variables, a change of 2 or more points in psychological health, physical health or quality of life scores (measured on 0-10 scales) was the minimum clinically meaningful change. Conclusions: Clinically meaningful change thresholds have been proposed for Australian Treatment Outcomes Profile substance use and health and wellbeing items, based on statistical reliability and subject matter expert assessment. These will be used in the development of an outcomes metric for assessing change and assigning meaning in aggregated data for evaluation of services.

Addiction (Abingdon, England) · 1 citationsread the source →

Global, regional, and national estimates and trends in stillbirths from 2000 to 2019: a systematic assessment.

Background: Stillbirths are a major public health issue and a sensitive marker of the quality of care around pregnancy and birth. The UN Global Strategy for Women's, Children's and Adolescents' Health (2016-30) and the Every Newborn Action Plan (led by UNICEF and WHO) call for an end to preventable stillbirths. A first step to prevent stillbirths is obtaining standardised measurement of stillbirth rates across countries. We estimated stillbirth rates and their trends for 195 countries from 2000 to 2019 and assessed progress over time. Methods: For a systematic assessment, we created a dataset of 2833 country-year datapoints from 171 countries relevant to stillbirth rates, including data from registration and health information systems, household-based surveys, and population-based studies. After data quality assessment and exclusions, we used 1531 datapoints to estimate country-specific stillbirth rates for 195 countries from 2000 to 2019 using a Bayesian hierarchical temporal sparse regression model, according to a definition of stillbirth of at least 28 weeks' gestational age. Our model combined covariates with a temporal smoothing process such that estimates were informed by data for country-periods with high quality data, while being based on covariates for country-periods with little or no data on stillbirth rates. Bias and additional uncertainty associated with observations based on alternative stillbirth definitions and source types, and observations that were subject to non-sampling errors, were included in the model. We compared the estimated stillbirth rates and trends to previously reported mortality estimates in children younger than 5 years. Findings: Globally in 2019, an estimated 2·0 million babies (90% uncertainty interval [UI] 1·9-2·2) were stillborn at 28 weeks or more of gestation, with a global stillbirth rate of 13·9 stillbirths (90% UI 13·5-15·4) per 1000 total births. Stillbirth rates in 2019 varied widely across regions, from 22·8 stillbirths (19·8-27·7) per 1000 total births in west and central Africa to 2·9 (2·7-3·0) in western Europe. After west and central Africa, eastern and southern Africa and south Asia had the second and third highest stillbirth rates in 2019. The global annual rate of reduction in stillbirth rate was estimated at 2·3% (90% UI 1·7-2·7) from 2000 to 2019, which was lower than the 2·9% (2·5-3·2) annual rate of reduction in neonatal mortality rate (for neonates aged <28 days) and the 4·3% (3·8-4·7) annual rate of reduction in mortality rate among children aged 1-59 months during the same period. Based on the lower bound of the 90% UIs, 114 countries had an estimated decrease in stillbirth rate since 2000, with four countries having a decrease of at least 50·0%, 28 having a decrease of 25·0-49·9%, 50 having a decrease of 10·0-24·9%, and 32 having a decrease of less than 10·0%. For the remaining 81 countries, we found no decrease in stillbirth rate since 2000. Of these countries, 34 were in sub-Saharan Africa, 16 were in east Asia and the Pacific, and 15 were in Latin America and the Caribbean. Interpretation: Progress in reducing the rate of stillbirths has been slow compared with decreases in the mortality rate of children younger than 5 years. Accelerated improvements are most needed in the regions and countries with high stillbirth rates, particularly in sub-Saharan Africa. Future prevention of stillbirths needs increased efforts to raise public awareness, improve data collection, assess progress, and understand public health priorities locally, all of which require investment. Funding: Bill & Melinda Gates Foundation and the UK Foreign, Commonwealth and Development Office.

Lancet (London, England) · 371 citationsread the source →

[Global health of unaccompanied refugee minors in Gironde (France) between 2011 and 2013].

Unlabelled: The lack of clinical practice recommendations for the care of the Unaccompanied Refugee Minors (URM) causes significant disparities depending on which department they arrive. By studying their global health we're willing to promote a standard of care for them. Methods: Data descriptive study from a systematic medical procedure proposed to URM who came in Gironde between January, 2011 and December, 2013. Results: 235 URM were included, from Africa (71%), Asia (21%) and from Eastern Europe (8%). Among them, 143 medical files were complete. The most frenquently diagnosed diseases, and/or the most serious, were digestive parasitoses (50%), schistosomiasis (7%), filariasis (6%), hepatitis B (chronic 6%, seroprevalence 28%), iron deficiency (26%, 4 % with anaemia), G6PD deficiency (8%) and tooth decays (29%). About mental disorders, 45% of the URM had a clinical presentation compatible with post-traumatic stress disorder, 4% had suicidal thoughts. Conclusion: URM accumulate the health risks of teenagers and those of illegal immigrants. Consequently they require an oriented and particular care.

Bulletin de la Societe de pathologie exotique (1990) · 10 citationsread the source →

Association between breastfeeding and intelligence, educational attainment, and income at 30 years of age: a prospective birth cohort study from Brazil.

Background: Breastfeeding has clear short-term benefits, but its long-term consequences on human capital are yet to be established. We aimed to assess whether breastfeeding duration was associated with intelligence quotient (IQ), years of schooling, and income at the age of 30 years, in a setting where no strong social patterning of breastfeeding exists. Methods: A prospective, population-based birth cohort study of neonates was launched in 1982 in Pelotas, Brazil. Information about breastfeeding was recorded in early childhood. At 30 years of age, we studied the IQ (Wechsler Adult Intelligence Scale, 3rd version), educational attainment, and income of the participants. For the analyses, we used multiple linear regression with adjustment for ten confounding variables and the G-formula. Findings: From June 4, 2012, to Feb 28, 2013, of the 5914 neonates enrolled, information about IQ and breastfeeding duration was available for 3493 participants. In the crude and adjusted analyses, the durations of total breastfeeding and predominant breastfeeding (breastfeeding as the main form of nutrition with some other foods) were positively associated with IQ, educational attainment, and income. We identified dose-response associations with breastfeeding duration for IQ and educational attainment. In the confounder-adjusted analysis, participants who were breastfed for 12 months or more had higher IQ scores (difference of 3·76 points, 95% CI 2·20-5·33), more years of education (0·91 years, 0·42-1·40), and higher monthly incomes (341·0 Brazilian reals, 93·8-588·3) than did those who were breastfed for less than 1 month. The results of our mediation analysis suggested that IQ was responsible for 72% of the effect on income. Interpretation: Breastfeeding is associated with improved performance in intelligence tests 30 years later, and might have an important effect in real life, by increasing educational attainment and income in adulthood. Funding: Wellcome Trust, International Development Research Center (Canada), CNPq, FAPERGS, and the Brazilian Ministry of Health.

The Lancet. Global health · 382 citationsread the source →

Knowledge and perceptions of human trafficking among community-based and faith-based organization members in South Los Angeles.

The objectives of this study were (1) to assess the knowledge and perceptions of human trafficking (HT) among leaders and staff from 11 community-based organizations (CBOs) and faith-based organizations (FBOs) in South Los Angeles, and (2) to identify gaps in knowledge of HT and inform community organizations regarding possible best practices in health promotion for addressing this emerging public health problem. A self-administered survey was conducted during the period from 4 December 2015 to 28 January 2016. Descriptive statistics were generated and a logistic regression model was constructed using SAS 9.3. A total of 277 CBO and FBO leaders and staff completed the survey. Participants demonstrated high levels of knowledge of HT but their knowledge was not comprehensive, as gaps exist in recognizing the context in which HT usually takes place; understanding the local laws that govern this activity; and ways to follow related policies/procedures when the problem is suspected. A majority (a) believed there were not enough services in Los Angeles County to help survivors of HT, (b) could not recognize the signs of HT, and (c) did not know what steps to take if they suspected this criminal activity. A statistically significant association was found between education and participants' knowledge of HT, and with their beliefs and attitudes toward this violation of human rights. Study findings suggest that, generally, CBO/FBO leaders and staff in South Los Angeles have good knowledge about HT. However, notable gaps in knowledge and misperceptions remain, suggesting opportunities for Public Health to further educate and intervene.

Global health promotion · 1 citationsread the source →

Identification of Modifiable Social and Behavioral Factors Associated With Childhood Cognitive Performance.

Importance: Inequities in social environments are likely associated with a large portion of racial disparities in childhood cognitive performance. Identification of the specific exposures associated with cognitive development is needed to inform prevention efforts. Objective: To identify modifiable factors associated with childhood cognitive performance. Design, setting, and participants: This longitudinal pregnancy cohort study included 1503 mother-child dyads who were enrolled in the University of Tennessee Health Science Center-Conditions Affecting Neurodevelopment and Learning in Early Life study between December 1, 2006, and July 31, 2011, and assessed annually until the children were aged 4 to 6 years. The analytic sample comprised 1055 mother-child dyads. A total of 155 prenatal, perinatal, and postnatal exposures were included to evaluate environment-wide associations. Participants comprised a community-based sample of pregnant women who were recruited between 16 weeks and 28 weeks of gestation from 4 hospitals in Shelby County, Tennessee. Women with high-risk pregnancies were excluded. Data were analyzed from June 1, 2018, to April 15, 2019. Exposures: Individual and neighborhood socioeconomic position, family structure, maternal mental health, nutrition, delivery complications, birth outcomes, and parenting behaviors. Main outcomes and measures: Child's full-scale IQ measured by the Stanford-Binet Intelligence Scales, Fifth Edition, at age 4 to 6 years. Results: Of 1055 children included in the analytic sample, 532 (50.4%) were female. Among mothers, the mean (SD) age was 26.0 (5.6) years; 676 mothers (64.1%) were Black, and 623 mothers (59.0%) had an educational level of high school or less. Twenty-four factors were retained in the least absolute shrinkage and selection operator regression analysis and full models adjusted for potential confounding. Associations were noted between child cognitive performance and parental education and breastfeeding; for each increase of 1.0 SD in exposure, positive associations were found with cognitive growth fostering from observed parent-child interactions (β = 1.12; 95% CI, 0.24-2.00) and maternal reading ability (β = 1.42; 95% CI, 0.16-2.68), and negative associations were found with parenting stress (β = -1.04; 95% CI, -1.86 to -0.21). A moderate increase in these beneficial exposures was associated with a notable improvement in estimated cognitive test scores using marginal means (0.5% of an SD). Black children experienced fewer beneficial cognitive performance exposures; in a model including all 24 exposures and covariates, no racial disparity was observed in cognitive performance (95% CIs for race included the null). Conclusions and relevance: The prospective analysis identified multiple beneficial and modifiable cognitive performance exposures that were associated with mean differences in cognitive performance by race. The findings from this observational study may help guide experimental studies focused on reducing racial disparities in childhood cognitive performance.

