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A recent meta-analysis of antidepressant trials is the largest conducted to date. Although it claims to prove antidepressant effectiveness beyond dispute, the main outcome is response rates, which are derived from continuous data in a process that can inflate differences between groups. The standardised mean difference of 0.3 is in line with other meta-analyses that show small differences between antidepressants and placebo that are unlikely to be clinically significant. Other factors likely to exaggerate the effects are discussed, and evidence on associations between antidepressant effects and severity and outcomes of long-term treatment is considered. Clinicians need to have open discussions with patients about the limitations of antidepressant research, the lack of evidence that antidepressants correct a chemical imbalance or other brain abnormality, and the range of adverse effects and mental and physical alterations they can produce.
This article explores an alternative understanding of how psychiatric drugs work that is referred to as the drug-centred model of drug action. Unlike the current disease-centred model, which suggests that psychiatric drugs work by correcting an underlying brain abnormality, the drug-centred model emphasises how psychiatric drugs affect mental states and behaviour by modifying normal brain processes. The alterations produced may impact on the emotional and behavioural problems that constitute the symptoms of mental disorders.
Arguments are put forward that justify the consideration of the drug-centred model. The research necessary to support the prescription of drugs according to such a model is explored.
Evidence from neurochemistry and comparative drug trials do not confirm the disease-centred model of drug action. Since psychiatric drugs are recognised to have mind- and behaviour-altering properties, the drug-centred model constitutes a plausible alternative. The drug-centred model suggests that research is needed to identify all the alterations produced by various sorts of drugs, both acute and long term, and how these might interact with the symptoms and problems associated with different mental disorders. This requires detailed animal and volunteer studies and data from patients prescribed drug treatment long term, along with placebo-controlled and comparative trials that look at the overall impact of drug-induced alterations on well-being and functioning as well as symptoms. Research is also needed on alternative ways of fulfilling the function of drug treatment. The moral aspect of using drugs to modify behaviour rather than treat disease needs honest and transparent consideration.
It is hoped this discussion will encourage the psychiatric and pharmaceutical research community to provide more of the information that is required to use psychiatric drugs safely and effectively.
Immediate-release (IR) quetiapine has been used to treat schizophrenia since 1997, although all the principal placebo-controlled trials have >50% missing outcome data. New studies with relatively lower rates of participant withdrawal have since been published.
To assess the efficacy and adverse effects of quetiapine IR for schizophrenia, with consideration of outcome quality and clinical meaningfulness of results, and to examine the potential impact of missing data on the main efficacy findings.
We conducted a systematic review and meta-analysis of randomised controlled trials comparing quetiapine IR and placebo (or subtherapeutic dose in relapse prevention trials) for the treatment of schizophrenia (PROSPERO registration CRD4201100165). Primary outcomes were change in overall symptoms and response rates. We also examined whether high rates of participant withdrawal (⩾50%) attenuated effect sizes, and assessed the impact of making different assumptions about these people's outcomes.
We identified 15 relevant trials (including 2 unpublished), providing the first 12-week data for this drug and the first data on self-reported quality of life. We found quetiapine IR to have a weighted mean difference (WMD) of 6.5 points (95% CI −8.9 to −4) on Positive and Negative Syndrome Scale (PANSS) total scores, which corresponds to a standardised mean difference (SMD) of −0.33 (95% CI −0.46 to −0.21). Longer trials reported larger mean differences favouring quetiapine IR, but the overall estimate was smaller if more conservative assumptions about the outcomes of people who left the trial early were made. Approximately 21 people needed to take quetiapine IR for 1 person to experience at least a 50% improvement in PANSS score. No difference in quality of life was observed (two RCTs), although small to moderate improvements in social functioning were found (three RCTs). Quetiapine IR caused sedation and increased rates of clinically significant weight gain, but no extrapyramidal effects were observed.
Quetiapine IR has a small beneficial effect on overall psychotic symptoms over 2–12 weeks, but also leads to weight gain and sedation.