JAMA pediatrics · 40 citationsread the source →

Acoustic stimulation during sleep improves cognition and ameliorates Alzheimer's disease pathology in APP/PS1 mice.

Nonpharmacological therapies for Alzheimer's disease (AD) have become a popular research topic, and acoustic stimulation during sleep is one such promising strategy for the clinical treatment of AD. Some animal experiments have illustrated that acoustic stimulation at a specific frequency can ameliorate AD-related pathology or improve cognition in mice, but these studies did not explore the effective time window of auditory stimulation. Here, we explored the effects of acoustic stimulation during wakefulness and acoustic stimulation during sleep on cognition and AD-related pathology in APP/PS1 mice and the underlying mechanisms. In this study, forty APP/PS1 mice were equally divided into the following 4 groups and treated for 28 days: the chronic sleep deprivation (CSD) group (exposed to sleep deprivation from zeitgeber time [ZT] 0 to ZT 12 each day), the normal sleep and stress exposure (NSS) group (exposed to a stressor from ZT 0 to ZT 12 each day), the acoustic stimulation during wakefulness (ASW) group (exposed to sleep deprivation and 40 Hz acoustic stimulation from ZT 0 to ZT 12 each day) and the acoustic stimulation during sleep (ASS) group (exposed to sleep deprivation from ZT 0 to ZT 12 and 40 Hz acoustic stimulation from ZT 12 to ZT 24 each day). After the intervention, cognition was assessed by behavioural experiments. The amyloid-β burden was analysed by Western blotting, immunofluorescence and enzyme-linked immunosorbent assay. Tau pathology was assessed by Western blotting. Mitochondrial function was evaluated by transmission electron microscopy, Western blotting and fluorescence intensity measurement. We found that the NSS and ASS groups had better cognitive functions than the CSD and ASW groups. The Aβ burden and tau phosphorylation were lower in the NSS and ASS groups than in the CSD and ASW groups. Mitochondrial function was better in the NSS and ASS groups than in the CSD and ASW groups. However, the differences in these parameters between the NSS and ASS groups and between the CSD and ASW groups were not significant. Our findings suggest that acoustic stimulation at a specific frequency during sleep, but not during wakefulness, reduces the amyloid-β burden by inhibiting amyloid beta precursor protein-binding protein 2, hinders tau phosphorylation by blocking glycogen synthase kinase 3 beta, and restores mitochondrial function by elevating mitophagy and promoting mitochondrial biogenesis.

Experimental gerontology · 6 citationsread the source →

Simplified sleep restriction for insomnia in general practice: a randomised controlled trial.

Background: Insomnia is common in primary care. Cognitive behavioural therapy for insomnia (CBT-I) is effective but requires more time than is available in the general practice consultation. Sleep restriction is one behavioural component of CBT-I. Aim: To assess whether simplified sleep restriction (SSR) can be effective in improving sleep in primary insomnia. Design and setting: Randomised controlled trial of patients in urban general practice settings in Auckland, New Zealand. Method: Adults with persistent primary insomnia and no mental health or significant comorbidity were eligible. Intervention patients received SSR instructions and sleep hygiene advice. Control patients received sleep hygiene advice alone. Primary outcomes included change in sleep quality at 6 months measured by the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and sleep efficiency (SE%). The proportion of participants reaching a predefined 'insomnia remission' treatment response was calculated. Results: Ninety-seven patients were randomised and 94 (97%) completed the study. At 6-month follow-up, SSR participants had improved PSQI scores (6.2 versus 8.4, P<0.001), ISI scores (8.6 versus 11.1, P = 0.001), actigraphy-assessed SE% (difference 2.2%, P = 0.006), and reduced fatigue (difference -2.3 units, P = 0.04), compared with controls. SSR produced higher rates of treatment response (67% [28 out of 42] versus 41% [20 out of 49]); number needed to treat = 4 (95% CI = 2.0 to 19.0). Controlling for age, sex, and severity of insomnia, the adjusted odds ratio for insomnia remission was 2.7 (95% CI = 1.1 to 6.5). There were no significant differences in other outcomes or adverse effects. Conclusion: SSR is an effective brief intervention in adults with primary insomnia and no comorbidities, suitable for use in general practice.

The British journal of general practice : the journal of the Royal College of General Practitioners · randomised controlled trial · 40 citationsread the source →

Metabolic Impact of Intermittent Fasting in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Interventional Studies.

Context: Intermittent fasting (IF) has been proposed as a weight-loss strategy with additional cardiometabolic benefits in individuals with obesity. Despite its growing popularity, the effect of IF in patients with type 2 diabetes (T2DM) remains unclear. Objective: We conducted a systematic review and meta-analysis to evaluate the metabolic impact of IF compared to standard diet in patients with T2DM. Methods: Embase, PubMed, and clinicaltrials.gov between 1950 and August 12, 2020 were searched for randomized, diet-controlled studies evaluating any IF intervention in adults with T2DM. We examined the impact of IF on weight loss and glucose-lowering by calculating pooled estimates of the absolute differences in body weight and glycated hemoglobin A1c (HbA1c) compared to a control group using a random-effects model. Results: Seven studies (n = 338 participants; mean body mass index [BMI] 35.65, mean baseline HbA1c 8.8%) met our inclusion criteria. IF induced a greater decrease in body weight by -1.89 kg (95% CI, -2.91 to -0.86 kg) compared to a regular diet, with no significant between-study heterogeneity (I2 21.0%, P = .28). The additional weight loss induced by IF was greater in studies with a heavier population (BMI > 36) (-3.43 kg [95% CI, -5.72 to -1.15 kg]) and in studies of shorter duration (≤ 4 months) (-3.73 kg [95% CI, -7.11 to -0.36 kg]). IF was not associated with further reduction in HbA1c compared to a standard diet (HbA1c -0.11% [95% CI, -0.38% to 0.17%]). Conclusion: Current evidence suggests that IF is associated with greater weight loss in patients with T2DM compared with a standard diet, with a similar impact on glycemic control.

The Journal of clinical endocrinology and metabolism · meta-analysis · 62 citationsread the source →

Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.

Background: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality. Findings: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5-36·0] of 129 patients), depressed mood (42 [32·6%; 24·7-40·9] of 129), anxiety (46 [35·7%; 27·6-44·2] of 129), impaired memory (44 [34·1%; 26·2-42·5] of 129), and insomnia (54 [41·9%; 22·5-50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5-14·1] of 332 patients), insomnia (34 [12·1%; 8·6-16·3] of 280), anxiety (21 [12·3%; 7·7-17·7] of 171), irritability (28 [12·8%; 8·7-17·6] of 218), memory impairment (44 [18·9%; 14·1-24·2] of 233), fatigue (61 [19·3%; 15·1-23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9-37·3] of 181) and sleep disorder (14 [100·0%; 88·0-100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7-42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1-18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1-19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1-84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. Interpretation: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. Funding: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.

The lancet. Psychiatry · meta-analysis · 1531 citationsread the source →

E-mental health interventions for the treatment and prevention of eating disorders: An updated systematic review and meta-analysis.

Objectives: E-mental health (digital) interventions can help overcome existing barriers that stand in the way of people receiving help for an eating disorder (ED). Although e-mental health interventions for treating and preventing EDs have been met with enthusiasm, earlier reviews brought attention to poor quality of evidence, and offered solutions to enhance their evidence base. To assess developments in the field, we conducted an updated meta-analysis on the efficacy of e-mental health interventions for treating and preventing EDs, paying attention to whether trial quality and outcomes have improved in recent trials. We also assessed whether user-centered design principles have been implemented in existing digital interventions. Method: Four databases were searched for RCTs of digital interventions for treating and preventing EDs. Thirty-six RCTs (28 prevention- and 8 treatment-focused) were included. Results: Some evidence that study quality improved in recent prevention-focused trials was found. Few trials involved the end-user in the design or development stage of the intervention. Issues with intervention engagement were noted, and 1 in 4 participants dropped out from prevention- and treatment-focused trials. Digital interventions were more effective than control conditions in reducing established risk factors and symptoms in prevention- (g's = 0.19 to 0.43) and treatment-focused trials (g's = 0.29 to 0.69), respectively. Effect sizes have not increased in recent trials. Few trials compared a digital intervention with a face-to-face intervention. Whether digital interventions can prevent ED onset is unclear. Conclusion: Digital interventions are a promising approach to ED treatment and prevention, but improvements are still needed. Three key recommendations are provided. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Journal of consulting and clinical psychology · meta-analysis · 152 citationsread the source →

Efficacy of treatments for anxiety disorders: a meta-analysis.

To our knowledge, no previous meta-analysis has attempted to compare the efficacy of pharmacological, psychological and combined treatments for the three main anxiety disorders (panic disorder, generalized anxiety disorder and social phobia). Pre-post and treated versus control effect sizes (ES) were calculated for all evaluable randomized-controlled studies (n = 234), involving 37,333 patients. Medications were associated with a significantly higher average pre-post ES [Cohen's d = 2.02 (1.90-2.15); 28,051 patients] than psychotherapies [1.22 (1.14-1.30); 6992 patients; P < 0.0001]. ES were 2.25 for serotonin-noradrenaline reuptake inhibitors (n = 23 study arms), 2.15 for benzodiazepines (n = 42), 2.09 for selective serotonin reuptake inhibitors (n = 62) and 1.83 for tricyclic antidepressants (n = 15). ES for psychotherapies were mindfulness therapies, 1.56 (n = 4); relaxation, 1.36 (n = 17); individual cognitive behavioural/exposure therapy (CBT), 1.30 (n = 93); group CBT, 1.22 (n = 18); psychodynamic therapy 1.17 (n = 5); therapies without face-to-face contact (e.g. Internet therapies), 1.11 (n = 34); eye movement desensitization reprocessing, 1.03 (n = 3); and interpersonal therapy 0.78 (n = 4). The ES was 2.12 (n = 16) for CBT/drug combinations. Exercise had an ES of 1.23 (n = 3). For control groups, ES were 1.29 for placebo pills (n = 111), 0.83 for psychological placebos (n = 16) and 0.20 for waitlists (n = 50). In direct comparisons with control groups, all investigated drugs, except for citalopram, opipramol and moclobemide, were significantly more effective than placebo. Individual CBT was more effective than waiting list, psychological placebo and pill placebo. When looking at the average pre-post ES, medications were more effective than psychotherapies. Pre-post ES for psychotherapies did not differ from pill placebos; this finding cannot be explained by heterogeneity, publication bias or allegiance effects. However, the decision on whether to choose psychotherapy, medications or a combination of the two should be left to the patient as drugs may have side effects, interactions and contraindications.

International clinical psychopharmacology · meta-analysis · 298 citationsread the source →

Interventions to support the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic: a mixed methods systematic review.

Background: Evidence from disease epidemics shows that healthcare workers are at risk of developing short- and long-term mental health problems. The World Health Organization (WHO) has warned about the potential negative impact of the COVID-19 crisis on the mental well-being of health and social care professionals. Symptoms of mental health problems commonly include depression, anxiety, stress, and additional cognitive and social problems; these can impact on function in the workplace. The mental health and resilience (ability to cope with the negative effects of stress) of frontline health and social care professionals ('frontline workers' in this review) could be supported during disease epidemics by workplace interventions, interventions to support basic daily needs, psychological support interventions, pharmacological interventions, or a combination of any or all of these. Objectives: Objective 1: to assess the effects of interventions aimed at supporting the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic. Objective 2: to identify barriers and facilitators that may impact on the implementation of interventions aimed at supporting the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic. Search methods: On 28 May 2020 we searched the Cochrane Database of Systematic Reviews, CENTRAL, MEDLINE, Embase, Web of Science, PsycINFO, CINAHL, Global Index Medicus databases and WHO Institutional Repository for Information Sharing. We also searched ongoing trials registers and Google Scholar. We ran all searches from the year 2002 onwards, with no language restrictions. Selection criteria: We included studies in which participants were health and social care professionals working at the front line during infectious disease outbreaks, categorised as epidemics or pandemics by WHO, from 2002 onwards. For objective 1 we included quantitative evidence from randomised trials, non-randomised trials, controlled before-after studies and interrupted time series studies, which investigated the effect of any intervention to support mental health or resilience, compared to no intervention, standard care, placebo or attention control intervention, or other active interventions. For objective 2 we included qualitative evidence from studies that described barriers and facilitators to the implementation of interventions. Outcomes critical to this review were general mental health and resilience. Additional outcomes included psychological symptoms of anxiety, depression or stress; burnout; other mental health disorders; workplace staffing; and adverse events arising from interventions. Data collection and analysis: Pairs of review authors independently applied selection criteria to abstracts and full papers, with disagreements resolved through discussion. One review author systematically extracted data, cross-checked by a second review author. For objective 1, we assessed risk of bias of studies of effectiveness using the Cochrane 'Risk of bias' tool. For objective 2, we assessed methodological limitations using either the CASP (Critical Appraisal Skills Programme) qualitative study tool, for qualitative studies, or WEIRD (Ways of Evaluating Important and Relevant Data) tool, for descriptive studies. We planned meta-analyses of pairwise comparisons for outcomes if direct evidence were available. Two review authors extracted evidence relating to barriers and facilitators to implementation, organised these around the domains of the Consolidated Framework of Implementation Research, and used the GRADE-CERQual approach to assess confidence in each finding. We planned to produce an overarching synthesis, bringing quantitative and qualitative findings together. Main results: We included 16 studies that reported implementation of an intervention aimed at supporting the resilience or mental health of frontline workers during disease outbreaks (severe acute respiratory syndrome (SARS): 2; Ebola: 9; Middle East respiratory syndrome (MERS): 1; COVID-19: 4). Interventions studied included workplace interventions, such as training, structure and communication (6 studies); psychological support interventions, such as counselling and psychology services (8 studies); and multifaceted interventions (2 studies). Objective 1: a mixed-methods study that incorporated a cluster-randomised trial, investigating the effect of a work-based intervention, provided very low-certainty evidence about the effect of training frontline healthcare workers to deliver psychological first aid on a measure of burnout. Objective 2: we included all 16 studies in our qualitative evidence synthesis; we classified seven as qualitative and nine as descriptive studies. We identified 17 key findings from multiple barriers and facilitators reported in studies. We did not have high confidence in any of the findings; we had moderate confidence in six findings and low to very low confidence in 11 findings. We are moderately confident that the following two factors were barriers to intervention implementation: frontline workers, or the organisations in which they worked, not being fully aware of what they needed to support their mental well-being; and a lack of equipment, staff time or skills needed for an intervention. We are moderately confident that the following three factors were facilitators of intervention implementation: interventions that could be adapted for local needs; having effective communication, both formally and socially; and having positive, safe and supportive learning environments for frontline workers. We are moderately confident that the knowledge or beliefs, or both, that people have about an intervention can act as either barriers or facilitators to implementation of the intervention. Authors' conclusions: There is a lack of both quantitative and qualitative evidence from studies carried out during or after disease epidemics and pandemics that can inform the selection of interventions that are beneficial to the resilience and mental health of frontline workers. Alternative sources of evidence (e.g. from other healthcare crises, and general evidence about interventions that support mental well-being) could therefore be used to inform decision making. When selecting interventions aimed at supporting frontline workers' mental health, organisational, social, personal, and psychological factors may all be important. Research to determine the effectiveness of interventions is a high priority. The COVID-19 pandemic provides unique opportunities for robust evaluation of interventions. Future studies must be developed with appropriately rigorous planning, including development, peer review and transparent reporting of research protocols, following guidance and standards for best practice, and with appropriate length of follow-up. Factors that may act as barriers and facilitators to implementation of interventions should be considered during the planning of future research and when selecting interventions to deliver within local settings.

The Cochrane database of systematic reviews · meta-analysis · 415 citationsread the source →

Health and financial costs of adverse childhood experiences in 28 European countries: a systematic review and meta-analysis.

Background: Adverse childhood experiences (ACEs) are associated with increased health risks across the life course. We aimed to estimate the annual health and financial burden of ACEs for 28 European countries. Methods: In this systematic review and meta-analysis, we searched MEDLINE, CINAHL, PsycINFO, Applied Social Sciences Index and Abstracts, Criminal Justice Databases, and Education Resources Information Center for quantitative studies (published Jan 1, 1990, to Sept 8, 2020) that reported prevalence of ACEs and risks of health outcomes associated with ACEs. Pooled relative risks were calculated for associations between ACEs and harmful alcohol use, smoking, illicit drug use, high body-mass index, depression, anxiety, interpersonal violence, cancer, type 2 diabetes, cardiovascular disease, stroke, and respiratory disease. Country-level ACE prevalence was calculated using available data. Country-level population attributable fractions (PAFs) due to ACEs were generated and applied to 2019 estimates of disability-adjusted life-years. Financial costs (US$ in 2019) were estimated using an adapted human capital approach. Findings: In most countries, interpersonal violence had the largest PAFs due to ACEs (range 14·7-53·5%), followed by harmful alcohol use (15·7-45·0%), illicit drug use (15·2-44·9%), and anxiety (13·9%-44·8%). Harmful alcohol use, smoking, and cancer had the highest ACE-attributable costs in many countries. Total ACE-attributable costs ranged from $0·1 billion (Montenegro) to $129·4 billion (Germany) and were equivalent to between 1·1% (Sweden and Turkey) and 6·0% (Ukraine) of nations' gross domestic products. Interpretation: Availability of ACE data varies widely between countries and country-level estimates cannot be directly compared. However, findings suggest ACEs are associated with major health and financial costs across European countries. The cost of not investing to prevent ACEs must be recognised, particularly as countries look to recover from the COVID-19 pandemic, which interrupted services and education, and potentially increased risk factors for ACEs. Funding: WHO Regional Office for Europe.

The Lancet. Public health · meta-analysis · 140 citationsread the source →

From grief, guilt pain and stigma to hope and pride - a systematic review and meta-analysis of mixed-method research of the psychosocial impact of stillbirth.

Background: Despite improvements in maternity healthcare services over the last few decades, more than 2.7 million babies worldwide are stillborn each year. The global health agenda is silent about stillbirth, perhaps, in part, because its wider impact has not been systematically analysed or understood before now across the world. Our study aimed to systematically review, evaluate and summarise the current evidence regarding the psychosocial impact of stillbirth to parents and their families, with the aim of improving guidance in bereavement care worldwide. Methods: Systematic review and meta-summary (quantitative aggregation of qualitative findings) of quantitative, qualitative, and mixed-methods studies. All languages and countries were included. Results: Two thousand, six hundred and nineteen abstracts were identified; 144 studies were included. Frequency effect sizes (FES %) were calculated for each theme, as a measure of their prevalence in the literature. Themes ranged from negative psychological symptoms post bereavement (77 · 1) and in subsequent pregnancies (27 · 1), to disenfranchised grief (31 · 2), and incongruent grief (28 · 5), There was also impact on siblings (23 · 6) and on the wider family (2 · 8). They included mixed-feelings about decisions made when the baby died (12 · 5), avoidance of memories (13 · 2), anxiety over other children (7 · 6), chronic pain and fatigue (6 · 9), and a different approach to the use of healthcare services (6 · 9). Some themes were particularly prominent in studies of fathers; grief suppression (avoidance)(18 · 1), employment difficulties, financial debt (5 · 6), and increased substance use (4 · 2). Others found in studies specific to mothers included altered body image (3 · 5) and impact on quality of life (2 · 1). Counter-intuitively, Some themes had mixed connotations. These included parental pride in the baby (5 · 6), motivation for engagement in healthcare improvement (4 · 2) and changed approaches to life and death, self-esteem, and own identity (25 · 7). In studies from low/middle income countries, stigmatisation (13 · 2) and pressure to prioritise or delay conception (9) were especially prevalent. Conclusion: Experiencing the birth of a stillborn child is a life-changing event. The focus of the consequences may vary with parent gender and country. Stillbirth can have devastating psychological, physical and social costs, with ongoing effects on interpersonal relationships and subsequently born children. However, parents who experience the tragedy of stillbirth can develop resilience and new life-skills and capacities. Future research should focus on developing interventions that may reduce the psychosocial cost of stillbirth.