People with schizophrenia are often found to have smaller brains and larger brain ventricles than normal, but the role of antipsychotic medication remains unclear.
We conducted a systematic review of magnetic resonance imaging (MRI) studies. We included longitudinal studies of brain changes in patients taking antipsychotic drugs and we examined studies of antipsychotic-naive patients for comparison purposes.
Fourteen out of 26 longitudinal studies showed a decline in global brain or grey-matter volume or an increase in ventricular or cerebrospinal fluid (CSF) volume during the course of drug treatment, including the largest studies conducted. The frontal lobe was most consistently affected, but overall changes were diffuse. One large study found different degrees of volume loss with different antipsychotics, and another found that volume changes were associated with taking medication compared with taking none. Analyses of linear associations between drug exposure and brain volume changes produced mixed results. Five out of 21 studies of patients who were drug naive, or had only minimal prior treatment, showed some differences from controls in volumes of interest. No global differences were reported in three studies of drug-naive patients with long-term illness. Studies of high-risk groups have not demonstrated differences from controls in global or lobar brain volumes.
Some evidence points towards the possibility that antipsychotic drugs reduce the volume of brain matter and increase ventricular or fluid volume. Antipsychotics may contribute to the genesis of some of the abnormalities usually attributed to schizophrenia.
One manner in which elephants utilize trees is by removing their bark. This type of utilization is concentrated on the largest trees in the landscape. The role of bark removal in increasing the vulnerability of large trees to fire and the mechanism through which fire damage is mediated were investigated in Kruger National Park, South Africa, by experimentally removing bark and burning Acacia nigrescens stems with diameters ranging between 30 and 68 mm. Also, field surveys were conducted subsequent to natural fires in order to investigate mortality patterns of large trees with dbh greater than 15 cm with bark removed by elephants. An increasing probability of mortality was associated with increasing amounts of bark removal but only if trees were burned. When trees had bark removed but were not burnt, simulating damage only to cambium and phloem, none of the 12 treated stems died in the 4-mo period over which the experiment ran. Moreover, low levels of cambium damage were detected in large burned stems. This suggests that bark removal increases fire-induced xylem damage and that this damage contributes towards stem mortality. In a survey of 437 large trees, bark removal by elephants was frequent on large stems (44%) and larger trees have greater amounts of bark removed. Post-fire mortality of large trees was significantly associated with increasing bark removal and stem diameter. These results indicate that bark removal by elephants increases the vulnerability of stems to fire, resulting in mortality of large stems otherwise protected from fire.
The vectorial capacity of Biomphalaria pfeifferi from Ndiangue, Senegal, was investigated with an allopatric isolate of
Schistosoma mansoni from Nkolbisson, Cameroon. The snail infection rate after exposure to a single miracidium per snail
(MD1) was 56·3%, and 91·6% for snails exposed to 5 miracidia per snail (MD5). The minimum pre-patent period was
21 days. The mean total cercarial production for the MD1 group was 18511 cercariae per snail, and 9757 cercariae for
the MD5 group. The maximum production of cercariae for 1 day was 4892 observed in a snail from the MD1 group at
day 43 post-infection. The mean longevity of snails was higher in group MD1 (88 days p.i.) than in group MD5 (65 days
p.i.). The chronobiological emergence pattern revealed a circadian rhythm with one shedding peak at mid-day. Comparisons
are made with the vectorial capacity of the sympatric combination of B. pfeifferi Senegal/S. mansoni Senegal.