BMC pregnancy and childbirth · meta-analysis · 201 citationsread the source →

Cognitive behavioural therapy for anxiety disorders in children and adolescents.

Background: Previous Cochrane Reviews have shown that cognitive behavioural therapy (CBT) is effective in treating childhood anxiety disorders. However, questions remain regarding the following: up-to-date evidence of the relative efficacy and acceptability of CBT compared to waiting lists/no treatment, treatment as usual, attention controls, and alternative treatments; benefits across a range of outcomes; longer-term effects; outcomes for different delivery formats; and amongst children with autism spectrum disorders (ASD) and children with intellectual impairments. Objectives: To examine the effect of CBT for childhood anxiety disorders, in comparison with waitlist/no treatment, treatment as usual (TAU), attention control, alternative treatment, and medication. Search methods: We searched the Cochrane Common Mental Disorders Controlled Trials Register (all years to 2016), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO (each to October 2019), international trial registries, and conducted grey literature searches. Selection criteria: We included randomised controlled trials of CBT that involved direct contact with the child, parent, or both, and included non-CBT comparators (waitlist/no treatment, treatment as usual, attention control, alternative treatment, medication). Participants were younger than age 19, and met diagnostic criteria for an anxiety disorder diagnosis. Primary outcomes were remission of primary anxiety diagnosis post-treatment, and acceptability (number of participants lost to post-treatment assessment), and secondary outcomes included remission of all anxiety diagnoses, reduction in anxiety symptoms, reduction in depressive symptoms, improvement in global functioning, adverse effects, and longer-term effects. Data collection and analysis: We used standard methodological procedures as recommended by Cochrane. We used GRADE to assess the quality of the evidence. Main results: We included 87 studies and 5964 participants in quantitative analyses. Compared with waitlist/no treatment, CBT probably increases post-treatment remission of primary anxiety diagnoses (CBT: 49.4%, waitlist/no treatment: 17.8%; OR 5.45, 95% confidence interval (CI) 3.90 to 7.60; n = 2697, 39 studies, moderate quality); NNTB 3 (95% CI 2.25 to 3.57) and all anxiety diagnoses (OR 4.43, 95% CI 2.89 to 6.78; n = 2075, 28 studies, moderate quality). Low-quality evidence did not show a difference between CBT and TAU in post-treatment primary anxiety disorder remission (OR 3.19, 95% CI 0.90 to 11.29; n = 487, 8 studies), but did suggest CBT may increase remission from all anxiety disorders compared to TAU (OR 2.74, 95% CI 1.16 to 6.46; n = 203, 5 studies). Compared with attention control, CBT may increase post-treatment remission of primary anxiety disorders (OR 2.28, 95% CI 1.33 to 3.89; n = 822, 10 studies, low quality) and all anxiety disorders (OR 2.75, 95% CI 1.22 to 6.17; n = 378, 5 studies, low quality). There was insufficient available data to compare CBT to alternative treatments on post-treatment remission of primary anxiety disorders, and low-quality evidence showed there may be little to no difference between these groups on post-treatment remission of all anxiety disorders (OR 0.89, 95% CI 0.35 to 2.23; n = 401, 4 studies) Low-quality evidence did not show a difference for acceptability between CBT and waitlist/no treatment (OR 1.09, 95% CI 0.85 to 1.41; n=3158, 45 studies), treatment as usual (OR 1.37, 95% CI 0.73 to 2.56; n = 441, 8 studies), attention control (OR 1.00, 95% CI 0.68 to 1.49; n = 797, 12 studies) and alternative treatment (OR 1.58, 95% CI 0.61 to 4.13; n=515, 7 studies). No adverse effects were reported across all studies; however, in the small number of studies where any reference was made to adverse effects, it was not clear that these were systematically monitored. Results from the anxiety symptom outcomes, broader outcomes, longer-term outcomes and subgroup analyses are provided in the text. We did not find evidence of consistent differences in outcomes according to delivery formats (e.g. individual versus group; amount of therapist contact time) or amongst samples with and without ASD, and no studies included samples of children with intellectual impairments. Authors' conclusions: CBT is probably more effective in the short-term than waiting lists/no treatment, and may be more effective than attention control. We found little to no evidence across outcomes that CBT is superior to usual care or alternative treatments, but our confidence in these findings are limited due to concerns about the amount and quality of available evidence, and we still know little about how best to efficiently improve outcomes.

The Cochrane database of systematic reviews · meta-analysis · 162 citationsread the source →

Probiotics for the prevention of pediatric antibiotic-associated diarrhea.

Background: Antibiotics alter the microbial balance commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via providing gut barrier, restoration of the gut microflora, and other potential mechanisms of action. Objectives: The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. Search methods: MEDLINE, Embase, CENTRAL, CINAHL, and the Web of Science (inception to 28 May 2018) were searched along with registers including the ISRCTN and Clinicaltrials.gov. We also searched the NICE Evidence Services database as well as reference lists from relevant articles. Selection criteria: Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion. Data collection and analysis: Study selection, data extraction, and risk of bias assessment were conducted independently by two authors. Dichotomous data (incidence of AAD, adverse events) were combined using a pooled risk ratio (RR) or risk difference (RD), and continuous data (mean duration of diarrhea) as mean difference (MD), along with corresponding 95% confidence interval (95% CI). We calculated the number needed to treat for an additional beneficial outcome (NNTB) where appropriate. For studies reporting on microbiome characteristics using heterogeneous outcomes, we describe the results narratively. The certainty of the evidence was evaluated using GRADE. Main results: Thirty-three studies (6352 participants) were included. Probiotics assessed included Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., orStreptococcus spp., alone or in combination. The risk of bias was determined to be high in 20 studies and low in 13 studies. Complete case (patients who did not complete the studies were not included in the analysis) results from 33 trials reporting on the incidence of diarrhea show a precise benefit from probiotics compared to active, placebo or no treatment control. After 5 days to 12 weeks of follow-up, the incidence of AAD in the probiotic group was 8% (259/3232) compared to 19% (598/3120) in the control group (RR 0.45, 95% CI 0.36 to 0.56; I² = 57%, 6352 participants; NNTB 9, 95% CI 7 to 13; moderate certainty evidence). Nineteen studies had loss to follow-up ranging from 1% to 46%. After making assumptions for those lost, the observed benefit was still statistically significant using an extreme plausible intention-to-treat (ITT) analysis, wherein the incidence of AAD in the probiotic group was 12% (436/3551) compared to 19% (664/3468) in the control group (7019 participants; RR 0.61; 95% CI 0.49 to 0.77; P <0.00001; I² = 70%). An a priori available case subgroup analysis exploring heterogeneity indicated that high dose (≥ 5 billion CFUs per day) is more effective than low probiotic dose (< 5 billion CFUs per day), interaction P value = 0.01. For the high dose studies the incidence of AAD in the probiotic group was 8% (162/2029) compared to 23% (462/2009) in the control group (4038 participants; RR 0.37; 95% CI 0.30 to 0.46; P = 0.06; moderate certainty evidence). For the low dose studies the incidence of AAD in the probiotic group was 8% (97/1155) compared to 13% (133/1059) in the control group (2214 participants; RR 0.68; 95% CI 0.46 to 1.01; P = 0.02). Again, assumptions for loss to follow-up using an extreme plausible ITT analysis was statistically significant. For high dose studies the incidence of AAD in the probiotic group was 13% (278/2218) compared to 23% (503/2207) in control group (4425 participants; RR 0.54; 95% CI 0.42 to 0.70; P <0.00001; I² = 68%; moderate certainty evidence).None of the 24 trials (4415 participants) that reported on adverse events reported any serious adverse events attributable to probiotics. Adverse event rates were low. After 5 days to 4 weeks follow-up, 4% (86/2229) of probiotics participants had an adverse event compared to 6% (121/2186) of control participants (RD 0.00; 95% CI -0.01 to 0.01; P < 0.00001; I² = 75%; low certainty evidence). Common adverse events included rash, nausea, gas, flatulence, abdominal bloating, and constipation. After 10 days to 12 weeks of follow-up, eight studies recorded data on our secondary outcome, the mean duration of diarrhea; with probiotics reducing diarrhea duration by almost one day (MD -0.91; 95% CI -1.38 to -0.44; P <0.00001; low certainty evidence). One study reported on microbiome characteristics, reporting no difference in changes with concurrent antibiotic and probiotic use. Authors' conclusions: The overall evidence suggests a moderate protective effect of probiotics for preventing AAD (NNTB 9, 95% CI 7 to 13). Using five criteria to evaluate the credibility of the subgroup analysis on probiotic dose, the results indicate the subgroup effect based on high dose probiotics (≥ 5 billion CFUs per day) was credible. Based on high-dose probiotics, the NNTB to prevent one case of diarrhea is 6 (95% CI 5 to 9). The overall certainty of the evidence for the primary endpoint, incidence of AAD based on high dose probiotics was moderate due to the minor issues with risk of bias and inconsistency related to a diversity of probiotic agents used. Evidence also suggests that probiotics may moderately reduce the duration of diarrhea, a reduction by almost one day. The benefit of high dose probiotics (e.g. Lactobacillus rhamnosus orSaccharomyces boulardii) needs to be confirmed by a large well-designed multi-centered randomized trial. It is premature to draw firm conclusions about the efficacy and safety of 'other' probiotic agents as an adjunct to antibiotics in children. Adverse event rates were low and no serious adverse events were attributable to probiotics. Although no serious adverse events were observed among inpatient and outpatient children, including small studies conducted in the intensive care unit and in the neonatal unit, observational studies not included in this review have reported serious adverse events in severely debilitated or immuno-compromised children with underlying risk factors including central venous catheter use and disorders associated with bacterial/fungal translocation.

The Cochrane database of systematic reviews · meta-analysis · 162 citationsread the source →

Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis.

Background: Inflammatory bowel disease (IBD) is a lifelong condition with no cure. Patients with IBD might experience symptoms of common mental disorders such as anxiety and depression because of bidirectional communication via the gut-brain axis and chronicity of symptoms, and because of impaired quality of life and reduced social functioning. However, uncertainties remain about the magnitude of this problem. We aimed to assess prevalence of symptoms of anxiety or depression in adult patients with IBD. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, and PsycINFO for papers published from inception to Sept 30, 2020, reporting observational studies that recruited at least 100 adult patients with IBD and that reported prevalence of symptoms of anxiety or depression according to validated screening instruments. We excluded studies that only used a structured interview to assess for these symptoms and studies that did not provide extractable data. We extracted data from published study reports and calculated pooled prevalences of symptoms of anxiety and depression, odds ratios (OR), and 95% CIs. Findings: Of 5544 studies identified, 77 fulfilled the eligibility criteria, including 30 118 patients in total. Overall, pooled prevalence of anxiety symptoms was 32·1% (95% CI 28·3-36·0) in 58 studies (I2=96·9%) and pooled prevalence of depression symptoms was 25·2% (22·0-28·5) in 75 studies (I2=97·6%). In studies that reported prevalence of anxiety or depression in patients with Crohn's disease and ulcerative colitis within the same study population, patients with Crohn's disease had higher odds of anxiety symptoms (OR 1·2, 95% CI 1·1-1·4) and depression symptoms (1·2, 1·1-1·4) than patients with ulcerative colitis. Overall, women with IBD were more likely to have symptoms of anxiety than were men with IBD (pooled prevalence 33·8% [95% CI 26·5-41·5] for women vs 22·8% [18·7-27·2] for men; OR 1·7 [95% CI 1·2-2·3]). They were also more likely to have symptoms of depression than men were (pooled prevalence 21·2% [95% CI 15·4-27·6] for women vs 16·2% [12·6-20·3] for men; OR 1·3 [95% CI 1·0-1·8]). The prevalence of symptoms of anxiety (57·6% [95% CI 38·6-75·4]) or depression (38·9% [26·2-52·3]) was higher in patients with active IBD than in patients with inactive disease (38·1% [30·9-45·7] for anxiety symptoms and 24·2% [14·7-35·3] for depression symptoms; ORs 2·5 [95% CI 1·5-4·1] for anxiety and 3·1 [1·9-4·9] for depression). Interpretation: There is a high prevalence of symptoms of anxiety and depression in patients with IBD, with up to a third of patients affected by anxiety symptoms and a quarter affected by depression symptoms. Prevalence was also increased in patients with active disease: half of these patients met criteria for anxiety symptoms and a third met criteria for depression symptoms. Encouraging gastroenterologists to screen for and treat these disorders might improve outcomes for patients with IBD. Funding: None.

The lancet. Gastroenterology & hepatology · meta-analysis · 514 citationsread the source →

Therapist-supported Internet cognitive behavioural therapy for anxiety disorders in adults.

Background: Cognitive behavioural therapy (CBT) is an evidence-based treatment for anxiety disorders. Many people have difficulty accessing treatment, due to a variety of obstacles. Researchers have therefore explored the possibility of using the Internet to deliver CBT; it is important to ensure the decision to promote such treatment is grounded in high quality evidence. Objectives: To assess the effects of therapist-supported Internet CBT (ICBT) on remission of anxiety disorder diagnosis and reduction of anxiety symptoms in adults as compared to waiting list control, unguided CBT, or face-to-face CBT. Effects of treatment on quality of life and patient satisfaction with the intervention were also assessed. Search methods: We searched the Cochrane Depression, Anxiety and Neurosis Review Group Specialised Register (CCDANCTR) to 16 March 2015. The CCDANCTR includes relevant randomised controlled trials from MEDLINE, EMBASE, PsycINFO and CENTRAL. We also searched online clinical trial registries and reference lists of included studies. We contacted authors to locate additional trials. Selection criteria: Each identified study was independently assessed for inclusion by two authors. To be included, studies had to be randomised controlled trials of therapist-supported ICBT compared to a waiting list, attention, information, or online discussion group; unguided CBT (that is, self-help); or face-to-face CBT. We included studies that treated adults with an anxiety disorder (panic disorder, agoraphobia, social phobia, post-traumatic stress disorder, acute stress disorder, generalized anxiety disorder, obsessive compulsive disorder, and specific phobia) defined according to the Diagnostic and Statistical Manual of Mental Disorders III, III-R, IV, IV-TR or the International Classification of Disesases 9 or 10. Data collection and analysis: Two authors independently assessed the risk of bias of included studies and judged overall study quality. We used data from intention-to-treat analyses wherever possible. We assessed treatment effect for the dichotomous outcome of clinically important improvement in anxiety using a risk ratio (RR) with 95% confidence interval (CI). For disorder-specific and general anxiety symptom measures and quality of life we assessed continuous scores using standardized mean differences (SMD). We examined statistical heterogeneity using the I(2) statistic. Main results: We screened 1736 citations and selected 38 studies (3214 participants) for inclusion. The studies examined social phobia (11 trials), panic disorder with or without agoraphobia (8 trials), generalized anxiety disorder (5 trials), post-traumatic stress disorder (2 trials), obsessive compulsive disorder (2 trials), and specific phobia (2 trials). Eight remaining studies included a range of anxiety disorder diagnoses. Studies were conducted in Sweden (18 trials), Australia (14 trials), Switzerland (3 trials), the Netherlands (2 trials), and the USA (1 trial) and investigated a variety of ICBT protocols. Three primary comparisons were identified, therapist-supported ICBT versus waiting list control, therapist-supported versus unguided ICBT, and therapist-supported ICBT versus face-to-face CBT.Low quality evidence from 11 studies (866 participants) contributed to a pooled risk ratio (RR) of 3.75 (95% CI 2.51 to 5.60; I(2) = 50%) for clinically important improvement in anxiety at post-treatment, favouring therapist-supported ICBT over a waiting list, attention, information, or online discussion group only. The SMD for disorder-specific symptoms at post-treatment (28 studies, 2147 participants; SMD -1.06, 95% CI -1.29 to -0.82; I(2) = 83%) and general anxiety symptoms at post-treatment (19 studies, 1496 participants; SMD -0.75, 95% CI -0.98 to -0.52; I(2) = 78%) favoured therapist-supported ICBT; the quality of the evidence for both outcomes was low. One study compared unguided CBT to therapist-supported ICBT for clinically important improvement in anxiety at post-treatment, showing no difference in outcome between treatments (54 participants; very low quality evidence). At post-treatment there were no clear differences between unguided CBT and therapist-supported ICBT for disorder-specific anxiety symptoms (5 studies, 312 participants; SMD -0.22, 95% CI -0.56 to 0.13; I(2) = 58%; very low quality evidence) or general anxiety symptoms (2 studies, 138 participants; SMD 0.28, 95% CI -2.21 to 2.78; I(2) = 0%; very low quality evidence).Compared to face-to-face CBT, therapist-supported ICBT showed no significant differences in clinically important improvement in anxiety at post-treatment (4 studies, 365 participants; RR 1.09, 95% CI 0.89 to 1.34; I(2) = 0%; low quality evidence). There were also no clear differences between face-to-face and therapist supported ICBT for disorder-specific anxiety symptoms at post-treatment (7 studies, 450 participants; SMD 0.06, 95% CI -0.25 to 0.37; I(2) = 60%; low quality evidence) or general anxiety symptoms at post-treatment (5 studies, 317 participants; SMD 0.17, 95% CI -0.35 to 0.69; I(2) = 78%; low quality evidence).Overall, risk of bias in included studies was low or unclear for most domains. However, due to the nature of psychosocial intervention trials, blinding of participants and personnel, and outcome assessment tended to have a high risk of bias. Heterogeneity across a number of the meta-analyses was substantial, some was explained by type of anxiety disorder or may be meta-analytic measurement artefact due to combining many assessment measures. Adverse events were rarely reported. Authors' conclusions: Therapist-supported ICBT appears to be an efficacious treatment for anxiety in adults. The evidence comparing therapist-supported ICBT to waiting list, attention, information, or online discussion group only control was low to moderate quality, the evidence comparing therapist-supported ICBT to unguided ICBT was very low quality, and comparisons of therapist-supported ICBT to face-to-face CBT were low quality. Further research is needed to better define and measure any potential harms resulting from treatment. These findings suggest that therapist-supported ICBT is more efficacious than a waiting list, attention, information, or online discussion group only control, and that there may not be a significant difference in outcome between unguided CBT and therapist-supported ICBT; however, this latter finding must be interpreted with caution due to imprecision. The evidence suggests that therapist-supported ICBT may not be significantly different from face-to-face CBT in reducing anxiety. Future research should explore heterogeneity among studies which is reducing the quality of the evidence body, involve equivalence trials comparing ICBT and face-to-face CBT, examine the importance of the role of the therapist in ICBT, and include effectiveness trials of ICBT in real-world settings. A timely update to this review is needed given the fast pace of this area of research.

The Cochrane database of systematic reviews · meta-analysis · 158 citationsread the source →

Temperature dependence of long-term cadmium toxicity in the zebrafish is not explained by liver oxidative stress: evidence from transcript expression to physiology.