New data on sulphur valence and magmatic oxidation state for Central Andean volcanic rocks, in combination with published data for experimental and natural samples, allow derivation of a simple relationship between magma oxidation state and sulphur speciation. For a number of highly oxidized Central Andean volcanic rocks fO2 has been calculated using magnetite-ilmenite or olivine-spinel pairs and the sulphur valence in glasses has been measured using the peak shift of S-Kα radiation relative to a pyrite standard. Previously published experimental and natural data have been incorporated with a wider range in fO2 and S valence. The variation in sulphur speciation (as S2- or SO42-) as a function of log fO2 is described by an empirical polynomial fit which reproduces the data to within ±0.5 log units and allows use of electron microprobe measurements of the S-Kα wavelength shift for estimation of magmatic oxygen fugacities. This approach is applicable for fO2 between FMQ-2 and FMQ+6, encompassing most terrestrial magmas. The method has been used to calculate the in fO2 conditions under which melt inclusions were trapped in andesitic magmas before magma mixing in two Central Andean volcanoes, and to calculate the oxygen fugacity of a slowly-cooled pyroclastic flow in which the Fe-Ti oxide phases have subsequently re-equilibrated. In combination with Fe-Ti oxide data, two distinct trends emerge for Lascar volcano. Basaltic andesite-andesitic magma chambers follow T-fO2 trends which parallel the FMQ buffer curve, indicating ferrous-ferric iron buffering of oxygen fugacity. Dacitic anhydrite-bearing magmas with admixed basaltic andesite and andesite follow trends of increasing fO2 with decreasing temperature, indicative of buffering of fO2 by SO2-H2S in a co-magmatic gas phase. This trend continues into the metamorphic aureole of the magma chamber, resulting in highly oxidized (close to magnetite-hematite) conditions.
The experiment examined the effect of breed, diet and sex on pig performance and carcass quality. Eight sires of the Duroc and Large White breeds each produced four experimental litters. Two boar and two female pigs from each litter were reared under standard conditions to 38 kg and then one of each sex was allocated to each of two finishing diets. These were cereal-based diets with and without 16 g/kg soya oil. Following slaughter at 80 kg, loin chops taken from half of the pigs (two litters per sire) were subjected to detailed investigation of physical, chemical and organoleptic characteristics. Lifetime live-weight gain was similar for both breeds but Duroc-sired pigs had greater voluntary food intakes and poorer food conversion efficiencies in the finishing stage. They also had greater killing-out proportions (775 v. 755 g/kg, P < 0·001) and backfat thickness at slaughter (284 v. 27·2 mm at P1 + P3, P < 0·05). Fat firmness measured by penetrometer at 4°C was lower in Duroc-sired pigs (738 v. 792 units, P < 0·001). The proportion of extractable intramuscular lipid was greater in chops from Duroc-sired pigs (13·8 v. 10·4 g/kg, P < 0·001). There were no significant effects of breed or diet on the eating quality of the grilled chops as assessed by a trained taste panel and a consumer panel.
During 1988 and 1989, the mesenteric veins of 901 cattle were examined for the presence of schistosomes at the Kandy slaughterhouse (Sri Lanka). The overall prevalence of infection was 31·2%. Animals younger than 2 years were less infected (21·3%) than those older than 5 years (47·9%). Based on the number of paired worms counted, three intensities of infection were recognized: low (1–20 pairs), moderate (21–100 pairs) and heavy (> 100 pairs). Intensities increased with the age of the animals but remained low (average 10 worm pairs). The worm burden increased by approximately 20% for each step in age group. The number of miracidia/100 g faeces was measured in 85 animals of all age groups and intensities of infection; 77% of the samples contained less than 100 miracidia. Miracidia counts decreased with age; moderately and heavily infected animals in each age group had the highest and the lowest counts, respectively. This may be due to a host immune response. The results raise questions on the sensitivity of faecal egg counts as a diagnostic method for visceral schistosomiasis in cattle.
Increasing concern has been expressed about deterioration in the handling and eating quality of pigmeat produced in modern U.K. circumstances. Many of the problems are attributed to excessive leanness. It has been suggested that the Duroc breed may produce a better quality product than current U.K. white breeds as a result of its higher level of intramuscular fat. Diet composition has also changed over time, with increasing use of a wider variety of ingredients and added fats. This experiment was carried out to examine the effects of breed and dietary fat on pigmeat quality characteristics.