Standard ecotoxicity tests are performed at species' specific standard temperatures, but temperature is known to affect chemical toxicity. A temperature increase has been shown to increase cadmium toxicity in several aquatic species but information in fish is scarce. Based on literature we hypothesize that with increasing temperature, cadmium accumulation and oxidative stress increase, resulting in increased toxicity. In this study zebrafish acclimated to 12, 18, 26 (standard temperature) or 34°C for one month, were exposed to 5 μM cadmium for 4 or 28 days at the respective acclimation temperature. Cadmium toxicity (mortality) increased with increasing temperature. PCA showed that the high mortality at 34°C was closely correlated to an increasing tissue cadmium accumulation with increasing temperature, but not to liver oxidative damage under the form of protein carbonyl content or lipid peroxidation (measured as malondialdehyde levels) or liver antioxidative potential. Instead, acclimation to 12°C induced the highest oxidative damage to liver proteins and lipids, and transcript levels of glucose-6P-dehydrogenase, 6P-gluconate-dehydrogenase and glutathione peroxidase were particularly good markers of cold-induced oxidative stress. At this low temperature there was no interaction with cadmium exposure and there was no sign of cadmium sensitivity. Contrastingly, the combined effect of high temperature and cadmium exposure on mortality proved synergistic. Therefore we conclude that interactions between temperature and cadmium toxicity increased with increasing temperature and that this probably played part in increasing cadmium sensitivity. Increased cadmium compartmentalization and protein carbonyl content in liver of zebrafish acclimated to the standard temperature of 26°C probably played part in increased sensitivity towards the same cadmium body burden compared to lower temperatures. On the one hand we recognize and this study even confirms the importance of applying standard temperatures in standard ecotoxicity tests to ensure inter-study comparability. On the other hand temperatures in the field may deviate from standard temperatures and accounting for deviating temperatures, which can alter chemical sensitivity, in regulation can improve environmental protection.

Aquatic toxicology (Amsterdam, Netherlands) · 38 citationsread the source →

Treatment Approaches for Problematic Pornography Use: A Systematic Review.

Problematic pornography use (PPU) is an emerging condition associated with several negative psychological and sexual outcomes. This study aimed to systematically review treatment approaches for PPU. Potentially eligible studies were searched for in PubMed/MEDLINE, Embase, PsycINFO, and Web of Science up to April 1, 2023. The quality of the evidence was assessed with the use of the Joanna Briggs Institute's checklists, the Cochrane risk-of-bias tools, and the GRADE approach. A total of 8936 references were retrieved, and 28 studies were included in the systematic review (n = 500 participants). Included studies were case reports (k = 16), case series (k = 1), quasi-experimental investigations (k = 7), and randomized clinical trials (k = 4). The majority of included studies presented overall low quality and significant risk of bias, with all interventions receiving a low or very low rating according to the GRADE approach. Most studies investigated psychological interventions, with the predominance of second and third wave cognitive behavioral therapy interventions. Pharmacological treatments included opioid antagonists (naltrexone in most cases) and antidepressants, while one study investigated a protocol that included rTMS. Several investigations described the combination of psychological and pharmacological approaches. Most studies did not report on side effects, with online and self-help interventions presenting significant issues in terms of treatment adherence. Even though there are promising options that may have efficacy for the treatment of patients with PPU, the literature in the topic still presents significant limitations that compromise the reaching of more definitive conclusions.

Archives of sexual behavior · systematic review · 9 citationsread the source →

Psychosocial experiences of prostate cancer survivors after treatment: a systematic review of qualitative studies.

Background: Prostate cancer, the second most common male malignancy worldwide, treatment-related complications cause both physical dysfunction and psychosocial sequelae, significantly impairing quality of life. Now requires integrated biopsychosocial rehabilitation beyond disease-focused treatment, comprehensive assessment of psychosocial adaptation and illness perception is essential for developing evidence-based, patient-centered rehabilitation strategies to optimize post-therapy recovery. Objective: This study aims to systematically review and synthesize qualitative evidence on post-treatment psychosocial experiences in prostate cancer patients, thoroughly analyze patients' lived experiences and coping strategies, and provide an evidence-based foundation for establishing a tiered psychosocial support system and developing clinical intervention protocols. Methods: This systematic review followed the Joanna Briggs Institute (JBI) methodology for qualitative meta-aggregation, with reporting structured according to the ENTREQ statement. Evidence was graded using the ConQual approach and critically appraised with the JBI Qualitative Assessment and Review Instrument (JBI-QARI). We systematically searched six major English databases for qualitative or mixed-methods studies investigating psychosocial experiences in post-treatment prostate cancer patients, with the literature search updated to February 28, 2024. Two reviewers independently performed study selection, followed by collaborative thematic synthesis to identify core themes. Results: A total of 22 studies from 12 countries were included, with 65 findings extracted and categorized into 4 synthesized findings consisting of 8 distinct categories: (1) Psychological and emotional responses (fear and anxiety responses, depression and emotional distress); (2) Healthcare information and systemic barriers (disease-related information needs, barriers in healthcare systems); (3) Social support and interpersonal adaptation (support system needs, social role and relationship adaptation); (4) Internal adaptation and external actions (internal psychological adjustment, external coping behaviors). Conclusion: Prostate cancer survivors face multifaceted psychosocial challenges during post-treatment recovery, with psychological and social responses impacting rehabilitation outcomes. Inadequate social support systems and gaps in healthcare information emerge as major barriers to recovery. To address these issues, healthcare providers should enhance communication effectiveness, while policymakers need to strengthen social support networks, government and corporate sectors should implement targeted policies, and family members should provide empathetic understanding and active encouragement, collectively fostering comprehensive patient support. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/recorddashboard, CRD42024537363.

Frontiers in public health · systematic review · 3 citationsread the source →

Breastfeeding at the workplace: a systematic review of interventions to improve workplace environments to facilitate breastfeeding among working women.

Background: Breastfeeding can be affected by maternal employment. This is important considering that in 2019, 47.1% of women globally participated in the labor force. The aim of this study was to review workplace interventions to promote, protect and support breastfeeding practices among working mothers globally. Methods: A systematic review was conducted following the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Observational, experimental and qualitative peer-reviewed studies in English and Spanish, published between 2008 and 2019 were included. The review focused on working women who were pregnant, breastfeeding or who recently had a child, and women's working environments. The outcomes of interest included breastfeeding intentions, initiation, exclusivity and duration, confidence in breastfeeding or breastmilk extraction, and perceived support at workplace. Quality was assessed according to National Institute for Health and Care Excellence (NICE) checklist for systematic reviews. It was registered on PROSPERO (#140624). Results: Data was extracted from 28 quantitative and 9 qualitative studies. The most common interventions were designated spaces for breastfeeding or breastmilk extraction (n = 24), and the support from co-workers (n = 20). The least common interventions were providing breast pumps (n = 4) and giving mothers the flexibility to work from home (n = 3). Studies explored how interventions affected different breastfeeding outcomes including breastfeeding duration, breastfeeding exclusivity, confidence in breastmilk expression, and breastfeeding support. The evidence suggests that workplace interventions help increase the duration of breastfeeding and prevent early introduction of breastmilk substitutes. Having a lactation space, breastmilk extraction breaks, and organizational policies are key strategies. However, to achieve equitable working conditions for breastfeeding mothers, organizational and interpersonal changes need to occur as well. Conclusions: The systematic review revealed that interventions at the workplace are important in protecting, promoting and supporting breastfeeding among working mothers. To achieve equitable work environments and fair nutritional opportunities for infants of working mothers, interventions should focus at the three ecological layers - individual, interpersonal, and organizational. The quality of studies can be improved. There is a need for studies assessing impacts of workplace interventions on infant feeding practices, mothers' self-esteem and outcomes such productivity and abstentionism.

International journal for equity in health · systematic review · 119 citationsread the source →

The Use of Online Posts to Identify Barriers to and Facilitators of HIV Pre-exposure Prophylaxis (PrEP) Among Men Who Have Sex with Men: A Comparison to a Systematic Review of the Peer-Reviewed Literature.

Pre-exposure prophylaxis (PrEP) remains an under-utilized HIV prevention tool among men who have sex with men (MSM). To more comprehensively elucidate barriers and facilitators to PrEP use among US MSM, we conducted a systematic review of peer-reviewed published articles and content analysis of online posts about PrEP. We searched peer-reviewed databases (Medline, Web of Science, Google Scholar) using MESH headings and keywords about PrEP and/or HIV prevention from 2005 to 2015. We included original studies among MSM in the US that reported on barriers, facilitators, or other factors related to PrEP use. We also searched online posts and associated comments (news articles, opinion pieces, blogs and other social media posts) in diverse venues (Facebook, Slate Outward, Huffington Post Gay Voices, Queerty, and My PrEP Experience blog) to identify posts about PrEP. We used content analysis to identify themes and compare potential differences between the peer-reviewed literature and online posts. We identified 25 peer-reviewed articles and 28 online posts meeting inclusion criteria. We identified 48 unique barriers and 46 facilitators to using PrEP. These 94 themes fit into six overarching categories: (1) access (n = 14), (2) attitudes/beliefs (n = 24), (3) attributes of PrEP (n = 13), (4) behaviors (n = 11), (5) sociodemographic characteristics (n = 8), and (6) social network (n = 6). In all categories, analysis of online posts resulted in identification of a greater number of unique themes. Thirty-eight themes were identified in the online posts that were not identified in the peer-reviewed literature. We identified barriers and facilitators to PrEP in online posts that were not identified in a systematic review of the peer-reviewed literature. By incorporating data both from a systematic review of peer-reviewed articles and from online posts, we have identified salient and novel information about barriers to and facilitators of PrEP use. Traditional research approaches may not comprehensively capture current factors important for designing and implementing PrEP related interventions.

AIDS and behavior · systematic review · 68 citationsread the source →

Twitter as a Tool for Health Research: A Systematic Review.

Background: Researchers have used traditional databases to study public health for decades. Less is known about the use of social media data sources, such as Twitter, for this purpose. Objectives: To systematically review the use of Twitter in health research, define a taxonomy to describe Twitter use, and characterize the current state of Twitter in health research. Search methods: We performed a literature search in PubMed, Embase, Web of Science, Google Scholar, and CINAHL through September 2015. Selection criteria: We searched for peer-reviewed original research studies that primarily used Twitter for health research. Data collection and analysis: Two authors independently screened studies and abstracted data related to the approach to analysis of Twitter data, methodology used to study Twitter, and current state of Twitter research by evaluating time of publication, research topic, discussion of ethical concerns, and study funding source. Main results: Of 1110 unique health-related articles mentioning Twitter, 137 met eligibility criteria. The primary approaches for using Twitter in health research that constitute a new taxonomy were content analysis (56%; n = 77), surveillance (26%; n = 36), engagement (14%; n = 19), recruitment (7%; n = 9), intervention (7%; n = 9), and network analysis (4%; n = 5). These studies collectively analyzed more than 5 billion tweets primarily by using the Twitter application program interface. Of 38 potential data features describing tweets and Twitter users, 23 were reported in fewer than 4% of the articles. The Twitter-based studies in this review focused on a small subset of data elements including content analysis, geotags, and language. Most studies were published recently (33% in 2015). Public health (23%; n = 31) and infectious disease (20%; n = 28) were the research fields most commonly represented in the included studies. Approximately one third of the studies mentioned ethical board approval in their articles. Primary funding sources included federal (63%), university (13%), and foundation (6%). Conclusions: We identified a new taxonomy to describe Twitter use in health research with 6 categories. Many data elements discernible from a user's Twitter profile, especially demographics, have been underreported in the literature and can provide new opportunities to characterize the users whose data are analyzed in these studies. Twitter-based health research is a growing field funded by a diversity of organizations. Public health implications. Future work should develop standardized reporting guidelines for health researchers who use Twitter and policies that address privacy and ethical concerns in social media research.

American journal of public health · systematic review · 368 citationsread the source →

The effectiveness of mental health interventions involving non-specialists and digital technology in low-and middle-income countries - a systematic review.

Background: Combining non-specialists and digital technologies in mental health interventions could decrease the mental healthcare gap in resource scarce countries. This systematic review examined different combinations of non-specialists and digital technologies in mental health interventions and their effectiveness in reducing the mental healthcare gap in low-and middle-income countries. Methods: Literature searches were conducted in four databases (September 2023), three trial registries (January-February 2022), and using forward and backward citation searches (May-June 2022). The review included primary studies on mental health interventions combining non-specialists and digital technologies in low-and middle-income countries. The outcomes were: (1) the mental health of intervention receivers and (2) the competencies of non-specialists to deliver mental health interventions. Data were expressed as standardised effect sizes (Cohen's d) and narratively synthesised. Risk of bias assessment was conducted using the Cochrane risk-of-bias tools for individual and cluster randomised and non-randomised controlled trials. Results: Of the 28 included studies (n = 32 interventions), digital technology was mainly used in non-specialist primary-delivery treatment models for common mental disorders or subthreshold symptoms. The competencies of non-specialists were improved with digital training (d ≤ 0.8 in 4/7 outcomes, n = 4 studies, 398 participants). The mental health of receivers improved through non-specialist-delivered interventions, in which digital technologies were used to support the delivery of the intervention (d > 0.8 in 24/40 outcomes, n = 11, 2469) or to supervise the non-specialists' work (d = 0.2-0.8 in 10/17 outcomes, n = 3, 3096). Additionally, the mental health of service receivers improved through digitally delivered mental health services with non-specialist involvement (d = 0.2-0.8 in 12/27 outcomes, n = 8, 2335). However, the overall certainty of the evidence was poor. Conclusion: Incorporating digital technologies into non-specialist mental health interventions tended to enhance non-specialists' competencies and knowledge in intervention delivery, and had a positive influence on the severity of mental health problems, mental healthcare utilization, and psychosocial functioning outcomes of service recipients, primarily within primary-deliverer care models. More robust evidence is needed to compare the magnitude of effectiveness and identify the clinical relevance of specific digital functions. Future studies should also explore long-term and potential adverse effects and interventions targeting men and marginalised communities.

BMC public health · systematic review · 30 citationsread the source →

Digital Mental Health Interventions for Depression, Anxiety, and Enhancement of Psychological Well-Being Among College Students: Systematic Review.

Background: College students are increasingly reporting common mental health problems, such as depression and anxiety, and they frequently encounter barriers to seeking traditional mental health treatments. Digital mental health interventions, such as those delivered via the Web and apps, offer the potential to improve access to mental health treatment. Objective: This study aimed to review the literature on digital mental health interventions focused on depression, anxiety, and enhancement of psychological well-being among samples of college students to identify the effectiveness, usability, acceptability, uptake, and adoption of such programs. Methods: We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (registration number CRD42018092800), and the search strategy was conducted by a medical research librarian in the following databases: MEDLINE (Ovid), EMBASE (Elsevier), PsycINFO (EbscoHost), the Cochrane Library (Wiley), and Web of Science (Thomson Reuters) from the date of inception to April 2019. Data were synthesized using a systematic narrative synthesis framework, and formal quality assessments were conducted to address the risk of bias. Results: A total of 89 studies met the inclusion criteria. The majority of interventions (71/89, 80%) were delivered via a website, and the most common intervention was internet-based cognitive behavioral therapy (28, 31%). Many programs (33, 37%) featured human support in the form of coaching. The majority of programs were either effective (42, 47%) or partially effective (30, 34%) in producing beneficial changes in the main psychological outcome variables. Approximately half of the studies (45, 51%) did not present any usability or acceptability outcomes, and few studies (4, 4%) examined a broad implementation of digital mental health interventions on college campuses. Quality assessments revealed a moderate-to-severe risk of bias in many of the studies. Conclusions: Results suggest that digital mental health interventions can be effective for improving depression, anxiety, and psychological well-being among college students, but more rigorous studies are needed to ascertain the effective elements of these interventions. Continued research on improving the user experience of, and thus user engagement with, these programs appears vital for the sustainable implementation of digital mental health interventions on college campuses.

Journal of medical Internet research · systematic review · 426 citationsread the source →

Behavioural and cognitive-behavioural interventions for outwardly directed aggressive behaviour in people with intellectual disabilities.

Background: Outwardly directed aggressive behaviour in people with intellectual disabilities is a significant issue that may lead to poor quality of life, social exclusion and inpatient psychiatric admissions. Cognitive and behavioural approaches have been developed to manage aggressive behaviour but the effectiveness of these interventions on reducing aggressive behaviour and other outcomes are unclear. This is the third update of this review and adds nine new studies, resulting in a total of 15 studies in this review. Objectives: To evaluate the efficacy of behavioural and cognitive-behavioural interventions on outwardly directed aggressive behaviour compared to usual care, wait-list controls or no treatment in people with intellectual disability. We also evaluated enhanced interventions compared to non-enhanced interventions. Search methods: We used standard, extensive Cochrane search methods. The latest search date was March 2022. We revised the search terms to include positive behaviour support (PBS). Selection criteria: We included randomised and quasi-randomised trials of children and adults with intellectual disability of any duration, setting and any eligible comparator. Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were change in 1. aggressive behaviour, 2. ability to control anger, and 3. adaptive functioning, and 4. Adverse effects: Our secondary outcomes were change in 5. mental state, 6. medication, 7. care needs and 8. quality of life, and 9. frequency of service utilisation and 10. user satisfaction data. We used GRADE to assess certainty of evidence for each outcome. We expressed treatment effects as mean differences (MD) or odds ratios (OR), with 95% confidence intervals (CI). Where possible, we pooled data using a fixed-effect model. Main results: This updated version comprises nine new studies giving 15 included studies and 921 participants. The update also adds new interventions including parent training (two studies), mindfulness-based positive behaviour support (MBPBS) (two studies), reciprocal imitation training (RIT; one study) and dialectical behavioural therapy (DBT; one study). It also adds two new studies on PBS. Most studies were based in the community (14 studies), and one was in an inpatient forensic service. Eleven studies involved adults only. The remaining studies involved children (one study), children and adolescents (one study), adolescents (one study), and adolescents and adults (one study). One study included boys with fragile X syndrome. Six studies were conducted in the UK, seven in the USA, one in Canada and one in Germany. Only five studies described sources of funding. Four studies compared anger management based on cognitive behaviour therapy to a wait-list or no treatment control group (n = 263); two studies compared PBS with treatment as usual (TAU) (n = 308); two studies compared carer training on mindfulness and PBS with PBS only (n = 128); two studies involving parent training on behavioural approaches compared to wait-list control or TAU (n = 99); one study of mindfulness to a wait-list control (n = 34); one study of adapted dialectal behavioural therapy compared to wait-list control (n = 21); one study of RIT compared to an active control (n = 20) and one study of modified relaxation compared to an active control group (n = 12). There was moderate-certainty evidence that anger management may improve severity of aggressive behaviour post-treatment (MD -3.50, 95% CI -6.21 to -0.79; P = 0.01; 1 study, 158 participants); very low-certainty evidence that it might improve self-reported ability to control anger (MD -8.38, 95% CI -14.05 to -2.71; P = 0.004, I2 = 2%; 3 studies, 212 participants), adaptive functioning (MD -21.73, 95% CI -36.44 to -7.02; P = 0.004; 1 study, 28 participants) and psychiatric symptoms (MD -0.48, 95% CI -0.79 to -0.17; P = 0.002; 1 study, 28 participants) post-treatment; and very low-certainty evidence that it does not improve quality of life post-treatment (MD -5.60, 95% CI -18.11 to 6.91; P = 0.38; 1 study, 129 participants) or reduce service utilisation and costs at 10 months (MD 102.99 British pounds, 95% CI -117.16 to 323.14; P = 0.36; 1 study, 133 participants). There was moderate-certainty evidence that PBS may reduce aggressive behaviour post-treatment (MD -7.78, 95% CI -15.23 to -0.32; P = 0.04, I2 = 0%; 2 studies, 275 participants) and low-certainty evidence that it probably does not reduce aggressive behaviour at 12 months (MD -5.20, 95% CI -13.27 to 2.87; P = 0.21; 1 study, 225 participants). There was low-certainty evidence that PBS does not improve mental state post-treatment (OR 1.44, 95% CI 0.83 to 2.49; P = 1.21; 1 study, 214 participants) and very low-certainty evidence that it might not reduce service utilisation at 12 months (MD -448.00 British pounds, 95% CI -1660.83 to 764.83; P = 0.47; 1 study, 225 participants). There was very low-certainty evidence that mindfulness may reduce incidents of physical aggression (MD -2.80, 95% CI -4.37 to -1.23; P < 0.001; 1 study; 34 participants) and low-certainty evidence that MBPBS may reduce incidents of aggression post-treatment (MD -10.27, 95% CI -14.86 to -5.67; P < 0.001, I2 = 87%; 2 studies, 128 participants). Reasons for downgrading the certainty of evidence were risk of bias (particularly selection and performance bias); imprecision (results from single, often small studies, wide CIs, and CIs crossing the null effect); and inconsistency (statistical heterogeneity). Authors' conclusions: There is moderate-certainty evidence that cognitive-behavioural approaches such as anger management and PBS may reduce outwardly directed aggressive behaviour in the short term but there is less certainty about the evidence in the medium and long term, particularly in relation to other outcomes such as quality of life. There is some evidence to suggest that combining more than one intervention may have cumulative benefits. Most studies were small and there is a need for larger, robust randomised controlled trials, particularly for interventions where the certainty of evidence is very low. More trials are needed that focus on children and whether psychological interventions lead to reductions in the use of psychotropic medications.

The Cochrane database of systematic reviews · systematic review · 6 citationsread the source →

Comparative effectiveness of continuation and maintenance treatments for persistent depressive disorder in adults.

Background: Persistent depressive disorder (PDD) is defined as a depressive disorder with a minimum illness duration of two years, including four diagnostic subgroups (dysthymia, chronic major depression, recurrent major depression with incomplete remission between episodes, and double depression). Persistent forms of depression represent a substantial proportion of depressive disorders, with a lifetime prevalence ranging from 3% to 6% in the Western world. Growing evidence indicates that PDD responds well to several acute interventions, such as combined psychological and pharmacological treatments. Yet, given the high rates of relapse and recurrences of depression following response to acute treatment, long-term continuation and maintenance therapy are of great importance. To date, there has been no evidence synthesis available on continuation and maintenance treatments of PDDs. Objectives: To assess the effects of pharmacological and psychological (either alone or combined) continuation and maintenance treatments for persistent depressive disorder, in comparison with each other, placebo (drug/attention placebo/non-specific treatment control), and treatment as usual (TAU). Continuation treatments are defined as treatments given to currently remitted people (remission is defined as depressive symptoms dropping below case level) or to people who previously responded to an antidepressant treatment. Maintenance therapy is given during recovery (which is defined as remission lasting longer than six months). Search methods: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 28 September 2018. An earlier search of these databases was also conducted for RCTs via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 Dec 2015). In addition we searched grey literature resources as well as the international trial registers ClinicalTrials.gov and ICTRP to 28 September 2018. We screened reference lists of included studies and contacted the first author of all included studies. Selection criteria: We included randomized (RCTs) and non-randomized controlled trials (NRCTs) in adults with formally diagnosed PDD, receiving pharmacological, psychological, or combined continuation and maintenance interventions. Data collection and analysis: Two review authors independently selected studies and extracted and analyzed data. The primary efficacy outcome was relapse/recurrence rate of depression. The primary acceptance outcome was dropout due to any reason other than relapse/recurrence. We performed random-effects meta-analyses using risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). Main results: We included 10 studies (seven RCTs, three NRCTs) involving 840 participants in this review, from which five studies investigated continuation treatments and five studies investigated maintenance treatments. Overall, the included studies were at low-to-moderate risk of bias. For the three NRCTs, the most common source of risk of bias was selection of reported results. For the seven RCTs, the most common sources of risk of bias was non-blinding of outcome assessment and other bias (especially conflict of interest due to pharmaceutical sponsoring).Pharmacological continuation and maintenance therapiesThe most common comparison was antidepressant medication versus tablet placebo (five studies). Participants taking antidepressant medication were probably less likely to relapse or to experience a recurrent episode compared to participants in the placebo group at the end of the intervention (13.9% versus 33.8%, RR 0.41, 95% CI 0.21 to 0.79; participants = 383; studies = 4; I² = 54%, moderate quality evidence). Overall dropout rates may be similar between participants in the medication and placebo group (23.0% versus 25.5%, RR 0.90, 95% CI 0.39 to 2.11; RCTs = 4; participants = 386; I² = 64%, low quality evidence). However, sensitivity analyses showed that the primary outcome (rate of relapse/recurrence) showed no evidence of a difference between groups when only including studies with low risk of bias. None of the studies compared pharmacological or psychological treatments versus TAU.Psychological continuation and maintenance therapiesOne study compared psychological therapies versus attention placebo/non-specific control. One study compared psychotherapy with medication. The results of the studies including psychotherapy might indicate that continued or maintained psychotherapy could be a useful intervention compared to no treatment or antidepressant medication. However, the body of evidence for these comparisons was too small and uncertain to draw any high quality conclusions. Combined psychological and pharmacological continuation and maintenance therapiesThree studies compared combined psychological and pharmacological therapies with pharmacological therapies alone. One study compared combined psychological and pharmacological therapies with psychotherapeutic therapies alone. However, the body of evidence for these comparisons was too small and uncertain to draw any high quality conclusionsComparison of different antidepressant medications Two studies reported data on the direct comparison of two antidepressants. However, the body of evidence for this comparison was too small and uncertain to draw any high quality conclusions. Authors' conclusions: Currently, it is uncertain whether continued or maintained pharmacotherapy (or both) with the reviewed antidepressant agents is a robust treatment for preventing relapse and recurrence in people with PDD, due to moderate or high risk of bias as well as clinical heterogeneity in the analyzed studies. For all other comparisons, the body of evidence was too small to draw any final conclusions, although continued or maintained psychotherapy might be effective compared to no treatment. There is need for more high quality trials of psychological interventions. Further studies should address health-related quality of life and adverse events more precisely, as well as assessing follow-up data.

The Cochrane database of systematic reviews · systematic review · 29 citationsread the source →

Randomized Controlled Trials of Psychoeducation Modalities in the Management of Bipolar Disorder: A Systematic Review.

Objective: This review sought to summarize the extant literature on the efficacy of 4 modalities of psychoeducation (individual, group, family, internet- based) in the management of patients with bipolar disorder. Data sources: We searched the digital databases (Science Direct, Scopus, PubMed/MEDLINE) for relevant randomized controlled trials (RCTs) pertaining to psychoeducation in bipolar disorder from inception to February 2017. Keywords and combinations used included psychoeducation, bipolar disorder, individual, family, group, and internet. Reference lists of review articles were also used for retrieval of relevant articles. Study selection: We retrieved 48 studies and ultimately reviewed 40 RCTs meeting inclusion criteria. Studies were included if they were in English, were RCTs of different psychoeducation modalities managing patients with bipolar disorder, and used standardized assessment of outcomes of psychoeducation. Data extraction: We examined each of the selected publications for relevant data. Results: The majority of psychoeducation RCTs (28 of 40 studies, 70.0%) focused on group and family psychoeducation, with positive benefits reported in clinical outcomes, treatment, and functioning measures. Group psychoeducation was associated with reduced illness recurrences, decreased number and duration of hospitalizations, increased time to illness relapse, better treatment adherence, higher therapeutic lithium levels, and reduced stigma. Family psychoeducation was associated with reductions in illness recurrence, hospitalization rates, and better illness trajectory as well as increased caregiver knowledge, skills, support, and sense of well-being and reduced caregiver burden. There are fewer RCTs on individual and internet-based psychoeducation, with findings being inconsistent or negative. Conclusions: Future studies may include direct comparisons of different psychoeducation modalities to elucidate specific benefits of unique psychoeducation interventions at different phases of bipolar disorder.

The Journal of clinical psychiatry · systematic review · 27 citationsread the source →

Rational snacking: young children's decision-making on the marshmallow task is moderated by beliefs about environmental reliability.

Children are notoriously bad at delaying gratification to achieve later, greater rewards (e.g., Piaget, 1970)-and some are worse at waiting than others. Individual differences in the ability-to-wait have been attributed to self-control, in part because of evidence that long-delayers are more successful in later life (e.g., Shoda, Mischel, & Peake, 1990). Here we provide evidence that, in addition to self-control, children's wait-times are modulated by an implicit, rational decision-making process that considers environmental reliability. We tested children (M=4;6, N=28) using a classic paradigm-the marshmallow task (Mischel, 1974)-in an environment demonstrated to be either unreliable or reliable. Children in the reliable condition waited significantly longer than those in the unreliable condition (p<0.0005), suggesting that children's wait-times reflected reasoned beliefs about whether waiting would ultimately pay off. Thus, wait-times on sustained delay-of-gratification tasks (e.g., the marshmallow task) may not only reflect differences in self-control abilities, but also beliefs about the stability of the world.

Cognition · 171 citationsread the source →

A patient-level meta-analysis of studies evaluating vagus nerve stimulation therapy for treatment-resistant depression.

Objective: To compare response and remission rates in depressed patients with chronic treatment-resistant depression (TRD) treated with vagus nerve stimulation (VNS) Therapy(®) plus treatment as usual (VNS + TAU) or TAU alone in a meta-analysis using Bayesian hierarchical models. Data sources and study selection: Six outpatient, multicenter, clinical trials that have evaluated VNS + TAU or TAU in TRD, including two single-arm studies of VNS + TAU (n = 60 and n = 74), a randomized study of VNS + TAU versus TAU (n = 235), a randomized study of VNS + TAU comparing different VNS stimulation intensities (n = 331), a nonrandomized registry of VNS + TAU versus TAU (n = 636), and a single-arm study of TAU (n = 124) to provide longer-term, control data for comparison with VNS-treated patients. Data extraction: A systematic review of individual patient-level data based on the intent-to-treat principle, including all patients who contributed more than one post-baseline visit. Response was based on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions scale's Improvement subscale (CGI-I), as these were the two clinician-rated measures common across all or most studies. Remission was based on the MADRS. Results: Outcomes were compared from baseline up to 96 weeks of treatment with VNS + TAU (n = 1035) versus TAU (n = 425). The MADRS response rate for VNS + TAU at 12, 24, 48, and 96 weeks were 12%, 18%, 28%, and 32% versus 4%, 7%, 12%, and 14% for TAU. The MADRS remission rate for VNS + TAU at 12, 24, 48, and 96 weeks were 3%, 5%, 10%, and 14% versus 1%, 1%, 2%, and 4%, for TAU. Adjunctive VNS Therapy was associated with a greater likelihood of response (odds ratio [OR] = 3.19, 95% confidence interval [CI]: 2.12, 4.66) and remission (OR = 4.99, CI: 2.93, 7.76), compared with TAU. For patients who had responded to VNS + TAU at 24 weeks, sustained response was more likely at 48 weeks (OR = 1.98, CI: 1.34, 3.01) and at 96 weeks (OR = 3.42, CI: 1.78, 7.31). Similar results were observed for CGI-I response. Conclusion: For patients with chronic TRD, VNS + TAU has greater response and remission rates that are more likely to persist than TAU.

Medical devices (Auckland, N.Z.) · 91 citationsread the source →